SAJCH Vol 9, No 4 (2015)

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

November 2015

Volume 9

No. 4

• EPI and vitamin A coverage in KZN • Transfer of critically ill children to tertiary care • Acute pain management in children with sickle cell anaemia • Effect of lactose-free formula feeds on growth • Feeding practices in neonatal wards

CHILD HEALTH THE SOUTH AFRICAN JOURNAL OF

November 2015

Volume 9

No. 4

CONTENTS

Editorial

P Cooper

Articles

V Comley, N Nkwanyana, A Coutsoudis

107 Cerebral palsy in South Africa: Perinatal factors and later neurological handicap in infants born at or near term

112 A retrospective review of the transfer of critically ill children to tertiary care in KwaZulu-Natal Province, South Africa C Royal, N H McKerrow

119 Acute pain management in children with sickle cell anaemia during emergency admission to a teaching hospital in Lagos, Nigeria

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

108 Immunisation and vitamin A capsule coverage in a semi-urban area of KwaZulu-Natal Province, South Africa

EDITOR J M Pettifor

K A Oshikoya, B Edun, I A Oreagba

CEO AND PUBLISHER Hannah Kikaya EDITOR-IN-CHIEF Janet Seggie CONSULTING EDITOR J P de V van Niekerk EXECUTIVE EDITOR Bridget Farham MANAGING EDITOR Ingrid Nye TECHNICAL EDITORS Emma Buchanan Paula van der Bijl

124 Factors associated with bacteraemia in febrile, non-neonatal children <5 years old at the paediatric outpatient clinic of University of Port Harcourt Teaching Hospital, Nigeria

PRODUCTION MANAGER Emma-Jane Couzens

DTP, LAYOUT & SETTING Carl Sampson

U C Onubogu, I C Anochie

127 Persistent and new-onset anaemia in children aged 6 - 8 years from KwaZulu-Natal Province, South Africa

T P Gwetu, M Chhagan, M Craib, M Taylor, S Khauchali

130 The effect of lactose-free formula feeds on growth responses among severely malnourished HIV-infected children in Durban, South Africa

E Binka, D Montoya-Fontalvo, M Healy, M Sobieszczyk, P LaRussa, R Bobat, M Archary

Review

L Sepeng, D E Ballot

Short Report

M Nandi, S Sarkar, R Mondal, T Dhibar

Case Report

R Moodley, E Naicker, R Bhimma

142

CPD Questions

HEAD OF SALES AND MARKETING Diane Smith (012) 481 2069 | dianes@samedical.org ISSN 1994-3032 JOURNAL WEBSITE: www.sajch.org.za

133 Audit of feeding practices in the neonatal wards at the Charlotte Maxeke Johannesburg Academic Hospital

137 Posterior reversible encephalopathy syndrome: Some novel associations

140 Congenital nephrotic syndrome: A diagnostic and management dilemma

ublished by Health and Medical Publishing Group, P Suites 9 & 10, Lonsdale Building, Gardener Way, Pinelands 7405 apers for publication should be addressed to the Editor, P via website: www.sajch.org.za Tel: (021) 532 1281 E-mail: publishing@hmpg.co.za Cover: Courtney, Red Cross War Memorial Children's Hospital Primary School

©Copyright: Health and Medical Publishing Group (Pty) Ltd

Manuscripts containing plagiarism will not be considered for publication in the SAJCH. For information on our plagiarism policy, please visit the editorial policy section on our website. (http://www.sajch.org.za/index.php/ sajch/about/editorialPolicies)

EDITORIAL

Cerebral palsy in SA: Perinatal factors and later neurological handicap in infants born at or near term It has been recognised in high-income countries for many years that most cases of cerebral palsy are not due to complications of labour and delivery. In a report published in 2004, Jacobsson and Hagberg[1] concluded that 70 - 80% of cases of cerebral palsy were due to prenatal factors, whereas birth asphyxia accounted for <10% of cases.

This was reiterated in a recent review by Nelson and Blair,[2] who quoted other studies that have produced similar figures.However, these studies have been confined to high-income countries and are unlikely to be applicable to low- and middle-income countries (LMICs).

The target year for the Millennium Development Goals (MDGs), 2015, has been reached. One of these goals was to reduce mortality of infants and children under the age of 5 years by two-thirds, with the figure for 1990 as the baseline. While this goal was not reached globally, a reduction of just over 50% was achieved – an impressive amount. However, neonatal mortality rates have declined more slowly than postneonatal mortality, with the result that, globally, 44% of all under-5 deaths occur in the neonatal period, of which onequarter are owing to intrapartum-related factors, i.e. intrapartum hypoxia or what is commonly referred to as birth asphyxia.[3] The vast majority of these deaths occur in LMICs. South African (SA) data are similar; hypoxia-related deaths make up 28% of all early neonatal deaths. However, when only infants with birth weight >1 000 g are analysed, hypoxia-related deaths make up 41% of all early neonatal deaths, the single largest category of cause of death.[4] While accurate figures for intrapartum-related causes of cerebral palsy in SA are not known, with this large number of deaths due to intrapartum hypoxia, the number of infants surviving such an insult with neurological damage is likely to be substantially higher than that given for high-income countries. This conclusion was supported by a retrospective study by Mahlaba (J Rodda and N Mahlaba, personal communication), who reviewed children attending the cerebral palsy clinic at Chris Hani Baragwanath Academic Hospital. Of the 144 cases reviewed, 88 had neuroimaging reports available and 42% of these showed findings compatible with a hypoxic ischaemic injury. Imaging results were not available for the other cases, but the above example still illustrates that intrapartum hypoxia is a significantly more common cause of cerebral palsy compared with high-income countries.

Ascribing subsequent cerebral palsy to intrapartum events has been the subject of many publications in the literature. A consensus statement on this was published by MacLennan[5] in 1999, which was supported by national obstetric, paediatric and midwifery organisations from a number of countries.According to this consensus statement, three essential requirements needed to be fulfilled before it could be concluded that later handicap could be attributed to intrapartum events, namely: (i) severe metabolic acidosis demonstrated on cord blood or blood taken from the neonate within 1 hour of birth; (ii) moderate or severe neonatal encephalopathy; and (iii) cerebral palsy of the spastic quadriplegic or dyskinetic type. These criteria could only be applied when the gestation was ≤34 weeks.

As knowledge was gained from brain magnetic resonance imaging (MRI) of infants who had well-documented intrapartum hypoxic events, additional imaging criteria were added. However, it became clear that these criteria were too rigid and that lesser degrees of acidosis could still be associated with neurological damage occurring intrapartum, and that there was a spectrum of neurological handicap, including other forms of cerebral palsy, that could – albeit much less commonly – result from intrapartum hypoxia. However, moderate or severe neonatal encephalopathy remains the sine qua non for linking SAJCH

intrapartum events to later handicap. In view of this, the American College of Obstetricians and Gynecologists (ACOG) recently published an updated report, endorsed by the American Academy of Pediatrics, on the relationship between neonatal encephalopathy and neurological outcome. The report stressed that all relevant factors should be taken into account to evaluate the likelihood of such a relationship, rather than the more rigid requirement for essential criteria as outlined by the MacLennan consensus. The ACOG report acknowledged that there were still significant knowledge gaps, that neurological injury may occur at multiple points during gestation and that these insults occurring at different times may be additive.[6] In recent years, SA has seen a major increase in litigation involving those responsible for the care of women during labour and delivery, with payouts of many millions of rand (ZAR) for neurological damage in the child. This has occurred in both the public and the private sector.

From the private sector perspective, the result has been that, similar to what has happened in a number of other countries, obstetricians now face prohibitive rates for malpractice insurance. With regard to the public sector, grave concern has been expressed that the extent of this litigation is threatening to have a major financial effect on the public healthcare system. More recently, the actions of those responsible for resuscitation of the neonate and subsequent ongoing management have also become the focus of litigation.

In addition to healthcare worker issues, systems failure – especially in the public sector – also plays an important role. There may be long delays in transporting a mother from a primary care facility to one able to expedite delivery. In other cases, significant delays from the time the decision is taken to do a caesarean section and the actual time of delivery frequently occur due to heavy patient load.

It is therefore clear that SA has a major problem not only with a high neonatal mortality due to intrapartum and immediate postnatal events, but also with respect to neurological handicap in survivors. Additional training of healthcare workers at all levels is essential for the care of mothers during pregnancy, labour and delivery as well as for neonatal resuscitation and early neonatal care. Measures need to be put in place to ensure that the healthcare system is able to provide for efficient and seamless care of mothers and babies across all levels of care and that adequate resources are in place to cope with heavy patient load.

References

1. Jacobsson B, Hagberg G. Antenatal risk factors for cerebral palsy. Best Pract Res Clin Obstet Gynecol 2004;18(3):425-436. [http://dx.doi.org/10.1016/j. bpobgyn.2004.02.011] 2. Nelson KB, Blair E. Prenatal factors in singletons with cerebral palsy born at or near term. N Engl J Med 2015;373(10):946-953. [http://dx.doi.org/10.1056/nejmra1505261] 3. UNICEF, World Health Organization. Every Newborn: An Action Plan to End Preventable Deaths. 2014. http://www.everynewborn.org/Documents/Fullaction-plan-EN.pdf (accessed 2 November 2015).

4. Pattinson R, Rhoda N. Saving babies 2012 - 2113: Ninth report on perinatal care in South Africa. http://www.ppip.co.za/wp-content/uploads/SavingBabies-2012-2013.pdf (accessed 2 November 2015).

