SAJCH Vol 12, No 2 (2018)

CHILD HEALTH SOUTH AFRICAN JOURNAL OF

June 2018

Volume 12

Number 2

• Pulmonary hydatidosis: Still unrecognised in endemic regions • Use of the Road-to-Health card by doctors in a tertiary hospital • Sphenoid mucocoele - unusual cause for headaches in teenage boy • Neonatal haemolytic anaemia - a diagnostic approach

CHILD HEALTH SOUTH AFRICAN JOURNAL OF

June 2018

Volume 12

Number 2

CONTENTS Editorial

43 How do we survive and grow to support South African and African paediatrics in the future?

J M Pettifor

44 Monitoring well-baby visits in primary healthcare facilities in a middle-income country 48

FOUNDING EDITOR Prof. N P Khumalo EDITORIAL BOARD Prof. M Adhikari (University of KwaZuluNatal, Durban) Prof. M Kruger (Stellenbosch University) Prof. H Rode (Red Cross War Memorial Children's Hospital, Cape Town) Prof. L Spitz (Emeritus Nuffield Professor of Paediatric Surgery, London) Prof. A Venter (University of the Free State, Bloemfontein) Prof. A Westwood (Red Cross War Memorial Children's Hospital, Cape Town) Prof. D F Wittenberg (University of Pretoria) HEALTH & MEDICAL PUBLISHING GROUP:

Research

EDITOR Prof. J M Pettifor

D G Sokhela, M N Sibiya, N S Gwele

Pulmonary hydatidosis: Still unrecognised in endemic regions – a 10-year review

M Ndlovu, S A Thula, R E M Mphahlele, R Masekela

52 Pattern of cerebral palsy seen in children attending the outpatient paediatric physiotherapy clinics in Osun State tertiary hospitals in Nigeria J O Omole, S A Adegoke, K O Omole, O A Adeyemi

58 Health-related quality of life in children and adolescents with end-stage renal disease receiving dialysis in Johannesburg P N Obiagwu, B Sangweni, G Moonsamy, T Khumalo, C Levy

63 The use of the Road-to-Health card by doctors in a tertiary paediatric hospital setting J I Wiles, G H Swingler

68 The role of kidney injury molecule-1, interleukin-18 and glutathione-S-transferase-π in paediatric HIV-associated nephropathy

CEO AND PUBLISHER Hannah Kikaya EXECUTIVE EDITOR Bridget Farham MANAGING EDITORS Claudia Naidu Naadia van der Bergh TECHNICAL EDITORS Naadia van der Bergh Kirsten Morreira PRODUCTION MANAGER Emma Jane Couzens SENIOR DESIGNER Clinton Griffin CHIEF OPERATING OFFICER Diane Smith | Tel. 012 481 2069 Email: dianes@hmpg.co.za ONLINE SUPPORT Gertrude Fani | Tel. 021 532 1281 Email: publishing@hmpg.co.za

L Nandlal, R Bhimma, T Naicker

FINANCE Tshepiso Mokoena

Case Report

HMPG BOARD OF DIRECTORS Prof. M Lukhele (Chair), Dr M R Abbas, Mrs H Kikaya, Dr M Mbokota, Dr G Wolvaardt

73

Jellyfish envenomation: A chilling toxidrome of seizures and cyanosis – a case report

S Mundkur, S Shashidhara, S Hebbar, A Kumar, S Kanaparthi

76

Sphenoid mucocoele – an unusual cause for headaches in a teenage boy

S E Adam, M Merven

79 The immigration of anaemia – presentation of sickle cell disease in children admitted to a district hospital in Johannesburg: A case series D Azar

81 Neonatal haemolytic anaemia – a diagnostic approach to red cell membrane disorders

84

HEAD OFFICE Block F, Castle Walk Corporate Park, Nossob Street, Erasmuskloof Ext. 3, Pretoria, 0181 EDITORIAL OFFICE Suite 11, Lonsdale Building, Lonsdale Way, Pinelands, 7405 Tel. 021 532 1281 Email: publishing@hmpg.co.za

L Swart, K Naidoo, E Schapkaitz, J Poole,T L Coetzer

ISSN 1999-7671

CPD

Use of editorial material is subject to the Creative Commons Attribution – Noncommercial Works Licence. http://creativecommons.org/licenses/by-nc/4.0 ublished by the Health and Medical Publishing Group, P Suite 11, Lonsdale Building, Lonsdale Way Pinelands 7405 apers for publication should be addressed to the Editor, P via the website: www.sajch.org.za Tel | 021 532 1281 E-mail | publishing@hmpg.co.za ©Copyright: Health and Medical Publishing Group (Pty) Ltd

Cover: Tazzlin, Red Cross War Memorial Children's Hospital Primary School

EDITORIAL

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

How do we survive and grow to support South African and African paediatrics in the future?

Over the past decade, the milieu in which the South African Journal of Child Health (SAJCH) finds itself operating has changed dramatically.

The journal, which is now in its 12th year, is one of a number of specialist journals in the South African Medical Association (SAMA) stable published by its wholly owned publishing company, the Health and Medical Publishing Group. The journal has created a successful niche in supporting the publication of research by young and emerging researchers in the broad field of child health, particularly as it pertains to southern and sub-Saharan Africa. The journal particularly prides itself on supporting the publication of postgraduate research, such as that produced by registrars doing their MMed degrees for specialist registration in South Africa (SA) and other African regions. Its current acceptance rate is just over 50%.

At the time of establishment of the journal, funding of specialist journals was heavily supported by advertising revenue from the pharmaceutical industry, which initially allowed the SAJCH to produce four print issues per year. Although advertising revenue to the SAMA stable of journals has dwindled dramatically over the last two decades, which has necessitated online-only publication, it has been possible to continue to publish open-access issues without charging the authors an article processing or publication fee, through the continued financial support of and encouragement from the SAMA Board. This arrangement is no longer possible, as a result of of the continued escalation in costs. The HMPG Board has proposed the introduction of a publication fee to all its specialist journal editors. The fee is to be paid by the authors on the acceptance of their manuscript for publication by the journal. The details of the publication fee, and which articles and authors will attract it, have not yet been finalised, but as soon as they are, notification will be provided on the journal website.

Several suggestions related to the publication fee have been made, including that only articles attracting the Department of Higher Education and Training (DHET) subsidy will be charged, but that papers written by authors (first and/or senior) who are members of SAMA would have the fee partially or wholly waived,

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and that authors who have contributed substantially to the journal by reviewing articles for the SAJCH could have the fee discounted.

It must be emphasised that the introduction of a publication fee remains a proposal, and that the detail has not been finalised or agreed upon by all the editors involved; however, because of the likelihood that the publication fee will become a reality in the next few months, we felt it important that prospective authors be informed as soon as possible.

On the positive side, it should be pointed out that SAJCH is accredited by the DHET for subsidy purposes, and that the journal is listed, rated, ranked and extracted by Scopus. Further, its openaccess status and full-text availability on the SciELO (Scientific Electronic Library Online) website (http://www.scielo.org/php/ index.php?lang=en) means that full-text articles are available to researchers anywhere in the world.

In closing, I would like to pay tribute to the mainly SA reviewers who continue to provide detailed, independent, blinded assessments of the manuscripts submitted for publication. Many reviewers go beyond the call of duty and provide very helpful and supportive comments and edits using track changes, which provide authors with useful insights into the editorial changes necessary to improve the quality of their manuscript. These reviews maintain and improve the overall quality of the journal and help to separate the SAJCH from the profusion of predatory open-access journals that have flooded the online health journal space.

John M Pettifor

MB BCh, FCPaed (SA), PhD (Med), MASSAf Editor South African Journal of Child Health john.pettifor@wits.ac.za S Afr J Child Health 2018;12(2):42. DOI:10.7196/SAJCH.2018.v12i2.1578

JUNE 2018 Vol. 12 No. 2

RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Monitoring well-baby visits in primary healthcare facilities in a middle-income country D G Sokhela,1 D Nursing; M N Sibiya,2 D Tech Nursing; N S Gwele,3 PhD Department of Nursing, Faculty of Health Sciences, Durban University of Technology, South Africa Office of the Dean, Faculty of Health Sciences, Durban University of Technology, South Africa 3 Vice Chancellor’s Office, Durban University of Technology, South Africa 1 2

Corresponding author: D G Sokhela (dudus@dut.ac.za) Background. Globally, child health services are a priority, but are most acutely felt in underdeveloped and developing countries. Most of the children who live in such countries die from a disease or combination of diseases that could easily have been prevented through immunisations, or treated at a primary healthcare level. Undernutrition contributes to over a third of these deaths. Preventive measures are important to proactively prevent such disease and mortality burdens. Well-baby visits are for babies who come to the clinic for preventive and promotive health, and who are not sick. One of the goals in the National Core Standards is to reduce waiting time in health establishments. However, it is imperative that all necessary assessments are conducted during a well-baby visit. The Road to Health booklet (RtHB) contains the baby’s health record, and is issued to all caregivers, usually on discharge post-delivery. It also contains lists of appropriate assessments that should be performed during each well-baby visit according to age, including immunisations and health promotion messages for caregivers. In South Africa, infant morbidity and mortality rates are decreasing very slowly, requiring effective use of the RtHB to address important applied and research problems.

Objective. To investigate how ‘well babies’ were monitored in primary healthcare facilities.

Methods. A descriptive quantitative cross-sectional survey design was used for retrospective review of 300 babies’ RtHBs, using a checklist developed directly from the assessment page of this booklet. The clinical microsystem model was used to guide the study. Data were analysed using SPSS version 22.0.

Results. Babies were shown to have been immunised in 100% of records, while discussion of side-effects and the management thereof were only recorded in 9.7% (n=20) charts. Records indicated that 98.7% (n=296) of babies were weighed, but only 71% (n=213) of weights were ‘plotted’ and 56.3% (n=169) classified according to the integrated management of childhood illnesses norms.

Conclusion. Based on the findings, this research was able to make a contribution to the body of knowledge about baby monitoring practices in primary healthcare settings.

S Afr J Child Health 2018;12(2):44-47. DOI:10.7196/SAJCH.2018.v12i2.1262

In most middle- and low-income countries, especially in rural areas, child health services are a priority, as child morbidity and mortality remain high; children still die from vaccine-preventable diseases, malnutrition and HIV/AIDS-related illnesses. In South Africa (SA), infant morbidity and mortality rates are decreasing very slowly.[1] The SA democratic government has committed itself to the promotion of health through prevention and education strategies in primary healthcare (PHC) clinics.[2] To fulfil this mandate, the government has prioritised healthcare for children <6 years of age, and healthcare for pregnant and lactating women is provided for free (this policy has since been extended to all PHC users. Furthermore, of the sustainable development goals (SDGs), numbers 1 and 2 aim to reduce poverty and hunger, which remain a challenge in developing countries.

Children <5 years old are the worst affected, with inadequate heightfor-age scores (stunted growth). Poor nutrition causes deaths in these children.[3] Well-baby visits have been implemented for babies who come to the clinic for preventive and promotive healthcare, such as weighing, prophylactic treatments and immunisations.

The Road to Health booklet (RtHB) has been in use since 2011. It is a communication tool between caregivers and healthcare providers, and a health management and educational tool. It contains the revised immunisation schedule, as well as additional health promotion messages.[4] It replaced the Road to Health chart, which was smaller, and difficult to plot weight in. The RtHB lists the assessments to be performed at well-baby visits that are appropriate for age, for timeous and appropriate interventions, as well as a schedule of immunisations

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that must be given. Despite these provisions, there has still been little improvement in child morbidity and mortality. In well-baby clinic visits, care is delivered expeditiously, as this is one of the strategies in place to prevent unnecessary delays and decongest the facility.

Observation of well-baby clinical encounters in PHC facilities in a large SA city indicated that although health professionals were adequately trained and facilities well equipped, routine examination procedures were poorly performed, and there was insufficient growth monitoring and management.[5] Recording in the RtHBs indicated that not all children were weighed, or their weight correctly plotted and correctly interpreted. Immunisations were offered to all eligible babies, while developmental milestones were asked about in only a small percentage of children. Health promotion and prevention activities, such as growth monitoring, immunisation and developmental assessment, were not performed adequately, even though the healthcare providers had all the necessary means available.

The clinical microsystems model,[6] the smallest replicable unit of healthcare, guided the study. It is characterised by five elements: (i) purpose: why the clinical microsystem exists, which in this case is to provide expeditious service; (ii) patients: the people served by the clinical microsystem, well babies and children in this study; (iii) professionals: the staff working in the microsystem; (iv) processes: how care and services are delivered to meet patients’ needs – the care-giving support processes that the clinical microsystem uses to provide care and services; and (v) the patterns that characterise the clinical microsystem’s functioning. For the purposes of this article,

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RESEARCH the elements ‘patients’ and ‘processes’ are discussed. A PHC facility is a clinical microsystem within the administration it is under, and each different service rendered within the facility, such as, in this article, the ‘well-baby clinic’, forms a clinical microsystem within the larger clinic. Good practices in one microsystem can be replicated in other microsystems within the clinic, making their work run more smoothly. The aim of the study was to determine how thoroughly healthcare providers in the well-baby clinic monitor babies.

Methods Design

Ethical approval

The researcher obtained approval from the Durban University of Technology Ethics and Higher Degrees Committee (ref. no.

REC 33/13), as well as from gatekeepers of PHC facilities. Caregivers signed informed consent forms while waiting in the queue for the service. Participant codes were used to maintain confidentiality.

Results

A total of 300 baby records was reviewed. The age range of the babies was 0 - 59 months.

A descriptive cross-sectional design was used to conduct the study in randomly selected PHC facilities in eThekwini district in KwaZuluNatal Province, SA. There are 8 community health centres and 102 PHC facilities in the district. In addition to these, 28 mobile units service the hard-to-reach rural areas.

Patients

Sampling

Processes: Assessments in the well-baby clinic

Two-stage sampling was used: of facilities, and of caregivers. A sample of 20 (32%) of 62 facilities, with an average of 190 users of the wellbaby clinical microsystem a month, was randomly chosen using a fishbowl sampling technique. The names of clinics were written on pieces of paper, put in a bowl and blindly picked out. This technique afforded each facility an equal opportunity to be included in the sample. Thereafter, a systematic sample was taken, where every fifth parent or primary caregiver and legal guardian was asked for the use of the RtHB. Only parents or legal guardians could consent to the study.

Naing’s[7] sample size calculator was used to determine an adequate sample size of facilities, and Daniel’s[8] formula was used to calculate the sample size of RtHBs. It was assumed that 50% of caregivers would be carrying the RtHBs. In this study, a 95% confidence level and a margin of error of .05 was used to calculate the sample size. The sample size calculator produced a total of 285 observations in the 20 facilities within the study, which was rounded off to 300 record reviews of RtHBs, equalling 15 reviews conducted in each facility.

The RtHBs of 300 babies and children were therefore reviewed, in order to determine whether assessments had been captured. Records of babies and children brought in by caregivers who were not their legal guardians were excluded.

Data collection

A 16-item checklist, developed directly from items in the RtHB, was used to determine the recording of assessments conducted to monitor well babies. The items were: weight; weight plotted; integrated management of childhood illness (IMCI) classification of growth, prevention of mother-to-child transmission/HIV status and tuberculosis (TB) status; feeds; date; batch number of immunisation given; signature of the nurse who administered the immunisation; side-effects to be expected; management of side-effects; prophylaxis vitamin A and deworming; milestones; oral health; and next visit.

This ensured consistency and correct documentation, and enabled the researcher to go through a large number of records quickly without missing any items. A ‘yes’ or ‘no’ indicated whether the item had been recorded, and in some cases, ‘N/A’ indicated due to the baby’s age. The researcher sat in a private room for 10 minutes while reviewing the card and completing the checklist. The researcher visited each clinic every day until the required number of RtHBs had been reviewed.

Data analysis

Data were analysed using SPSS version 22 (IBM Corp., USA).

Descriptive statistics illustrating spread, such as proportions, frequencies, ranges and central tendencies such as means, modes medians and standard deviations were computed where appropriate.

Descriptive statistics were used to describe the data, such as the children’s demographic data, and their assessments.

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Demographic data on age and gender were collected. The mean age of the children was 2.49 months (standard deviation 1.957).

Records indicated that there were 51% (n=153) females and 49% (n=147) males.

Analysis of 300 RtHBs found that 208 babies and children had attended the clinic for immunisation, and all had had the immunisation date, batch number and signature of the nurse administering it recorded in 100% (n=208) of the charts. Records indicated that 98.7% (n=296) of babies were weighed, but only 71% (n=213) of the weights were ‘plotted’ in the RtHBs. Depending on the reading of the graph, weights are used to classify growth according to IMCI norms. Classification of growth was recorded in 56.3% (n=169) of the charts. There is a requirement that the HIV status or exposure to HIV from the mother is established from 3 days to 10 weeks of age, and at 6-monthly intervals thereafter until 18 months of age, and then whenever necessary.

There were 172 records in which this was expected to have been recorded; however, records indicated that ‘PMTCT [prevention of mother-to-child transmission]/HIV status’ was only recorded in 77.3% (n=133) of charts. Healthcare providers were supposed to ask about feeding options (exclusive breast or bottle feeding, or mixed feeding) from caregivers of babies that were from birth to 6 months old. Of 137 baby records, feeding was recorded as having been asked about in 73.7% (n=101) of baby records. Vitamin A and deworm prophylactic treatment is routinely given to babies from the age of 6 months, and every 6 months until the child is 60 months old. Baby charts indicated that ‘vitamin A prophylaxis’ was given in 99.3% (n=150) of 151 babies and children, and ‘deworm prophylaxis’ was recorded to have been given in 98.2% (n=113) of 115 babies and children. These included babies and children who were due for the prophylaxis according to age, and those who were catching up because of missing doses at the due age. Caregivers are given a date to bring babies for the next visit, and baby records indicated that ‘booklet next visit’ was recorded in 90% (n=270) of baby records.

However, the record review indicated the following elements as the least often recorded. According to the RtHB, milestones are supposed to be assessed on babies at 6 weeks, 14 weeks, 6 months, 9 months, 18 months, 36 months and 60 months of age, but in this study the milestones were recorded in only 33.5% (n=51) of 152 records of children who were of the correct age for the milestones to be assessed. TB status is supposed to be assessed from the age of 14 weeks, but it was found to be recorded in 12.6% (n=27) of the 214 records. Side-effects to immunisation and the management thereof are to be discussed with caregivers at every immunisation session, either by providing the information or checking previous knowledge. This was found to be recorded as having been done in 9.6% (n=20) of the 208 babies’ charts. Oral health should have been assessed and recorded in 154 charts; however, it was observed that it was not recorded in 100% of these charts (Table 1).

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RESEARCH Table 1. Items recorded in RtHBs Component*

Recorded, n (%)

Immunisation date (n=208) Signature for immunisation (n=208)

208 (100) 208 (100)

Immunisation batch no. (n=208) Weight (n=300) Booking next visit (n=300) Feeds (n=137) Weight plotted (n=300) IMCI growth classification (n=300) Prophylaxis vitamin A (n=151) IMCI - PMTCT/HIV status (n=172) Prophylaxis deworm (n=115) Milestones (n=152) TB status (IMCI) (n=214) Side-effects to be expected (n=208) Management of side-effects (n=208) Oral health (n=154)

208 (100) 296 (98.7) 270 (90) 101 (73.7) 213 (71) 169 (56.3) 150 (99.3) 133 (77.3) 113 (98.2) 51 (33.5) 27 (12.6) 20 (9.6) 20 (9.6) 0 (0)

to 57.3%.[16] After 2 years of treatment, there was significant weight gain in children.

Developmental milestones are normally achieved at different stages of growth and development, at a pace unique to each baby.

However, if these are not assessed, it could affect the baby’s entire future.[17] Children can suffer from tooth decay from a very young age, and so their teeth need to be cared for from as early as 1 year of age. Early childhood caries is a challenge throughout the world, as it may result in loss of teeth if not checked.[18]

Recommendations

RtHB = Right to Health booklet; IMCI = integrated management of childhood illness; PMTCT = prevention of mother-to-child transmission; TB = tuberculosis. *Numbers reflect number of babies whose booklets qualified them for each treatment/check at the time of study.

Discussion

Babies and children assessed in this clinical microsystem were between the ages of 0 and 59 months. Administration of immunisation, dates and batch numbers of vaccines were adequately documented. This indicates the efficiency of immunisation services in the process of the clinical microsystem. If the child becomes sick within 72 hours of receiving an immunisation, an adverse event is recorded. This enables all vaccines with the same batch number to be checked, and all babies who received immunisations from that batch to be monitored for signs of side-effects.

Regular weighing and recording of babies assists in early detection of malnutrition, which may prevent vulnerability to diseases and death, and allow early intervention to be implemented.[9] Deviation from the pattern of child growth indicates that the child might have an illness, or alternatively, lack nutrients in the body.[10] The classification of growth directs the health worker to the relevant/suitable intervention for the child’s nutritional status. It was envisaged that the RtHB would increase the likelihood of interpreting weight and classifying growth.[11] The SA government in 2011 declared support for the promotion of breastfeeding in all health establishments in the Tshwane Declaration[12] as a strategy to curb malnutrition.

Currently, HIV and TB are major health problems in SA. In order to improve maternal and child health, HIV and TB services were integrated into maternal and child healthcare in 2009.[13] Good progress has been made in PMTCT, such as polymerase chain reaction (PCR) testing at birth and prophylactic antiretroviral therapy (ART), as well as lifelong ART for HIV-positive pregnant women, irrespective of CD4 count.

The timing of vitamin A administration was designed to coincide with immunisation, to minimise clinic visits for children 6 - 59 months old.[14] Vitamin A reduces deaths from measles and diarrhoea, and the overall mortality of children <5 years of age. Government has mandated the fortification of staple foods such as maize meal and wheat flour, and products containing 90% of these foods, such as bread, with vitamin A.[15] Worm infestation contributes to anaemia and poor growth. In Nigeria, after deworming with a single dose of albendazole tablet 400 mg, the number of children with normal haemoglobin increased 46

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Good practices found in this clinical microsystem should be replicated in other clinical microsystems within the facility. Health­ care providers need to be reminded of or given in-service training on the use of the RtHB. Emphasis has to be placed on the importance of well babies’ assessments, to improve child morbidity and mortality, which remain a challenge in SA. If healthcare providers were to carry the assessments out appropriately, the country could be well on the way to overcoming some of the obstacles to reaching the SDGs. Improved and effective communication with caregivers about sideeffects to look out for following immunisation is recommended, as this would minimise hospital admissions and deaths. Discussions on how some of these could be managed at home, and which ones to bring the child back to the clinic for, should be seen as vital.

Supportive supervision by clinic managers may assist in identifying staff development requirements regarding child assessments and the recording thereof. Assessment of milestones is very important for early intervention and referral to relevant agents where required, to improve the lives of children.

Limitations

The RtHBs of babies and children brought in by other people other than biological parents and legal guardians were not reviewed.

Crucial information might have been missed from these records.

Conclusion

Well-baby care is an important component of PHC, as all assessments are critical, because the child’s future may depend on them.

Abnormalities might not be detected if these aspects of the RtHB are not completed, recorded and acted upon, which could result in major problems later. Good recording practices are crucial for continuity of care, especially for babies and children, as they are still growing and some abnormalities can still be corrected.

Acknowledgements. I thank the university for the opportunity to study, the supervisors for their support during the study, and SANTRUST for the research methodology training and guidance.

Author contributions. The first author (DGS) was the primary researcher, MNS the supervisor and NSG the co-supervisor of the project.

Funding. The university research and postgraduate office provided funding for the study.

Conflicts of interest. None.

1. United Nations International Children’s Emergency Fund. Young Child Survival and Development. New York: UNICEF, 2011. http://www.unicef.org/ childsurvival/ (accessed 12 March 2015).

2. African National Congress (ANC). The National Health Plan for South Africa.

Pretoria: ANC, 1994.

3. United Nations. Sustainable Development Goals. Washington DC: UN, 2015.

4. Republic of South Africa. Minister Botha Launches Road to Health Booklet.

Pretoria: Government of South Africa, 2011. http://www.gov.za/ministerbotha-launches-road-health-booklet (accessed 5 December 2015).

5. Thandrayen K, Saloojee H. Quality of care offered to children attending primary healthcare clinics in Johannesburg, South Africa. S Afr J Child Health 2010; 4(3):73-77.

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RESEARCH 6. Nelson EC, Batalden PB, Godfrey MM. Value by Design: Developing Clinical Microsystems to achieve Organizational Excellence. London: Jossey-Bass, 2011.

7. Naing L, Winn T, Rusli BN. Sample Size Calculator for Prevalence Studies.

2006. http://www.kck.usm.my/ppsg/stats_resources.htmNaing (accessed 12 March 2013).

8. Daniel WW. Biostatistics: A Foundation for Analysis in the Health Sciences. 7th edition. New York: John Wiley & Sons, 1999 .

9. Brink HI, van Rensburg G, van der Walt C. Fundamentals of Research Methodology for Health Care Professionals. Cape Town: Juta, 2012.

10. Ezekiel J, Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical?

JAMA 2000;283(20):2701-2711. https://doi.org/10.1001/jama.283.20.2701 11. KwaZulu-Natal Department of Health. District Health Plan 2014/2015.

EThekwini District. Durban: KZN DoH, 2013.

12. World Health Organization, United Nations International Childrenâ&#x20AC;&#x2122;s Emergency Fund, Republic of South Africa. Integrated Management of Childhood Illnesses. Geneva: WHO, UNICEF, 2014.

13. Cloete I, Daniels L, Jordaan J, Derbyshire C, Volmink L, Schubl C. Knowledge and perceptions of nursing staff on the new Road to Health Booklet growth charts in primary healthcare clinics in the Tygerberg subdistrict of the Cape Town metropole district. S Afr J Clin Nutr 2013;26(3):141-146. http:// academic.sun.ac.za/Health/Media_Review/2013/18Nov13/files/Knowlege.pdf (accessed March 2015).

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14. Norris SA, Griffiths P, Pettifor JM, Dunger DB, Cameron N. Implications of adopting the WHO 2006 Child Growth Standards: Case study from urban South Africa, the Birth to Twenty cohort. Ann Hum Biol 2008;36(1):21-27. https://doi.org/10.1080/03014460802620694 15. National Department of Health, South Africa. Infant and Young Child Feeding Policy. Pretoria: NDoH, 2012.