5. MacLennan A. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: International consensus statement. BMJ 1999;319(7216):1054-1059. [http://dx.doi.org/10.1136/bmj.319.7216.1054] 6. Neonatal encephalopathy and neurological outcome, second edition. Pediatrics 2014;133(5);e1482-1488. [http://dx.doi.org/10.1542/peds.2014-0724]

Prof. P Cooper Academic Head, Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand; and Chief Paediatrician, Charlotte Maxeke Johannesburg Academic Hospital S Afr J Child Health 2015;9(4):107. DOI:10.7196/SAJCH.2015.v9i4.1064

NOVEMBER 2015 Vol. 9 No. 4

107

ARTICLE

Immunisation and vitamin A capsule coverage in a semi-urban area of KwaZulu-Natal Province, South Africa V Comley,1 MB BCh, FCPaed (SA); N Nkwanyana,2 MSc (Statistics); A Coutsoudis,1 PhD 1 2

epartment of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa D Public Health Medicine, University of KwaZulu-Natal, Durban, South Africa

Corresponding author: V Comley (vanessacomley@yahoo.com)

Background. The Expanded Programme on Immunisation (EPI) in South Africa (SA) has had a large effect on vaccine-preventable illnesses, yet there is little in the literature describing access to and utilisation of the programme beyond 1 year of age. Coverage of vita­min A supplementation is examined through District Health Information System data, but this does not give a fair assessment of the lifetime coverage in a child or provide any correlation with the immunisation status of the child.

Objectives. To describe utilisation and dropout rate with the vitamin A and immunisation programmes over the first 6 years of life among children aged 6 - 8 years in a semi-urban population in KwaZulu-Natal (KZN) Province, SA. A secondary objective was to investigate whether access and dropout rates are associated between these two programmes.

Methods. A retrospective cohort analysis was performed on 923 anonymised Road-to-Health cards, extracting information on immunisation and vitamin A coverage.

Results. Overall, 92.9% (95% confidence interval (CI) 91.2 - 94.6) and 88.5% (95% CI 86.4 - 90.5) of children were fully immunised by 12 months and 18 months of age, respectively. The percentage of children fully immunised by 6 years of age dropped to 44% (95% CI 41.2 - 47.6). The dropout rates for measles, and diphtheria, pertussis and tetanus 1 - 3 vaccination were 2.4% and 1.2%, respectively.

Vitamin A had an overall coverage of 34.9% during 6 - 60 months of life for this population, with children receiving, on average, three doses (interquartile range 2 - 5).

Conclusion. Despite good immunisation coverage in the first 18 months of life, there was relatively poor vitamin A coverage, suggesting a need for re-evaluation of the current vitamin A capsule distribution programme.

S Afr J Child Health 2015;9(4):108-111. DOI:10.7196/SAJCH.2015.v9i4.925

Several public health programmes targeting children have been introduced in developing countries in order to increase efforts to prevent disease and poor health. Two such well-established programmes, recommended by the World Health Organization (WHO) to reduce morbidity and mortality are the Expanded Programme on Immunization (EPI) and the vitamin A supple­ mentation programme.

The EPI was established in 1974 by the WHO,[1] with the outcome goal that by 2010, 90% of <1-year-olds should receive routine immunisations nationally, and that each district should achieve 80% coverage rates.[2] The South African (SA) EPI came into effect in 1995, with updates occurring in 2009 to include pneumococcus and rotavirus vaccines. The national coverage for 2010/2011 was 86.7%,[3] below the 90% target set by the WHO, which had been reached during 2008 and 2009. Only 30 of the 52 districts in SA reached the target of 80% coverage set out by the WHO.[3] The vitamin A supplementation programme was introduced by the WHO and international agencies to combat the effects of vitamin A deficiency in children, viz. blindness, impaired functioning of the immune system, increased risk of diarrhoea and measles and the associated increased number of childhood deaths.[4] A systematic review and meta-analysis published in 2011 reported that vitamin A supplementation was associated with a 24% reduction in childhood mortality and morbidity, including blindness.[5] Vitamin A supplementation has therefore, for the last one or two decades, been promoted as a cost-effective strategy to improve childhood 108

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outcome with WHO guidelines recommending high-dose vitamin A for infants and children aged 6 - 59 months in settings where vitamin A deficiency is a public health concern.[6] In 2003 SA implemented a policy of routine supplementation to children aged 6 - 59 months every 6 months and to postpartum women.[6] The utilisation of this programme has not been well documented and there has been considerable discussion on the most appropriate means of correcting vitamin A deficiency, and whether alternative strategies to high-dose vitamin A capsules should be considered.

While the vitamin A schedule calls for supplementation every 6 months, the EPI has a different schedule with vaccine delivery at birth, 6 weeks, 10 weeks, 14 weeks, 9 months, 18 months and 6 years, so that delivery of the two programmes only overlaps at 18 months.

SA’s biggest source of data on immunisation is derived from data collected by the DHIS (District Health Information System), which only supplies information during infancy (<1 year of age).

Therefore, the primary objective of this study was to determine access throughout the immunisation schedule and not just during the infancy period. The second objective of this study was to determine the level of utilisation of the vitamin A programme and to investigate whether access and dropout rates in these two programmes are associated.

Methods

Study population

This Immunisation and Vitamin A Coverage (IVAC) study is an ancillary study linked to the Asenze study of children and

NOVEMBER 2015 Vol. 9 No. 4

their primary caregivers in the Valley of a Thousand Hills, part of the Outer West eThekwini district, KwaZulu-Natal (KZN) Province, SA. The population is of Zulu ethnic background, living in five local tribal authorities and municipal wards, and numbers ~67 000. Children in these communities are at high risk of missing opportunities for preventive health services. Most of the families live in adverse socioeconomic conditions with low levels of formal education and high levels of unemployment, and are simultaneously experiencing the effects of the HIV epi­ demic in KZN. Although the community is well serviced with seven primary healthcare clinics and mobile clinics throughout the five wards, the physical terrain nevertheless makes access difficult.

The objective of the Asenze study was to determine the prevalence of neuro­ developmental disability and identify poten­ tial health, contextual and psychosocial predic­ tors of disability among children living in this semi-urban area in KZN. [7,8] During years 2008 - 2010, the Asenze study (phase 1) recruited children aged 4 - 6 years, through a door-to-door survey.

Phase 2 follow-up was done 18 - 24 months later, at which time the Road-to-Health cards (RTHCs) of the children were copied.

The IVAC study data were extracted from copies of RTHCs that had been used in the parent Azenze study.

Sampling

The RTHCs of this cohort of children were used as source data for this study. Of the 1 078 children's RTHCs copied, data were only extracted from 938 owing to poor copy quality.

Of these 938 cards, 923 were included in the study, with 15 cards being excluded because they were identified as duplicates.

Of the 923 cards, 917 had information on immunisation and 653 had records concerning vitamin A supplementation.

The reason for the large discrepancy in the number with vitamin A information compared with immunisation is that in the parent study, the page containing vitamin A records was not initially photocopied; this portion was only copied after interest was shown in this study.

RTHCs were used to collect data on date of birth and sex of the child, vitamin A supplementation status, immunisation status according to the EPI schedule and any outof-stock vaccines.

Statistical analysis

Data were collected and entered into a Microsoft (USA) Excel spreadsheet and analysed in SPSS version 22 (IBM, USA) and Microsoft Excel.

Table 1. Summary of immunisation results Total records, n

Immunised, n (%)

95% CI

Fully immunised at 12 months

917

852 (92.9)

91.2 - 94.6

Fully immunised at 18 months

917

812 (88.5)

86.4 - 90.5

Fully immunised at 6 years

917

407 (44.4)

41.2 - 47.6

OPV5

912*

440 (48.2)

44.9 - 51.4

DT

911

440 (48.3)

45.0 - 51.5

†

Measles 1

917

886 (96.6)

95.4 - 97.7

Measles 1 and measles 2

917

865 (94.3)

92.8 - 95.8

DPT1

917

900 (98.1)

97.2 - 99.0

DPT1 and DPT3

917

889 (96.9)

95.8 - 98.0

*Five records reported that the vaccine was out of stock. † Six records reported that the vaccine was out of stock.

Proportions with two-sided 95% confi­ dence intervals (CIs) for immunisation drop­out rates, and immunisation coverage at 12 months, 18 months and 6 years, were computed.

McNemar’s χ2 test was used to test for association between reception of full immunisation and vitamin A supplementation. The significance level was set at p<0.05.

Ethical considerations

Ethics approval was obtained from the Bio­ medical Research Ethics Committee of the University of KwaZulu-Natal (Ref: BREC 267/12).

All RTHCs were anonymised prior to viewing and data collection, and there was no direct interaction between the study population and the investigators.

Results

Immunisation

Of the 923 RTHCs analysed, 49.3% were for male children and 917 had information regarding immunisation. The percentage of children who had received full immunisation at 12 months, 18 months and 6 years, as well as percentages of children who received the oral polio vaccine (OPV) 5 antigen, diphtheria and tetanus (DT) vaccine, measles immunisations and diphtheria, pertussis and tetanus (DPT) 1 - 3 immunisation are presented in Table 1.

Results in Table 1 depict that the dropout rates for measles 1 and 2, and for DPT1 - 3, were 2.4% and 1.2%, respectively.

Vitamin A

Of the 923 cards analysed, 653 contained information regarding vitamin A doses.

The highest level of coverage for vitamin A administration was at 6 months, when 408 of the 653 children (62.5%, 95% CI 58.7 - 66.2%) received vitamin A. This figure gradually decreased to 69 of the 653 children

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Table 2. Immunisation and vitamin A at 12 months Full 1-year immunisation

Received vitamin A up to 1 year, n (%) No

Yes

No

25 (83.3)

5 (16.7)

Yes

359 (58.2)

258 (41.8)

(10.6%, 95% CI 8.2 - 12.9%) receiving a vitamin A dose at 5 years.

Twenty-four of 653 RTHCs (3.7%, 95% CI 2.3 - 5.1%) had no recorded doses of vitamin A. Of these 24 children, 23 were fully immunised at 1 year of age (95.8%, 95% CI 87.7 -100%), 22 were fully immunised at 18 months of age (91.7%, 95% CI 80.6 100%) and 11 had received all vaccines in the EPI at 6 years (45.8%, 95% CI 25.8 - 65.7%).

Vitamin A coverage as defined by the DHIS is two doses of vitamin A within 1 year. [9] The percentage of children who received full dosage of vitamin A decreased gradually as the children grew older. Specifically, the percentages of children who had received the full dosage of vitamin A at 12 months, 18 months and 5 years of age were 40.9%, 29.1% and 0.9%, respectively. Over the lifetime of the children in this study population, a total of 2 280 doses of vitamin A were given to all babies during the study period; therefore vitamin A coverage was 34.9%. The average number of doses for each child was three (interquartile range 2 - 5) doses within the age period of 6 60 months.

The children in this study were compared with DHIS data spanning 2004 - 2010, as the study children were born between 2003 and 2005 and the youngest child in the study would have been 5 years of age by 2010.[9] The national and KZN statistics on average vitamin A supplementation as reported by DHIS are shown in Fig. 1.

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40

Table 3. Immunisation and vitamin A at 18 months

No

Yes

No

41 (87.2)

6 (12.8)

Yes

418 (69.7) 182 (30.3)

Of the 923 RTHCs analysed, 647 had information recorded for both immunisation and vitamin A supplementation.

McNemar’s χ2 test was used to test for association between receipt of full immunisation and vitamin A supplemen­ ta­ tion. It showed that receiving full immunisation for 12 months does not necessarily imply that full vitamin A supplementation is received – only 41.8% of those children who were fully immunised in the first 12 months of life received two doses of vitamin A (p<0.05) (Table 2). A similar pattern was seen at 18 months (Table 3), where only 30% of those who were fully immunised had received three vitamin A doses at 6-monthly intervals (p<0.05).

Discussion

Immunisation

30 Coverage (%)

Full 18-months immunisation

35

Received vitamin A up to 18 months, n (%)

The first year immunisation figure of 92.9% coverage is in keeping with the WHO target of coverage above >90%, and exceeds national figures as well as those of the province and many districts. The national immunisation coverage for 2006/2007 was 85.4% and for 2007/2008 was 84.2%.[3] This study population falls under the district of eThekwini and performed above the overall KZN provincial coverage of 78.8%,[3] according to DHIS data.

Data from the current study were compared with national data from this timeframe (2007/2008) as it correlated to the time period when the youngest children in this study were >1 year of age, and was therefore comparable with DHIS data. Although data from this study exceeded national and district averages, it should be borne in mind that DHIS data are not without fault or human error, being dependent on clinic registers and population estimates, and subject to population migration. What is notable is the reported large variations between districts across the country, with some districts reporting coverage figures of 123% at 1 year of age, while others reported figures as low as 31%. [10] What is unique about the data from this study is that it assessed the coverage for immunisations at 6 years of age (i.e. diptheria and tetanus (DT)1 and OPV5) and showed coverage of 48.3% for DT and 48.2% for OPV5.

These data are not collected at a district or national level from registers and therefore

25 20

KZN

15

SA

10 5 0

2004

2005

2006

2007

2008

2009

2010

This study

Fig. 1. Coverage (%) of vitamin A supplementation in KZN and SA compared with this study.

no source data for comparison are available.

One study in the Ga-Rankuwa community (Gauteng Province) found 20% coverage for DT1 and 40% for OPV5 for the year 2007.[2] This study did not explain the difference in the DT1 and OPV5 coverage rates (as one would not expect them to differ), nor did it describe the decline in immunisation programme utili­ sa­­tion beyond the first year of life.

This IVAC study had a lifetime immunisation coverage (up to 5 years, in accordance with EPI definition) of 44%, the decline in which is probably attributable to underutilisation of healthcare facilities in later childhood, as children become more robust with stronger immune systems and less susceptible to life-threatening illness.

Migration of communities and changes in primary caregivers may also be contributory.

The DPT1 - 3 immunisation dropout rate measures the percentage of children who dropped out between the first and the third dose of the DPT-Hib vaccine. This study detected a dropout rate for DPT1 - 3 of 1.2%, lower than the national 3.4% dropout rate for 2007/2008.[10] This shows good utilisation and access to immunisation schedules within the first year of life.

The measles dropout rate of 2.4% is below the overall dropout rate of >5% for the surrounding eThekwini area for 2006/2007.

The poorest-performing province during this timeframe was the Free State, with a dropout rate of 14.7%.[10] However, some districts in the Western Cape performed better than the study population, with rates as low as 0.6% for the same timeframe.[10] There were no measles vaccination mass campaigns during this time to explain an improved immunisation coverage or improved dropout rate.

Vitamin A

The DHIS defines vitamin A coverage as two doses within a 1-year period between ages

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12 and 59 months. As seen in Fig. 1, the coverage rate ranges from 14.4% in KZN and 12.8% nationally in 2004 to 32.8% in KZN and 34.6% nationally in 2010.[9] DHIS data are collected by assessing registers from primary healthcare (PHC) facilities – the numerator is the number of vitamin A doses given to all children aged between 6 and 60 months and the denominator is the population estimate of children aged between 6 and 60 months, according to figures submitted to DHIS from Stats SA. RTHCs are not used in the assessment and the denominator is based on population estimates, so coverage statistics may not be completely accurate. In order to attempt to make the figures comparable we calculated the average coverage for this population (i.e. calculated actual number of doses given to all patients until 5 years of age, divided by the total number of doses they should have received in this timeframe).

The coverage of 34.9% (Fig. 1) across this population was similar to the coverage nationally and in KZN for years 2009 and 2010. We see a low level of coverage in the first few years of implementation, followed by a gradual increase and then a plateau from 2009, with an overall suboptimal uptake of the programme. This is surprising given the resources placed on education and promotion of the vitamin A supplementation programme.[11] Tables 2 and 3 show that there was no corre­ lation between those children who were fully immunised and vitamin A supplementation, indicating a weakness in our vitamin A supple­ mentation programme, despite parents making use of healthcare facilities.

The 24 children who received no vitamin A doses had higher immunisation levels than the general population, indicating that the lack of recorded vitamin A doses was not an indicator of decreased use of the healthcare system.

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Possible explanations for this discrepancy include the difference in timing and intervals between the vaccination schedule and vitamin A administration, as well as a possible lack of education and drive behind the vitamin A campaign.

The sobering findings of low coverage with vitamin A capsule supplementation in an area with a health system clearly capable of delivering vaccines suggests that there are factors other than health system capabilities at play. While this study is not able to unravel the causes for this low coverage, the data suggest a need for further exploration; we should go back to the evidence base and reassure ourselves that blanket vitamin A supplementation, in SAâ&#x20AC;&#x2122;s current context, will save lives, and if this is true, urgently implement strategies to improve delivery. However, if, as has been suggested by several groups in the last few years, high-dose vitamin A supplementation to young children does not save lives to the extent that it was originally purported to, then we need a rethink.[12-14] Mason et al.[12] point out that the studies that informed the current WHO guidelines were all conducted over 10 - 20 years ago in a world that was very different to the world of today: many more vaccines are available, diarrhoea and measles (the infections that vitamin A targeted) rates have diminished, and many foods are fortified with vitamin A.[13,14] The only study reported recently is a very large randomised control trial (RCT) conducted in India with over 1 million children, which showed no effect on mortality.[15] More concerning is a very recent report from Guinea-Bissau[16] of an RCT testing high-dose vitamin A or placebo given in conjunction with vaccines in children aged 6 - 23 months, which showed that vitamin A supplementation had no overall effect on mortality. Furthermore, in disaggregated data, boys tended to have an increase in mortality suggesting again the need for rethinking the current vitamin A capsule distribution policy.

Evidence is mounting for the following: vitamin A supplementation may no longer be a child survival strategy; and use of high pharmacological doses to correct any vitamin A deficiency may actually be dangerous. Therefore, food-based solutions seem more sensible and should be encouraged. In an impoverished community in the Northern Cape with poor anthropometric status (36.9% stunting), and where liver is routinely consumed by children and adults, the mean vitamin A intake in children 24 - 59 months of age was 537 Îźg.[17] This far exceeds the estimated average requirement for preschool children and suggests that food-based approaches are possible. It also suggests that caution needs to be taken in widespread roll-out of the IVAC distribution programme, as children who are vitamin A replete could be getting far more than they need.

Study limitations

Data were collected retrospectively and accuracy of documentation could not be assessed. Furthermore, coverage may be underestimated owing to doses not being accurately recorded, and therapeutic vitamin A doses given in hospital may not have been recorded.