16. National Department of Health, South Africa Guidelines for the Management of HIV in Children. 2nd edition. Pretoria: NDoH, 2010.

17. Sufiyan B, Sabita K, Mande AT. Evaluation of effectiveness of deworming and participatory hygiene education strategy in controlling anaemia among children age 6 - 16 years in Gadagau community, Giwa LGA, Kaduna, Nigeria.

Ann Afr Med 2011;10(1):6-12. https://doi.org/10.4103/1596-3519.76561 18. Awasthi S, Peto R, Read S, et al. Population deworming every 6 months with albendazole in 1 million pre-school children in North India: DEVTA, a clusterrandomised trial. Lancet 2013;381(9876):1478-1486. https://doi.org/10.1016/ S0140-6736(12)62126-6

Accepted 21 December 2017.

JUNE 2018 Vol. 12 No. 2

ARTICLE

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Pulmonary hydatidosis: Still unrecognised in endemic regions – a 10-year review M Ndlovu, MB ChB; S A Thula, FCPaed; R E M Mphahlele; MB ChB; R Masekela, PhD Department of Maternal and Child Health, Inkosi Albert Luthuli Central Hospital, and College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Corresponding author: M Ndlovu (meendlovu@gmail.com) Background. Echinococcus disease in still endemic in many low-middle-income countries, with 1 million people infected at any one time.

Surgery, the mainstay of its treatment, is costly.

Objectives. To describe the presentation, clinical features and outcomes of children referred with pulmonary hydatid disease at Inkosi Albert Luthuli Central Hospital in Durban, South Africa.

Methods. A 10-year review of children with pulmonary hydatid disease at Inkosi Albert Luthuli Hospital was carried out. The data collected were demographic, clinical, laboratory and radiological. Cases were mapped geographically to analyse for clustering of cases.

Spearman’s correlation was used to assess for correlations between laboratory markers.

Results. A total of 24 subjects, 75% of whom were male, were included. The mean (standard deviation) age at diagnosis was 8.9 (3.4) years.

The mean delay in diagnosis was 5.8 (5.7) months. Of the subjects, 15 (71.4%) were from the Eastern Cape and 9 from KwaZulu-Natal provinces. Seventy-nine percent of the patients had been exposed to dogs, while 8% reported exposure to either sheep or cattle. There was right-sided preponderance, with 11 right- and 7 left-sided cysts; 6 patients had bilateral cysts, and 4 associated extrapulmonary cysts.

Indirect haemagglutination assay was positive in 70%, and blood eosinophilia was present in 45% of the subjects, with no correlation between the two markers (p=0.22). Surgery was the only modality of treatment in 18 (75%) subjects, while 5 had had prior medical therapy for disseminated disease. The mean intensive care stay postoperatively was 2 (2) days with no mortality.

Conclusion. Despite exposure to known risk factors and living in endemic regions, there is often a significant delay in diagnosis of pulmonary hydatid disease at Inkosi Albert Luthuli Hospital.

S Afr J Child Health 2018;12(2):48-51. DOI:10.7196/SAJCH.2018.v12i2.1433

Human hydatid disease, or cystic echinococcosis (CE), is a worldwide health problem, especially in regions where dogs, sheep and cattle are common livestock, such as South America, Australia, India, the Middle East, sub-Saharan Africa and the Mediterranean countries, including Turkey.[1-4] The World Health Organization states that over 1 million individuals are infected with Echinococcus worldwide annually.[5] The epidemiology of CE is poorly understood in South Africa (SA). A retrospective data analysis of the National Health Laboratory Service (NHLS) information system on echinococcosis serology, microscopy and histopathology results in eight provinces (excluding KwaZulu-Natal) showed an overall positivity rate in submitted diagnostic samples of 17.0% (1056/6211). The Eastern Cape (30.4%), North West (19.0%) and Northern Cape (18.0%) provinces showed the highest rates.[6] The risk factors proposed in the literature are rural background, farming community, low socioeconomic status, cattle rearing, ineffective veterinary care, lack of potable water supply and male sex.[5,7] Traditionally four species of Echinococcus have been recognised.

E. granulosus and E. multilocularis are the most important forms in humans, and they cause cystic and alveolar echinococcosis, respectively. Two additional species have been identified: E. shiquicus and E. felidis, but their zoonotic transmission potential is unknown.[8] Humans acquire infection by accidentally ingesting tapeworm eggs eliminated from dogs infected with E. granulosus, which has a lifecycle that includes dogs and sheep.[2,9,10] The tapeworm of E. granulosus lives in the intestine of dogs, which are the definitive hosts. Eggs are passed with faeces by dogs, and are ingested by intermediate hosts (usually sheep, goats, swine, cattle, horses and camels); the eggs hatch in the small bowel and release oncospheres that penetrate the intestinal wall and migrate through the circulatory system into various organs, especially the liver and 48

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lungs. In these organs, the oncospheres develop into cysts that enlarge gradually, producing protoscolices and daughter cysts that fill the cyst interior. The definitive host becomes infected when it ingests the cyst-containing organs of the infected intermediate host, following which protoscolices evaginate and attach to the intestinal mucosa of the definitive host before they develop into adult stages in 32 - 80 days.

Hydatid disease most frequently involves the parenchyma of the liver (55% - 75%); however, some parasites escape through the microvascular barrier and reach the lungs (15% - 40%).[11] In children it classically involves the liver, lungs and brain, but can involve almost any organ, and numerous organs simultaneously.[12] The lungs are the most common organ infected by the larval form of Echinococcus in children.[3,9] In a study in Uruguay comparing the prevalence of pulmonary cystic disease in adults and children, 70% of children and 25% of adults had pulmonary cysts.[8] The majority of adults (72%) had liver cysts.[8] In children, the lung allows faster growth of cysts, owing to its compressible nature, vascularisation and negative pressure.[3,9] Several studies have indicated that major symptoms of pulmonary hydatidosis are related to the mass effect from the cyst volume, and they include cough, fever, chest pain, dyspnoea, mucopurulent sputum and haemoptysis.[1,3] The principal complication is cyst rupture and resultant spillage of protoscolices into the bronchial tree, producing cough and haemoptysis. Rupture into pleural space produces pleural effusion and empyema.[3] Management depends on cyst location, cyst size and number of cysts, and can include antihelminths or surgical removal, or a combination of the two modalities.

There is limited data on pulmonary hydatid disease in a paediatric population in SA and Africa in general, with local studies limited to laboratory studies. Furthermore, a large amount of the literature

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Methods

A 10-year retrospective chart review of patients <18 years of age who were referred to Inkosi Albert Luthuli Central Hospital in Durban, SA, with pulmonary echinococcus cysts was conducted. This is a quaternary hospital accepting referrals from the KwaZulu-Natal (KZN) and Eastern Cape (EC) provinces for paediatric pulmonology and cardiothoracic management. According to the Children’s Institute,[13] the public healthcare systems of the two provinces each serve large populations of children living in rural areas (2.47 million and 1.66 million in KZN and EC, respectively). These account for 60% and 63% of children living in these two provinces, respectively.

The study period was between June 2006 and June 2016.

Electronic medical-record data were collected for all participants.

The demographic data collected were the age, gender and geographic location of subjects. The clinical data encompassed age at presentation, presenting symptoms (presence and duration of cough, haemoptysis and chest pain), age at diagnosis, time from symptoms to diagnosis and number and location of cysts. Data on exposure to animals and management modalities were also collected.

Laboratory investigations comprised of full blood count, specifically noting for the presence or absence of eosinophilia. Additionally, a blood indirect haemagglutination assay (IHA) for Echinococcus was used and serum Echinococcus IgG assay test was utilised.

Data were analysed using Stata version 13.0 software (StataCorp, USA). Descriptive analysis was employed to analyse demographic data (age, gender and geographical location), clinical characteristics (delay in diagnosis, exposure to animals and management) and laboratory investigations (blood IHA and blood eosinophilia).

Spearman’s correlation was used to analyse the relationship between blood eosinophil count and blood indirect haemagglutination assays.

Full ethical approval was granted by the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (ref. no. IRB BE 353/16).

Results

A total of 24 participants met the inclusion criteria, of whom 18 (75%) were males. All the subjects were black African children.

The mean (standard deviation) age at diagnosis of hydatid disease was 8.9 (3.4) years, with a range of 3.0 - 16.0 years (Table 1). There was a delay of 5.8 (5.7) months between first presentation of lung disease and actual diagnosis of pulmonary hydatid disease. Of the patients, 79% reported exposure to dogs, while 8% had been exposed to sheep and cattle. Exposure for the remaining 13% was unknown.

Five children (22%) received antituberculosis therapy owing to the clinical and radiological changes observed at the primary healthcare centres prior to referral to a higher level of care.

Eleven patients had right-sided cysts, while 7 had cysts on the left (Table 2). Six patients had bilateral disease, and 4 had additional cysts in the liver, spleen or orbit. Overall, 70% had positive IHA for Echinococcus, and blood eosinophilia was present in 45% of the subjects. This gives a positive predictive value of 0.7. There was no significant correlation between IHA and eosinophilia (p=0.22).

With regards to treatment, all subjects received albendazole 20 mg/ kg, as a daily dose or as a twice-daily divided dose, both pre- and postoperatively (Table 1). Surgical enucleation was performed in 75% of the cases. A conservative approach using albendazole only was adopted for patients who had multiple pulmonary cysts and/or cysts in multiple sites. Of the four patients with disseminated disease, two were lost to follow-up, one had persistence of cysts in the spleen and 49

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one improved following enucleation and percutaneous drainage of liver cysts. Postoperatively, 67% of the patients were admitted to the intensive care unit (ICU), with an ICU stay of 2 (2) days. Four patients required invasive positive pressure ventilation for an average of 2 days while in ICU. The mean hospital stay was 20 (13.8) days, with the majority of subjects having a prolonged hospital stay. There were no deaths reported.

With respect to geographical location, 63% of the patients were from the EC, with the majority from Mthatha (50%). The nearby areas, Libode and Tsolo contributed 8% and 5%, respectively (Fig. 1 shows numerical distribution; Fig. 2 shows geographical location in EC). The remaining 37% were from various parts of rural KZN: Empangeni, Vryheid and Ladysmith.

Discussion

Hydatid disease remains a significant cause of morbidity in SA, but very little is known about the true epidemiology of pulmonary hydatid disease in children in SA. This study revealed a male predominance and geographical clustering of cases, particularly in the north-eastern region of the Eastern Cape. There was a delay in diagnosis of pulmonary hydatid cysts in most cases, with a mean delay of 5.8 months. Despite the delay, there was a successful outcome in all patients, although 71% required surgical intervention.

Laboratory markers, particularly the Echinococcus IgG assay, were poor screening tools for the diagnosis of pulmonary hydatid disease.

Table 1. Demographic and clinical data of children with hydatid cysts (N=24) Variable Mean (SD) Age (years) Gender (M/F) Delay in diagnosis (months) Cysts, n Days in ICU, n

8.9 (3.4) 18/6 5.8 (5.7) 1.5 (0.7) 2.0 (2.0)

ICU = intensive care unit.

Table 2. Anatomical location of hydatid cysts, and frequency (N=24) Location of cyst Frequency, n Right upper lobe Right middle lobe Right lower lobe Left upper lobe Left lower lobe Bilateral Extrapulmonary

5 2 4 2 5 6 4

14

Eastern Cape Province

12

12

KwaZulu-Natal Province

10 Patients, n

focuses on uncomplicated cases that were managed conservatively with benzimidazoles. The aim of this study, therefore, is to describe the epidemiology, clinical presentation and outcomes of paediatric pulmonary hydatid disease of children referred to a quaternary hospital in KwaZulu-Natal Province.

8 6 4 2

2

1

3

2

3 1

0 Libode

Mthatha

Tsolo

Ladysmith

Durban

Vryheid

Empangeni

Region of origin

Fig. 1. Geographical origin of children with pulmonary hydatid cysts (N=24).

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Fig. 2. Geographical distribution showing clustering of cases in the Eastern Cape Province (red circle).

In a Turkish report of 100 pulmonary hydatidosis cases, the largest group comprised of school-aged children aged 3 - 9 years.[2] In our study, the age distribution was comparable. In another Turkish study, the children were found to be older, with a mean (standard deviation) age of 10.2 (3.9) years.[14] The number of males with hydatid cysts exceeded that of females at a ratio of 6:1. This male predominance has been noted in previous studies.[11,15-17] In one study, the male prevalence was 76%.[15] This may be related to traditional practices wherein the rearing of livestock is left to males, especially young boys. The risk factors for hydatid disease are well known, and include exposure to animals such as dogs, sheep, cats and cattle. In the current study the subjects reported exposure mainly to dogs, sheep and cattle.

With regard to geographical distribution, more than 90% of our patients were from the rural parts of the EC and KZN provinces, and this is in keeping with studies from Eastern European countries, where most of the patients were from rural settings.[18] Interestingly, most of our patients were from three parts of the EC, namely Mthatha, Tsolo and Libode, which are in close proximity to each other. This demonstrates the clustering found in the current study.

However, a number of other studies have documented hydatid cysts in urban populations. One such study by Anadol et al., showed an equal distribution between urban and rural children.[2] Visits and migration from urban to rural areas may explain the cases of hydatid disease in urban areas. Two of the patients in the current study were children who reside in Durban, an urban setting.

Our study revealed that the diagnosis of hydatid disease at primary healthcare level was often delayed by about 6 months. This may be attributed to the fact that healthcare workers at that level are not familiar with pulmonary hydatid disease. Twenty-two percent of the patients had a trial of TB treatment for their symptoms, prior to referral to a tertiary hospital. In countries where cystic hydatid disease is endemic, neither the frequency or duration of delays in diagnosis is documented. The definitive diagnosis of pulmonary hydatid disease is made through radiological and serological investigations.

In the current study the IHA for Echinococcus had a low positive predictive value. Previous studies have shown that serology has a low specificity. Eosinophilia may or may not be present; in this study 45% had positive eosinophilia. Newer tests such as counterimmunelectrophoresis and an enzyme-linked immunosorbant assay that have high sensitivities should be utilised, both for follow-up and as screening tests.[2] However, the NHLS in KZN does not offer the newer tests, owing to cost constraints.

The anatomical location of cysts favoured the right lung, which was more frequently affected than the left lung, and this finding is supported by those of other studies.[11,14,18] A study in Turkey revealed equal distribution of cysts between the right and left lung.[16] In a 10-year 50

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Turkish review of 33 patients with pulmonary hydatidosis, 10 patients also had cysts in other organs, namely the liver, brain and spleen.[15] In our study, 4 patients had additional cysts in the liver, spleen or orbit.

The management of >70% of our patients involved surgical enucleation of cysts. Posterolateral thoracotomy for the lung cysts was used as the approach, and this replicated the results in many studies.[3,12,17,19] In one study patients with bilateral lung involvement had a second thoracotomy 6 - 8 weeks after the initial one.[19] All the patients in this present study received albendazole 20 mg/kg/day, both pre- and postoperatively. Previous studies have demonstrated that low doses and short courses of albendazole are not effective in treating hydatid disease. In a small study by Aggarwal et al.,[20] albendazole at a dose of 10 mg/kg/day for 8 weeks was ineffective in the treatment of hydatid disease of the lung.The adverse effects of albendazole are few and tend to be mild, and although gastrointestinal upset, dizziness, rash and/or alopecia can occur, these side-effects do not warrant discontinuation of the drug.[21] According to Brahim et al.,[21] cysts that do not show any signs of radiographic involution must be treated for at least 18 months for pulmonary cysts, and 3 years for hepatic cysts, for good results.

Two-thirds of subjects in the current study required postoperative ICU admission, with an average ICU stay of 2.6 days. This resource may not be available in many low-middle-income countries, but no subjects required invasive ventilation, suggesting that access to high care facilities may be sufficient in most cases where technologically complex ventilation is not possible. There was no mortality in this study, and this is comparable with the results of other studies.[17,19] A strength of this study is that we analysed data on pulmonary hydatid disease in children from two rural provinces in South Africa, which has not been studied before. The limitations of the study are its retrospective nature and the small number of patients. Larger studies are required to validate the findings.

Conclusion

In conclusion, despite exposure to risk factors and living in endemic regions, there is a significant delay in diagnosis of pulmonary hydatid disease.

The indication of geographic clustering in parts of the Eastern Cape Province signals a need to improve feedback to healthcare providers to maintain a high index of suspicion in school-age boys presenting with chronic respiratory complaints in the region. Prevention and control strategies need to be implemented to eradicate hydatid disease in this region. Health education of communities and primary healthcare workers is essential, to enable timely diagnosis and referral to healthcare centres capable of treating pulmonary hydatid disease. An over-reliance on a serology test as a rule-out test needs to be de-emphasised.

Acknowledgements. The authors wish to thank the department of cardiothoracic surgery and the paediatric intensive care unit at Inkosi Albert Luthuli Central Hospital for their assistance with management of the cases.

Author contributions. MN: Data acquisition, analysis and interpretation, drafting of manuscript. ST: Acquisition of data, revision.

REMM: Study conception and design, critical revision. RM: Study topic, conception and design, analysis and interpretation of data, critical revision and overall supervision.

Funding. None.

Conflicts of interest. None.

1. Aslanabadi S, Zarrintan S, Abdoli-Oskouei S, et al. Hydatid cyst in children: A 10-year experience from Iran. Afr J Paediatr Surg 2013;10(2):140-144. https:// doi.org/10.4103/0189-6725.115040 2. Anadol D, Göçmen A, Kiper N, Özçelik U. Hydatid disease in childhood: A retrospective analysis of 376 cases. Pediatr Pulmonol 1998;26(3):190-196. https:doi.org//10.1002/(SICI)1099-0496(199809)26:3<190::AID-PPUL6>3.0//.

CO;2-P

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ARTICLE 3. Santivanez S, Garcia HH. Pulmonary cystic echinococcosis. Curr Opin Pulm Med 2010;16(3):257-261. https://doi.org/10.4103/0189-6725.11504010.1097/ MCP.0b013e3283386282 4. Jordanova DP, Harizanov RN, Kaftandjiev IT, Rainova IG, Kantardjiev TV. Cystic echinococcosis in Bulgaria 1996 - 2013, with emphasis on childhood infections. Eur J Clin Microbiol Inf Dis 2015;34(7):1423-1428. https://doi. org/10.1007/s10096-015-2368-z 5. World Health Organization. Echinococcus Fact Sheet. Geneva: WHO, 2018. http://www.who.int/mediacentre/factsheets/fs377/en/ (accessed 18 February 2017).

6. Mogoye B, Menezes CN, Grobusch MP, Walers K, Frean J. Human cystic echinococcosis in South Africa 2014. Onderstepoort J Vet Res 2012;79(2):1. https://doi.org/10.4102/ojvr.v79i2.469 7. Gupta R, Sharma SB, Prabhakar G, Mathur P. Hydatid disease in children: Our experience. Formosan J Surg 2014;47(6):211-220. https://doi.org/10.1016/j. fjs.2014.12.001 8. Moro P, Schantz PM. Echinococcosis: A review. Int J Infect Dis 2009;13(2):125133. https://doi.org/10.1016/j.ijid.2008.03.037 9. Sakamoto T, Gutierrez C. Pulmonary complications of cystic echinococcosis in children in Uruguay. Pathol Int 2005;55(8):497-503. https://doi.org/10.1111/ j.1440-1827.2005.01859.x 10. Kurkcuoglu IC, Eroglu A, Karaoglanoglu N, Turkyilmaz A, Tekinbas C, Basoglu A. Surgical approach of pulmonary hydatidosis in childhood. Int J Clin Pract 2005;59(2):168-172. https://doi.org/10.1111/j.1742-1241.2004.00275.x 11. Cevik M, Boleken ME, Kurkcuoglu IC, Eser I, Dorterler ME. Pulmonary hydatid disease is difficult recognized in children. Pediatr Surg Int 2014;30(7):737-741. https://doi.org/10.1007/s00383-014-3514-x 12. Andronikou S, Welman CJ, Kader E. Classic and unusual appearances of hydatid disease in children. Pediatr Radiol 2002;32(11):817-828. https://doi. org/10.1007/s00247-002-0785-5

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13. Hall K, Meintjes H, Sambu W. Demography of South Africa’s children. South African Child Gauge. Cape Town: Children’s Institute, 2014.

14. Koca T, Dereci S, Gener A, et al. Cystic Echinococcosis in childhood: Five years of experience from a single center. Turk Soc Parasitol 2016;40(1):2631. https://doi.org/10.5152/tpd.2016.4381 15. Rebhandl W, Turnbull J, Felberbauer FX, et al. Pulmonary echinococcosis (hydatidosis) in children: Results of surgical treatment. Pediatr Pulmonol 1999;27(5):336-340. https://doi.org/10.3347%2Fkjp.2009.47.4.427 16. Todorov T, Boeva V. Echinococcosis in children and adolescents in Bulgaria: A comparative study. Ann Trop Med Parasitol 2000;94(2):135-144. https:// doi.org/10.1016/S1010-7940(01)01140-X 17. Dincer SI, Demir A, Sayar A, Gunluoglu MZ, Kara HV, Gurses A. Surgical treatment of pulmonary hydatid disease: A comparison of children and adults. J Pediatr A Surg 2006;41(7):1230-1236. https://doi.org/10.1016/j. jpedsurg.2006.03.053 18. Djuricic SM, Grebeldinger S, Kafka DI, Djan I, Vukadin M, Vasiljevic ZV. Cystic echinococcosis in children – the seventeen-year experience of two large medical centers in Serbia. Parasitol Int 2010;59(2):257-261. https:// doi.org/10.1016/j.parint.2010.02.011 19. Tü rkyılmaz Z, Sö nmez K, Karabulut R, et al. Conservative surgery for treatment of hydatid cysts in children. World J Surg 2004;28(6):597-601. https://doi.org/10.1007/s00268-004-7029-9 20. Aggarwal P, Wali JP. Albendazole in the treatment of pulmonary echinococcosis.

Thorax 1991;46(8):599-600. https://doi.org/10.1136/thx.46.8.599 21. Ben Brahim M, Nouri A, Ksia A, et al. Management of multiple echinococcosis in childhood with albendazole and surgery. J Pediatr Surg 2008;43(11):2024-2030. https://doi.org/10.1016/j.jpedsurg.2008.04.024 Accepted 12 September 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Pattern of cerebral palsy seen in children attending the outpatient paediatric physiotherapy clinics in Osun State tertiary hospitals in Nigeria J O Omole,1 B Physio, MSc (PT); S A Adegoke,2,3 MB ChB, FWACP, MPH, PhD; K O Omole,3 MBBS, FWACP; O A Adeyemi,4 BSc, MSc (Public Health) Department of Physiotherapy, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Osun State, Nigeria Department of Paediatrics and Child Health, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria 3 Department of Paediatrics, Obafemi Awolowo University Teaching Hospitals Complex, Wesley Guild Unit, Ilesha, Osun State, Nigeria 4 Department of Physiotherapy, Ladoke Akintola University Teaching Hospital, Osogbo, Osun State, Nigeria 1 2

Corresponding author: J O Omole (elidrwiz@yahoo.com) Background. Cerebral palsy (CP) is a major cause of disability in children and the most commonly encountered neurologic condition by paediatric physiotherapists in Nigeria. Local data on the pattern of presentation of CP and standardised management protocols are lacking.

Objectives. To assess the pattern of CP seen in children attending paediatric physiotherapy clinics in Osun State tertiary hospitals.

Methods. A hospital-based cross-sectional study was conducted in three tertiary hospitals within Osun State, Nigeria. Data were collected using caregiver questionnaires, medical records and physical assessment (Gross Motor Function Measure-88) and were recorded on a standardised case record form. Data were analysed using appropriate statistical tests with alpha set at p<0.05.

Results. A total of 187 children with CP were seen during the six-month period. The male to female ratio was 1.2:1 and the children were aged 12 months to 12 years. The majority of the mothers (63.6%) were primiparous and, at the time of delivery, most mothers were aged between 28 and 33 years. Spastic (72.7%) and quadriplegic (69.5%) presentations were the leading sub-types of CP, with 76.5% of children having one or more associated problems. Birth asphyxia (57.2%) was the leading aetiology of CP while speech impairment was common in 63.6% of cases. One hundred and fourteen (61%) children were classified as being severely disabled and 53.5% had a gross motor function measure score of less than 40.9%.

Conclusion. Severe CP is commonly encountered in the region, with children most frequently presenting with spastic quadriplegia and speech impairment. A good knowledge of the pattern of CP seen in south-western Nigeria is one of the first steps in developing a standardised protocol.

S Afr J Child Health 2018;12(2):52-57. DOI:10.7196/SAJCH.2018.v12i2.1452

Neurological disorders are common in childhood, with cerebral palsy (CP) being one of the leading causes of disability.[1,2] CP is a disorder of abnormal posture with scarcity of movement caused by lesions in an immature or developing brain with varying degrees of associated problems including seizure disorders, intellectual disabilities, communication difficulties, learning difficulties, visual impairment, bladder and bowel control problems and swallowing difficulties.[3] The prevalence of CP in well-resourced countries is between 1.5 to 2.5 per 1 000 live births while in Africa the prevalence is between 1.5 and 10 per 1 000 live births.[ 4-8] Reasons for this disparity have been attributed to poor government policies on healthcare, harmful traditional beliefs, higher rates of unsupervised deliveries and inadequate equipment to implement resuscitative procedure following complicated labour in many African countries.[9] CP can occur during the prenatal, perinatal or postnatal stages.[10] In some cases, the aetiology of CP is not known, however, some common identifiable causes include birth asphyxia, severe jaundice/ kernicterus, infections, neonatal seizures, prematurity and low birth weight.[5,10] Diagnosis of CP is made by clinical evaluation with or without cerebral imaging. Failure to identify aetiology in a child with a neurological condition does not exclude CP, provided the brain injury that resulted in the motor function deficits occurred before the child was older than three years of age.[10] Children with CP require lifelong healthcare, by a range of professional disciplines (including paediatrician, neurologist, orthopaedic surgeon, physiotherapist, occupational therapist and speech therapist), using substantial human and financial resources.[11,12] 52

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Physiotherapy plays a major role in the management of children with CP.[13] The aims of physiotherapy intervention include: strengthening of the mother-to-child bonding, optimisation of functional skills, physical endurance and motor development, therein facilitating school participation via provision of mobility devices, advising and facilitating appropriate handling and positioning and preventing complications such as contractures and other deformities.