The data analysed were routinely collected and there is therefore a possibility of some inaccuracies in the data.

Owing to having children whose birth year spanned across 3 years and analysing the RTHCs in retrospect, this study was unable to break down the coverage for vitamin A in discrete timeframes for comparison with national data for one specific year. The initial RTHCs did not have the vitamin A data page copied, so vitamin A coverage was actually only assessed in the latter 70% of the cohort. There were however no special vitamin A mass campaigns or stock-outs during this study period, which would have lead to differential coverage.

This study did not look at possible socioeconomic reasons for vitamin A and immunisation success or failure. This would be beneficial, and is a suggested research avenue for further studies.

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Conclusion

This study population showed good immunisation coverage compared with national and district data. Although the coverage of vitamin A supplementation was low, it was in line with national data, showing a relatively poor uptake of the vitamin A supplementation programme.

There was no correlation between full immunisation status and high coverage of vitamin A supplementation, suggesting that good use of primary healthcare facilities for immunisation does not necessarily imply good uptake of the vitamin A supplementation programme. A failing vitamin A supplementation programme warrants a thorough evaluation as to the possible reasons for failure; this could be an opportune time to assess whether SA still needs an untargeted vitamin A capsule distribution programme. We believe the time has come to reconsider the value of blanket distribution of vitamin A capsules and rather consider targeted vitamin A for specific situations.

Acknowledgements. The authors acknowledge Prof. Meera Chhagan for providing access to the Asenze study data and for her contribution to the study design of this project. The authors would like to thank the staff of Asenze for their assistance as well as the participants of the Asenze study.

We also acknowledge the local Health Committee and community health centre for their support.

References 1. World Health Organization (WHO). Review of National Immunization Coverage 1980 - 2006: South Africa. Geneva: WHO, 2007.

2. Wright S, Maja T, Furaha S. The impact of mothersâ&#x20AC;&#x2122; knowledge on the immunization of children younger than five in Ga-Rankuwa, South Africa. Afr J Nurs Midwifery 2011;13(2):29-42.

3. Day C, Barron P, Massyn N, Padarath A, English R. The District Health Barometer 2010/2011. Johannesburg: Health Systems Trust, 2011.

4. Black RE, Allen LH, Bhutta ZA, et al. Maternal and child undernutrition: Global and regional exposures and health consequences. Lancet 2008;371(9608):243260. [http://dx.doi.org/10.1016/S0140-6736(07)61690-0] 5. Mayo-Wilson E, Imdad A, Herzer K, Yakoob MY, Bhutta ZA. Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: Systematic review and meta-analysis. BMJ 2011;343:d5094. [http:// dx.doi.org/10.1136/bmj.d5094] 6. World Health Organization (WHO). Guideline: Vitamin A Supplementation in Infants and Children 6 - 59 months. Geneva: WHO, 2011.

7. Chhagan MK, Mellins AM, Kauchali S, et al. Mental health disorders among caregivers of preschool children in the Asenze Study in KwaZulu-Natal, South Africa. Matern Child Health J 2014;18(1):191-199. [http://dx.doi.org/10.1007/ s10995-013-1254-5] 8. Uwemedimo O, Arpadi SM, Chhagan MK, et al. Compliance with referrals for non-acute child health conditions: Evidence from the longitudinal ASENZE study in KwaZulu-Natal, South Africa. BMC Health Serv Res 2014;14:242. [http://dx.doi.org/10.1186/1472-6963-14-242] 9. National Department of Health. District Health Information System Database. http://indicators.hst.org.za/healthstats/241/data (accessed November 2014).

10. Ford-Ngomane T. Health Barometer Report 2007/2008. Output Indicators, Health Systems Trust. Johannesburg; Health Systems Trust, 2009.

11. Department of Health, South Africa. Roadmap for Nutrition in South Africa 2012 - 2016. www.doh.gov.za (accessed November 2013).

12. Mason J, Greiner T, Shrimpton R, Sanders D, Yukich J. Vitamin A policies need rethinking. Int J Epidemiol 2014;Oct:1-10, advance access publication. [http:// dx.doi.org/10.1093/ije/dyu194] 13. Kapil U. Time to stop giving indiscriminate massive doses of synthetic vitamin A to Indian children. Public Health Nutr 2009;12(2):285-286. [http://dx.doi. org/10.1017/S1368980008004448] 14. Kapil U, Sachdev HP. Universal vitamin A supplementation programme in India: The need for a re-look. Natl Med J India 2010;23(5):257-260.

15. Awasthi S, Peto R, Read S, et al. Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial. Lancet 2013;381(9876):1469-1476. [http://dx.doi. org/10.1016/S0140-6736(12)62125-4] 16. Fisker AB, Bale C, Rodrigues A, et al. High-dose vitamin A with vaccination after 6 months of age: A randomized trial. Pediatrics 2014;134(3):e739-748. [http://dx.doi.org/10.1542/peds.2014-0550] 17. Nel J, van Stuijvenberg ME, Schoeman SE, Dhansay MA, du Plessis LM. Liver intake in 24 - 59 month-old children from an impoverished South African community provides enough vitamin A to meet requirements. Public Health Nutr 2014;17(12):2798-2805. [http://dx.doi.org/10.1017/S1368980013003212]

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ARTICLE

A retrospective review of the transfer of critically ill children to tertiary care in KwaZulu-Natal Province, South Africa C Royal,1 MB ChB, FC Paed; N H McKerrow,1,2 MB ChB, BA, DCH (SA), FC Paed, MMed (Paed), PG Dip (Int Res Ethics) Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, Faculty of Health Sciences, University of KwaZuluNatal, Durban, South Africa 2 Department of Health, KwaZulu-Natal, South Africa 1

Corresponding author: C Royal (candiceroyal@gmail.com) Background. Obtaining care for an acutely ill child in specialised paediatric services relies on referral from lower-level facilities. In South Africa, it is common practice for acutely ill children to be transported far distances by non-specialist teams with limited equipment, knowledge and skills.

Objectives. To describe the transfer of these children and to determine whether they deteriorate from the time of referral to the time of arrival at a tertiary centre. Furthermore, we sought to identify modifiable factors that might improve outcomes during resuscitation and transfer.

Methods. The study was a retrospective review of emergency referrals of children aged 1 month - 12 years to Grey’s Hospital paediatric ward or paediatric intensive care unit (PICU), from lower-level facilities in KwaZulu-Natal between January and June 2012. In conjunction with an assessment by the receiving clinician at Grey’s Hospital, Triage Early Warning Signs (TEWS) scores were obtained during telephonic referral and compared with the TEWS score on arrival in order to determine if a deterioration had occurred.

Results. A total of 57 PICU referrals and 79 ward referrals were analysed. The mortality rate prior to transportation was 8.8%. Mean transfer distance was 131 km and mean transfer time 9 hours. Advanced life support teams undertook transportation in 76.7% of PICU and 25% of ward transfers and few adverse events were reported in transfer logs. However, 31.5% of PICU and 11.3% of ward referrals required immediate resuscitation on arrival.

When the TEWS scoring system was applied 78.5% of PICU and 30.4% of ward referrals fell into the ‘very urgent’ and ‘emergency’ categories.

Conclusion. Pretransport and in-transit care failed to stabilise children and this may reflect lack of skill of attending healthcare workers, transport delays or illness progression. Interventions to improve resuscitation and transfer are needed, and the use of retrieval teams should be investigated.

S Afr J Child Health 2015;9(4):112-118. DOI:10.7196/SAJCH.2015.v9i4.913

The centralisation of specialised services such as paediatric intensive care units (PICUs) relies on the support of a functional peripheral health service and appropriate referral system. In this context, the role of these peripheral services is the early recognition, stabilisation and safe transfer of critically ill children to the centralised service. The South African (SA) experience suggests that the peripheral health service has limited capacity[1] to manage an acutely ill child, as evidenced by 34% mortality in children within the first 24 hours of admission to a health facility.[2] Children are referred to higher-level facilities to access the skills, know­ ledge and resources needed to make a diagnosis or provide treatment.

The practice of centralising paediatric intensive care services, specifi­ cally, has been associated with lower mortality rates and costs.[3-6] These intensive care units are able to provide high-quality care due to their familiarity with the management of seriously ill children.[7] Children admitted to PICUs in SA have been shown to differ substantially from those in developed countries, tending to be younger and requiring management of infective illnesses.[8,9] Late presentation and delayed referral of acutely ill children contribute to an increased disease severity at admission.[2] Furthermore, it is common practice for acutely ill children to be transported far distances by non-specialist teams with limited equipment, knowledge and skills.

The pathways to care study in Cape Town evaluated 285 patients over 1 year from illness onset to PICU admission.[10] Shortfalls in care were identified in 74% of cases. These shortfalls were grouped into four categories: identification of the critically ill child; resuscitation; transfer; and ICU access/flow management.

Walls et al.’s[11] experience in Washington DC showed that 22% of paediatric patients referred from community hospitals to a central 112

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teaching hospital received suboptimal care prior to transport.

Hatherill et al.[12] reported a high incidence of transfer-related adverse events during transfers to Cape Town’s Red Cross War Memorial Children’s Hospital PICU, as did Goh et al.[6] in Malayasia.

Our objective was to describe the journey of a critically ill child from referral to arrival at tertiary care, and to identify modifiable factors that could improve outcomes during the resuscitation and transfer process.