Physiotherapy treatment approaches include neurodevelopmental therapy, sensory integration therapy, conductive education, constraint induced movement therapy, context focused therapy, advance neuromotor rehabilitation, biofeedback and physical activity training.[13,14] Despite the important rehabilitative role of physiotherapy in the management of children with CP in Nigeria, standardised protocols or guidelines are lacking. Therefore, the aim of this study was to describe the pattern of CP in children attending the paediatric physiotherapy clinics located in tertiary hospitals, Osun State, Nigeria, to inform the development of a standardised clinical guideline for the physiotherapy management of the children.

Methods

Study design and participants

This was a hospital-based, cross-sectional, descriptive study of consecutive children attending the paediatric physiotherapy clinics of three tertiary hospitals in Osun State, Nigeria, over a six-month period. There are also primary and secondary healthcare facilities available in the state but the physiotherapy services are inadequate at secondary centres. Children were eligible for inclusion if they were

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ARTICLE aged between 12 months and 12 years, and had a documented referral from a paediatrician or neurologist confirming the diagnosis of CP. Children with other neurological conditions such as spina bifida, Down’s syndrome, and poliomyelitis were excluded from the study.

Procedure

Ethical approval (ref. no. ERC/2017/06/34) was obtained from the Ethics and Research Committee of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. Approval was also obtained from the heads of the Departments of Physiotherapy and Paediatrics at the study sites. Informed consent for participation of the children in the study was obtained from the parents/caregivers prior to enrolment. Parents/caregivers accompanying the children were asked to fill in a questionnaire. Information obtained included present age (mother, child, and primary caregiver if not the mother), sex, the birth order of the child with CP in the family, level of education of the primary caregiver and their spouse, occupation of the primary caregiver and their spouse, and monthly income.

Information obtained from medical records and physical assessment included: aetiology; classification of CP based on the topographical distribution (diplegia, hemiplegia and quadriplegia); nature of the movement disorder (spastic, dyskinetic, ataxic, mixed and hypotonic); severity of CP using the Gross Motor Function Classification System – Expanded and Explained (GMFCS-ER); the extent of motor impairments using the Gross Motor Function Measure-88 (GMFM-88); and associated problems such as intellectual disabilities, seizure disorders, and speech and hearing impairments.

The GMFCS-ER is a reliable and valid tool for assessment of the severity of CP.[15] The tool focuses on sitting, transfer and mobility ,which are all self-initiated movements. It assesses five levels of function, with Level I indicating that ambulation is possible with no restriction, while Level V indicates that self-ambulation is not possible and mobility is only achievable using a wheelchair. Five age categories are used in this scale: <2 years, 2 - 4 years, 4 - 6 years, 6 - 12 years and 12 - 18 years.[15]

Table 1. General characteristics of children with cerebral palsy and their mothers (N=187) Variables Age of children (years), median (IQR) Mother᾽s age at child᾽s birth (years), median (IQR) Parents᾽/caregivers᾽ age (years) during study, median (IQR) Children’s sex Male Female Children’s age at first contact during study (years) 1-2 2-4 4-6 6 - 12 Children’s birth order 1st 2nd 3rd 4th ≥5th Age range of mothers (at child’s birth) of children with CP (years) 17 - 21 22 - 27 28 - 33 34 - 39 ≥40 Socioeconomic status Upper class Middle class Lower class Educational background Primary Secondary Post secondary Monthly income in Nigerian Naira (₦) <18 000 18 000 - 50 000 51 000 - 100 000 101 000 - 150 000 >150 000 IQR = interquartile range; GMFCS = Gross Motor Function Classification System. *Unless otherwise specified.

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n (%)* 3.0 (1.0 - 5.0) 28.0 (24.0 - 33.0) 34.0 (28.0 - 39.0) 103 (55.1) 84 (44.9) 48 (25.7) 44 (23.5) 52 (27.8) 43 (23.0) 119 (63.6) 37 (19.8) 15 (8.0) 7 (3.8) 9 (4.8) 10 (5.3) 67 (35.8) 78 (41.7) 23 (12.3) 9 (4.8) 44 (23.5) 61 (32.6) 82 (43.9) 15(8) 71 (38) 101 (54) 52 (27.8) 66 (35.3) 32 (17.1) 24 (12.8) 13 (7)

ARTICLE Table 2. Aetiology of cerebral palsy and associated problems (N=187) Aetiology, n (%) Birth asphyxia CNS infection Kernicterus Neonatal seizure Premature birth Trauma Unknown Associated problems, n (%) Speech impairment Bladder control problems OMI Intellectual disability Learning disability Seizure disorders Emotional and behavioural disorder Visual impairment Hearing impairment None

107 (57.2) 32 (17.1) 22 (11.8) 3 (1.6) 14 (7.5) 3 (1.6) 6 (3.2) 119 (63.6) 22 (11.8) 25 (13.4) 9 (4.8) 10 (5.3) 40 (21.4) 4 (2.1) 11 (5.9) 4 (2.1) 44 (23.5)

CNS = central nervous system (meningitis, cerebral malaria and encephalitis); OMI = oral motor impairment (including problems with feeding, swallowing and drooling).

The GMFM – 88 is also a reliable and valid tool consisting of 88 domains sub-divided into the following 5 items: Item A - Lying and Rolling, Item B – Sitting, Item C – Crawling and Kneeling, Item D – Standing and Item E – Walking, Running and Jumping.

Scoring ranges from 0 (῾does not initiate᾽) to 3 (῾completes᾽).[16] The advantage of this scale is that it allows professionals to objectively assess motor performance changes over time.[17]

Data analysis

Socioeconomic status of parents of children with CP was calculated using the Ogunlesi et al.[18] classification of social class. The method is a modification of an earlier classification done by Oyedeji.[19] The previous classification did not take into account the parents᾽ income to assign socioeconomic scores – hence the need for this modification. In summary, socioeconomic scores were allotted to both educational qualification and occupation based on the equivalents of each parent᾽s mean income using their percentile incomes.[18] Socioeconomic class was scored as 1, 2, 3, 4 and 5, with the social class represented as I, II, III IV and V, respectively.

Socioeconomic class was further sub-classified as: (i) a total score of 1 or 2 representing social classes I and II were sub-classified as upper class; (ii) a total score of 3 representing social class III was sub-classified as middle class; (iii) a total score of 4 or 5 representing social classes IV and V were sub-classified as lower class.

Continuous variables such as age were summarised using median and interquartile range (IQR), while categorical variables such as sex, motor type, and topography were summarised using percentages and proportions. Associations between categorical variables were determined using the χ2 test. Data were analysed using Statistical Programme for Social Sciences (SPSS) for Windows version 22.0 (IBM Corp., USA). The alpha level was set at 0.05.

Results

A total of 187 children with CP were included during the six months’ study period. The median (IQR) age of the children was 3.0 (1.0 - 5.0) years with a male to female ratio of 1.2:1 while the median (IQR) age of mothers (at child᾽s birth) was 28.0 (24.0 - 33.0) years. General 54

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characteristics of children with CP and their mothers/caregivers was captured (Table 1). First-born children constituted the highest prevalence of CP cases seen in this study (63.6%), while mothers in the age range of 28 - 33 years (41.7%) gave the highest frequency.

The parental/caregivers᾽ socioeconomic status showed that upper class families constituted 23.5%, while lower class families were 43.9%. Post-secondary education of parents/caregivers constituted the highest prevalence seen (54%) in this study, while monthly income between ₦18 000 and ₦50 000 was 35.3%. The three most common individual aetiology were: birth asphyxia (57.2%), central nervous system infection (18.2%) and kernicterus (11.7%) whilst the three most associated problems seen in this study were: speech impairments (63.6%), seizure disorders (21.4%) and oral motor impairment (including problems with feeding, swallowing and drooling) (13.4%) (Table 2).

Distribution of children’s severity levels, motor type, topography, age categories, and number of associated problems per child were also captured (Table 3). Spastic CP was the most common motor type (72.7%) with severe deficits (GMFCS Levels IV and V) occurring in 73.5% of this group. Quadriplegic CP was the most common topographical distribution (69.5%), accompanied by severe deficits in 79.2% of cases. Mild deficits (GMFCS Levels I and II) were generally associated with one or no co-morbidities; while more severe CP tended to present with more than one associated problems χ2=53.22 and p=0.001. A breakdown of the type of associated problems was conducted (Table 4). Speech impairment was the most prevalent single associated problem (25.7%) whilst a combination of the three associated problems of speech impairment, visual impairment and seizure disorder (3.7%) were the most prevalent. The pattern and relationship between gross motor function classification system and the gross motor function measure was analysed (Table 5). Mild deficits (Level I and II) of CP were associated with a lesser degree of motor impairment (80 - 100%) while severe deficits of CP related to a higher degree of motor impairment (0 - 20.9%) (χ2=291.82; p=0.002).

The gross motor function classification system was also significantly associated with other variables, i.e. socioeconomic status (χ2=22.42; p=0.004); topography (χ2=144.26; p=0.001); motor type (χ2=74.79; p=0.001); and birth order (χ2=55.77; p=0.001) (Table 6).

Discussion

This study showed a slight male bias of 1.2:1, in line with previous studies.[20-22] Reasons for this bias may be attributed to male susceptibility to genetic mutations and variants in recessive X-linked chromosomes.[23] A greater proportion of children who were firstborns (63.6%) presented with CP in this study. Reasons for this may be due to the nature of healthcare delivery in Nigeria. Cultural preference and financial resource limitations may affect the choices of mothers in terms of home v. institutional delivery, and that the facilities and expertise available amongst different institutions are highly variable.[9] Primigravid women are more at risk of prolonged obstructed labour, which may lead to birth asphyxia in babies and subsequent development of CP.[24] Hashim et al.[25] concluded that primigravids were a high-risk factor for both maternal and perinatal outcome because they were prone to prolong second-stage labour and fetal distress.

The top three most common causes of CP in this study were birth asphyxia, CNS infections and kernicterus. This finding is in agreement with previous studies in Nigeria.[1,2,22] In well-resourced environments, prenatal events have been reported to account for about 75% - 95% of all cases of CP seen,[26,27] while perinatal asphyxia only accounts for 6% - 7%.[26] Prenatal aetiologies include vascular injuries, placental conditions, maternal infections and genetic factors, amongst others.[26-28] Vascular injuries such as periventricular haemorrhages could occur during the critical stages of brain development, particularly from the 24th to the

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ARTICLE Table 3. Pattern of motor type, topography, age and number of associated problems according to level of severity (N=187) GMFCS, n (%) Variables Level I Level II Level III Level IV Motor type Spastic (n=136) Dyskinetic (n=11) Ataxic (n=17) Mixed (n=19) Hypotonic (n=4) Topographical distribution Diplegia (n=15) Hemiplegia (n=42) Quadriplegia (n=130) Age distribution of children (years) 1 - 2 (n=48) 2 - 4 (n=44) 4 - 6 (n=52) 6 - 12 (n=43) Number of associated problems per child None (n=44) 1 (n=70) 2 (n=50) 3 (n=15) ≥4 (n=8) Total (N=187)

Level V

13 (9.6) 3 (27.3) 4 (23.5) 2 (10.5) 0 (0)

17 (12.5) 2 (18.2) 13 (76.5) 7 (36.8) 1 (25)

6 (4.4) 0 0 4 (21.1) 1 (25)

21 (15.4) 4 (36.4) 0 4 (21.1) 1 (25)

79 (58.1) 2 (18.2) 0 2 (10.5) 1 (25)

0 15 (35.7) 7 (5.40)

5 (33.3) 17 (40.5) 18 (13.8)

7 (46.7) 2 (4.8) 2 (1.5)

2 (13.3) 6 (14.3) 22 (16.9)

1 (6.7) 2 (4.8) 81 (62.3)

1 (2.1) 2 (4.5) 5 (9.6) 14 (32.6)

10 (20.8) 10 (22.7) 11 (21.2) 9 (20.9)

6 (12.5) 4 (9.1) 1 (1.9) 0

10 (20.8) 10 (22.7) 6 (11.5) 4 (9.3)

21 (43.8) 18 (40.9) 29 (55.8) 16 (37.2)

10 (22.7) 8 (11.4) 3 (6) 1 (6.7) 0 22

17 (38.6) 16 (22.9) 7 (14) 0 0 40

6 (13.6) 4 (5.7) 1 (2) 0 0 11

5 (11.4) 14 (20) 7 (14) 4 (26.7) 0 30

6 (13.6) 28 (40) 32 (64) 10 (66.7) 8 (100) 84

GMFCS = gross motor function classification system.

34th week of gestation. For these reasons, the term hypoxic ischemic encephalopathy has been replaced with the term neonatal encephalopathy since, in most child deliveries, no evidence exists of either an acute hypoxia or ischaemic birth. Furthermore, only 13% of neonatal encephalopathy seen in newborn babies actually results in CP.[23] However, birth asphyxia remains a common cause of CP in developing nations such as Nigeria. Reasons for this include poor health service delivery, particularly in primary health centres, insufficient number of professional health workers, and lack of basic obstetric and neonatal resuscitation equipment.[9] Most parents/caregivers of children with CP came from a lower socioeconomic background. Findings from this study are consistent with those of previous studies.[2,29] Having a lower educational status does not leave many opportunities for a high-paying job. However, it was observed from this study that only 8% of parents/caregivers stopped at primary school education while over 50% went ahead to complete tertiary education. Nevertheless, the income of 118 (63.1%) parents/caregivers was <N51 000 per month, which is equivalent to USD137 and about 3 days᾽ minimum wage.[30] This may imply that less purchasing power rather than ignorance resulted in mothers seeking poor antenatal and delivery care centres.[29] CP can be classified either by using the nature of movement disorder (motor type) or topographical distribution.[26] In this study, the most predominant movement disorder type was spastic CP (73.3%). These findings were similar to previous studies done by Frank-Briggs and Alikor,[2] and Ogunlesi et al.[29] Four children (≥4 years at the time of this study) with CP (2.1%) were observed to be hypotonic. Hypotonia is common during infancy; however, most children with CP will begin to develop spasticity, athetosis or ataxia transiently over the first two years of life.[31] Permanent hypotonia has previously been described in children with CP, most commonly associated with congenital CP.[26]

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Quadriplegia (67.4%) was the most prevalent topographical distribution of CP, in agreement with previous studies.[21,29] About two-thirds (67.6%) of children with spastic CP were quadriplegic.

Both the spastic motor and quadriplegic sub-types of CP showed a high affinity for Level V of the GMFCS: 58.1% and 62.3% respectively.

The GMFCS is an assessment tool used to determine both the severity of CP and likely prognosis.[15] A child with a GMFCS of level V simply implies that voluntary control of movement is greatly restricted due to the child’s body impairment and will require a high level of assistance from caregivers (parents, relatives or guardians) for mobility, usually requiring a wheelchair and a high level of dependence for other activities of daily living.[15] There was a greater proportion of children with severe disability (GMFCS IV and V; 60.9%) in this study, with only 33.2% of children presenting with mild CP (GMFCS I and II). This finding is contrary to the work done by Obembe et al.,[32] who reported that the prevalence of severe and mild disability was similar at 28.6% and 36.3% respectively. The results of this study may present a selection bias, as there is an active community awareness programme in Osun State, with education about what CP is and the role of physiotherapy in managing a child with CP. Mothers of children with severe disability are encouraged to bring their wards to the physiotherapy clinics for assessment and rehabilitation. This may explain the disparity observed between studies.

Children with mild disability (GMFCS I and II) tend to have fewer associated problems, while those with severe disability (GMFCS IV and V) tend to present with one or more associated problems. Associated problems are additional health conditions that are seen in children with CP which may affect the quality of life of the child.[3] Associated problems include intellectual disability, seizure disorders, sleep disorder, pain, bladder incontinence and deafness.[3]

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ARTICLE Table 4: Breakdown of the number of associated problems Associated problems n (%) None Speech impairment only Learning disability only Seizure disorders only Oral motor impairment only Speech impairment + seizure disorders Speech impairment + intellectual disability Speech impairment + oral motor impairment Speech impairment + visual impairment SI + BBCP HI + VI + SI SI + VI + SZD SI + OMI + BBCP SI + BBCP + EBP HI + OMI + SZD + ID VI + SZD + SI + OMI + BBCP SI + SZD + BBCP + OMI

44 (23.5) 48 (25.7) 10 (5.3) 11 (5.9) 1 (0.5) 15 (8.0) 6 (3.2) 13 (7.0) 2 (1.1) 14 (7.5) 1 (0.5) 7 (3.7) 3 (1.6) 4 (2.1) 3 (1.6) 1 (0.5) 4 (2.1)

SI = speech impairment; BBCP = bladder and bowel control problems; HI = hearing impairment; VI = visual impairment; SZD = seizure disorders; OMI = oral motor impairment (including problems with feeding, swallowing and drooling); EBP = emotional and behavioural problems; ID = intellectual disability.

The GMFM is an assessment tool used by physiotherapist and other healthcare professionals to objectively determine the gross motor capacity of a child with CP. This observational instrument is usually used in clinics as an outcome measure to record changes in gross functional abilities of children with CP from baseline to a predetermined duration of physiotherapy or other therapeutic interventions.[16,17] In this study, it was observed that the lower the gross motor functional scores (GMFM), the higher the level of severity (GMFCS Levels IV and V); while the higher the gross motor functional scores, the lower the level of severity (Levels I and II).

Study limitations

This study was a hospital-based (tertiary institutions only) study and so there is a possibility that our observations may not be a complete representation of all children with CP in Osun State. Also, data of respondents without cerebral palsy during this study were not collected. Therefore, a statistical analysis of the difference between children with CP and those without CP could not be computed.

However, the pattern of children with CP seen in tertiary hospitals in Osun State has been highlighted.

Conclusion

Children with CP have various challenges with activities and participation as a result of impairments to their body structure.

Management of children with CP by a paediatric physiotherapist is long-term and demanding. Developing locally relevant, standardised protocols/guidelines for the treatment of children with CP may

Table 5. Pattern of GMFM of children with cerebral palsy according to level of severity as determined by GMFCS GMFCS, n (%)

Level I

Variables GMFM 0 - 20.9 21 - 40.9 41 - 60.9 61 - 80.9 81 - 100 Total

49 51 31 21 35 187

Level II

0 (0) 0 (0) 0 (0) 1 (4.8) 21 (60) 22

0 (0) 0 (0) 8 (25.8) 18 (85.7) 14 (40) 40

Level III

Level IV

Level V

χ2

0 (0) 0 (0) 10 (32.3) 1 (4.8) 0 (0) 11

2 (4.1) 17 (33.3) 10 (32.3) 1 (4.8) 0 (0) 30

47 (95.9) 34 (66.7) 3 (9.7) 0 (0) 0 (0) 84

291.82

p-value 0.002

GMFM = gross motor function measure; GMFCS = gross motor function classification system. *GMFM scores is in percentages but categorised.

Table 6. Association between each of the level of severity, socioeconomic status, topography, motor type, associated problems and birth order Variables GMFCS SES Topography Motor type AP Birth order

SES

χ2 p χ2

1.000 22.42

Topography

p χ2

0.004* 144.26

1.000 11.76

p χ2 p χ2 p χ2 p

0.001* 74.79 0.001* 53.22 0.001* 55.77 0.001

0.162 27.62 0.001* 14.70 0.065 29.05 0.001

GMFCS

Motor type AP Birth order

1.000 55.55 0.001* 64.67 0.001* 61.04 0.001

1.000 11.62 0.770 26.71 0.144

1.000 43.65 0.002

GMFCS = gross motor function classification system; SES = socioeconomic status; GMFM = gross motor function measure; AP = associated problems. *Statistically significant at p<0.05.

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1.000 1.000

ARTICLE optimise the physiotherapy management of these children, and improve functional outcomes. This study provides information regarding the pattern of CP in children in Osun State, Nigeria, as one of the first steps to develop a physiotherapy management protocol for the region.

Acknowledgements. The authors gratefully acknowledge the parents of the study respondents for giving consent to participate in the study.

Author’s contribution. JOO: conceptualised the study, collected and analysed the data and wrote the manuscript. SAA: analysis and critical review of the manuscript. KOO: analysis and critical review of the manuscript. OAA: critical review of the manuscript. All the authors approved the final version of the manuscript.

Funding. None.

Conflicts of interest. None.

1. Lagunju IA, Okafor, OO. An analysis of disorders seen at the paediatric neurology clinic, University College Hospital, Ibadan, Nigeria. West Afr J Med 2009;28(1):38-42. https://doi.org/10.4314/wajm.v28i1.48424 2. Franks-Briggs AI, Alikor EAD. Sociocultural issues and causes of cerebral palsy in Port Harcourt, Nigeria. Nig J Paediatr 2011;38(3):115-119. https://doi. org/10.4314/njp.v38i3.72266 3. Novak I, Hines M, Goldsmith S, Barclay R. Clinical prognostic messages from a systematic review on Cerebral Palsy. Pediatr 2012;130(5):e1285-1312. https:// doi.org/10.1542/peds.2012-0924 4. Reddihough DS, Collins KJ. The epidemiology and causes of cerebral palsy. Aust J Physiother 2003;49(1):7-12. https://doi.org/10.1016/S0004-9514 (14)60183-5 5. Olney SJ, Wright MJ. Cerebral palsy. In: Campbell SK, Vander-Linden DW, Palisano RJ, eds. Physical Therapy for Children. St Louis: Saunders-Elsevier.

2006:625-664.

6. Dambi JM, Jelsma J, Mlambo T. Caring for a child with cerebral palsy: The experience of Zimbabwean mothers. Afri J Disabil 2015;4(1):168. https://doi. org/10.4102/ajod.v4i1.168 7. El-Tallawy HN, Farghaly WMA, Shehata GA, et al. Cerebral palsy in Al-Quseir City, Egypt: Prevalence, subtypes, and aetiology. Neuropsychiatr Dis Treat 2014;10:1267-1272. https://doi.org/10.2147/NDT.S59599 8. Couper J. Prevalence of childhood disability in rural KwaZulu-Natal. S Afr Med J 2002;92(7):549-552. https://www.ajol.info/index.php/samj/article/ viewFile/132073/121672 9. Duru EJ, Nwagbos CI. The problems and prospects of public health care development in Nigeria’s local government system. Glob J Soc Sci 2007;6(1):5156. https://doi.org/10.4314/gjss.v6i1.22826 10. Alikor EAD. Common Growth and Development Problems. In: Azubuike JC, Nkanginieme KEO, eds. Paediatrics and Child Health in a Tropical Region. Port Harcourt: University of Port Harcourt Press, 2007:70-83.

11. Potharaju NR. Seizures in Cerebral Palsy. Indian J Cereb Palsy 2016;2(1):3-21. https://doi.org/10.4103/2395-4264.188150 12. Johnston MV. Encephalopathies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelpha: SaundersElsevier; 2007:680.

13. Anttila H, Autti-Rämö I, Suoranta J, Mäkelä M, Malmivaara A. Effectiveness of physical therapy interventions for children with cerebral palsy: A systematic review. BMC Pediatr 2008;8:14. https://doi.org/10.1186/1471-2431-8-14

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14. Patel DR. Therapeutic interventions in cerebral palsy. Indian J Pediatr 2005; 72(11):979-983. https://doi.org/10.1007/bf02731676 15. Palisano RJ, Rosenbaum P, Bartlett D, Livingston MH. Content validity of the expanded and revised Gross Motor Function Classification System. Dev Med Child Neurol 2008;50(10):744-750. https://doi.org/10.1111/j.14698749.2008.03089.x 16. Palisano RJ, Hanna SE, Rosenbaum PL, et al. Validation of a model of gross motor function for children with cerebral palsy. Phys Ther 2000;80(10):974-985. https:// doi.org/10.1093/ptj/80.10.974 17. Alotaibi M, Long T, Kennedy E, Bavishi S. The efficacy of GMFM-88 and GMFM66 to detect changes in gross motor function in children with cerebral palsy (CP): A literature review. Disabil Rehabil 2014;36(8):617-627. https://doi.org/10.3109/ 09638288.2013.805820 18. Ogunlesi TA, Dedeke IOF, Kuponiyi OT. Socio-economic classification of children attending specialist paediatric centres in Ogun State, Nigeria. Nig Med Practitioner 2008;54(1):21-25. https://doi.org/10.4314/nmp.v54i1.28943 19. Oyedeji GA. Socioeconomic and cultural background of hospitalized children in Ilesha. Nig J Paediatr 1985;12(4):111-117.

20. Peters GO, Adetola A, Fatudimu MB. Review of paediatric neurological conditions seen in the physiotherapy department of a children’s hospital in Ibadan, Nigeria.

Afr J Biomed Res 2008;11:281-284. https://doi.org/10.4314/ajbr.v11i3.50735 21. Hamzat TK, Fatudimu MB. Caregivers or care providers: Who should assess motor function in cerebral palsy? J Pediatr Neurol 2008;6(4):345-350. https://doi. org/10.1055/s-0035-1557480 22. Okike CO, Onyire BN, Ezeonu CT, Agumadu HU, Adeniran KA, Manyike PC. Cerebral palsy among children seen in the neurology clinic of Federal Medical Centre (FMC), Asaba. J Community Health 2013;38(2):257-260. https://doi. org/10.1007/s10900-012-9608-2 23. MacLennan AH, Thompson SC, Gecz J. Cerebral palsy: Causes, pathways, and the role of genetic variants. Am J Obstet Gynecol 2015;213(6):779-788. https:// doi.org/10.1016/j.ajog.2015.05.034 24. Indra, Usharani N, Bendigeri M. A study on clinical outcome of obstructed labour. Int J Reprod Contracept Obstet Gynecol 2017;6(2):439-442. https://doi. org/10.18203/2320-1770.ijrcog20170027 25. Hashim N, Nagvi S, Khanam M, Jafry HF. Primiparity as an intrapartum obstetric risk factor. J Pak Med Assoc 2012;62(7):694-698.

26. Beaman J, Kalisperis FR, Miller-Skomorucha K. The infant and child with cerebral palsy. In: Tecklin JS, ed. Pediatric Physical Therapy. Philadelphia: Lippincott Wolters Klumer; 2015:187-246.