Methods

The study was a retrospective review of the medical records of children referred as emergency cases to Grey’s Hospital, Pietermaritzburg, January - June 2012. Ethical approval was obtained from the University of KwaZulu-Natal Biomedical Research Ethics Committee.

Inclusion criteria were: (i) age 1 month - 12 completed years; (ii) emergency referrals to the Paediatric Department of Grey’s Hospital; and (iii) children referred to the paediatric medical service.

Exclusion criteria were: (i) neonates (<28 days); (ii) elective referrals; (iii) internal referrals from within Grey’s Hospital; and (iv) children referred to the surgical service.

All requests for transfer to the Paediatric Department in Grey’s Hospital are assessed by a registrar or medical officer, recorded in a call register and then discussed with a consultant paediatrician prior to the acceptance or refusal of the request. The call register is a standardised, comprehensive questionnaire that covers resuscitation and vital signs, and prompts advice for further resuscitation (Appendix 1). The register was reviewed to identify cases for inclusion in the study. The clinical records were retrieved and data extracted from the case notes, transfer logs and referral letters. SPSS version 18 (IBM, USA) was used for statistical analysis.

NOVEMBER 2015 Vol. 9 No. 4

Two methods were used to assess the outcome of patient transfers: • Method 1: The clinical assessment of the receiving clinician on arrival of the child. Children were assessed as stable or unstable.

They were deemed unstable on arrival if they required any one of the following: intubation and ventilation, correction of shock, abortion of seizures or the correction of hypoglycaemia (whole blood glucose <3 mmol/L) or hypothermia (axillary temperature <35°C).

• Method 2: Each child was assigned a triage category by identifying clinical signs and calculating the Triage Early Warning Signs (TEWS) score at the time of referral and on arrival (Appendix 2).

TEWS is a composite, age-appropriate physiological scoring system that is the basis of the SA Triage Scale.[13] The use of TEWS has been validated in the Western Cape as a sensitive and specific method of identifying potentially seriously ill children.[13,14] The process of triaging a patient telephonically requires a rapid, efficient assessment, akin to the triaging of a patient in the accident and emergency department. TEWS scoring provides a rapid, validated assessment of patient stability with data that are readily available retrospectively.

Based on the TEWS scores, patients were grouped into emergency, very urgent, urgent and routine priority categories. Children who had a documented emergency sign such as active convulsions or oxygen saturations <92% were placed in the emergency category.

Children who arrived on a ventilator were not scored.

The Wilcoxon signed rank test was used to determine the correlation of patient diagnosis by referring and receiving clinicians. The t-test was used to evaluate a change in TEWS scores between the time of referral and time of arrival.

Results

During the 6-month study period, 229 children were accepted as acute referrals to Grey’s Hospital. Of these, 93 children were excluded from the study – 31 because their primary problem was surgical and a further 62 due to missing or incomplete clinical records.

A total of 136 children were enrolled in the study – 57 acute referrals to the PICU and 79 referrals to the paediatric wards. Twelve of the PICU referrals demised prior to transfer and 124 were admitted to Grey’s Hospital. A profile of these children is presented in Table 1.

Children admitted to the PICU were of a younger median age than those admitted to the wards. The gender split was similar within the two groups. Children admitted to the PICU were more likely to be of normal weight and unknown HIV status, while children referred to the wards were likely to have had a longer pretransfer stay and thus opportunity for their HIV status to be determined. HIV infection is not an exclusion criterion for admission to the PICU. Children referred to both the PICU and the paediatric wards generally had more than one problem identified by the referring doctor. The most common problem referred to the PICU was pneumonia (46.9%), followed by gastrointestinal problems (18.1%), which was diarrhoeal disease in 17% of the cases, and to the paediatric wards was a neurological problem (32.8%) (Table 2). Seizures were the most common primary problem identified at the time of referral to the wards (12.7%). The Wilcoxon signed rank test revealed no significant differences between the primary problem identified at the referring and referral centers (PICU p=0.108; wards p=0.789).

Indication for referral to the PICU was for treatment in 97.8% of cases, 51.1% specifically for ventilation. A need for radiological investigations to reach a diagnosis was the indication for referral for the remaining case. In contrast, the indication given by the referring centre for children referred to the paediatric wards was for assistance in making a diagnosis in all 79 cases. Further investigation was required in 58.2% of the children, while 41.8% required a specialist opinion.

The referring clinician was an intern, community service officer or medical officer in 78.9% of PICU referrals and 94% of ward referrals.

For 20% of referrals to the PICU and 18% to the wards, transfer SAJCH

followed on-site assessment by a paediatrician. Prior to transportation, 8.8% of children demised; all of these had been referred to the PICU. Distances between facilities relied on Department of Health data on the distance of each facility to its head office, which is 4 km from Grey’s Hospital. The distance travelled averaged 131.5 km, with a range of 4.4 km to 424.9 km and a median of 110 km. The total time to transfer a child, from acceptance for transfer and arrival at Grey’s Hospital, is presented in Table 3. Of note is that the mean transfer time to the PICU was longer than to the wards.

Characteristics of the transfers are presented in Table 4. All transfers to the wards and 92.5% of PICU transfers were undertaken by road. Advanced life support (ALS) teams were used for 76.7% of PICU and 25% of ward transfers.

Table 1. Population characteristics PICU (n=45)

Wards (n=79)

Age (months), median

6

19

Gender (male), n (%)

23 (51.1)

46 (58.2)

Normal, n (%)

30 (73.2)

33 (50.0)

Underweight for age, n (%)

11 (26.8)

32 (48.5)

Overweight for age, n (%)

0 (0)

1 (1.5)

Infected, , n (%)

4 (9.3)

15 (21.1)

Uninfected, n (%)

11 (25.6)

28 (39.4)

Unknown, n (%)

28 (65.1)

28 (39.4)

Nutritional status (n=106)

HIV status (n=114)

Table 2. Referral diagnosis Patient problem

PICU (n=88), n (%)

Wards (n=131), n (%)

Respiratory

41 (46.9)

25 (19.1)

Neurological

9 (10.2)

43 (32.8)

Cardiac

4 (4.5)

14 (10.7)

Gastrointestinal

16 (18.1)

14 (10.7)

Renal

0

10 (7.6)

Haematological

0

4 (3.0)

Metabolic

1 (1.1)

0

Infective

0

15 (11.5)

Other

17 (19.3)

6 (4.6)

Table 3. Transfer times and distances PICU

Wards

Range

3.80 - 18.75

1.5 - 25.5

Mean

9.5

8.6

Mode

8.6

4.0

Range

4.4 - 424.9

4.4 - 271.0

Mean

130

133

Median

110

110

Transfer time (h)

Transfer distance (km)

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113

No children being transported to the wards experienced problems in transit, compared with 15.5% of those destined for the PICU. The majority of these problems related to modalities of care. Children were ventilated during transfer in 28% of referrals to PICU and complications were experienced en route in 12.5%.

At the time of referral request, 82.4% of children referred to the PICU were unstable compared with 15% referred to the wards.

Over half of the children required respiratory support while 24.4% required correction of shock. This resuscitation appears to have been short-lived, as on arrival 78.5% of children admitted to the PICU and 30.4% to the wards fell into the ‘very urgent’ and ‘emergency’ categories when TEWS was applied. A comparison of these scores reveals no statistically significant difference (PICU p=0.202; wards p=1.810). The mean change in TEWS was –0.52 for the PICU and –0.6 for ward referrals. Table 5 depicts the TEWS score at time of requesting transfer, subsequent resuscitation prior to transfer and the TEWS score on arrival at Grey’s Hospital.

The subjective assessment on arrival by the receiving clinician revealed that 31.5% and 11.3% of referrals to the PICU and the wards, respectively, required immediate resuscitation. On arrival at Grey’s Hospital, 14% of children referred to the PICU required intubation Table 4. Characteristics of transfers PICU

Wards

Road

92.5

100

Air

7.5

0

ALS

76.7

25.0

Basic life support

23.3

75.0

Nil

38 (84.4)

79 (100)

Required intubation

2 (4.4)

0

Lost intravascular access

3 (6.7)

0

Seizures in transit

1 (2.2)

0

Intercostal drain dislodged

1 (2.2)

0

Method of transportation (%)

Expertise undertaking transportation (%)

Problems in transit, n (%)

and ventilation, 17.5% were assessed to be shocked and 5% had no intravenous access.

Discussion

Every day, children are referred from lower-level facilities to specialised paediatric services, yet little is known about the effect of such referrals on the acutely ill child in developing countries. Evidence from the developed world confirms the value of a specialised transfer process that includes the appropriate pre- and intratransfer care provided by specialised staff.[15,16] This study was conducted in a health service without specialised transfer teams and in a context characterised by unstable children, high pretransfer mortality, prolonged transfer time and high rates of adverse events in transit.

Pretransport care

Pretransport care is essential to ensuring a safe paediatric referral.

The 8.8% of referrals who died before transfer is a concern. These children had a similar profile to those who were transferred. Most had pneumonia and a third of the deaths occurred at the time of intubation.

These deaths could be the result of multiple factors, including: advanced disease, poor care and limited skills at the referring facility, especially in paediatric intubation; or transport delays. At the time of this study the inpatient death rate for children <5 years was 5.2% in KwaZuluNatal. [17] The discrepancy between these figures underlines that the children who are being referred represent an at-risk group.