27. Nelson KB, Blair E. Prenatal factors in singletons with cerebral palsy born at or near term. New Engl J Med 2015;373(10):946-953. https://doi.org/10.1056/ nejmra1505261 28. Neufeld MD, Frigon C, Graham AS, Mueller BA. Maternal infection and risk of cerebral palsy in term and preterm infants. J Perinatol 2005;25(2):108-113. https://doi.org/10.1038/sj.jp.7211219 29. Ogunlesi T, Ogundeyi M, Adekanmbi F, Fetuga B, Ogunfowora O, Olowu A. Socio-clinical issues in cerebral palsy in Sagamu, Nigeria. S Afr J Child Health 2008;2(3):120-124.

30. United States Department of Labor. Wage and Hour Division (WHD): Minimum Wage Laws in the States – July 1, 2017. https://www.dol.gov/whd/minwage/ america.htm (accessed 1 September 2017).

31. Miller F. Cerebral palsy management. In: Physical Therapy of Cerebral Palsy. New York: Springer; 2007:51-106.

32. Obembe AO, Johnson OE, Olaogun MOB, Ogunleye MC. Gross motor function in cerebral palsy: The association with motor type and topographical distribution.

Nig J Med Rehab 2013;16(2):1-17.

Accepted 1 February 2018.

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ARTICLE

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Health-related quality of life in children and adolescents with end-stage renal disease receiving dialysis in Johannesburg P N Obiagwu,1,2 MBBS, FWACP (Paed); B Sangweni,2 RN, MSc; G Moonsamy,2 MB ChB, FCPaed (SA); T Khumalo,2 MB ChB, FCPaed (SA); C Levy,2 MB ChB, FCPaed (SA) 1

Paediatric Nephrology Unit, Department of Paediatrics, Aminu Kano Teaching Hospital and Bayero University, Kano, Nigeria Division of Paediatric Nephrology, Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital and the University of Witwatersrand, Johannesburg, South Africa

2

Corresponding author: P N Obiagwu (patience.obiagwu@gmail.com) Background. Limitations in daily activities can have a major impact on the quality of life in children and adolescents. Long-term dialysis tends to restrict children from carrying out similar activities to those of their peers.

Objective. To analyse the health-related quality of life of children and adolescents with end-stage renal disease on dialysis in Johannesburg.

Methods. A hospital-based, cross-sectional study which assessed the health-related quality of life (HRQOL) of patients undergoing haemodialysis (HD), automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) using the Pediatric Quality of Life Inventory (PedsQL 3.0) and end-stage renal disease (ESRD) module as the instrument. The instrument is a questionnaire comprising 7 domains with a total of 34 questions/items. Child reports as well as parent proxy reports were obtained. Questionnaires were administered to all patients and parents/caregivers of children on all forms of chronic dialysis.

Results. Twenty-seven children and adolescents were studied. The mean (standard deviation (SD)) age of the study participants was 14.4 (4.8) years (range 5 - 25). Fourteen patients were on HD while 13 were on peritoneal dialysis (8 on APD and 5 on CAPD). Those on HD were significantly older, with a mean (SD) age of 16.6 (3.2) years, compared with the mean (SD) age of those on PD, which was 12.1 (5.3) years (p=0.007). Moreover, those on HD had been on dialysis for a longer period of time, with a mean (SD) period of 4.5 (3.3) years, compared with those on PD who had been on dialysis for a mean (SD) duration of 1.7 (0.8) years (p=0.006). The HRQOL was lower in most domains in the HD group compared with the PD group. Among the patients on PD, the HRQOL scores were lower in the APD group compared with the CAPD group (p>0.05). The ratings by the parent proxies were higher than those reported by the children themselves in most domains. When compared with the population mean HRQOL scores derived from a healthy paediatric population, the mean HRQOL scores of the children with ESRD on dialysis were significantly lower for both child (t=–11.1; p=0.001) and parent proxy reports (t=–7.2; p=0.001).

Conclusion. HRQOL is low in children with ESRD receiving chronic dialysis. It tends to be much lower in children on HD when compared with those on PD. PD appears to be more acceptable to children and parents/caregivers than HD. S Afr J Child Health 2018;12(2):58-62. DOI:10.7196/SAJCH.2018.v12i2.1457

Chronic kidney disease (CKD) is a significant public health problem, particularly in sub-Saharan Africa where resources for management are limited. End-stage renal disease (ESRD), which is the extreme stage in the spectrum of CKD, implies that the patient requires some form of renal replacement therapy (RRT) which could be haemodialysis (HD), peritoneal dialysis (PD) or renal transplantation.

The care of a child with ESRD is fraught with challenges for the parent, the caregiver as well as the healthcare system. The child is burdened with physical, social, emotional and psychological issues, and these affect the child’s quality of life.[1-3] The subjective perception of how health-related factors affect well-being and life satisfaction is known as the health-related quality of life (HRQOL).[4] The importance of the assessment of the HRQOL in children with ESRD cannot be overemphasised as technological advances have made it possible to extend their duration of survival. They can therefore reach adulthood but find themselves facing several other challenges, specifically financial challenges. Moreover, as they grow to become young adults, children with ESRD are faced with challenges of independent living such as securing gainful employment and maintaining relationships. Optimal care of the paediatric patient with ESRD should therefore include an assessment of their HRQOL to better understand these challenges and to keep these in focus such that holistic care may be administered.

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HRQOL is usually assessed using various instruments such as the Kinder Lebensqualitat Fragebogen (KINDL) questionnaire,[5] the Kidney Disease Quality of Life – Short Form (KDQOL-SF)[6] and the Paediatric Inventory of Quality of Life Core Scales (PedsQL version 4.0).[7] These instruments have been validated for use in healthy and sick children. The PedsQL Version 4.0 has been validated for use in children with a wide variety of chronic illnesses including ESRD.[8,9] Numerous studies on HRQOL in children with ESRD have been conducted in developed countries.[7, 9-17] The reported results have varied, with some studies reporting better HRQOL in PD patients compared with HD patients,[7,15,16] while others report no differences between patients on either modality.[9,12,14] A uniform finding of several of these studies, however, is that children with chronic conditions such as ESRD have lower HRQOL scores when compared with healthy children.[7-9,12,14-17] There are no studies on the HRQOL of children with CKD in sub-Saharan Africa. Unfortunately, the region is fraught with several socioeconomic, health and psychologic challenges which affect healthcare quality, affordability, availability and delivery, and these could affect the health-related quality of life of the children. Furthermore, sociocultural characteristics of the region might not afford the children opportunities to express

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ARTICLE their concerns and challenges fully as they relate to their health conditions and specific needs.

Objective

The aim of the study was to analyse the HRQOL of children and adolescents with ESRD on dialysis in Johannesburg, and compare their reports with those given by their caregivers. We hypothesised that children receiving dialysis would have lower HRQOL scores than healthy counterparts, that children on APD would have higher HRQOL scores than those on HD or CAPD, and that the parents or proxies would report higher HRQOL scores when compared with those reported by the children.

Methods

This was a cross-sectional study carried out on children and adolescents receiving either chronic HD or chronic PD at the nephrology unit of Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). CMJAH is a tertiary referral centre which provides specialist care to all persons from the referral regions of the province and neighbouring provinces. Each participant in this study had his/her HRQOL assessed. Patients were eligible if they were on a form of chronic dialysis. Children who had been hospitalised within the preceding two weeks, and those who had received a kidney transplant were excluded. All children and adolescents receiving chronic dialysis at the hospital, as well as their caregivers, participated in the study.

Participants

Baseline sociodemographic and clinical details were obtained from the participants, as well as from a folder review. These included age, gender, baseline diagnosis, mode of dialysis, date of commencement and duration on dialysis, number of medications, number of routine clinic visits, number of hospital visits for dialysis and dialysis-related complaints and number of hospitalisations within the previous 6 months, attendance at hospital school as well as any significant nonrenal comorbidities diagnosed in the patient. The hospital school is a school established within the hospital for children with chronic conditions such as ESRD to attend because of the long hours they spend at the hospital for procedures such as dialysis. Having a school on the hospital premises allows the children to receive as much holistic care as possible while they receive treatment for their medical conditions.

Assessment of HRQOL

We assessed the HRQOL of patients undergoing HD, automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD) using the Pediatric Quality of Life Inventory (PedsQL) End Stage Renal Disease module version 3.0 as the instrument. We received the user agreement from Mapi Research Trust in Lyon, France. The instrument is a questionnaire comprising 7 domains with a total of 34 questions/items. The domains include: general fatigue (4 items), about my kidney disease (5 items), treatment problems (4 items), family and peer interactions (3 items), worry (10 items), perceived physical appearance (3 items) and communication (5 items). The PedsQL ESRD module 3.0 is available in 5 age-specific report versions: toddler (2 - 4 years, only by caregiver proxy report), young child (5 - 7 years), child (8 - 12 years), teen (13 - 18 years) and young adult (18 - 25 years). Child reports as well as parent proxy reports were obtained. Questionnaires were administered to all patients and parents/caregivers of children on all forms of chronic dialysis. Children and caregivers had the questionnaires administered to them in the language they felt most comfortable with and an interpreter was used in cases of language barriers. The questionnaires were orally administered to the children

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during HD sessions, PD or HD clinic visits, or completed at home and returned to the primary investigator. A Likert response scale (reverse scoring with linear transformation) was used in assigning scores, with higher scores indicating better HRQOL.

Ethical considerations

Each participant was given an information sheet which explained in detail what was involved in the study. Signed informed consent was obtained from either a parent/legal guardian or child older than 8 years while verbal assent was obtained from the younger children.

The study was approved by the Human Research Ethics Committee of the University and the Clinical Directorate of the hospital (ref. no.

M141133).

Data analysis

Data were entered into a spreadsheet and analysed using the SPSS statistical software package version 20.0 (IBM Corp., USA). Baseline characteristics were summarised as continuous data and presented as mean (SD). Discrete variables were summarised as counts and percentages. Differences in continuous data were analysed with Student’s t-test while those for categorical data were analysed using the χ2 test. The primary outcome of interest was the disease-specific quality of life score. Secondary outcomes included scores for the 7 domains of the PedsQL ESRD module 3.0. The independent variables were patients’ characteristics as determined from baseline patient data obtained from the folder review. Mean HRQOL scores were calculated for each domain for the APD, CAPD and HD sample groups, and differences were compared using the independent samples t-test or analysis of variance (ANOVA). A univariate analysis was performed to find which variables were associated with HRQOL scores of both HD and PD patients. A p-value of <0.05 was considered to be statistically significant in all analyses.

Results

Twenty-seven children and adolescents and their basic characteristics were studied (Table 1). There were 14 male and 13 female subjects (M:F = 1.08:1). The mean (SD) age was 14.4 (4.8) years (range 5 – 25) years. Fourteen patients were on in-centre HD while 13 were on PD (8 on APD and 5 on CAPD). Those who were on HD were significantly older, with a mean (SD) age of 16.6 (3.2) v. 12.1 (5.3) years (p=0.013), and had been on dialysis much longer, for a mean (SD) duration of 4.5 (3.3) v. 1.7 (0.9) years (p=0.006), than those who were on PD. There was no significant difference in the mean number of medications, hospitalisations and routine clinic visits in the preceding 6 months among the children on the three modes of dialysis. However, the patients receiving HD had a significantly higher number of hospital visits for dialysis and dialysis-related complaints than those who were on PD. Half of the children on HD attended the hospital school.

There was a wide range of underlying diagnoses of the aetiology of ESRD in the patients (Table 2). Eleven children (40.7%) had significant non-renal comorbidities. Of these, 5 children were on APD and 6 were on HD. The comorbidities comprised HIV infection in 5 children, dilated cardiomyopathy in 4, spina bifida in 2, 1 case of mitochondrial myopathy and 1 severe hearing impairment. Two children, one on HD and one on APD, had a combination of HIV infection and dilated cardiomyopathy. The mean (SD) HRQOL scores were lower in children who had the presence of a significant non-renal comorbidity – 59.7 (13.3), compared with those who did not have significant non-renal comorbidity – 55.3 (10.4), but this was not of statistical significance (F=0.829, p=0.371). There was also no association between the presence and number of significant non-renal comorbidities with mode of dialysis (df=2; F=0.833; p=0.447).

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ARTICLE Table 1. Basic characteristics of participants with ESRD (N=27) Total Parameter (N=27) Age (years), mean (SD) Gender Male Female Hours on dialysis, mean (SD) Number of medications, mean (SD) Number of routine clinic visits in past 6 months, mean (SD) Number of hospital visits for dialysis and dialysis-related complaints, mean (SD) Number of hospitalisations in past 6 months, mean (SD) Attends hospital school, n (%)

HD (n=14)

APD (n=8)

CAPD (n=5)

p-value

14.4 (4.8)

16.6 (3.2)

12.2 (3.7)

11.8 (7.8)

0.047

14 13 3.1 (2.8) 10.1 (3.0) 5.2 (1.4) 40.0 (32.8)

11 3 4.5 (3.3) 9.5 (2.6) 5.0 (1.6) 71.0 (1.6)

2 6 1.6 (0.5) 11.7 (3.8) 5.7 (1.0) 6.6 (0.9)

1 4 1.9 (1.3) 9.4 (1.5) 5.0 (1.2) 6.6 (1.1)

0.024 0.198 0.461 0.000

1.1 (1.4)

1.2 (1.4) 7 (50)

0.9 (1.4) 0 (0)

1.2 (1.6) 1 (20)

0.860 0.039

HD = haemodialysis; APD = automated peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis; ESRD = end-stage renal disease.

Table 2. Underlying diagnoses in children with ESRD Underlying aetiology of ESRD n (%) Focal segmental glomerulosclerosis Posterior urethral valves HIV immune complex kidney disease Neuropathic bladder Congenital nephrotic syndrome Cystinosis Membranoproliferative glomerulonephritis Cystic kidneys Haemolytic uraemic syndrome Crescentic glomerulonephritis HIV-associated nephropathy Immunoglobulin A nephropathy Haemolytic uraemic syndrome with secondary global sclerosis Immune-mediated glomerulonephritis Unknown

6 (22.2) 3 (11.1) 2 (7.4) 2 (7.4) 2 (7.4) 2 (7.4) 2 (7.4) 1 (3.7) 1 (3.7) 1 (3.7) 1 (3.7) 1 (3.7) 1 (3.7) 1 (3.7) 1 (3.7)

Discussion

ESRD = end-stage renal disease.

HRQOL scores

The mean (SD) HRQOL scores for the study population was 57.9 (12.2) for the children and 60.5 (15.4) for the parent proxies. The mean (SD) HRQOL scores for both male and female genders were 53.8 (11.2) and 62.4 (11.9), respectively (t=1.928; p=0.066 in the study population). Females reported higher mean HRQOL scores in all domains except the ESRD Worry domain. However, this was not of statistical significance (p>0.05 in all domains).

The mean (SD) HRQOL score for children on HD was 54.7 (9.7) while it was 57.8 (15.3) and 67.1 (10.4) for those on APD and CAPD respectively (F=2.049; p=0.151). The mean (SD) HRQOL scores for children and parent proxies in the various domains were studied and the HRQOL was lower in most domains in the HD group compared with the PD group as a whole. However, none reached statistical significance except in the ESRD General Fatigue domain (Table 3).

The mean differences in HRQOL scores between parent proxies and the children with ESRD were compared (Table 4). The parent proxies reported mean HRQOL scores which were mostly higher than those reported by the children themselves in all domains except the General Fatigue domain and the About My Kidney Disease domain. However, the mean difference was only significant in the Communication domain (t=2.312; p=0.030).

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Although the children who were on HD had spent a significantly longer time on therapy than had those on PD, there was no significant effect of duration on dialysis on HRQOL scores when comparing children who had spent 1 (F=2.272; p=0.144), 2 (F=0.242; p=0.627), 3 (F=0.237; p=0.631) or 4 years (F=0.229; p=0.637) on dialysis.

Among the patients who were on PD, the HRQOL scores were lower in most domains in the APD group when compared with the CAPD group. This was, however, only significant in the domain of General Fatigue in which the children who had CAPD reported statistically significantly higher HRQOL scores than those who had APD (p=0.032). This significance was not found on comparison of other domains or among the parent proxies.

When compared with the population sample mean HRQOL scores of a healthy paediatric population,[17] the mean HRQOL scores of the children with ESRD on dialysis were significantly lower for both child and parent proxy reports (p<0.05 in all cases).

The HRQOL scores did not vary regarding attendance at hospital school after controlling for the mode of dialysis (F=1.109; p=0.302).

To the best of our knowledge, this study is the first to report on the HRQOL of children and adolescents with ESRD in sub-Saharan Africa. The number of RRT procedures which are carried out in South Africa (SA) are much more than in other parts of sub-Saharan Africa, and the findings from this study may be applicable to other regions as well.[18] The only other study carried out in SA was done on adults.[19] The present study found low mean HRQOL scores among children with ESRD receiving dialysis. This is similar to findings of several other authors.[8,9,12-15] The overall mean HRQOL scores were found to be significantly lower in all patients in our cohort compared withpopulation sample mean HRQOL scores of healthy controls.[17] This compares to the report by Goldstein et al.[9] Moreover, Buyan et al.[14] also reported significantly higher HRQOL scores in healthy controls in almost all domains tested compared with children with chronic kidney disease which included children on either HD or PD and children who had received a kidney transplant. The Buyan et al.[20] study, however, utilised the KINDL scoring system and reported no significant differences between the scores in the HD and PD groups.[14] Our finding of lower HRQOL scores in children with ESRD was not surprising as it has been reported that even children with only mild to moderate stages of CKD already have significantly lower HRQOL scores than their healthy counterparts. Children with ESRD are more often than not unable to participate in usual activities with their peers because of the very nature of the disease, which affects physical, emotional and psychosocial aspects of life.

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ARTICLE Table 3. Mean HRQOL Scores for children and parent proxies for different modes of dialysis Child scores, mean (SD) Parent proxy scores, mean (SD) PedsQL ESRD HD APD CAPD Total HD APD CAPD Total Domains (n=14) (n=8) (n=5) (N=27) F* p-value (n=13) (n=8) (n=5) (n=26) F

p-value

General fatigue

1.5

0.24

1.3

0.30

1.8

0.19

0.4

0.66

0.1

0.93

0.7

0.51

0.7

0.51

0.8

0.44

About my kidney disease Treatment problems Family and peer interaction Worry Perceived physical appearance Communication Total

60.3 (12.9) 56.4 (13.9) 57.1 (13.6) 48.2 (16.7) 52.3 (18.9) 43.4 (32.7) 62.1 (19.5) 54.7 (9.7)

63.3 (22.8) 71.2 (18.3) 62.5 (22.2) 51.0 (26.5) 49.1 (22.4) 52.1 (22.2) 61.2 (18.7) 57.8 (15.3)

90.0 (16.3) 71.0 (24.6) 77.5 (20.5) 53.3 (38.0) 49.0 (8.4) 70.0 (27.4) 79.0 (17.5) 67.0 (10.4)

66.7 (19.8) 63.5 (18.3) 62.5 (18.7) 50.0 (23.6) 50.7 (18.1) 50.9 (19.4) 65.0 (19.4) 57.9 (12.1)

5.9

0.01

2.4

0.11

2.4

0.11

0.1

0.91

0.1

0.90

1.5

0.24

1.7

0.21

2.0

0.15

59.6 (22.8) 59.2 (22.9) 66.3 (16.4) 46.1 (35.9) 54.8 (25.5) 48.7 (29.6) 70.8 (29.0) 58.4 (18.6)

62.5 (21.1) 56.2 (11.9) 58.6 (25.0) 61.4 (20.4) 51.2 (22.6) 51.0 (18.6) 76.2 (24.9) 58.7 (9.9)

80.0 (14.2) 75.0 (26.0) 80.0 (18.9) 60.0 (43.5) 53.0 (11.6) 63.3 (21.7) 86.0 (16.7) 69.0 (12.7)

64.4 (21.6) 61.3 (21.1) 66.6 (20.4) 53.5 (33.1) 53.4 (21.9) 52.2 (25.0) 75.4 (25.6) 60.5 (15.4)

HRQOL = health-related quality of life; PedsQL = Paediatric Inventory of Quality of Life Core Scales; ESRD = end-stage renal disease; HD = haemodialysis; APD = automated peritoneal dialysis; CAPD = continuous ambulatory peritoneal dialysis.

F-statistic and P values represent differences in mean scores between the various modes of dialysis for either group.

Table 4. Mean differences in HRQOL scores between parent proxies and children with ESRD Mean (SD) difference between parent proxies and children’s PedsQL ESRD domain reports t-statistic

p-value

General fatigue About my kidney disease Treatment problems Family and peer interaction Worry Perceived physical appearance Communication Total

0.603 0.595 0.532 0.424 0.571 0.802 0.030 0.403

–2.3 (21.3) –2.6 (24.2) 3.0 (23.7) 5.0 (30.7) 2.7 (23.5) 1.3 (26.3) 10.2 (22.1) 2.56 (15.0)

–0.527 –0.538 0.634 0.814 0.574 0.253 2.312 0.852

HRQOL = health-related quality of life; ESRD = end-stage renal disease; PedsQL = Paediatric Inventory of Quality of Life Core Scales.

Our study also found that, although not achieving statistical significance, the mean HRQOL scores were higher for children who were on PD when compared with those on HD. Goldstein et al.,[9] McKenna et al.[12] and Kilis-Pstrusinska et al.,[15] who also used the PedsQL instrument, did not find any significant difference in HRQOL scores between children on HD and those on PD. Buyan et al.[14] also had the same findings although they used the KINDL instrument in their study. The study on adults carried out in Cape Town in South Africa had similar findings, although a different instrument, the KDQOL-SF, was used.[19] In the study by Kilis-Pstrusinska et al.[15] a large multicentre study carried out on Polish children with CKD, using the PedsQL instrument found that the HRQOL was significantly higher with the use of PD compared with HD. Juergensen et al.,[21] in a study of adults with ESRD in the USA, reported that patients on PD reported a significantly higher satisfaction compared to those on HD. However, their study used a questionnaire developed solely for the purpose of their study. The use of various instruments or assessment measures makes it difficult to make direct comparisons between different renal replacement modalities. This has been alluded to by McKenna et al.[12] and Lai.[22] In analysing HRQOL scores for children on PD, it was found that children who were on CAPD reported higher scores than

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those on APD. This was an unexpected finding as we had assumed that the use of APD would make the dialysis procedure less cumbersome for the patients and caregivers, with less interference in the patients’ lives and thus would be preferred. Possible reasons for the apparent preference for CAPD v.s APD may be the flexibility of CAPD compared with APD and the possibly negative psychological effect of having to be attached to the APD machine for long hours at a time.

Our study did not find any significant influence of age, gender, mode of dialysis, duration of dialysis, number of medications, hospitalisations and routine clinic visits or attendance at the hospital school on the reported HRQOL scores by both children and their caregivers. This finding is similar to reports by Gerson et al.[20] and Amr et al.[23] Surprisingly, although the children with significant non-renal comorbidities had lower HRQOL scores, the presence or absence of a non-renal comorbidity did not appear to have a significant impact on the HRQOL scores.

It has been reported that youths who have had CKD for a long period of time had better HRQOL scores in the physical and emotional functioning domains.[20] The explanation for this could be that the children and their caregivers learn to adapt to having multiple comorbidities and are able to handle such situations better.

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ARTICLE The present study found higher reported mean HRQOL scores from the parent proxies when compared with those of the children on dialysis treatment, although this was not of statistical significance.

Several studies have reported varying HRQOL scores between parent-proxies and patients.[9,12-15,20,24] The differences reported in these studies were generally not statistically significant but Buyan et al.,[14] Gerson et al.[20] and Chiu et al.[24] found that parents reported mean HRQOL scores that were higher than those reported by their children, while Goldstein et al.,[9] McKenna et al.,[12] Neul et al.[13] and Kilis-Pstrusinska et al.[15] reported the opposite, with the children’s scores being higher than those reported by their parent-proxies. Only the study by Buyan et al.[14] reported significant differences for almost all the domains tested. Kilis-Pstrusinska et al.[15] found the difference to be significant for children who were on PD but not so with children on HD. These highly varied findings appear to imply that parents do not really understand the effects of ESRD and its treatment modality on the general health of their children, as their perceptions either overestimate or underestimate those of their children. It is therefore important to obtain reports from both the children and their parent proxies so that management and counseling can be better tailored to the specific needs of each family.

Conclusion

Children with ESRD receiving dialysis have low HRQOL scores.

Those on PD reported better HRQOL than those on HD, which implies that children on HD may require even more special support.

Furthermore, parent proxies reported higher scores than those reported by the children. This raises concern about the extent of care and support being given to the children on either modality of RRT, as well as parental motivation. The importance of assessing the HRQOL of children with chronic conditions such as ESRD, with the aim of offering them care which is as holistic as possible, cannot be overemphasised.

Acknowledgements. The authors are thankful to the patients and their caregivers for their participation in the study. The authors also wish to acknowledge the International Society of Nephrology and the International Paediatric Nephrology Association for sponsoring the corresponding author (PNO) in paediatric nephrology subspecialty training at Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa.

Author contributions. Study conception and design: PNO, CL. Data collection: PNO, BS, TK. Data analysis and interpretation: PNO, TK, GM, CL. Conceptualising and writing the manuscript: PNO. Technical review of manuscript: PNO, BS, TK, GM, CL. Approval of final manuscript: PNO, BS, TK, GM, CL. Funding. None.

Conflict of interest. None.

1. Copelovitch L, Warady BA, Furth SL. Insights from the chronic kidney disease in children (CKiD) study. Clin J Am Soc Nephrol 2011;6(8):2047-2053. https:// doi.org/10.2215/cjn.10751210.

2. Bruce MA, Beech BM, Sims M, et al. Social environmental stressors, psychological factors, and kidney disease. J Investig Med 2009;57(4):583-589. https://doi.org/10.231/jim.0b013e31819dbb91.

3. Kaptein AA, van Dijk S, Broadbent E, Falzon L, Thong M, Dekker FW. Behavioural research in patients with end-stage renal disease: A review and research agenda. Patient Educ Couns 2010;81(1):23-29. https://doi. org/10.1016/j.pec.2009.10.031.

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4. The World Health Organization Quality of Life assessment (WHOQOL): Position paper from the World Health Organization. Soc Sci Med 1995;41(10):1403-1409. https://doi.org/10.1016/0277-9536(95)00112-k 5. Eser E, Yuksel H, Baydur H, et al. The psychometric properties of the new Turkish generic health-related quality of life questionnaire for children (Kid-KINDL).

Turk Psikiyatri Derg 2008;19(4):409-417.

6. Hays RD, Kallich JD, Mapes DL, Coons SJ, Amin N, Carter WB. Kidney disease quality of life short form (KDQOL-SF), version 1.3: A manual for use and scoring. http://www.rand.org/content/dam/rand/pubs/papers/2006/P7994.pdf (accessed 13 June 2016).

7. Varni JW, Seid M, Kurtin PS. PedsQL 4.0: Reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care 2001;39(8):800-812. https://doi.org/10.1097/00005650200108000-00006 8. Goldstein SL, Graham N, Warady BA, et al. Measuring health-related quality of life in children with ESRD: Performance of the generic and ESRD-specific instrument of the Pediatric Quality of Life Inventory (Peds QL). Am J Kidney Dis 2008;51(2):285-297. https://doi.org/10.1053/j.ajkd.2007.09.021 9. Goldstein SL, Graham N, Burwinkle T, Warady B, Farrah R, Varni JW. Health-related quality of life in pediatric patients with ESRD. Pediatr Nephrol 2006;21(6):846-850. https://doi.org/10.1007/s00467-006-0081-y 10. Eijsermans RM, Creemers DG, Helders PJ, Schroder CH. Motor performance, exercise tolerance, and health-related quality of life in children on dialysis. Pediatr Nephrol 2004;19(11):1262-1266. https://doi.org/10.1007/s00467-004-1583-0.

11. Gerson AC, Riley A, Fivush BA, et al. Assessing health status and health care utilisation in adolescents with chronic kidney disease. J Am Soc Nephrol 2005;16(5):1427-1432. https://doi.org/10.1681/asn.2004040258 12. McKenna AM, Keating LE, Vigneux A, Stevens S, Williams A, Geary DF. Quality of life in children with chronic kidney disease – patient and caregiver assessments.

Nephrol Dial Transplant 2006;21(7):1899-1905. https://doi.org/10.1093/ndt/ qfl091 13. Neul SK, Minard CG, Currier H, Goldstein SL. Health-related quality of life functioning over a 2-year period in children with end-stage renal disease. Pediatr Nephrol 2013;28(2):285-293. https://doi.org/10.1007/s00467-012-2313-7.

14. Buyan N, Turkmen MA, Bilge I, et al. Quality of life in children with chronic kidney disease (with child and parent assessments). Pediatr Nephrol 2010;25(8):14871496. https://doi.org/10.1007/s00467-010-1486-1 15. Kilis-Pstrusinska K, Medynska A, Chmielewska IB, et al. Perception of health-related quality of life in children with chronic kidney disease by the patients and their caregivers: Multicenter national study results. Qual Life Res 2013;22(10):2889-2897. https://doi.org/10.1007/s11136-013-0416-7 16. Varni JW, Limbers CA, Burwinkle TM. Impaired health-related quality of life in children and adolescents with chronic conditions: A comparative analysis of 10 disease clusters and 33 disease categories/severities utilizing the PedsQL 4.0 Generic Core Scales. Health Qual Life Outcomes 2007;5:43. https://doi. org/10.1186/1477-7525-5-43 17. Varni JW, Burwinkle TM, Seid M, Skarr D. The PedsQL 4.0 as a pediatric population health measure: Feasibility, reliability and validity. Ambul Pediatr 2003;3(6):329-341. https://doi.org/10.1367/1539-4409(2003)003<0329:tpaapp>2 .0.co;2 PMID: 14616041 18. Naicker S. End-stage renal disease in sub-Saharan and South Africa. Kidney Int Suppl 2003;83:S119-S122. https://doi.org/10.1046/j.1523-1755.63.s83.25.x 19. Okpechi IG, Nthite T, Swanepoel CR. Health-related quality of life in patients on hemodialysis and peritoneal dialysis. Saudi J Kidney Dis Transpl 2013;24(3):519526. https://doi.org/10.4103/1319-2442.111036 20. Gerson AC, Wentz MA, Abraham AG, et al. Health-related quality of life of children with mild to moderate chronic kidney disease. Pediatrics 2010;125(2):e349–e357. https://doi.org/10.1542/peds.2009-0085 21. Juergensen E, Wuerth D, Finkelstein SH, Juergensen PH, Bekui A, Finkelstein FO. Hemodialysis and peritoneal dialysis: Patients’ assessment of their satisfaction with therapy and the impact of the therapy on their lives. Clin J Am Soc Nephrol 2006;1(6):1191-1196. https://doi.org/10.2215/cjn.01220406 22. Lai WM. Quality of life in children with end-stage renal disease: Does treatment modality matter? Perit Dial Int 2009;29(Suppl 2):S190-S191.

23. Amr M, Bakr A, El Gilany AH, Hammad A, El-Refaey A, El-Mougy A. Multimethod assessment of behavior adjustment in children with chronic kidney disease. Pediatr Nephrol 2009;24(2):341-347. https://doi.org/10.1007/s00467008-1012-x.

24. Chiu MC, Ng CF, Lee LP, Lai WM, Lau SC. Automated peritoneal dialysis in children and adolescents – benefits: A survey of patients and parents on healthrelated quality of life. Perit Dial Int 2007;27(Suppl 2):S138-S142.

Accepted 22 November 2017.

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RESEARCH

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

The use of the Road-to-Health card by doctors in a tertiary paediatric hospital setting J I Wiles,1 MB ChB, DCH, FCPaed, MMed; G H Swingler,1 MB ChB, FCPaed, PhD 1

Department of Paediatrics, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

Corresponding author: J I Wiles (jodiwiles@gmail.com) Background. Low possession of the Road-to-Health card (RTHC) by parents, as well as inadequate use of the RTHC by health professionals, have reduced its efficacy.

Objectives. To describe the level of possession of the RTHC by a sample of patients admitted to the Red Cross War Memorial Children’s Hospital (RCWMCH), and to determine the extent and accuracy of doctors’ transfer of clinical information between the RTHC and hospital records.

Methods. A cross-sectional analytical study conducted in four general paediatric wards over six weeks, during which data were extracted from participants’ RTHC and hospital record. The presence or absence of selected items of information on the RTHC and the hospital record was recorded; the primary outcome was the transfer of the specified items of information between records.

Results. A total of 133 (81%) eligible caregivers had the RTHC on their person. Variables including perinatal information, immunisation record and weight-for-age chart were well-documented on the RTHC prior to hospital admission, and mostly well-transferred to the hospital record. In general, new information in the hospital record was poorly transferred to the RTHC on discharge; for example, weight (31%), diagnosis (63%) and treatment (48%).

Conclusions. The possession rate of RTHCs within the study sample was within an acceptable range. Although doctors generally made use of the RTHC as a reference source, their recording of new clinical information on the RTHC was poor, missing the opportunity to use it as a communication tool for continuity of care.

S Afr J Child Health 2018;12(1):63-67. DOI:10.7196/SAJCH.2018.v12i2.1458

Patient-retained personal child health records (PCHRs) are used globally as a tool for the coordination of healthcare and to promote preventative health strategies.[1-23] The South African version of the PCHR is the Road-to-Health Card (RTHC) with two versions currently in use: a 1995 chart version, and an updated 2011 booklet version.[4,5] The Booklet is a more comprehensive record that contains space for clinical notes, updated growth charts and a recent version of the South African public immunisation schedule.

Low possession and retention of PCHRs, and inadequate use of PCHRs by health professionals, have lessened its efficacy. An international report advised that the median prevalence rate should not fall below 80% if vaccination coverage and health care co-ordination are to be achieved.[6] Numerous international and local studies have highlighted three weak links in the use of the PCHR by health professionals: failure to request the record from the caregiver, failure to use the record as a reference source of the child’s medical background, and failure to comprehensively and accurately record new information in the record.[7-20] Much of the research on the weak links has relied on participant recall, which in many cases has not matched the health professional’s medical notes. Few studies have examined both the PCHR and institutional clinical records to determine what information has been transferred in either direction.[16,18,19] In this study, we sought to describe the level of possession of the RTHC by caregivers of patients admitted to Red Cross War Memorial Children’s Hospital (RCWMCH), and to assess the degree and accuracy of doctors’ use of the RTHC. The study was approved by the Human Research Ethics Committee of the University of Cape Town (ref. no. HREC 119/2012) and the Hospital Research Committee of RCWMCH.

Methods

A descriptive, cross-sectional analytical study was conducted in four general paediatric wards at RCWMCH, a public sector teaching 63

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hospital in Cape Town providing a range of general and tertiary paediatric services. The four wards in which the study took place represented both acute care (short-stay wards) and longer-term care (long-stay wards).

Consecutive patients were enrolled at discharge from these wards during office hours between 23 March and 30 April 2012. Exclusion criteria were: admission for <24 hours; absence of a caregiver; or absence of informed consent.

Following informed consent and enrolment, the primary author photographed all relevant pages of the RTHC. Data were extracted from the photographs of the RTHC and the participants’ original hospital records. Two types of hospital records were in use at the time: an old version with a simple front sheet that was used to record a few patient and medical details, and a new version with a more comprehensive front section modelled on the RTHC Booklet, which was being phased in. Both the Chart and the Booklet versions of the RTHC were included. Only the front sections of the hospital record, the admission and discharge notes, and the treatment chart relevant to the most recent hospital stay were examined.

Demographic details, duration of hospital stay, primary diagnosis, and the presence or absence of pre-specified items of information on the RTHC and hospital record were recorded (Tables 1 and 2).

It was assumed that the inward transfer of information occurred on admission, and outward transfer at admission and/or discharge. No attempt was made to categorise the clinical appropriateness of prespecified information items in specific clinical cases.

The primary outcome was the proportion of pre-specified information that was transferred between RTHC and hospital clinical records, in both directions.

Target sample size was estimated by calculating 95% confidence intervals (CIs) for a range of potential sample sizes. A sample of 150 participants would have given confidence limits of 42% - 58% for a point estimate of 50%, and 6% - 16% for an estimate of 10%. Those were judged to be meaningfully precise for the purpose of the study.

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RESEARCH Data were captured in Epidata 3.1, using patient code numbers to maintain anonymity. Thereafter the captured data were exported to a Microsoft Excel 2013 spreadsheet, in which much of the analysis was conducted. Data cleaning and analyses were performed using SPSS Statistics version 22 (IBM Corp., USA).

The database was stored securely on the main author’s personal computer (PC) and on Google Drive, accessible only by the main author and the study supervisor (GS). Digital photographs were stored on the main author’s PC and destroyed after review.

The presence of the pre-specified items of information in each record, and the transfer of available items between the records, were presented as proportions with Clopper-Pearson (exact) binomial CIs. A sub-group analysis was performed for 5 variables judged to be essential to any child’s hospital admission, regardless of the child’s age or diagnosis. Transfer proportions of these variables were compared by type of ward (short-stay v. long-stay), type of RTHC (chart v. booklet) and type of hospital record (old v. new). χ2 or Fisher’s exact tests were used, as appropriate, for hypothesis testing.

Results

A total of 133 (81%) eligible participants had an RTHC with them and were recruited for this study (Fig. 1). Two of the hospital records

were missing and 4 photos were incomplete, therefore only 127 participants were included in the analysis. The study population was classified according to various characteristics (Table 3.). Almost twothirds of the participants were <1 year old (63.8%). The duration of stay for many of the patients was 3 - 7 days, and the distribution of patients between short-stay and long-stay wards was similar (57.5% and 42.5% respectively). Most of the participants possessed the RTHC Booklet (72.4%) and very few of the hospital records (7.1%) were in the new format. The two most common diagnoses were acute gastroenteritis (29%) and pneumonia (27%).

Information recorded on the patient’s RTHC in most cases was well-transferred to the hospital record (Table 1). HIV status information was poorly transferred to the hospital record, except for maternal HIV status (transfer proportion 84.9%). Information on exposure to tuberculosis (TB) was mostly well-transferred (73.7%) but tuberculin skin test results were neither well-documented in the RTHC (4.7%; 95% CI 1.8 - 10) nor well-transferred to the hospital record (33.3%). Less than half (43.7%) of the full immunisation records were copied into the hospital record (95% CI 34.5 - 52.4) but the presence of completed age-appropriate, up-to-date (UTD) immunisations were transferred in 84.8% of cases. Weight-for-age scores were transferred in 84.7% of cases.

Table 1. Items of information present on RTHC and transferred to hospital record (HR) on admission (N=127) Item Recorded in the RTHC, n (%) Recorded in the HR, n (%) Percentage transferred (%) Gestational age at birth Mode of delivery Birth weight Apgar scores Mother’s HIV status Maternal ART PMTCT Patient’s HIV status Cotrimoxazole Patient ART Tuberculosis exposure Tuberculin skin testing Tuberculosis treatment Immunisation record Up-to-date immunisations Weight-for-age

93 (73.2) 114 (89.8) 124 (97.6) 117 (92.1) 53 (41.7) 19 (15.0) 26 (20.5) 22 (17.3) 10 (7.9) 3 (2.4) 19 (15.0) 6 (4.7) 3 (2.4) 126 (99.2) 92 (72.4) 118 (92.9)

71 (55.9) 95 (74.8) 106 (83.5) 94 (74.0) 45 (35.4) 5 (3.9) 15 (11.8) 18 (14.2) 3 (2.4) 3 (2.4) 14 (11.0) 2 (1.6) 3 (2.4) 55 (43.3) 78 (61.4) 100 (78.7)

76.3 83.3 85.5 80.3 84.9 26.3 57.7 81.8 30.0 100 73.7 33.3 100 43.7 84.8 84.7

ART = antiretroviral treatment; PMTCT = prevention of mother-to-child transmission; RTCH = Road-to-Health card

Table 2. Items of new information available and transferred to RTHC on discharge (N=127) Item Recorded in the HR, n (%) Recorded in the RTHC, n (%)

Percentage transferred (%)

PMTCT Patient’s HIV status Cotrimoxazole Patient ART Tuberculosis exposure Tuberculin skin testing Tuberculosis prophylaxis Tuberculosis treatment Up-to-date immunisations Weight Diagnosis Treatment

5.9 20.0 0.0 14.3 11.1 26.5 62.5 40.0 38.1 31.4 63.5 48.0

17 (13.4) 95 (74.8) 7 (5.5) 7 (5.5) 72 (56.7) 48 (38.6) 8 (6.3) 10 (7.9) 21 (16.5) 118 (92.9) 126 (99.2) 125 (98.4)

1 (0.8) 19 (15.0) 0 (0.0) 1 (0.8) 8 (6.3) 13 (10.2) 5 (3.9) 4 (3.1) 8 (6.3) 37 (29.1) 80 (63.0) 60 (47.2)

PMTCT = Prevention of mother-to-child transmission; ART = antiretroviral treatment; RTHC = Road-to-Health card.

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Total discharges during study period (N=818)

90

35/42

Excluded N=30 Admission <24 hours (n=23) No caregiver available (n=6) Refused consent (n=1)

Information transferred (%)

80

Unable to make contact before discharge (N=563)

Short-stay (n=73) Long-stay (n=54)

45/49 43/50

55/69 48/72

70

32/54

60 50

27/54

40 30 20

7/49

10 0 Up-to-date immunisations Weight-for-age

Included (N=164)

Weight*

From RTHC to hospital record

Unable to analyse (N=37) Incomplete records (n=6) RTHC not available (n=31)

33/71

30/69

Diagnosis

Treatment

From hospital record to RTHC

Fig. 2. Transfer proportions of key items of information according to ward type.

(RTHC = Road-to-health card.) (*Risk ratio 3.04.)

Analysed (N=127) 100 90 Information transferred (%)

Fig. 1. Flow diagram illustrating the study participant selection process.

Table 3. Characteristics of study population (N=127) Characteristic n (%) Gender Male Female Age (years) <1 1-5 >5 Duration of stay (days) 0-3 4-7 >7 Ward Short-stay Long-stay Type of RTHC Chart Booklet Type of hospital record Old New

70 (44.9) 57 (55.1)

Chart (n=35) Booklet (n=92) 23/34

70 60 50

57/92 46/92

15/33

14/33

40 30

22/85

10 0 Up-to-date immunisations Weight-for-age From RTHC to hospital record

64 (50.4) 27 (21.3) 36 (28.3)

Weight*

Diagnosis

Treatment

From hospital record to RTHC

Fig. 3. Transfer proportions of key items of information RTHC type. (*Risk ratio 1.76; 95% CI 1.045 - 2.95; p=0.033.)

73 (57.5) 54 (42.5)

There was no statistically significant difference in the transfer proportions of key items of information by type of ward, type of RTHC and type of hospital record, except for the transfer of weight from the RTHC to the hospital record on discharge. The risk ratio for the transfer of weight data from the hospital record to RTHC in short-stay wards compared with long-stay wards was 3.04 (95% CI 1.46 - 6.36, p=0.003), and was 1.76 (95% CI 1.045 - 2.95, p=0.033) for the RTHC chart compared with the RTHC booklet (Figs 2 and 3, respectively). The sample size of new hospital records was too small (n=9) for any comparison with the older hospital records.

35 (27.6) 92 (72.4) 118 (92.9) 9 (7.1)

RTHC = Road-to-Health card.

In general, the new information in the patient’s hospital record was poorly recorded on the RTHC (Table 2). HIV status was available in 74.8% (95% CI 66.3 - 82.1) of hospital records but transferred to the RTHC in only 20% of such cases. Queries about TB exposure and the occurrence of tuberculin skin testing was noted relatively often in the hospital record, but not well-transferred to the RTHC (in only 11.1% and 26.5% of cases, respectively). The patient’s weight was recorded or plotted in 92.9% (95% CI 87.0 - 96.7) of hospital records but transferred to RTHCs in only 31.4% of cases. The patient’s diagnosis and treatment were almost always recorded in the hospital record but transferred in 63% and 48% respectively.

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73/83 27/35

20

81 (63.8) 44 (34.6) 2 (1.6)

65

80

57/65 21/27

Discussion

This study sought primarily to determine the accuracy of bi-directional information transfer between patient-held records and institutional clinical records by comparing information in both sources of information. Whereas most previous research has focused on the possession of, and information recorded on, the PCHR, this study provides process information about key steps in the use of the PCHR as a tool for the continuity of health care i.e. transfer of information from the PCHR to institutional records, and of institutional information to the PCHR. This is also the first published study of the use of the South African 2011 RTHC Booklet

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RESEARCH in operational conditions that described its effectiveness as a means of communication between health professionals.

This study focused on practice in a specialised children’s hospital, a small niche in the context of child health; but such hospitals remain important participants in the flow of clinical information about children with complex health problems.

The RTHC possession rate of 81% was just within the generally accepted recommended range of 80% or more[6] and is a considerable improvement on the findings of previous research conducted at RCWMCH in 1991 (43%)[21] and 1995 (61%).[22] This study found that doctors at RCWMCH generally examined the RTHC and transferred relevant clinical information to the hospital record during admission. However, documentation of perinatal HIV information in the RTHC before arrival at RCWMCH was poor, and even what was available on admission was not well transferred. This probably reflects the social sensitivity of HIV infection in South Africa. The 2010 National Prevention of Motherto-Child Transmission effectiveness survey showed that only 34% of the 10 612 included mothers had a clear indication of their HIV status on their child’s RTHC.[23] The low proportion of transfer to the hospital record in this study is presumably due to the priority given by busy clinicians to more recent data such as the patient’s HIV and antiretroviral therapy status.

This study showed that the recording of new clinical information relating to the patient’s hospital stay was poorly recorded on the RTHC. Much of the previous research on the RTHC, and PCHRs in general, has taken the form of simple audits that did not explicitly distinguish between information that was truly missing and information that was unavailable for transfer in the first place.

Some studies have aimed to assess agreement between the original medical record and the PCHR, generally showing that the transfer to the PCHR was poor. Although the findings of a 2008 French study showed excellent agreement for perinatal information, the transfer of Apgar scores (felt to be a socially sensitive subject) was poor.[19] A 1998 South African study observed that, although new information was often entered on the RTHC during consultations, these details were often incomplete when compared with the clinic notes.[16] Similarly, in a recent audit performed at RCWMCH, only 65% of the 41 RTHCs examined contained a clinical note pertaining to the patient’s hospital visit.[24] It is policy on discharge from RCWMCH to give the patient’s caregivers a written summary of their hospital stay, and also to record salient information in the RTHC. This probably contributes to the poor recording of information on the RTHC, undermining its role and suggesting that it be used as the sole means of communication for less complex admissions.

However, the use of a separate discharge letter nullifies the unique purpose of the RTHC to act as a central record of the child’s health.

These findings serve to confirm that the optimal use of the RTHC by doctors as a tool of communication for continuity of patient care was lacking.

No attempt was made to specify what information was clinically relevant to each child’s age, diagnosis and reason for admission.

However, in the subgroup analyses by types of ward, RTHC and hospital record, only variables that were deemed to be essential to any hospital admission, regardless of the child’s age or diagnosis, were analysed. In this way, the study attempted to identify associations between transfer proportions and these three contexts. It was found that the probability of having weight transferred to the RTHC in short-stay wards was in short-stay wards compared with long-stay wards. Interpretation of this finding is difficult because differences in the health conditions managed in short-stay and long-stay wards could at least partially explain this difference, e.g. discharge weight would be essential information for children with acute gastroenteritis. Age was 66

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equally distributed across the wards and is unlikely to have been a contributing factor.

A convenience sample was used because of resource constraints, which undermines the generalisability of the findings to the study population (served by the four hospital wards in question).

Misclassification could have occurred as some information recorded in the hospital record may have been obtained through history given verbally by the caregiver and not by only referencing the RTHC. This study may not exclusively represent the use of the RTHC by doctors, as no strategies were applied to identify information that may have been recorded by other types of health professionals. The unusual context for the use of this card in a specialist hospital further complicates the application of the findings to non-specialist health care settings. Nevertheless, these identified areas of weakness are likely to exist elsewhere, albeit to different degrees.

Conclusions

The level of possession of the RTHC by the children’s caregivers admitted during the study period was acceptable. In a tertiary paediatric hospital setting, doctors used the RTHC as a reference source but failed to record new clinical information relating to the patient’s hospital stay on the RTHC.

Recommendations

This audit serves as an initial step for an audit cycle at RCWMCH. Exploring barriers to the optimal use of the RTHC could be a first step to development and testing of interventions to improve performance, at RCWMCH and beyond.

Acknowledgements. The authors thank the caregivers who participated in this study and the hospital staff for their assistance and cooperation.

We acknowledge the contributions from the UCT Writing Centre (translation of the consent form to Xhosa) and the UCT Department of Statistical Sciences (the statistical analysis).

Author contributions. JW and GS designed the study and developed the methodology. JW collected the data, performed most of the analyses and prepared the manuscript. The study was supervised by GS; the final manuscript was reviewed and edited by GS. This study was submitted by JW to UCT in partial fulfilment of an MMed in Paediatrics.

Funding. Funding was received from the UCT Department of Paediatric and Child Health and was used for payment of the statisticians; it was otherwise funded by the main author.

Conflicts of interest. None.Chopra M, Sanders D. Growth monitoring. In: Kibel M, Saloojee H, Westwood T, eds. Child Health for All: A manual for Southern Africa. Cape Town: Oxford University Press South Africa; 2012:108-109.

1. UNICEF. Home-based vaccination record repository. New York: UNICEF, 2003. http://www.immunizationcards.org/ (accessed 29 November 2015).

2. Turner KE, Fuller S. Patient-held maternal and/or child health records: Meeting the information needs of the patients and healthcare providers in developing countries? Online J Public Health Inform 2011;3(2). https://doi.org/10.5210/ ojphi.v3i2.3631 3. Western Cape Government Department of Health. The Road to Health Card.

Western Cape Government; 2015. https://www.westerncape.gov.za/generalpublication/road-health-card (accessed 29 November 2015).

4. Western Cape Government Department of Health. Minister Botha launches Road to Health Booklet. Western Cape Government; 2015. https://www. westerncape.gov.za/news/minister-botha-launches-road-health-booklet (accessed 29 November 2015).

5. Brown DW, Gacic-Dobo M. Home-based record prevalence among children aged 12–23 months from 180 demographic and health surveys. Vaccine 2015;33(22):258-293. https://doi.org/10.1016/j.vaccine.2015.03.101 6. Tarwa C, de Villiers FPR. The use of the Road to Health Card in monitoring child health. SA Fam Pract 2007;49(1):15c-15d. https://doi.org/10.1080/2078 6204.2007.10873497 7. Yach D, Metcalf C, Lachman P, et al. Missed opportunities for measles immunisation in selected Western Cape hospitals. S Afr Med J 1991;79(8):437-439.

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RESEARCH 8. Metcalf CA, Yach D, De Beer ZJ. Missed opportunities for immunisation at hospitals in the Western Cape – a reappraisal. S Afr Med J 1994;84(3):149-152.

9. Jeffs D, Nossar V, Bailey F, Smith W, Chey T. Retention and use of personal health records: A population based study. J Paediatr Child Health 1994;30(3):248-252 http://dx.doi.org/10.1111/j.1440-1754.1994.tb00627.x 10. Jeffs D, Harris M. The personal health record. Making it work better for general practitioners. Aust Fam Physician 1993;22(8):1417-1427.

11. Stacy RD, Sharma M, Torrence WA. Evaluation of the use of a parent-held Child health record by pregnant women and mothers of young children. Calif J Health Promot 2008;6(1):138-142.

12. Kitenge G, Govender I. Nurses’ monitoring of the Road to Health Chart at primary healthcare level in Makhado, Limpopo Province. SA Fam Pract 2013;55(3):275-280. https://doi.org/doi.org/10.1080/20786204.2013.10874350 13. Young S, Fasher M. An observational study of the NSW parent-held record in a GP setting. Aust Fam Physician 1994;23(4):704-712.

14. Donald PR, Hesseling PB. The ‘Road to Health’ card in a paediatric outpatient department. S Afr Med J 1987;72(5):356.