Resuscitation at the referring facility was required in 70 (51%) of all referrals, and 34 children, three of whom were initially referred to the paediatric wards, required intubation and ventilation prior to transfer. This failure of referring clinicians to appreciate the unstable condition of their patient reflects the lack of confidence and competencies in the ability to care for critically ill children at a district facility. These concerns have been cited in the South African study by Nkabinda et al.,[18] who reviewed community service medical officers’ experience of working in district hospitals in KwaZulu-Natal and identified paediatric resuscitation and intubation as a skill domain in which confidence was lacking. We propose interventions to improve resuscitation and intubation skills in the periphery.

Respiratory problems accounted for 46.9% of referrals to the PICU. This finding is in line with the developed world and reiterates the need for pretransport care to be undertaken by those experienced in paediatric ventilation.[19] Only 20% of PICU referrals had been seen by a paedia­tri­ cian. Incentives to attract specialists to outlying areas need to be explored.

Table 5. TEWS and resuscitation at referring centre PICU

Wards

TEWS at time of referral

TEWS on arrival

TEWS at time of referral TEWS on arrival

Mean (SD)

6.43 (1.70)

5.91 (2.15)

4.20 (1.91)

3.6 (2.29)

Median

10

6

4

3

Routine, %

5.4

7.1

24.6

42.0

Urgent, %

13.5

14.3

35.1

27.5

Very urgent, %

24.3

32.1

21.1

11.6

Emergency, %

56.8

46.4

19.3

18.8

TEWS score

Resuscitation at referring centre, n (%) Nil

9 (20.1)

67 (84.8)

Ventilation

31 (56.3)

3 (3.7)

Correction of shock

11 (24.4)

3 (3.7)

Other

5 (11.1)

6 (7.5)

114

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NOVEMBER 2015 Vol. 9 No. 4

In-transit care

Transportation occurred almost exclusively by road and time delays were a major problem, with a mean delay of 9 hours from time of referral to time of arrival. This may be attributed to the lack of availability of Emergency Medical Service crews, especially those with ALS skills, as well as ambulances with appropriate equipment such as transport ventilators. Transfer distances occurred over relatively long distances, with a mean transfer distance for PICU referrals of 130 km in contrast to 31 km reported in England and Wales.[15] Staff with skills limited to basic life support were responsible for in-transit care for 75% of ward transfers and 25% of PICU transfers.

A study in the UK reported 81% use of retrieval teams for PICU transfers.[15] Although this figure is not dissimilar to the use of ALS crews used in our study, it must be recognised that the UK retrieval teams include a doctor proficient in the care of critically ill paediatric patients, a skills set that an ALS-trained paramedic does not necessarily have.

On review of transfer logs, 15.6% of PICU referrals reported problems during transportation although no problems were reported from the ward referrals. International studies vary with regard to the incidence of adverse events in transfer, from 87.5% with nonspecialised teams[6] to 4% with retrieval teams.[15] The paucity of adverse events reported coupled with the high proportion of both PICU and ward patients falling into the emergency and very urgent groups by TEWS scoring suggests a lack of insight in those undertaking these transfers.

Outcome of the referral

Although resuscitation occurred at referring facilities, on arrival at Grey’s Hospital the majority of children referred to the PICU and almost a third referred to the wards still fell into the very urgent and emergency categories of triage acuity. Additionally, 31.5% of children referred to the PICU and 11.3% referred to the wards required immediate resuscitation. Children’s vital signs did not improve toward physiological ranges during referral as represented by the lack of statistically significant difference between TEWs at referral and on arrival. Pretransport and in-transit care failed to stabilise children and this may reflect lack of skill of attending healthcare workers, transport delays or illness progression.

Study limitations

As this was a retrospective study, incomplete clinical records and inadequate documentation was a limitation. This is notable in that not all children could be ascribed a TEWS score at base and/or on arrival owing to a lack of recording or measuring of vital signs.

Recommendations

From this study it is apparent that paediatric referrals are hampered by time delays and that pretransport and in-transit care is suboptimal. A need for improved competencies in the management of the acutely ill child at district level hospitals is highlighted. Further research is required to assess the feasibility and the potential benefit of the institution of retrieval teams in a developing world setting, particularly for the transfer of patients to the PICU.

Conclusion

In SA’s current public health system, paediatric specialist care and intensive care specifically is centralised to tertiary institutions, with a resultant reliance on a referral system. The drainage area of tertiary facilities varies but often encompasses multiple district facilities with a large geographic distribution. Attempts to bring specialist paediatric services to district-level facilities are underway but are

SAJCH

unlikely to be realised in the short term. Moreover, critical care in a tertiary PICU remains preferable. Child Healthcare Problem Identification Programme (Child PIP) data has repeatedly identified lack of access to high care or ICU beds as a modifiable factor in child deaths. Advances such as telemedicine have a role in connecting district facilities with specialists, but are less useful in the care and stabilisation of an acutely ill child.

This study has shown that paediatric referrals in KwaZulu-Natal are both inefficient and take place over long distances. Acutely ill children are not successfully stabilised at base or during transfer, resulting in a higher morbidity and mortality than in the developed world. The use of retrieval teams requires urgent investigation if there is to be an improvement in paediatric care and a reduction in childhood mortality.

References 1. Department of Health, South Africa. The First Triennial Report of the Committee on Morbidity and Mortality in Children under 5 years (CoMMiC), April 2011. www.health.gov.za/docs/reports/2011/morbreport.pdf (accessed on 20 February 2014).

2. Stephen CR, Bamford LJ, Patrick ME, Wittenberg DF, eds. Saving Children 2009: Five years of Data. A sixth survey of child healthcare in South Africa.

Pretoria: Tshepesa Press, MRC, CDC, 2009.

3. Pearson G, Shann F, Barry P, et al. Should paediatric intensive care be centralized? Trent versus Victoria. Lancet 1997;349(9060):1213-1217. [http:// dx.doi.org/10.1016/S0140-6736(96)12396-5] 4. Pollack MM, Alexander SR, Clarke N, Ruttimann UE, Tesselaar HM. Improved outcomes from tertiary center paediatric intensive care: A statewide comparison of tertiary and nontertiary care facilities. Crit Care Med 1991;19(2):150-159. [http://dx.doi.org/10.1097/00003246-199102000-00007 ] 5. Edwards ED, Fardy CH. Which children need to be transferred to the paediatric intensive care unit? Paediatr Child Health 2007;17(7):295-299. [http://dx.doi. org/10.1016/j.paed.2007.04.002 ] 6. Goh AY, Abdel-Latif Mel A, Lum LC, Abu-Bakar MN. Outcome of children with different accessibility to tertiary pediatric intensive care in a developing country--a prospective cohort study. Intensive Care Med 2003;29(1):97-102.

7. Bennett NR. Transfer of the critically ill child. Current Paediatrics 1995;5(1):4-9.

8. Morrow BM, Argent AC, Jeena PM, Green RJ. Guidelines for the diagnosis, treatment and prevention of paediatric ventilator-associated pneumonia. S Afr Med J 2009;99(4):255-267.

9. Delport SD, Brisley T. Aetiology and outcome of severe community-acquired pneumonia in children admitted to a paediatric intensive care unit. S Afr Med J 2002, 92(11):907-911.

10. Hodkinson P, Argent A, Wallis L. Paediatric emergency and critical care: Learning points and possible interventions from a longitudinal study of paediatric emergency care and referral pathways. www.eci-sa.org/faculty/ hodkinson/pathways-to-care (accessed 20 January 2015).

11. Walls TA, Chamberlain JM, Strohm-Faber J, Klein BL. Improving pretransport care of emergency pediatric patients: An assessment of referring hospital care. Pediatr Emerg Care 2010;26(8):567-570. [http://dx.doi.org/10.1097/ PEC.0b013e3181ea71f8] 12. Hatherill M, Waggie Z, Reynolds L, Argent A. Transport of critically ill children in a resource-limited setting. Intensive Care Med 2003;29(9):1547-1554. [http://dx.doi.org/10.1007/s00134-003-1888-7] 13. Twomey M, Cheema B, Buys H, et al. Vital signs for children at triage: A multicenter validation of the revised South African Triage Scale (SATS) for children. S Afr Med J 2013;103(5):304-308. [http://dx.doi.org/10.7196/ SAMJ.6877] 14. Cheema B, Stephen C, Westwood A. Paediatric triage in South Africa. S Afr J Child Health 2013;7(2):43-45. [http://dx.doi.org/10.7196/sajch.585] 15. Ramnarayan P, Thiru K, Parslow RC, Harrison DA, Draper ES, Rowan KM. Effects of specialist retrieval teams on outcomes in children admitted to paediatric intensive care units in England and Wales: A retrospective cohort study. Lancet 2010;376(9742):698-704. [http://dx.doi.org/10.1016/S01406736(10)61113-0] 16. Stroud MH, Tautman MS, Meyer K, et al. Pediatric and neonatal interfacility transportation: Results from a national consensus conference. Pediatrics 2013;132(2):359-366. [http://dx.doi.org/10.1542/peds.2013-0529] 17. District Health Information System (DHIS) Database. National Department of Health. http://hisp.org/ (accessed September 2014).

18. Nkabinda TC, Ross A, Reid S, Nkwanyana NM. Internship training adequately prepares South African medical graduates for community service - with some important exceptions. S Afr Med J 2013;103(12): 930-934. [http://dx.doi. org/10.7196/SAMJ.6702] 19. Ajizian SJ, Nakagawa TA. Interfacility transfer of the critically ill pediatric patient.