15. Harrison D, Heese HD, Harker H, Mann MD. An assessment of the ‘Roadto Health’ card based on perceptions of clinic staff and mothers. S Afr Med J 1998;88(11):1424-1428. https://doi.org/10.4102/curationis.v28i4.1021 16. Lakhani AD, Avery A, Gordon A, Tait N. Evaluation of a home-based health record booklet. Arch Dis Child 1984;59(11):1076-1081. https://doi.org/10.1136/ adc.59.11.1076 17. Ferson MJ. Immunisation state and its documentation in hospital patients. Arch Dis Child 1990;65(7):763-767. https://doi.org/doi.org/10.1136/adc.65.7.763

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18. Troude P, L’Hélias LF, Raison-Boulley AM, Castel C, Bouyer J, de La Rochebrochard E. Perinatal factors reported by mothers: Do they agree with medical records? Eur J Epidemiol 2008;23(8):557-564. https://doi.org/doi. org/10.1007/s10654-008-9268-9 19. Troude P, L’Hélias LF, Raison-Boulley AM, Castel C, Bouyer J, de La Rochebrochard E. Apgar scores reported in personal child health records: vVYach D, Metcalf C, Lachman P, et al. Missed opportunities for measles immunisation in selected western Cape hospitals. S Afr Med J 1991;79(8):437-439.

20. Metcalf CA, Yach D, De Beer ZJ. Missed opportunities for immunisation at hospitals in the Western Cape – a reappraisal. S Afr Med J 1994;84(3):149-152.

21. Woldesenbet SA, Jackson D, Goga AE, et al. Missed opportunities for early infant diagnosis: Results of a national study in South Africa. J Acquir Immune Defic Syndr 2015;68(3):e26-32. https://doi.org/doi.org/10.1097/ QAI.0000000000000460 22. Eyharts, D, Daron A, Scott C. Audit on the use of Road to Health cards – RCWMCH August 2015. The Advocacy Committee, School of Child and Adolescent Health. Cape Town: University of Cape Town; 2014 (unpublished audit).

Accepted 10 April 2018.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

The role of kidney injury molecule-1, interleukin-18 and glutathione-S-transferase-π in paediatric HIVassociated nephropathy L Nandlal,1 MMedSci; R Bhimma,2 PhD, MD; T Naicker,1 PhD Department of Optics and Imaging, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Department of Paediatrics and Child Health, College of Health Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa 1 2

Corresponding author: L Nandlal (loun0406@gmail.com) Background. HIV-associated nephropathy (HIVAN) in sub-Saharan Africa remains a significant cause of morbidity and mortality in children. Early detection of kidney injury is essential for injury-specific interventions that may avert permanent kidney damage and delay progression of kidney injury. Kidney biopsy is presently the gold standard for diagnosis of related kidney disease; however, it is pervasive with attendant complications, and may not be representative owing to sampling error. Serum creatinine is an insensitive and non-specific marker for the diagnosis of various kidney diseases, particularly in HIV-infected patients, who usually have varying degrees of muscle wasting. Therefore, a non-invasive approach using additional biomarkers for early detection of HIV-related kidney diseases, particularly HIV-associated nephropathy (HIVAN), is urgently needed.

Objective. To determine the urinary concentrations of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) and glutathione-Stransferase-π (GST-π) in children with idiopathic focal segmental glomerulosclerosis (FSGS) and HIVAN. Methods. The study group comprised 34 children: 13 with HIVAN and 21 with idiopathic FSGS. The control groups were 19 HIV-positive and 16 HIV-negative children with no kidney disease. Urine samples collected from these 69 children were stored at –80ºC. Urinary concentrations of KIM-1, IL-18 and GST-π were quantified using Bio-Plex assay.

Results. A significant increase in urinary KIM-1 levels was observed in the HIVAN group compared with the HIV-positive (p=0.0039) and HIV-negative (p=0.0438) control groups. There was no significant increase in KIM-1 levels on comparison of the idiopathic FSGS group with the control groups (HIV-positive and HIV-negative children) (p=0.0737 and p=0.1757, respectively). No statistically significant differences were noted in urinary IL-18 and GST-π levels across all study groups.

Conclusion. Urinary KIM-1 levels are significantly elevated in children with HIVAN and may be a useful biomarker to detect kidney disease in HIV-1-infected children.

S Afr J Child Health 2018;12(2):68-72. DOI:10.7196/SAJCH.2018.v12i2.1470

The ravages of the HIV-1 epidemic in sub-Saharan Africa persist, despite stringent HIV screening and combined antiretroviral therapy (cART) rollout programmes. Globally, 150 000 children were newly infected with HIV in 2015, albeit a decrease from the 490 000 children in 2000.[1] In 2013, approximately 3.2 million children under the age of 15 years were living with HIV infection, of whom 90% were from sub-Saharan Africa.[1] At the time, an alarming 70% of these children were not on appropriate cART management.[1,2] It is well established that HIV-infected children are at greater risk of developing kidney disease than children without HIV-infection.[3] HIV-associated nephropathy (HIVAN), one of the most common manifestations of HIV-related kidney diseases, remains a significant cause of morbidity and mortality in children, particularly in Africa.[1] Currently, the only definitive way to diagnose HIVAN is by kidney biopsy, an invasive procedure that requires only a small portion of the kidney. However, there are several factors that limit the utility of a kidney biopsy. Sampling may be inadequate, the site of pathology may not be represented and the procedure, being invasive, is not without attendant complications.[4] To date, non-invasive strategies for detecting and monitoring the effect of kidney diseases in children primarily depend on: (i) abnormal urine sediments, including the presence of renal tubular epithelial and cast cells;[5] (ii) random urinary protein to creatinine ratio >1.0 mg/mg;[6] (iii) tubular disorders resulting in abnormalities in fluid and electrolyte balance; (iv) reduced glomerular filtration rate (GFR) <60 mL/min/1.73 m2; and (v) an elevated serum creatinine level based on cut-offs that 68

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vary with age. Several factors are posed against the utility of serum creatinine levels as these values are influenced by body weight, nutritional status, protein intake and muscle mass, all of which are affected in HIV-infected children.[7,8] Additionally, proteinuria can emanate from a variety of non-pathological factors, i.e. emotional stress, physical exertion, fever or orthostatic (postural) proteinuria.[9] Therefore the identification of novel biomarkers to aid definitive and early diagnosis of HIVAN could significantly influence the clinical care of HIV-infected children, as early institution of cART has been shown to improve the clinical outcome and survival.

Soler-Garcia et al. [10] assessed the value of 11 urinary proteins in children with HIVAN compared with HIV-infected children with no kidney disease. Although these proteins were elevated in children with HIVAN, no significant biomarker was reported from this study in predicting HIVAN. Previous studies reported neutrophil gelatinase-associated lipocalin (NGAL) as an established biomarker of HIVAN in adults[11] and a urinary biomarker profile comprised increased levels of fibroblast growth factor-2 (FGF-2) and matrix metalloproteinase-2 (MMP-2), and decreased levels of epidermal growth factor (EGF) was shown to be useful in identifying HIVAN in children.[10,12] Despite these contributions, new candidate biomarkers for children with HIVAN are urgently needed to improve the predictive value of biomarkers in the detection of HIVAN. Kidney injury molecule-1 (KIM-1) is a type I transmembrane glycoprotein, located on the apical membrane of dilated proximal tubules with a cleavable ectodomain (90 kDa).[13,14] It is negligibly

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RESEARCH expressed in normal kidneys (<1 mg/mL) yet is rapidly elevated and expressed in response to various types of kidney disease (3 - 7 ng/mL).[13] Interleukin-18 (IL-18), a member of the IL-1 family of cytokines, is synthesised as an inactive 23 kDa precursor by several tissues including proximal tubular epithelial cells, macrophages and monocytes.[15] Moreover, urinary IL-18 levels are elevated in patients with acute kidney injury and delayed graft function compared with normal subjects.[16] Recent studies have also focused on the diagnostic accuracy of IL-18 levels in predicting idiopathic focal segmental glomerulosclerosis (FSGS).[15] Glutathione-S-transferase (GST-π) is a soluble cytosolic enzyme that indicates distal tubular injury.[17] Increased levels of GST-π in the urine after nephrotoxic injury are attributed to leakage from the tubular epithelial cells into the tubular lumen secondary to cell damage.[18] Leakage and increased expression of this urinary protein serves as an important biomarker of FSGS. In an attempt to evaluate the accuracy of KIM-1, IL-18 and GST-π as predictors of kidney disease in HIV-infected children, notably HIVAN, we compared and contrasted the urinary levels of KIM-1, IL-18 and GST-π in children with HIVAN and idiopathic FSGS with children (HIV positive and HIV negative) with no kidney disease.

Method

Study design

Ethical approval (ref. no. BE094/16) to conduct the study was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal and informed consent was obtained from the parent or guardian and assent (where applicable) from the patient. Urine samples collected for another study (ref. no. BE321/13) from children attending the Inkosi Albert Luthuli Central Hospital in Durban, KwaZulu-Natal, South Africa, were used for the study.

Samples were collected about 2 - 4 years after the kidney biopsy was done and stored at –80°C for a period of about 2 months until analysed using Bio-Plex.

Study population

All children included in the study were black African children between 1 and 16 years. The study group (N=34) consisted of children with biopsy-proven HIVAN (n=13) and idiopathic FSGS (n=21). Comorbidity in the children with HIVAN included chronic lung disease (n=3), cardiomyopathy (n=5) and stunting (n=5).

None had fever or other evidence of secondary infections at the time of sample collection. The control group (N=35) consisted of children who were HIV positive with no kidney disease (n=19) and HIV negative with no kidney disease (n=16). The latter group comprised HIV-negative children recruited from follow-up clinics with no kidney disease, e.g. respiratory, neurology and endocrine clinics.

All 13 children with HIVAN were on cART and angiotensinconverting enzyme antagonists for a minimum of 2 years before recruitment. The 21 children with idiopathic FSGS (HIV negative) were on low-dose steroid, angiotensin inhibitors as well as additional immunonosuppressants such as calcinuerin inhibitors (cyclosporin or tacrolimus) or pulse doses of methylprednisolone at the time of sample collection. Children who were below the age of 1 year or over 16 years, HIV-positive children with kidney disease but absence of kidney biopsy or inadequate histology, and those with histological forms of nephrotic syndrome (NS) other than FSGS were excluded. Urine was aliquoted and stored in cryovials at –800C until analysis.

Diagnosis of HIVAN

The diagnosis of HIVAN was made following confirmation of HIV-1 infection and presence of persistent proteinura ≥1+ on

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urinary dipstick examination (on at least 3 separate occassions in non-febrile children) with one or more of the following: (i) presence of enlarged echogenic kidneys by renal ultrasound; (ii) abnormal urinary sediment; (iii) microcystic tubular dilation, a childhood variant of HIVAN in the absence of significant podocyte lesions; and (iv) histological finding of FSGS..[19,20]

Multiplex method

The urine samples were analysed for KIM-1, IL-18 and GST-π using the quantitative Bio-Plex Pro RBM Kidney Toxicity Assay (Panel 1) (Bio-Rad Laboratories, USA) according to the manufacturer’s instructions.[21] The analysis of each sample was performed by means of low photomultiplier tubes (PMT) (BioPlex 200). Data were collected and analysed using a BioPlex 200 instrument equipped with Bio-Plex Manager analysis software version 4.1. A standard curve was generated using the known concentration (ng/mL) of each analyte by plotting the median fluorescent intensity (MFI) signal against concentration. These standards were used to interpolate the concentration of the unknown samples. Intra-plate variability was determined with CV ˂20% and Observed concentration

×100 ) Expected concentration between 70% and 130% (r=0.8, p=0.05). The data were imported into an Excel spreadsheet for statistical analysis.

(

Statistical analysis

All statistical analysis was undertaken using GraphPad Prism version 5 (GraphPad, USA). To analyse non-normal data, we used the non-parametric t -test (Mann-Whitney U). One-way ANOVA was used to correct for the multiple comparisons among the four study groups. Spearman coefficients were used to evaluate correlations between biomarkers. A p-value <0.05 was considered as statistically significant. Graphical data were represented as median and interquartile range.

Results

All 34 children with biopsy proven FSGS had a histopathological pattern of FSGS not otherwise specified according to the Columbian classification.[22] Thirteen children (19%) were HIVpositive and were confirmed paediatric HIVAN whilst 21 (30%) children had idiopathic FSGS. The mean (SD) age for HIVAN and idiopathic FSGS was 14 (2.73) (range 8.2 - 16.3) and 10 (3.40) (range 4.1 - 16.4) years respectively. All patients presented with NS. The control group consisted of 35 children with no kidney disease; 16 children (23%) were HIV negative with a mean (SD) age of 5 (3.43) (range 1 - 11) years and 19 children (28%) were HIV-positive with a mean (SD) age of 11 (3.52) (range 5 - 15) years (Table 1).

The patients with established FSGS had stages 1 and 4 chronic kidney disease (CKD) according to the KDIGO classification.[8] In the idiopathic FSGS group, 14 patients had CKD stage 1; 4 stage 2; 2 stage 3; and 1 stage 4. In the HIVAN group, 10 patients were CKD stage 1, 1 stage 2, and 2 stage 4. Based on the WHO Disease Staging System for HIV Infection and Disease in Children,[23] 10 children were totally asymptomatic (Clinical Stage I) and 3 patients had persistent proteinuria (Clinical Stage 4). The latter patients were diagnosed with FSGS for a mean of 2.8 years with a range of 2.1 - 4.3 years prior to study entry. Kidney biopsy showed FSGS (not otherwise specified) in all patients with over 80% of glomeruli having more than 50% sclerosis.

To identify associations with the variability, we compared urinary protein concentration of KIM-1, IL-18 and GST- π with age, weight, creatinine, urea, albumin, cholesterol and estimated glomerular

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RESEARCH Table 1. Clinical, demographic and laboratory data of patients

Patient data

HIV-negative control (n=16)

Idiopathic FSGS (n=21)

Age (years) Weight (kg) Creatinine (μmol/L) Albumin (mg/dL) Urea (mmol/L) eGFR (mL/min/1.73 m) Cholesterol (mmol/L) CD4 count

5 (3.43) 18.20 (10.55) 30.64 (9.25) 26.89 (15.16) 2.71 (1.58) 214.00 (126.06) -

10 (3.40) 23.52 (9.31) 47.26 (9.22) 33.08 (9.39) 137.00 (106.73) 7.43 (4.06) -

Groups*

HIV-positive control (n=19)

HIVAN (n=13)

11 (3.52) 37.25 (13.73) 40.33 (9.25) 29.36 (8.96) 5.44 (0.98) 209.04 (61.04) 3.75 (0.68) 972.90 (644.00)

14 (2.73) 28.00 (11.39) 77.31 (8.82) 34.70 (8.21) 121.61 (61.67) 5.05 (2.68) 818.30 (666.17)

FSGS = focal segmental glomerulosclerosis; HIVAN = HIV-associated nephropathy; eGFR = estimated glomerular filtration rate. *Quantitative data expressed as mean (standard deviation).

A †

0.8

[KIM-1] ng/mL

0.6

HIV-negative control Idiopathic FSGS HIV-positive control HIVAN

0.4 0.2 0 Study groups

B 0.25

HIV-negative control Idiopathic FSGS HIV-positive control HIVAN

[IL-18] ng/mL

0.20 0.15 0.10 0.05 0.00

Study groups

C

HIV-negative control Idiopathic FSGS HIV-positive control HIVAN

[GST] ng/mL

80 60 40

filtration rate (eGFR) in the four groups of children. No significant correlations were observed between KIM-1, IL-18 and GST-π comparing the above clinical and biochemical findings, indicating that these factors had no major impact on the concentration of these urinary proteins in children.

Urinary concentration of KIM-1, IL-18 and GST-π

The urinary concentration of KIM-1, IL-18 and GST-π are displayed in Figs 1A, 1B and 1C, respectively. There was a significant increase of KIM-1 in the HIVAN group (mean 0.52 ng/mL; 95% confidence interval (CI) 0.035 - 0.0033) compared with the HIV positive control group (mean 0.048 ng/mL; 95% CI 0.074 - 0.022) (MannWhitney U=74.00; p=0.0039). KIM-1 levels were up-regulated in the idiopathic FSGS group (mean 0.17 ng/mL; 95% CI 0.29 - 0.050) compared with the HIV-negative control group (mean 0.072 ng/mL; 95% CI 0.14 - 0.0060); however, this did not reach statistical significance (Mann-Whitney U=88.00; p=0.18). There was also an increase in KIM-1 levels in the idiopathic FSGS group (mean 0.17 ng/mL; 95% CI 0.29 - 0.050) compared with the HIV-positive control group (mean 0.048 ng/mL; 95% CI 0.074 - 0.022) but once again this did not reach statistical significance (Mann-Whitney U=116.0; p=0.074). Although KIM-1 levels were higher in children with HIVAN (mean 0.52 ng/mL; 95% CI 0.035 - 0.0033) compared with children with idiopathic FSGS (mean 0.17 ng/mL; 95% CI 0.29 - 0.050), this increase was also not significant (Mann-Whitney U=114.5; p=0.22). There was a significant increase of KIM-1 in the HIVAN group (mean 0.52 ng/mL; 95% CI 0.035 - 0.0033) compared with the HIV-negative control group (mean 0.072 ng/mL; 95% CI 0.14 - 0.0060) (Mann-Whitney U=58.00; p=0.044). No statistically significant differences of IL-18 and GST-π levels were noted across the study groups (Table 2).

Discussion

20 0 Study groups

Fig. 1 The urinary concentrations of (a) KIM-1, (b) IL-18 and (c) GST-π in HIV-negative control, idiopathic FSGS, HIV-positive control and HIVAN groups (median (interquartile range)).

(KIM-1 = kidney injury molecule-1; IL-18 = interleukin-18; GST-π = glutathione-S-transferase-π; FSGS = focal segmental glomerulosclerosis; HIVAN = HIV-associated nephropathy.) (*Urinary concentration of KIM-1 was significantly different between HIV-negative control and HIVAN (p=0.044). †KIM-1 was significantly different between HIV-positive and HIVAN (p=0.0039).)

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In a large paediatric study conducted across a spectrum of HIVrelated kidney diseases in children from the province of KwaZuluNatal, we showed a 65.3% predominance of FSGS, of which cases 26.5% had collapsing glomerulopathy while 38.8% were the classical variant of FSGS (not otherwise specified).[20,22] In the present study, we report 3 candidate biomarkers (KIM-1, IL-18 and GST-π) in HIVAN (all with the classical variant of FSGS on histopathology) in children compared with idiopathic FSGS and HIV-positive and HIV-negative controls.

The only statistically significant increase was noted in urinary KIM-1 levels in the HIVAN group compared with the HIV-positive and HIVnegative control groups. In contrast, there was no significant difference in KIM-1 levels between the idiopathic FSGS group compared with

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RESEARCH the HIV-positive and HIV-negative control groups. These results indicate that KIM-1 is up-regulated in children with HIVAN. Our results are corroborated by previous studies that report a dramatic increase of KIM-1 in patients who develop CKD in contrast to the low expression of this biomarker in healthy individuals.[14,24] Notably, using histopathology as the gold standard, KIM-1 was found to have the highest sensitivity and specificity amongst 21 urinary biomarkers studied in identifying kidney injury.[25-27] To date, strategies for monitoring the effect of HIV on the kidney primarily depend on the surveillance of serum creatinine concentrations, which is an indicator of GFR rather than injury.

Previous studies have shown that KIM-1 could be used as a urinary biomarker of kidney injury. Therefore it has been used to monitor the impact of HIV infection on the kidney, as well as the effect of antiretroviral therapy (tenofovir) that causes proximal tubular damage.[28,29] The severity of pathology in CKD has also been associated with elevated urinary KIM-1 levels.[30,31] However, in our study, KIM-1 levels were not significantly elevated in children with idiopathic FSGS compared with HIV-positive and -negative children with no kidney disease (control). As KIM-1 is site specific, it is markedly expressed by proximal tubular cells in response to injury by shedding its ectodomain into the tubular lumen, and therefore may be particularly beneficial for detecting HIV-related kidney injury.[28] As KIM-1 may be an early marker of kidney injury emanating from damage to proximal tubular cells, in patients with CKD with established fibrosis the degree of ongoing tubular injury may have progressed to the stage where it may not significantly elevate levels of KIM-1. This possibly explains the slightly increased levels, albeit not statistically significant, in children with idiopathic FSGS with established disease compared with controls. Also, it is possible that the small sample size may be the reason that we did not detect significant differences across both study groups and controls.

KIM-1 is probably not specific for HIV infection as indicated in our study, as it was not significantly different in children with HIVAN compared with the idiopathic FSGS group. In the light of these findings, kidney biopsy will be required to confirm FSGS or other histological forms of kidney disease associated with HIV. In addition, our study did not determine the differences in KIM-1 between HIVAN and other histological forms of HIV-related kidney disease. We submit that although our study showed a significant difference in KIM-1 levels between children with HIVAN, and both HIV-positive and HIV-negative controls, its sensitivity and specificity will need to be assessed in larger studies and its use will need to be compared with other non-specific biomarkers such as microalbumin which is much cheaper and readily available.

A study conducted by Kiliś-Pstrusińska et al.[30] has reported elevated levels of urinary IL-18 in idiopathic nephrotic syndrome (NS). The results of the above study indicated the relationship between the active phase of idiopathic NS and levels of IL-18, thus suggesting the role of IL-18 in the pathogenesis of idiopathic NS as well as its association with the activity of the disease. Similarly, Deebii et al.[31] also reported that IL-18 can be used as an early marker of subclinical kidney tubular dysfunction in patients who are HIVinfected. IL-18 increases in urine only under conditions of marked tubular damage, apoptotic tubular cell shedding, and cell necrosis, all of which are associated with deterioration of kidney function.

Our study reports an increase in IL-18 in children with HIVAN and idiopathic FSGS compared with the controls (HIV-positive and HIV-negative), albeit non-significant. This finding may also be attributed to the small sample size used in our study, making it difficult to detect significant differences across the groups. Also, as IL-18 increases in the urine only under conditions of marked tubular damage, cell necrosis and apoptotic tubular cell shedding, this may 71

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have not been the case in our children who already had established disease.

Urinary GST-π excretions were also reported to be useful biomarkers of renal tubular injury.[32] GST-π is site specific, generally not present in the urine of normal subjects, but is markedly up-regulated in the distal tubular cells during renal injury.[33] Once again, we report a non-significant upwards trend in urinary GST-π levels in our study, although the levels were elevated in children with idiopathic FSGS compared with the controls. This lack of significant differences in GST-π levels between the study group and controls may again also be attributed to sample size or that our patients had established disease and were on treatment with arrested or markedly attenuated distal tubular cell injury.

There were few other limitations in our study, which was a retrospective study with urine samples stored at –80°C to prevent protein degradation. It is possible that with the length of time, storage may have resulted in a decrease of urinary proteins, thus negating any significant differences in urinary levels of the biomarkers we studied in the various groups. This study was a single-centre study in a homogeneous group of black African children and may therefore not be applicable to other population groups. Also, patients recruited into the study were on treatment, which could have affected the levels of urinary biomarkers studied.

Conclusion

The present study has demonstrated that KIM-1 is significantly elevated in children with HIVAN compared with HIV-positive and HIV-negative controls. Larger prospective studies to determine the role of KIM-1 in early detection of HIVAN, thus obviating the need for kidney biopsy, and allowing early institution of appropriate therapy, thereby improving clinical outcome and survival, are needed.

Acknowledgements. The authors thank Albert Luthuli and King Edward VIII Hospitals and all the patients who consented to participate in the study, and the Optics and Imaging Centre, DDMRI, College of Health Sciences, where the study was conducted.

Author contributions. We thank Dr Elaene Naicker for providing some of the study samples and clinical care of the children. R. Bhimma and T. Naicker were supported by the Medical Research Council and National Research Foundation.

Funding. Funding was received from the College of Health Sciences, University of KwaZulu-Natal.

Conflicts of interest. None.

1. UNAIDS. http://www.unaids.org/en/resources/fact-sheet. Geneva: UNAIDS, 2015.

2. UNAIDS. Gap Report. http://www.unaids.org/en/resources/documents/2016/ prevention-gap. Geneva: UNAIDS, 2016.

3. Pezzaro S, Soler-Garcia AA, Hathout Y, Jharma R.D, Ray PE. Urinary biomarkers of kidney diseases in HIV-infected children. Proteomics Clin Appl 2015; 9(5-6):490-500. https://doi.org/10.1002/prca.201400193.

4. Cameron JS, Hicks J. The introduction of renal biopsy into nephrology from 1901 to 1961: A paradigm of the forming of nephrology by technology. Am J Nephrol 1997;17(3-4):347-358. https://doi.org/10.1159/000169122 5. Ray PE, Rakusan T, Loechelt BJ, Selby DM, Liu XH, Chandra S. Human immunodeficiency virus (HIV)-associated nephropathy in children from the Washington, D.C. area: 12 years’ experience. Semin Nephrol 1998;18(4):396-405.

6. Chaparro AI, Mitchell CD, Abitbol CL, et al. Proteinuria in children infected with the human immunodeficiency virus. J Pediatr 2008;152(6):844-849. https://doi.org/10.1016/j.jpeds.2007.11.007 7. Coca SG, Parikh CR. Urinary biomarkers for acute kidney injury: Perspectives on translation. Clin J Am Soc Nephrol 2008;3(2):481-490. https://doi. org/10.2215/CJN.03520807 8. Levin A, Stevens PE. Summary of KDIGO 2012 CKD Guideline: Behind the scenes, need for guidance, and a framework for moving forward. Kidney Int 2014;85(1):49-61. https://doi.org/10.1038/ki.2013.444 9. Leung AK, Wong AH. Proteinuria in children. Am Fam Physician 2010;82(6):645-651.

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RESEARCH 10. Soler-Garcia AA, Rakhmanina NY, Mattison PC, Ray PE. A urinary biomarker profile for children with HIV-associated renal diseases. Kidney Int 2009;76(2):207-214. https://doi.org/10.1038/ki.2009.115 11. Paragas N, Nickolas TL, Wyatt C, et al. Urinary NGAL marks cystic disease in HIV-associated nephropathy. J Am Soc Nephrol 2009;20(8):1687-1692. https:// doi.org/10.1681/ASN.2009010065 12. Kiley SC, Chevalier RL. Urinary biomarkers: the future looks promising. Kidney Int 2009;76(2):133-134. https://doi.org/10.1038/ki.2009.124 13. Waanders F, van Timmeren MM, Stegeman CA, Bakker SJL, van Goor H. Kidney injury molecule-1 in renal disease. J Pathol 2010;220(1):7-16. https:// doi.org/10.1002/path.2642 14. Boettner, B. KIM-1 driving chronic kidney disease. SciBX 2013;39(6):1-2. https://doi.org/10.1038/scibx.2013.1085 15. Nickolas TL, Barasch J, Devarajan P. Biomarkers in acute and chronic kidney disease. Curr Opin Nephrol Hypertens 2008;17(2):127-132. https://doi. org/10.1097/MNH.0b013e3282f4e525 16. Hall IE, Yarlagadda SG, Coca SG, et al. IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation. J Am Soc Nephrol 2010;21(1):189-197. https://doi.org/10.1681/ASN.2009030264 17. Branten AJ, Mulder TP, Peters WH, Assmann KJ, Wetzels JF. Urinary excretion of glutathione S transferases alpha and pi in patients with proteinuria: Reflection of the site of tubular injury. Nephron 2000;85(2):120-126. https:// doi.org/10.1159/000045644 18. Harrison DJ, Kharbanda R, Cunningham DS, McLellan LI, Hayes JD. Distribution of glutathione S-transferase isoenzymes in human kidney: Basis for possible markers of renal injury. J Clin Pathol 1989;42(6):624-628. https:// doi.org/10.1136/jcp.42.6.624 19. Senguttuvan P, Gowtham S, Soundararajan P. Human immunodeficiency virusassociated nephropathy (HIVAN) in Indian children. Open Urol Nephrol J 2014;(1):1. https://doi.org/10.2174/1874303X01407010105 20. Ramsuran D, Bhimma R, Ramdial PK, et al. The spectrum of HIV-related nephropathy in children. Pediatr Nephrol 2012;27(5):821-827. https://doi. org/10.1007/s00467-011-2074-8 21. BioRad Laboratories. Bio-Plex Pro RBM Human Kidney Toxicity Assays.

California: BioRad Laboratories, 2016.

22. D’Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: A working proposal. Am J Kidney Dis 2004;43(2):368-382. https://doi.org/10.1053/j.aj9kd.2003.10.024

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23. World Health Organization. www.who.int/hiv/pub/guidelines/ HIVstaging150307. Geneva: World Health Organization, 2007.

24. Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: A sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006;290(2):517-529. https:// doi.org/10.1152/ajprenal.00291.2005 25. Dieterle F, Staedtler F, Grenet O, Cordier A, Perentes E. Qualification of biomarkers for regulatory decision making – a kidney safety biomarker project. Toxicol Off J Soc Toxicol 2007;96:381.

26. Han WK., Bailly V, Abichandani R, Thadhani R, Bonventre JV. Kidney injury molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury. Kidney Int 2002;62(1):237-244. https://doi.org/10.1046/j.15231755.2002.00433.x 27. Bonventre JV. Kidney injury molecule-1 (KIM-1): A urinary biomarker and much more. Nephrol Dialysis Transplant 2009;24(11):3265-3268. https://doi. org/10.1093/ndt/gfp010 28. Shlipak MG, Scherzer R, Abraham A, et al. Urinary markers of kidney injury and kidney function decline in HIV-infected women. J Acquir Immune Defic Syndr 1999;61(5):565. https://doi.org/10.1097/QAI.0b013e3182737706 29. Scherzer R, Estrella M, Li Y, Deeks SG, Grunfeld C, Shlipak MG. Association of tenofovir exposure with kidney disease risk in HIV infection. AIDS 2012;26(7):867. https://doi.org/10.1097/QAD.0b013e328351f68f 30. Kiliś-Pstrusińska K, Medyńska A, Zwolińska D, Wawro A. Interleukin-18 in urine and serum of children with idiopathic nephrotic syndrome. Kidney Blood Press Res 2008;31(2):122-126. https://doi.org/10.1159/000124284 31. Deebii NTI, Orluwene CG, Okerengwo AA, Obunge OK, Odum EP, Okojaja RI. Early diagnosis of renal tubular dysfunction in HIV infected patients; a case of interleukin (IL)-18 and other common indicators of renal toxicity.

Immunother Open Acc 2016;2:118. https://doi.org/10.4172/2471-9552.100011 32. Bashir M, Cawood T, O’Shea D, Lawless L, Brady J, Murray B. Obesity-related nephropathy; evidence of proximal tubular damage. Endocrine Abstracts 2008;15:123.

33. De Geus HR, Bakker J. Biomarkers for the prediction of acute kidney injury: A narrative review on current status and future challenges. Clin Kidney J 2012;2(5):102-108. https://doi.org/10.1093/ckj/sfs008

Accepted 18 January 2018.

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CASE REPORT

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Jellyfish envenomation: A chilling toxidrome of seizures and cyanosis – a case report S Mundkur,1 MBBS, DCH, DNB; S Shashidhara,1 MBBS, MD; S Hebbar,1 MBBS, MD; A Kumar,2 MBBS, MD, S Kanaparthi,1 MBBS, MD Department of Pediatrics, Women and Child Block, Kasturba Medical College, Madhav Nagar, Manipal Academy of Higher Education, Manipal, India 2 Department of Forensic Medicine, Kasturba Medical College, Madhav Nagar, Manipal University, Manipal, India 1

Corresponding author: S Shashidhara (sowmya.s@manipal.edu) Jellyfish envenomation is a common incident in coastal areas all over the world. While the majority of reported cases are self-limiting with few lasting complications, a few deadly species can cause life-threatening and debilitating illnesses with a prolonged recovery time.

Chrysaora spp. have been known to cause a diverse spectrum of manifestations. We report the case of a 7-year-old boy with jellyfish envenomation presenting with cyanosis, seizures and hypertension not previously described in association with the Chrysaora spp.

S Afr J Child Health 2018;12(2):73-75. DOI:10.7196/SAJCH.2018.v12i2.1429

Jellyfish are intriguing and are found ubiquitously in all oceans.

However, species predominance is seen across different marine ecosystems. The most common species seen across coastal India are Aurelia and Physalia.[1] Chrysaora spp. are widely dispersed across the Atlantic, Pacific and Indian oceans.[2] Most Chrysaora spp. envenomations are mild, with irritation of the skin and pain, requiring outpatient medical attention.[3] These species have rarely been reported to cause neurotoxicity or digital ischaemia, although they are an expected complication of the more toxic species.[4-6] In this case report, we describe a rare case of a Chrysaora spp. sting associated with dermatitis, neurotoxicity and vasospasm leading to hypertension.

Case report

A 7-year-old boy of European origin who was on vacation in coastal Karnataka, India, was brought to triage with complaints of a jellyfish sting belonging to species Chrysaora while bathing in the sea, resulting in a rash over both his hands and legs which had been progressively increasing over 12 hours. The parents described the rash as spread out over the sites of attachment of the tentacles of the jellyfish which had to be forcibly separated from the boy. Swelling of the right knee was subsequently noted by the parents, along with pain and a progressive bluish discolouration of the third, fourth and fifth fingers on his right hand.

His past medical history was unremarkable and he was developmentally healthy and appropriately immunised for his age.

His other family members were healthy and unaffected. He was seen by a primary care physician 10 - 12 hours after the sting and was referred to our institution.

The boy was observed at our triage after 15 hours after the sting.

He was conscious and oriented at the time and the following vitals were recorded: Glasgow Coma Scale score, 15/15; heart rate, 92 beats per minute; blood pressure, 104/60 (95th centile - 117/78); and respiratory rate, 16 breaths per minute. On examining the peripheral pulses, the right radial pulse was feeble with small volume; all other pulses were well felt. Spo2-right upper limb was not recordable. Left upper limb: 98%; right lower limb: 96%; left lower limb: 98%. The third, fourth and fifth digits of the right hand were cyanosed and swollen, with painful movements up to the proximal interphalangeal joints including the nail beds (Fig. 1). An erythematous maculopapular rash was present on both thighs, legs 73

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and forearms, and flagellate pigmentation was present over both thighs. Purpuric lesions over the right thigh and popliteal fossa, with a local rise in temperature and extreme pain on movement were also seen (Fig. 2). The respiratory, abdominal and cardiovascular examinations were normal. Neurological examination at admission showed no focal neurological deficits.

The patient’s laboratory parameters were as follows: alanine transaminase 13.0 IU/L; aspartate transaminase, 45.0 IU/L; C-reactive protein, 1.4 mg/L; serum creatinine, 0.4 mg/dL; serum potassium, 4.6 mmol/L; serum sodium, 134.0 mmol/L; serum urea, 25 mg/dL; erythrocyte sedimentation rate, 9 mm/hr; haemoglobin, 13.6g/dL; haematocrit, 41.8 %; mean corpuscular volume, 82.8 fl; platelet count, 299.0 × 10³/µL; red blood cell count, 5.06 × 106 /µL; RDW, 14.0 %; total white blood cells, 15.8 × 10³/µL; serum calcium, 9.3 mg/dL; serum chloride, 93.8 mmol/L; serum magnesium, 2.0 mg/dL; serum phosphorus, 5.7 mg/dL; complement C3 level, 131.0 mg/dL; complement C4 level, 19.0 mg/dL; anti-nuclear antibody profile, negative; urine examination: normal.

The right upper limb arterial Doppler showed attenuation of the axillary, brachial, radial and ulnar arteries with a regular colour flow, flow velocities and spectral waveforms with low biphasic resistance and diffuse subcutaneous oedema. The renal artery Doppler and 2D

Fig. 1. Digital ischaemia of the fingertips following jellyfish sting.

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CASE REPORT

Fig. 2. Papular flagellate rash at the site of attachment of the jellyfish tentacles.

echocardiograph were normal. An ultrasound demonstrated diffuse subcutaneous oedema with moderate knee-joint effusion with septation. Computed tomography angiography showed attenuation in the calibre of the distal two-thirds of the right brachial artery, radial and ulnar arteries and faint contrast opacification (Fig. 3).

Treatment was initiated with subcutaneous enoxaparin, intravenous dexamethasone, oral ecospirin and oral cilostazol. On the third day following the sting, the patient developed five episodes of generalised tonic-clonic seizures which required levetiracetam (40 mg/kg/day) and valproate (10 mg/kg/day). Magnetic resonance imaging of the brain revealed patchy bilateral asymmetrical T2/ FLAIR hyperintensities involving bilateral frontal-parietooccipital sulci in the cortex predominantly, with mild extension into the adjacent subcortical white matter and focal extension into the deep white matter (Fig. 4). Electroencephalography indicated a generalised disturbance of electrical function. The boy was found to be hypertensive on the fourth day, with a blood pressure reading of 140/100. The hypertension was controlled with oral nifedipine.

The rash over the arms worsened over the course of five days and required therapy with topical antibiotics, antihistamines and steroids.

The right knee effusion was treated conservatively.

The reappearance of the right radial pulse and reperfusion of the digits was observed after 7 days. He remained normotensive and seizure-free after the 8th day. However, a right-sided foot drop was noted on the 10th day, which responded minimally to therapy and rehabilitation. A residual reddish hue persisted as a remnant of the rash. He was normotensive and seizure-free on maintenance antiepileptics at discharge with a right foot drop.

Discussion

Jellyfish belong to the phylum Cnidaria, which has 10 000 species and only ~100 of those are toxic to humans. [7] Although only a few species contain tentacles, nematocysts are found in all. The length of the nematocysts in the vast majority are insufficient to penetrate the dermis and are therefore harmless.[8] Upon skin contact, the toxin produced by a number of species causes a local reaction involving the phospholipase A2 pathway, which leads to pain, swelling and skin necrosis in severe conditions.[9] Once in the general circulation, the toxin has gastrointestinal, cardiac, neurological, muscular and immunogenic effects. The venom also contains haemolytic and lethal fractions affecting the heart.[2] Jellyfish stings most frequently result in pain, itching, an intense burning sensation and redness in the majority of cases. However, a few studies show that allergic reactions and anaphylaxis are remote complications as the jellyfish toxin is known to act by inducing the release of inflammatory mediators.[10] The classical jellyfish dermatitis, also called seabatherâ&#x20AC;&#x2122;s eruption, is believed to occur 74

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Fig. 3. Computed tomography angiograph showing narrowing and spasm of the right brachial, radial and ulnar arteries.

Fig. 4. Magnetic resonance imaging of the brain: T2 weighted image showing hyperintensities of the fronto-parieto-occipital cortices.

due to the extended action of the jellyfish toxin leading to intense burning, pain, itching and erythematous papules for a prolonged time after the exposure.[11,12] Synonymous with this, the patient in our case presented as described and responded to topical corticosteroids and antihistamines.

The venom of the Chrysaora spp. has been demonstrated to cause calcium ion influx through voltage-gated channels and cause severe arterial spasm in experimental studies.[4] Jellyfish envenomation leads to acute regional vasospasm leading to cyanosis of the affected areas and absence of sweating and piloerection.[6,13] Chrysaora spp. causing these effects have been reported in rare cases across the Indian coast.[5,6] Analogously, our patient developed a delayed response to the sting with a severe spasm of the right brachial artery, swelling, pain and cyanosis of the right third and fourth digits. Sympathomimetic action of the venom is known to cause severe hypertension in a syndrome commonly called the Irukandji, which is accompanied by severe cardiotoxic manifestations mimicking a catecholamine crisis.[14] Hypertension, as described in these studies, was noted in our patient who was controlled with a direct arteriolar dilator such as cilostazol, a phosphodiesterase inhibitor, and nifedipine, a calcium channel blocker.

The toxin isolated from nematocysts of Chrysaora is known to depolarise nerve and muscle membranes and to increase the frequency

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CASE REPORT of miniature end-plate potentials.[15] Motor and sensory neurotoxic effects of cnidarian venoms have been reported in several cases of mononeuritis multiplex produced by different jellyfish.[16] There have also been reports of Guillain-Barré syndrome and dysphonia following jellyfish stings.[17-19] However, Chrysaora stings leading to neurological complications are seldom seen. Our patient developed seizures three days following exposure. Patchy bilateral hyper intensities were seen over the cortical areas on MRI. A point to consider here is that these changes may be due to a postictal state. However, after ten days he had a residual foot drop on the right side.

Treatment of jellyfish stings should begin by administration of basic life support. Appropriate methods for tentacle removal, such as flushing with sea water, using tweezers or scraping off with a card, should be done carefully as they carry the risk of further discharge of nematocysts.[20] The application of vinegar and an ice pack to the local area to reduce pain is recommended. The affected part should then be immersed in water as hot as is bearable if no proprietary meds are available. Skin inhibitor creams are commercially available which provide protection for swimmers against jellyfish stings.[21]

Conclusion

Jellyfish envenomation is usually harmless or causes mild illness.

However, in rare instances, it can manifest as a toxidrome of seizures, cyanosis and hypertension due to prolonged and delayed multisystem effects of the toxin, requiring continuous intensive monitoring during the acute phase. Residual neurological deficits can be anticipated following envenomation. Adequate awareness by seabathers, personal protection, and prompt medical intervention is necessary to prevent morbidity.

Acknowledgements. Grieselda Philomena Noronha and Varna Shetty are gratefully acknowledged for the CT angiography and MRI reports.

Author contributions. SS, SM, SH, SK: primary management of the patient, co-authored the manuscript and contributed to final editing. AK: assisted in species identification and toxicological aspects of the case, as well as drafting and editing of the manuscript.

Funding. None.

Conflicts of interest. None.

1. Venkataraman KR, Raghunathan C, Sreeraj CR Raghuraman R. Guide to the Dangerous and Venomous Marine Animals of India. Kolkata: Zoological Survey of India, 2012:1-98.

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2. Cegolon L, Heymann WC, Lange JH, Mastrangelo G. Jellyfish stings and their management: A review. Mar Drugs 2013;11(2):523-550. https://doi. org/10.3390/md11020523 3. Williamson JA, Fenner PJ, Burnett JW. The injuries, their incidence and the toxins that produce them. In: JA Williamson, Fenner PJ, Burnett JW, Rifkin JF, eds. Venomous and Poisonous Marine Animals: A Medical and Biological Handbook. Sydney: New South Wales University Press, 1996:63-87.

4. Burnett JW, Weinrich D, Williamson JA, Fenner PJ, Lutz LL, Bloom DA. Autonomic neurotoxicity of jellyfish and marine animal venoms. Clin Auton Res 1998;8(2):125-130.

5. Hach-Wunderle V, Mebs D, Frederking K, Breddin HK. Jellyfish poisoning. Deutsch Med Wochenschr 1987;112(48):1865-1868. https://doi. org/10.1055/s-2008-1068344 6. Williamson JA, Burnett JW, Fenner PJ, Hach-Wunderle V, Hoe LY, Adiga KM. Acute regional vascular insufficiency after jellyfish envenomation. Med J Aust 1988;149(11-12):698-701.

7. Kramp PL. Synopsis of the medusae of the world. J Marine Biol Assoc UK 1961;40:7-382. https://doi.org/10.1017/S0025315400007347 8. Barnes JH. Observations on jellyfish stingings in North Queensland. Med J Aust 1960;47(2):993.

9. Mariottini GL, Pane L. Mediterranean jellyfish venoms: A review on Scyphomedusae. Marine Drugs 2010;8(4):1122-1152. https://doi.org/10.3390/ md8041122 10. De Donno A, Idolo A, Bagordo F, Grassi T, Leomanni A, Serio F. Impact of stinging jellyfish proliferations along south Italian coasts: Human health hazards, treatment and social costs. Int J Environ Res Public Health 2014;11(3):2488-2503. https://doi.org/10.3390/ijerph110302488 11. Rossetto AL, Da Silveira FL, Morandini AC, Haddad V, Resgalla C. Seabather’s eruption: Report of fourteen cases. An Acad Bras Cienc 2015;87(1):431-436. https://doi.org/10.1590/0001-3765201520130468 12. Raupp U, Milde P, Goerz G, Plewig G, Burnett J, Heeger T. Case report of jellyfish injury. Hautarzt 1996;47(1):47-52.

13. Binnetoglu FK, Kizildag B, Topaloglu N, Kasapcopur O. Severe digital necrosis in a 4-year-old boy: Primary Raynaud’s or jellyfish sting. BMJ Case Rep 2013;2013. https://doi.org/10.1136/bcr-2013-201478 14. Bianchi R, Torella D, Spaccarotella C, Mongiardo A, Indolfi C. Mediterranean jellyfish sting-induced Tako-Tsubo cardiomyopathy. Eur Heart J 2011;32(1):18. https://doi.org/10.1093/eurheartj/ehq349 15. Dubois JM, Tanguy J, Burnett JW. Ionic channels induced by sea nettle toxin in the nodal membrane. Biophys J 1983;42(2):199-202.

16. Burnett JW WJ, Fenner PJ. Mononeuritis multiplex after coelenterate sting.

Med J Australia 1994;161:321-322.

17. Devere R. Guillain-Barre syndrome after a jellyfish sting. J Clin Neuromuscul Dis 2011;12(4):227. https://doi.org10.1097/CND.0b013e3181e1f046 18. Pang KA, Schwartz MS. Guillain-Barre syndrome following jellyfish stings (Pelagia noctiluca). J Neurol Neurosurg Psychiatry 1993;56(10):1133.

19. Burnett JW. Dysphonia: A new addition to jellyfish envenomation syndromes.

Wilderness Environ Med 2005;16(2):117-118.

20. Ward NT, Darracq MA, Tomaszewski C, Clark RF. Evidence-based treatment of jellyfish stings in North America and Hawaii. Ann Emerg Med 2012;60(4):399414. https://doi.org/10.1016/j.annemergmed.2012.04.010 21. Tonseth KA, Andersen TS, Pripp AH, Karlsen HE. Prophylactic treatment of jellyfish stings--a randomised trial. Tidsskr Nor Laegeforen 2012;132(1213):1446-1449. https://doi.org/10.4045/tidsskr.11.0652 Accepted 21 December 2017.

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This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

CASE REPORT

Sphenoid mucocoele – an unusual cause for headaches in a teenage boy S E Adam, MB ChB; M Merven, FCORL Department of Otorhinolaryngology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa Corresponding author: S E Adam (shaunadam1982@gmail.com) Isolated sphenoid sinus disease in childhood is uncommon and sphenoid mucocoeles (histologically benign, epithelium-lined, mucuscontaining sacs) are rare. They are thought to arise as a result of obstruction of the sinus ostium due to previous surgery, inflammation, trauma or irradiation, but may be idiopathic. We present a case of a sphenoid sinus mucocoele in a young boy and highlight the fact that headache may be the only symptom, therefore diagnosis may require a combination of imaging and exploratory surgery.

S Afr J Child Health 2018;12(2):76-78. DOI:10.7196/SAJCH.2018.v12i2.1450

Case report

A 15-year-old boy presented with retroorbital headaches for 5 years, right peri-orbital swelling for 3 years and diplopia for several months. He had no symptoms of chronic sinusitis, allergic rhinitis or epistaxis. He had no history of cranial trauma or surgery and reported normal sensation of smell and vision.

He presented to our otorhinolaryngology clinic in 2013, but was lost to follow-up until 2016.

On examination at his presentation in 2016, he was slight of build (like his mother) weighing 29.5 kg, which is below the 3rd centile for weight-for-age. He had right proptosis with infratemporal soft subdermal swelling (Figs 1A and 1B), normal visual acuity and no relative afferent pupillary defect. He experienced diplopia upon right lateral gaze, with reduced abduction and supraduction. There was reduced sensation in the distribution of the opthalmic (V1) and maxillary (V2) branches of the trigeminal nerve. On nasal endoscopy, a pale, soft, submucosal mass was visible in the nasal cavity.

Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a sphenoid-based locally expansile cystic lesion (Figs 2 and 3). Extensive bony erosion and remodeling was noted.

Extension intra-cranially with compression of the dura and cavernous sinus without invasion was noted. The lesion involved the orbital apex and extended into the pterygopalatine fossa and then through the pterygomaxillary fissure into the infra-temporal space where it was noted subdermally at the level of the zygoma.

A transcutaneous aspiration of this lateral facial swelling was performed in the clinic and revealed ‘motor oil-like’ fluid (Figs 1C and 1D). Serology for HIV and hydatid disease were negative.

A presumptive diagnosis of a mucocoele was made and an endoscopic transnasal

A

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C

D

Fig. 1. (A) Frontal pre-operative view showing the right infratemporal swelling. (B) Superior view. Note right proptosis. (C) Transcutaneous aspirate fluid. (D) Post aspiration lateral view. Note the skin dimple over the area of aspiration. Informed consent was obtained to use the images.

sphenoidotomy confirmed the diagnosis.

Good resolution of symptoms occurred by 1 month postoperatively. No sign of recurrence was noted clinically or on repeat CT at 8 months postoperatively (Fig. 4).

Discussion

Sphenoid sinuses are small recesses in the postero-superior nasal cavity and remain intra-nasal until 6 - 7 years of age. Secondary pneumatisation occurs and a true cavity is formed by 8 - 10 years of age, with maturation by 12 - 14 years of age.[1] Paranasal sinus mucocoeles are very rare in children and sphenoid mucocoeles 76

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make up only 1 - 2% of all paranasal sinus mucocoeles in all age groups.[2] To date, only 13 cases of paediatric sphenoid mucocoeles have been documented from 9 articles in the English literature.

Mucocoeles are histologically benign, epithelium-lined, mucus-containing sacs that affect the paranasal sinuses. They are thought to arise from obstruction of the sinus ostium due to previous surgery, inflammation, trauma or irradiation.

Other potential aetiologies include cystic dilatation of glandular structures and cystic development from embryonic epithelial residues.[2] Increased levels of fibroblast

CASE REPORT A

B

C

D

Fig. 2. (A) Axial computed tomography (CT) of orbital apex. (B) Axial CT of infra-orbital nerve (ION) relative to the right maxillary sinus (M). Note the compression of the ION by the mucocoele. (C) Coronal CT indicating the lateral extension (arrow) from the sphenoid sinus (sph) to the infra-temporal fossa (ITF) on the right. Note the deviation of the nasal septum (NS) to the left and the dehiscent middle cranial fossa (MCF) floor. (D) Sagittal CT showing the superior extent through dehiscent base of skull (BOS). (A = anterior; S = superior; OA = orbital apex; Z = zygoma; R = right; IT = inferior turbinate; F = frontal sinus.)

A

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prostaglandin E2 and collagenase enable osteolysis by mucocoeles, facilitating their local extension.[3] Presenting signs and symptoms are subtle until late in the disease process. In the literature, the most frequently reported manifestations are headache (89%), decreased visual acuity (57%), oculomotor palsies (56%) and exophthalmos (25%).[4,5] In this case, the dysfunction of the ophthalmic (V1) and maxillary (V2) divisions of the fifth cranial nerve (trigeminal) is unusual and would make invasive lesions more likely. However, these cranial nerve dysfunctions due to a sphenoid mucocoele have previously been reported by Yong et al.[6] V1 may be compressed or stretched at the cavernous sinus or the orbital apex where it passes through the superior orbital fissure to enter the orbit. Similarly, V2 may be involved at the cavernous sinus, pterygopalatine fossa (which houses the pterygopalatine ganglion), the pterygomaxillary fissure en route to the infratemporal fossa, or in the roof of the maxillary sinus (infra-orbital nerve). This presentation of a mucocoele with isolated lateral facial swelling due to the soft tissue extension through the abovementioned spaces is the first such report to the best of the authorsâ&#x20AC;&#x2122; knowledge.

Mucocoeles may have variable densities on CT and signal intensities on MRI depending on their protein content, inspissation and presence of infection. MRI is best to delineate extent and internal characteristics of the lesion, whereas CT demonstrates bony involvement better.[7] The sinus walls may be thinned or completely dehiscent with extensive advancement into surrounding structures as in this case.

Although isolated sphenoid sinus disease in childhood is rare, the differential is broad and includes inflammatory conditions (e.g. sphenoiditis, polyposis, fungal sphenoiditis, hydatid cyst); congenital conditions (e.g. dermoid cyst, epidermoid cyst, meningocoele, meningoencephalocoele, Rathkes cleft cyst, craniopharyngioma); benign lesions (e.g. mucocoele, nasopharyngeal angiofibroma, osteoma, lymphangioma, haemangioma, pituitary tumours, internal carotid artery aneurysm, fibrodysplasia) and malignant sphenoid lesions (although they have not yet been reported in this age group, but considerations would be lymphoma, rhabdomyosarcoma, Ewings sarcoma).