Chest 2007;132(4):1361-1367. [http://dx.doi.org/10.1378/chest.07-0222]

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Appendix 1. Paediatric monitoring and handover sheet Health: KwaZulu-Natal

Form Reference Number: Paed/29

Monitoring & handover sheet for paediatric transfers

Date:

Time:

(to be completed by referring and receiving doctors starting at time of referral)

Patient Name: 1)

Clinical Records: Paediatrics

Date of Birth:

DoA:

DoT:

REFERRING AND RECEIVING INFORMATION

Hospital

Ward

Doctor

Referring

Designation

Contact number

Junior: Senior:

Receiving

Junior: Senior:

2)

CAREGIVER INFORMATION

Accompanying caregiver: 3)

Normal

UWFA

Clinical

M-K

Exposed

Infected

No result

Stage I

Stage II

Stage III

Stage IV

Current

Ever

CURRENT CONDITION (CIRCLE APPLICABLE)

Vitals

Unknown

Weight:

_____kg

Not tested (but indicated) Not staged (but indicated)

Never (but indicated)

Not tested (not indicated) Not staged (not indicated)

Never (not indicated)

Unknown Unknown Unknown

TIME:

Temp:

Airway

PR:

RR:

Sats: Normal

Critical

Narrow

Breathing

Needs IPPV

Needs oxygen

Circulation

Shock (Cap refill > 3s) Unconscious

Convulsions

In hospital

Before arrival

Past

Never

Dehydration

10%

5%

Oedema

Normal

Consciousness (AVPU)

Infection

Hyperventilation

Normal

Hypovolaemia

Hypervolaemia

Normal

Response to Pain

Response to Voice

Alert

“Red”

“Yellow”

SIRS (“toxic shock”)

Needs IV agent

IMCI classification

“Green” Needs oral agent

No

SIGNIFICANT BIOCHEMICAL PROBLEMS (CIRCLE APPLICABLE)

Hypoxia (Sats in air____) 7)

Kwashiorkor

Negative

ARV

6)

Marasmus

HIV

Laboratory test

5)

Contact number:

NUTRITION

OWFA 4)

Relationship:

Hypoglycaemia

pH < 7.2

K+ < 2.0

K+> 6

Na+<120

Na+> 150

Albumin < 20

REASON FOR TRANSFER OR NON-ACCEPTANCE

Accepted(circle applicable):

YES

NO

ICD 10

Main diagnosis / problem: Other diagnoses / problems: Prognosis for survival:

Excellent

Good

Indeterminate

Guarded

Prognosis for normal outcome:

Excellent

Good

Indeterminate

Guarded

Main reason for transfer / non acceptance: 8)

URGENT MANAGEMENT

Specific Rx (circle or state) Airway Breathing Circulation/Shock Dehydration Consciousness Infection 9)

Other Rx

ETT / oral airway / none

Oxygen delivery:

IPPV / Bag / Spontaneous

Oxygen monitoring:

Intra-osseous / peripheral IV / central IV / none

Volume expand:

IV / Oral

½ DD / ORS:

Protect airway:

Coma position:

IV antibiotic stat:

Steroid / antipyretic:

PAIN ASSESSMENT

No pain Analgesia plan:

Mild pain A SAJCH

Moderate pain MONTH 20XX Vol. X No. X

Severe pain

Appendix 1 (cont.). Paediatric monitoring and handover sheet Health: KwaZulu-Natal

Form Reference Number: Paed/08

Clinical Records: Paediatrics

10) ONGOING MONITORING AND RESPONSIBILITY WHILE AWAITING EMRS

Name

Rank

Contact number

Doctor Nurse Time

Heart rate

Temp

Resp rate

Sats

O2 device

Fi O2

IV site secure

IV control device

IV rate

AVPU score

BP

Gluc.

Sign

On transfer to ambulance

11) PROBLEMS ARISING AND THEIR PLANS WHILE AWAITING EMRS

Problem

Plan

Discussed with

Verified by

12) PATIENT TRANSPORT INFORMATION Time accepted

Receiving Hospital

Doctor

Rank

Telephone

Plan

Sign

Time EMRS called

EMRS Ops Centre

Operator

Designation

Telephone

Plan

Sign

Time of EMRS arrival

Ambulance type

Paramedic

Designation

Telephone

Plan

Sign

Time of departure, AND receiving hospital notified

Receiving Hospital

Doctor

Rank

Telephone

Plan

Sign

Time of arrival at receiving hospital

Receiving Ward

Doctor

Rank

Telephone

Plan

Sign

13) PATIENT HANDOVER Handed over by Time

Handover Point

Name

Received by

Designation

Name

Designation

Sign

Referring hospital to EMRS EMRS to receiving hospital 14) CAREGIVER PLAN Name

Relationship

Contact number

Breastfeeding

Well/sick

Plan for transport to receiving hospital

y/n 15) OUTCOME Alive & not transferred

Died & not transferred

Died awaiting EMRS

Died in transit

Died within 24 hours of transfer

Died beyond 24 hours of transfer

Alive and transferred back to referring hospital

NB: this does not replace the usual referral letter containing ALL relevant SAJCH MONTH 20XX Vol. Xclinical No. Xdetails; A use the ‘Paediatric Discharge/Referral Letter’ proforma 2

2007/06/26

Appendix 1 TEWS Appendix 2. TEWS scoring

118

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NOVEMBER 2015 Vol. 9 No. 4

ARTICLE

Acute pain management in children with sickle cell anaemia during emergency admission to a teaching hospital in Lagos, Nigeria K A Oshikoya,1 MBBS, MSc, PhD; B Edun,2 BSc; I A Oreagba,2 BPharm, MSc, PhD 1 2

harmacology Department, Lagos State University College of Medicine, Ikeja, Lagos, Nigeria P Pharmacology, Therapeutics and Toxicology Department, College of Medicine University of Lagos, Idiaraba, Lagos, Nigeria

Corresponding author: K A Oshikoya (kazeemoshikoya@ymail.com) Background. Optimal pain management in children with sickle cell anaemia (SCA) begins with accurate and thorough pain assessment.

However, little or no evidence of this practice exists among SCA patients in developing countries.

Objectives. To evaluate pain management in children with SCA during emergency admission.

Methods. Children with SCA who were â&#x2030;¤12 years old, on admission for a painful crisis and who were not using herbal remedies for pain relief, were prospectively studied at the Lagos University Teaching Hospital (LUTH) over a period of 1 year. A proforma data collection form was used to obtain information about the demographics of the patients and their parents, as well as pain score, and non-pharmacological and pharmacological treatments documented in the patientsâ&#x20AC;&#x2122; case files. Pain was assessed for each patient using the Wong-Baker Faces Pain Rating Scale.

Results. The median age and weight of the patients were 4 years and 16 kg, respectively. Pain assessment by the physicians was documented in 10 (8.3%) patients. However, among those assessed for pain by the researchers, 90 (75%) had a moderate pain score of 5 - 8. Fluid therapy (n=110, 91.7%) and prayers (n=120, 100%) were the most common non-pharmacological therapies administered to the patients while admitted. Analgesics, either in combinations or as a single medicine, were administered to 100 (83.3%) patients. Paracetamol (n=90, 75%) and pentazocine (n=80, 66.7%) were the most frequently used analgesics. The dosage of the analgesics prescribed did not conform to the recommendations of the World Health Organization (WHO).

Conclusion. The SCA children in this study were managed sub-optimally with analgesics. Pain management among this group of children did not fully conform to the guidelines of the WHO. S Afr J Child Health 2015;9(4):119-123. DOI:10.7196/SAJCH.2015.v9i4.968

Sickle cell anaemia (SCA) is an incurable genetic disorder widespread in sub-Saharan Africa and among African descendants worldwide. It is an inherited disorder that is characterised by genetic abnormalities affecting β-haemoglobin, resulting in polymerisation and sickling of the red blood cells.[1] According to the World Health Organization (WHO), over 300 000 babies with severe haemoglobin disorders are born each year, with Nigeria accounting for about three-quarters of these births.[2] Sixty percent of these children die as infants.

Most SCA children are ambulatory and often enter the acute inpatient system for debilitating events such as crises or acute pain.

Crippling pain is the most frequent symptom associated with SCA.[3] It can be unrelenting, unpredictable and vary from acute to chronic or mixed. Acute pain is the leading cause of emergency department visits and hospitalisations among children with SCA in the USA.[4] It is an episodic pain that is primarily due to tissue ischaemia and vaso-occlusion of the microcirculation by sickled cells.[5] Frequently, it acts as a protective agent in response to tissue injury, thereby warning the body of the presence of potentially harmful agents.[6] Just as the injury heals, the pain disappears. The resolution of acute pain usually occurs in a few days to several weeks.[7] The arms, legs, abdomen, chest and back are the most common locations of pain episodes. Acute pain associated with SCA children is often described as aching, tiring and uncomfortable. This may be experienced as early as 6 - 12 months of age.

One of the most debilitating aspects of vaso-occlusive episodes is their unpredictable nature in terms of frequency, intensity, affected SAJCH

sites and duration of pain.[5] It is thought that vaso-occlusive episodes are triggered by various environmental and psychological states, such as high altitudes, extreme temperatures, infection, dehydration, stress and fatigue.[8] Painful episodes experienced by children with SCA often interfere with intellectual activities, such as attending school and completing homework, social activities such as participating in activities with family members and peers, and the quality and quantity of sleep. Currently, there are many means of managing pain in children with SCA, which include pharmacological and nonpharmacological approaches.[4] However, the effectiveness of the approaches has not been extensively reported in the literature.