Differentiating a mucocoele from these may be difficult with CT and MRI, as overlap in imaging characteristics is common. In this case, a meningocoele and meningomyelocoele were excluded after imaging showed no communication with intracranial spaces. The differential included a hydatid cyst (which was excluded on serology) and lymphangioma which could not be excluded. It may only be after surgery that a definitive diagnosis can be made. An external surgical approach was used in the past but an endoscopic transnasal route, with decompression of disease, has recently become the standard of care. This approach has a lower rate of complications and is effective regardless of size and pre-operative complications.[8]

Conclusion

C

D

Fig. 3. (A) Axial MRI of orbital apex (OA). Note the multi-loculated mucocoele (Muc). (B) Sagittal MRI showing superior compression of the dura (D). (C) Coronal MRI showing the superior compression of dura (D) and lateral extension into infratemporal fossa (ITF). (D) Sagittal MRI indicating compression of the dura (D) superiorly and the cavernous sinus (CS) superoposteriorly. (A = anterior; R = right S = superior; M = maxillary sinus; IT = inferior turbinate.)

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Childhood sphenoid mucocoele is rare and the presenting symptoms may be vague. A headache associated with other neurological symptoms or signs warrants specialist review with endoscopy and/ or further imaging. Combination CT and MRI is appropriate, but is not diagnostic in all cases. Even extensive or complicated disease is managed both safely and effectively with a diligent endoscopic transnasal approach.

Learning points

Isolated sphenoid sinus disease is very rare in children. â&#x20AC;˘ A deep-seated, retro-orbital headache in a child is suggestive of sphenoid sinus disease and warrants further investigation, especially if associated with other neurological symptoms or signs.

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CASE REPORT

A

B

C

Fig. 4. Postoperative axial computed tomography (CT) indicating the lateral extent of the mucocoele (Lat), which is now aerated space. The sphenoid sinus septum (SSS) is pushed across to the left side and the eroded clivus (C). (B) Postoperative coronal CT with dehiscent middle cranial fossa (MCF) floor and zygoma (Z).

(C) Postoperative sagittal CT. Note the clivus (Cl) erosion. (TNA = transnasal approach (surgical route of access); A = anterior; R = right; F = frontal sinus; ST = sella turcica; S = superior.)

• Cranial neuropathies must be excluded: optic > abducens > trigeminal > oculomotor > trochlear,[9] as these may be indicative of invasive disease, and would warrant urgent referral.

• Imaging is helpful but may not be diagnostic.

• Endoscopic drainage is the treatment of choice for sinonasal mucocoeles and carries low morbidity.

Acknowledgments. SEA thanks MM for guidance and advice in the writing process.

Author contributions. SEA: senior author, investigated the topic, collated the information and images, and produced the first draft. MM: co-author, assisted with selection of images and final editing of manuscript.

Funding. None.

Conflicts of interest. None.

1. Jang YJ, Kim SC. Pneumatization of the sphenoid sinus in children evaluated by magnetic resonance imaging. Am J Rhinology 2000;14(3):181-185. https://doi. org/10.2500/105065800782102771 2. Kösling S, Hintner M, Brandt S, et al. Mucoceles of the sphenoid sinus. Eur J Radiol 2004;51(1):1-5. https://doi.org/10.1016/j.ejrad.2003.09.002

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3. Lund VJ, Harvey W, Meghji S, Harris M. Prostaglandin synthesis in the pathogenesis of fronto-ethmoidal mucoceles. Acta Oto-laryngol 1988;106(1-2):145-151. https://doi.org/10.3109/00016488809107382 4. Levy J, Monos T, Puterman M. Bilateral consecutive blindness due to sphenoid sinus mucocele with unilateral partial recovery. Can J Ophthalmol 2005;40(4):506-508.

5. Sundar U, Sharma AL, Yeolekar ME, Pahuja V. Sphenoidal sinus mucocoele presenting as mono-ocular painless loss of vision. Postgrad Med J 2004;80(939):40.

6. Yong W-W, Zhou S-H, Bao Y-Y. Sphenoid sinus mucocele presenting with oculomotor nerve palsy and affecting the functions of trigeminal nerve: A case report. Int J Clin Experimental Med 2015;8(9):16854-16857.

7. Haloi AK, Ditchfield M, Maixner W. Mucocele of the sphenoid sinus. Pediatric Radiol 2006;36(9):987-990. https://doi.org/10.1007/s00247-006-0243-x 8. Malard O, Gayet-Delacroix M, Jegoux F, Faure A, Bordure P, de Montreuil CB. Spontaneous sphenoid sinus mucocele revealed by meningitis and brain abscess in a 12-year-old child. Am J Neuroradiol 2004;25(5):873-875.

9. Lawson W, Reino AJ. Isolated sphenoid sinus disease: An analysis of 132 cases.

Laryngoscope 1997;107(12):1590-1595. https://doi.org/10.1097/00005537199712000-00003

Accepted 1 February 2018.

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ARTICLE

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

The immigration of anaemia – presentation of sickle cell disease in children admitted to a district hospital in Johannesburg: A case series D M Azar, MB BCh Department of Paediatrics, Charlotte Maxeke Johannesburg Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Corresponding author: D M Azar (danielazar1234@gmail.com) Sickle cell disease (SCD) is the most common monogenic disorder and haemoglobinopathy worldwide and is unique in its distribution to tropical, malaria-endemic regions. SCD is typically rare in South Africa (SA) but the increasing immigration of foreign nationals over the last 20 years has the potential to alter the epidemiology of this life-threatening disease. With recent data from the Western Cape showing an increase in disease frequency, more evidence needs to be collected to determine the changes in the disease profile locally. This case series reviews the presentation and outcome of three patients diagnosed with SCD at a district hospital in Johannesburg, Gauteng.

S Afr J Child Health 2018;12(2):79-80. DOI:10.7196/SAJCH.2018.v12i2.1463

Sickle cell disease (SCD) is the most common monogenic disorder and affects ~70 million individuals worldwide, with the burden of disease uniquely distributed to malaria-endemic regions.[1] SCD is typically rare in South Africa (SA) but the increasing immigration of foreign nationals over the last 20 years has the potential to alter the epidemiology of this life-threatening disease locally. The abolishment of the apartheid regime and its laws has made immigration to SA more appealing to foreigners. This, along with political strife, poverty, war and famine in many other African countries, has resulted in an influx of foreign nationals into the country.[2] The exact number of immigrants living in SA is not known; however, according to the United Nations High Commissioner for Refugees, ~463 040 asylum seekers and 112 192 refugees reside in SA.[3] Recent data from Stats SA show that a significant influx of foreign nationals is seen each year and 106 173 temporary residence permits were issued in 2013 alone.[4] The majority of immigrants were from African countries (54.4%), with Zimbabwe, Nigeria, the Democratic Republic of Congo (DRC), Lesotho, Malawi, Angola and Cameroon the most common nations.[4] It is therefore not surprising that patients with SCD are seen more frequently in our hospitals and clinics. At the Red Cross War Memorial Children’s Hospital in the Western Cape, the annual frequency of SCD increased by 300 - 400% between 2001 and 2010.[5] All patients who have undergone genetic screening for sickle cell anaemia with the Department of Human Genetics at the National Health Laboratory Services (NHLS) in Johannesburg between 1983 and 2012 were foreign nationals and the majority were imigrants from sub-Saharan African countries, including the DRC, Angola, Nigeria and Zimbabwe.[6] More evidence needs to be collected to determine the changes of the disease profile locally. A retrospective descriptive study was carried out to review all paediatric admissions over a 16-month period at South Rand Hospital (SRH), a district hospital in Johannesburg, Gauteng Province. Patients who were admitted with SCD were identified and their clinical records were analysed to determine their presentation and outcome.

Case 1

A four-year-old boy, who was born in the DRC and living in SA as an asylum seeker, presented to SRH for admission on two occasions for complications arising from SCD. He first presented with a two79

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day history of vomiting, fever, non-productive cough and diarrhoea.

The patient was noted to be lethargic and pale on examination, with mild dehydration and inflammation of the pharynx and tonsils.

A diagnosis of pharyngitis was made. SCD was considered on the basis of his ethnicity and pale complexion. The patient was admitted and investigated for a local source of infection. A blood and urine culture, full blood count (FBC) and C-reactive protein (CRP) assay were performed. He was treated empirically with intravenous broadspectrum antibiotics (amikacin and ceftriaxone), given paracetamol for analgesia, supplemented with folic acid and rehydrated with alkali fluids (1 L 5% dextrose water supplemented with 10 mL 15% potassium chloride and 50 mL 8.5% sodium bicarbonate) at 70 mL/kg/day.

The FBC with a smear revealed hypochromic anaemia (Hb 7.1 g/dL) with marked anisocytosis and moderate sickle cells.

This prompted investigation with haemoglobin (Hb) electrophoresis that showed significantly elevated levels of HbF (16.2%) and HbS (78.5%), with decreased levels of HbA (2.3%) and an HbA2 of 3%.

Further studies revealed the absence of HbH, a normal glucose6-phosphate dehydrogenase (G-6-PD) level and a reticulocyte production index (RPI) of 3.7. These findings were in keeping with homozygous SCD. An infective locus could not be identified. The patient’s clinical condition improved during admission and he was well for discharge after five days of treatment. He was discharged on oral penicillin VK and folic acid, with a follow-up arranged at the haematology clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH).

One month later, the patient presented to SRH with a complaint of lower abdominal pain and lethargy for two days. He was noted to be pale and irritable with generalised abdominal tenderness without organomegaly. He was admitted with a diagnosis of an abdominal sickle cell crisis. A treatment approach similar to the first admission was followed and the patient was well for discharge after 5 days.

Case 2

A one-year-old boy, born in the DRC and living in SA with an unknown immigration status, presented to SRH with painful swelling of both feet. The swelling was reported to have started insidiously and had been present for two days. A diagnosis of septic arthritis was considered. A radiograph of the feet and ankles revealed

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ARTICLE no abnormalities but a FBC with a smear revealed a hypochromic, microcytic anaemia (Hb 8.2 g/dL) with teardrop cells, scanty pencil cells, target cells and mild poikilocytosis. This prompted investigation with Hb electrophoresis that showed significantly elevated levels of HbF (19.1%) and HbS (77.9%) with decreased levels of HbA2 (0%) and an HbA of 3%. Further studies revealed the absence of HbH, a normal G-6-PD level and an RPI of 2.8. The findings were in keeping with homozygous sickle cell disease. Managed as an outpatient, he was put onto folic acid and prophylactic oral penicillin VK and arrangements were made for follow-up at the haematology clinic at CMJAH. Four weeks after the confirmation of SCD, the patient presented in an acute pain crisis. He was noted to have a two-day history of generalised pain accompanied by a fever and lethargy. Examination revealed pallor with marked irritability, distress on handling and generalised abdominal tenderness. The patient was admitted and investigated for a local source of infection. A blood and urine culture, FBC and CRP were performed. He was treated empirically with intravenous broad-spectrum antibiotics (ampicillin and ceftriaxone), supplemented with folic acid, given paracetamol for analgesia and rehydrated with alkali fluids at 130 mL/kg/day. An infective locus could not be identified. The patient’s clinical condition improved and he was well for discharge after 7 days of treatment. He was discharged on oral penicillin VK and folic acid with a follow-up arranged at the haematology clinic at CMJAH.

Case 3

An eleven-month-old boy, born in Nigeria and living in SA with an unknown immigration status, presented to SRH after being referred from the local clinic with jaundice. Further questioning revealed a one-day history of vomiting with abdominal distention and lethargy without the presence of pruritis or discoloured urine or stool. The child was obviously jaundiced with abdominal distention and generalised pain. A 2 cm hepatomegaly with a rounded edge and smooth surface without splenomegaly was noted two days after admission. The patient was admitted and investigated for a local source of infection. A blood and urine culture, FBC, CRP and a liver function test (LFT) were performed. He was treated empirically with intravenous broad-spectrum antibiotics (amikacin and ceftriaxone), given paracetamol for analgesia and rehydrated with half-strength Darrow’s solution at 70 mL/kg/day.

A FBC with a smear on admission revealed a hypochromic, microcytic anaemia (Hb 7.3 g/dL) with target cells, spherocytes, oval macrocytes, poikilocytosis and Howel Jolly bodies. This prompted investigation with Hb electrophoresis that showed significantly elevated levels of HbF (16.3%) and HbS (80.7%), with decreased levels of HbA2 (3%) and an HbA of 0%. Further studies revealed the absence of HbH, a normal G-6-PD level and an RPI of 2.5. The

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patient also had a raised CRP of 184 mg/L and deranged LFTs with an unconjugated hyperbilirubinaemia and elevated ductal enzymes, i.e. alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT).

The findings were in keeping with homozygous SCD complicated by acute haemolysis. An infective locus could not be identified. The patient’s clinical condition improved and he was well for discharge after 7 days of treatment. He was discharged on oral penicillin VK and folic acid with a follow-up arranged at the haematology clinic at CMJAH.

Conclusion

Although SCD is rare in SA, it is being diagnosed and managed at the district level in Johannesburg. The changing demographics of SA should raise suspicion of this increasingly prevalent, life-threatening disease. SCD is a great masquerader with a wide range of differential diagnoses. Diagnosis of the disease should be considered in patients who are inherently at risk with suspicious symptoms. This requires an understanding of the background and ethnicity of the population group being treated. Management of the disease is complex. The acute crisis requires urgent care and, to prevent such crises and minimise long-term complications, long-term follow-up should be done at a specialist institution where available.

Acknowledgements. Dr Ramatsimele Mphahlele provided valuable advice and direction on the topic.

Author contributions. Sole author.

Funding. Self-funded.

Conflicts of interest. None.

1. Nazeer A, Moosa P, Hassan A, et al. Recommendations for the management of sickle cell disease in South Africa. S Afr Med J 2014;104(11):743-751. https:// doi.org/10.7196/samj.8470 2. Statistics South Africa (STATS SA). Community Survey 2016 – statistical release. Johannesburg: STATS SA, 2016. http://cs2016.statssa.gov.za/wpcontent/uploads/2016/07/NT-30-06-2016-RELEASE-for-CS-2016-_Statisticalreleas_1-July-2016.pdf (accessed 1 March 2017).

3. United Nations High Commisioner for Refugees (UNHCR). UNHCR operation in South Africa, Lesotho and Swaziland – September 2015 factsheet. Pretoria: UNHCR, 2015. http://www.unhrc.org (accessed 4 July 2017).

4. Statistics South Africa (STATS SA). Documented Immigrants in South Africa 2013. Johannesburg: STATS SA, 2013. http://beta2.statssa.gov.za/publications/ D03514/D035142013.pdf (accessed 1 March 2017).

5. Ambroise W, Chido P, Nan N, et al. The burden of sickle cell disease in Cape Town. S Afr Med J 2012;102(9):752-754. https://doi.org/10.7196/samj.5886 6. Krause A, Wainstein T, Essop FB, Goodyear Q. Testing for haemoglobinopathies in Johannesburg, South Africa: A 30-year review. SAMJ 2013;103(12):989-993. https://doi.org/10.7196/samj.7255

Accepted 10 April 2018.

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CASE REPORT

This open-access article is distributed under Creative Commons licence CC-BY-NC 4.0.

Neonatal haemolytic anaemia – a diagnostic approach to red cell membrane disorders L Swart,1 MB ChB; K Naidoo,1 MSc, PhD; E Schapkaitz,1 MB BCh, FCPath (SA), MMed (Haem); J Poole,2 MB BCh, FCPaed (SA), DCH (SA); T L Coetzer,1 BSc (Hons), PhD Department of Molecular Medicine and Haematology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 2 Department of Paediatrics, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 1

Corresponding author: L Swart (leanne.swart@icloud.com) In neonates presenting with a non-immune haemolytic anaemia, a high index of suspicion is raised for hereditary red cell membrane disorders.

The distinction between red cell membrane disorders, however, is often difficult in neonates in the absence of a complete family history. We describe a case of a 26-day-old female twin who presented with jaundice and severe haemolysis, which required multiple red cell transfusions.

Laboratory investigations revealed a non-immune haemolysis. Red cell membrane extraction and sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, including spectrin analysis, revealed the presence of mutant spectrin αI/74. A diagnosis of hereditary elliptocytosis with transient infantile poikilocytosis was favoured. On follow-up at 4 months, a decline in haemolysis was observed.

S Afr J Child Health 2018;12(2):81-83. DOI:10.7196/SAJCH.2018.v12i2.1483

The timely diagnosis and management of neonatal haemolytic anaemia is of critical importance in neonatal units. In neonates presenting with hyperbilirubinaemia, nonimmune haemolysis and a positive family history, a high index of suspicion is raised for hereditary red cell membrane disorders.

These include hereditary spherocytosis (HS), hereditary elliptocytosis (HE) and hereditary stomatocytosis (HSt). These disorders can often be diagnosed by the characteristic red blood cell (RBC) shape on peripheral blood smear (PBS) (Fig. 1). However, the RBC shape is not always specific for the particular red cell membrane disorder. Appropriate specialised investigations of both the neonate and parents are indicated, with further management by a paediatric haematologist. We present a case of a 26-day-old female twin who presented with a persistent non-immune haemolytic anaemia, which required multiple red cell transfusions.

Clinical history Evidence of haemolysis, history of jaundice, hepato-splenomegaly + Family history Autosomal dominant or less commonly autosomal recessive

Screening tests Full blood count (FBC) Peripheral blood smear (PBS) Haemolytic work-up: Increased reticulocyte count, low haptoglobin, negative direct Coombs, raised LDH and unconjugated hyperbilirubinaemia

Hereditary spherocytosis FBC: normal-high MCHC, low-normal Hb PBS: spherocytes

Hereditary stomatocytosis Overhydration FBC: Low Hb , increased MCV, decreased MCHC PBS: Stomatocytes, macrocytes Dehydration FBC: Normal Hb, normal-increased MCV, increased MCHC PBS: Stomatocytes, target cells

Specialised investigations Red cell membrane protein analysis (HS, HE, HPP) Spectrin analysis (HE, HPP) EMA test (HS, HPP) Molecular genetic testing PCR / gene sequencing (SAO, HS, HE, HPP) Cation flux/intracellular cation content (HSt)

Presence of a red cell membrane disorder HS: Reduction in spectrin (α and β), ankyrin, band 3 or protein 4.2, decreased EMA HE: Protein 4.1R deficiency or spectrin self-association defect, normal spectrin content HHP: Reduced αspectrin, severe spectrin self-association defect, decreased EMA SAO: 27 bp deletion in band 3 gene (SLC4A1) HSt: Abnormal cation flux/content

Case

A 26-day-old female neonate was referred to the Charlotte Maxeke Johannesburg Academic Hospital with a history of severe transfusion dependent haemolytic anaemia.

Neonatal jaundice developed within 12 hours of delivery. At birth, the haemoglobin (Hb) was 10.9 g/dL and the unconjugated bilirubin was 240 μmol/L. This female dizygotic twin (birth weight 1 910 g) was delivered by caesarian section at 34 weeks᾽ gestation for premature rupture of membranes. Both parents originated from Angola and an in vitro fertilisation pregnancy was performed

Hereditary elliptocytosis FBC: low-normal Hb, low MCV in HPP PBS: HE: Elliptocytes HPP: Fragmentation and poikilocytosis SAO: Ovalocytes

No red cell membrane disorder Red cell enzymopathy G6PD screen Individual enzyme levels Haemoglobinopathy Unstable Hb screen Hb electrophoresis

Fig. 1. A diagnostic approach for hereditary red cell membrane disorders. (LDH = lactate dehydrogenase; MCV = mean cell volume; MCHC = mean corpuscular haemoglobin concentration; Hb = haemoglobin; HS = hereditary spherocytosis; HE = hereditary elliptocytosis; HPP = hereditary pyropoikilocytosis; SAO = South East-Asian ovalocytosis; HSt = hereditary stomatocytosis; PCR = polymerase chain reaction; EMA = eosin-5’-maleimide; G6PD = glucose-6-phosphate dehydrogenase.)

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CASE REPORT with paternal sperm and a donor egg. As such, a complete family history could not be obtained.

The female twin continued to haemolyse and was referred to our centre for specialist investigations and management (Fig. 2). The laboratory parameters are presented in Table 1. The Hb was 7.10g/dL on admission, with a corrected reticulocyte count of 3.85 %. The PBS showed moderate polychromasia and numerous red cell fragments, as well as occasional spherocytes (Fig. 3). The direct Coombs test was negative. Specialist investigations for non-immune haemolysis were performed, namely Hb electrophoresis, glucose-6-phosphate dehydrogenase screen and unstable Hb analysis, which were all within normal limits. Analysis of isolated red cell membrane proteins using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) analysis revealed no abnormalities. Native PAGE of isolated spectrin and structural analysis by limited digestion with trypsin indicated the presence of mutant spectrin αI/74. This favoured the diagnosis of HE with transient infantile poikilocytosis.

At four months of follow-up, a decline in haemolysis was observed with a Hb level of 11.3 g/dL in the female twin. The PBS showed mild polychromasia, occasional spherocytes and red cell fragments.

The family returned to Angola and the patient was lost to follow-up.

The male twin developed mild jaundice after birth which responded to phototherapy. He had no associated anaemia. Red cell membrane protein analyses, in the male twin, were not performed.

and HE with transient infantile poikilocytosis is often difficult in neonates presenting with severe haemolysis. Clinically, HPP cases typically remain transfusion dependent until a splenectomy is performed, in contrast to HE with transient infantile poikilocytosis which evolves into the mild HE phenotype.[1-3] The diagnosis is confirmed by analysis of red cell membrane protein analysis, including spectrin analysis.

In this case, red cell membrane protein and spectrin analyses favoured the diagnosis of HE in association with transient infantile poikilocytosis. However, the FBC and PBS findings of a low mean cell volume (MCV), as a result of the significant red cell fragmentation and the absence of elliptocytes, suggested a diagnosis of HPP. Further, the clinical presentation was severe, with a requirement for multiple red cell transfusions. Since the proband had been transfused prior

Discussion

HE is a hereditary red cell membrane disorder, which is characterised by mechanical instability of the red cell membrane skeleton.[1] The majority of the HE membrane defects occur in α and β spectrin,[2] which result in disruption of the spectrin heterodimer self-association sites, impairing spectrin tetramer formation. This results in haemolysis.

HE is classified according to its clinical presentation into asymptomatic or non-haemolytic HE, HE with variable haemolysis, HE with transient infantile poikilocytosis and hereditary pyropoikiolcytosis (HPP).[2] The clinical severity of HE described in family studies is markedly heterogenous.[3] The most frequent presentation of HE is HE with variable haemolysis, which mostly follows a benign clinical course. This is typically inherited in an autosomal dominant fashion and the amount of mutant and normal spectrin are equivalent. In contrast, HE with transient infantile poikilocytosis and HPP present during the first year of life with severe transfusion dependent haemolytic anaemia. HPP is a severe autosomal recessive disorder. Cases of HPP show a marked spectrin dimer self-association defect and a decreased amount of spectrin.

This severely weakens the membrane skeleton, resulting in red cell fragmentation and severe haemolysis. The distinction between HPP

Fig. 3. The Giemsa-stained peripheral blood smear showing numerous red cell fragments (circle), mild polychromasia (arrow) and occasional spherocytes (square) (50× magnification).

Table 1. Presenting laboratory features at Charlotte Maxeke Academic Hospital Haemoglobin Platelet count Corrected reticulocyte count Total bilirubin Unconjugated bilirubin Peripheral blood smear

Haemoglobin (g/dL)

13.5 12

2u

2u

Direct Coombs test Lactate dehydrogenase Urea Creatinine Haemoglobin electrophoresis Unstable haemoglobin analysis Glucose-6-phosphate dehydrogenase screen Red cell membrane protein analysis*

1u

10.5 9 7.5 6 1

7

26

33

40

47

61

89

118

Time (days)

Fig. 2. Haemoglobin levels and red blood cell transfusions (indicated in arrow text boxes) from birth.

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7.10 g/dL 443 x 109/L 3.85 % 201 μmol/L 21 μmol/L Numerous red cell fragments Mild polychromasia Occasional spherocytes (post transfusion) Anisopoikilocytosis Negative 384 U/L 3.3 mmol/L 19 μmol/L Within normal limits Within normal limits Within normal limits Spectrin dimer self-association defect with mutant spectrin αI/74

*Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) analysis of red cell membrane proteins and spectrin analysis with native PAGE and tryptic digestion.

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CASE REPORT to performing specialist investigations, the presence of transfused red blood cells would have increased the relative amount of normal spectrin compared with the mutant spectrin. It is thus important to perform definitive diagnostic tests, such as red cell membrane protein studies prior to transfusion, in order to prevent diagnostic misinterpretations.

At ~4 months of age, there is a switch from fetal to adult Hb. This results in an increase in the stability of the red cell membrane skeleton. On follow-up, at 4 months of age in this case, there was a decline in haemolysis and the Hb was stable. The clinical and laboratory picture of HE usually emerges from ~18 months of age. A repeat spectrin analysis (performed at least 3 months post transfusion) is required to confirm the diagnosis. In addition, family studies are indicated. In members of the same family with this mutation, the clinical presentation may be heterogeneous with a phenotypically different disease. Unfortunately, the patient and her family have been lost to follow-up.

Conclusion

This case report emphasises the importance of reviewing the PBS routinely on all neonates presenting with anaemia and nonphysiological jaundice. At a primary care level, initial laboratory investigations should include an FBC, PBS examination, reticulocyte count, direct Coombs test and a haemolytic workup. It should be noted that the classic morphologic abnormalities of HE (elliptocytes)

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are usually not present during the first few weeks of life. Specific investigations include SDS-PAGE analysis of red cell membrane proteins, native PAGE for spectrin analysis and molecular diagnostic testing if the clinical and laboratory findings suggest a hereditary red cell membrane disorder. It is important to perform the appropriate specialised laboratory tests prior to transfusion to avoid a delay in diagnosis.

Acknowledgements. None.

Author contributions. Writing: LS, KN, ES, TLC. Concept and design: LS, KN, ES, TLC. Analysis and processing: KN, TLC. Interpretation: KN, TLC, LS, ES. Treating paediatrician: JP. Funding. None.

Conflicts of interest. None.

1. Coetzer TL. Erythrocyte membrane disorders. In: Williams Hematology. 9th ed. Kaushansky K, Lichtman MA, Prchal JT, et al. (eds). New York: McGraw Hill, 2016.

2. King MJ, Garcon L, Hoyer JD, et al. ICSH guidelines for the laboratory diagnosis of nonimmune hereditary red cell membrane disorders. Int J Lab Hematol 2015;37(3):304-325. https://doi.org/10.1111/ijlh.12335 3. An X, Mohandas N. Disorders of red cell membrane. Br J Haematol 2008;141(3):367-375. https://doi.org/10.1111/j.1365-2141.2008.07091.x

Accepted 31 January 2018.

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