The WHO has developed guidelines for pain management in children.[9] Pain management may, however, vary from one country to another[10,11] as well as from one institution to another.[12] The Standard Treatment Guidelines in Nigeria contain a step-by-step approach to managing acute pain in SCA, which is helpful for clinicians who care for children with pain crises.[13] Generally, the guidelines deal specifically with the pharmacological and nonpharmacological management of persisting (long-term) pain in children with medical illnesses, as well as those with SCA. Optimal pain management begins with an accurate and a thorough pain assessment. Pain assessment enables healthcare providers to treat pain and alleviate needless suffering. It should be carried out at regular intervals because the disease process and the factors that influence it may change over time, and regular assessment permits the measurement of the efficacy of different treatment strategies in relieving pain. The pain assessment process involves the child and their parents or caregivers, and the healthcare providers. Pain

NOVEMBER 2015 Vol. 9 No. 4

119

assessment is, therefore, an integral part of the clinical care of SCA children.

Holistic treatment of pain includes use of opioids,[14] non-opioids and adjuvant therapy that includes cognitive behavioural therapy and psychotherapy.[15] In order to avoid poor or inadequate treatment of children in pain, it is essential for clinicians to adequately assess the pain history and individual patient’s needs. However, one of the challenges for healthcare providers in treating pain in SCA is that there is no objective method for assessing underlying vaso-occlusive pathophysiological alterations directly.[16] Pain history is determined by self-report and there are usually no obvious biophysical signs.

A dearth of information on the manner in which clinicians manage acute pain in SCA children in developing countries necessitated this study. Therefore, our objective was to evaluate acute pain management in SCA children on admission to the emergency room in a typical Nigerian teaching hospital.

Methods

According to the 2006 National Census, Lagos State has an estimated population of over 17 million. Lagos is served by two teaching hospitals: the Lagos University Teaching Hospital (LUTH) and Lagos State University Teaching Hospital (LASUTH). LUTH is funded by the Federal Government of Nigeria while LASUTH is funded by the Lagos State Government. Both hospitals serve as major referral centres to the surrounding health facilities in South Western Nigeria and beyond because of the facilities and the high standard of care that is available.

This was a single-centre prospective study conducted at LUTH, IdiAraba, Surulere, Lagos state, South-West Nigeria between 1 January and 31 December 2014. The study involved children with SCA who were ≤12 years old, on admission for a painful crisis and not using herbal remedies for pain relief.

A proforma data collection sheet, purposively designed for this study, was used to obtain information about the demographics of the children (age, gender, weight) and their parents/caregivers (religion, and marital and employment status). Other sections of the proforma were used to obtain information on the duration of admission of the patients, pain score assessment by the physician before and after analgesic use, and non-pharmacological and pharmacological treatments documented in the patient’s case file. One of the researchers assessed each patient for pain using the Wong-Baker Faces Pain Rating Scale.[18] Detailed information about the medicines used during admission was also obtained from the case files of the patients. Attention was paid specifically to the type, dosage, duration and frequency of use, and route of administration of the analgesics administered to the patients. The dosages of the various analgesics used were compared with those recommended for children by the WHO[9] or Drugs.com (http://www.drugs.com/dosage/).[19] This enabled us to grade the dosages as normal, under or over.

The study protocol was approved by the Ethics Committee of LUTH. Data were analysed using SPSS version 13 (IBM, USA) and presented as simple descriptive statistics and pictograms.

[17]

Results

A total of 120 SCA patients were admitted during the period of study and constituted the population of patients studied. The median age and weight of the children were 4 years and 16 kg, respectively (Table 1). Heights were not recorded in their case files. All the parents were married and employed in a job.

Pain scoring by the physicians was done in only 10 (8.3%) patients.

Unfortunately, the pain assessment tools used by the physicians were not documented in the case files of these patients. However, one of the current study researchers conducted pain assessment on the patients on the same day (n=90, 75%), day 1 (n=20, 16.7%), and day 2 (n=10, 120

SAJCH

8.3%) of admission (Table 2). Most of the patients (n=90, 75%) had moderate pain scores of 5 - 8 on the day of admission.

Fluid therapy (n=110, 91.7%) and prayers (n=120, 100%) were the only non-pharmacological therapy administered to the patients during emergency admission.

Antibiotics were used, either in combination or as a single medicine, for 80 (66.7%) patients. The antibiotics used were Table 1. Demographics of children with sickle cell anaemia and their parents Demographics

Values (N=120)

Age (years), Q1 - Q3 (median)

3 - 9 (4)

Weight (kg), Q1 - Q3 (median)

12 - 20 (16)

Religion, n (%) Christianity

110 (91.7)

Islam

10 (8.3)

Marital status of parents (married), n (%)

120 (100)

Employment status of parent (employed), n (%)

120 (100)

Table 2. Pain assessment in children with sickle cell anaemia in painful crises as determined by the researchers Day of admission

Pain score*

n (%)

Same day

5

20 (16.7)

6

30 (25.0)

7

20 (16.7)

8

20 (16.7)

2

10 (8.3)

3

10 (8.3)

1

10 (8.3)

Day 1 Day 2

*Pain score, based on the assessment tool, ranges from 1 to 10.

Amikacin 8% Erythromycin 17%

Cefotaxime 8% Cefuroxime 42%

Ampiclox 17%

Cloxacillin 8%

Fig. 1. Pattern of antibiotics used for children with SCA admitted for painful crises.

NOVEMBER 2015 Vol. 9 No. 4

erythromycin, amikacin, cefuroxime, cefotaxime, ampicillin with cloxacillin (ampiclox), and cloxacillin alone (Fig. 1). Cefuroxime (n=50, 41.7%) was the most frequently used antibiotic recorded during the study.

Analgesics, either in combinations or as a single medicine, were administered to 100 (83.3%) patients. Figure 2 shows the pattern of analgesics administered to the patients during acute pain management. Paracetamol (n=90, 75%) and pentazocine (n=80, 66.7%) were the most frequently used analgesics (Fig. 2). Morphine and its derivatives, except hydromorphone, were rarely used.

Among the 90 SCA children prescribed paracetamol, 11.1% were prescribed a normal dose of 10 - 15 mg/kg/day, 33.3% were underdosed, and 55.6% were overdosed. Paracetamol was prescribed either intramuscularly or intravenously in 3 - 4 divided doses per day, and the duration of use was left open until the pain had adequately subsided. Among the 80 patients prescribed pentazocine, 75% were prescribed a normal dose of 0.5 - 1 mg/kg/day, none were underdosed and 25% were overdosed. After an intramuscular starting (statim) dose of pentazocine, it was subsequently administered when necessary (pro re nata). Among the 70 patients prescribed ibuprofen, 57.1% were prescribed a normal dose of 4 - 10 mg/kg/day, none were underdosed and 42.9% were overdosed. Ibuprofen was prescribed orally in three divided doses per day.

The analgesics prescribed were among those recommended by the WHO (Table 3). However, some of the individual doses of the analgesics administered were not in line with the WHO guidelines.

A few patients (n=10, 8.3%) were treated for acute malaria with artesunate. Prophylactic use of proguanil was observed in six patients. The dosage of proguanil prescribed was 50 mg daily and was given orally. Only 40 (30.3%) patients were administered medicines other than antimalarials, antibiotics and analgesics. Sedatives or tranquilisers were not administered to any of the patients. However, folic acid (33%), hydroxyurea (17%), furosemide (17%) and zinc

(17%), were administered as adjunct therapies to analgesics during the acute pain management (Fig. 3).

Discussion

Anthropometric parameters such as the age, weight and height are important in calculating or estimating drug dosages for children. Unfortunately, only the age and weight of the patients were documented in their case files. The implication of this is that the patients are at risk of over- or underdosing with analgesics and other adjunct medicines. Overdosing with medications could result in drug toxicity or adverse events, while underdosing could result in undertreatment, persistent pain and prolonged hospitalisation.[20] According to the World Health Organization (WHO),[9] initial pain assessment of a child should include a detailed pain history, a physical examination, the diagnosis of the causes, and the measurement of pain severity using an age-appropriate pain measurement tool.

Unfortunately, only a few of the guidelines were followed. Pain on admission was assessed by the physicians in only 8.3% of the SCA patients. The assessment was rather subjective since the tool used was not documented. It is imperative for the attending physician to ask and document what pain treatments have been used previously by the patients, as well as the efficacy of the treatments. Surprisingly, this was not documented in the case files, if ever asked.

One-time pain assessment was performed on a few of the patients by the physicians, which is grossly inadequate. Pain assessment should be performed at regular intervals (2 - 4 hourly) during the implementation of the pain management plan.[9] This permits the measurement of changes in the severity of pain over time, and the assessment of the adequacy and efficacy of the chosen treatment, enabling adjustments to be made, as necessary.

90

Zinc 17%

80

Proguanil 16%

Use (n)

70

Furosemide 17%

30

Folic acid 33% Hydroxyurea 17%

0 0 0 0 0 0 0 e l e l l e e n e n i n n ex o n n r fe ny do cin m spi br ho ado loxo odo ro ta ma o a e t p r z p n A e a u or eth yc Fe Tra Ce Na ac nt Ib Ox ar om M Pe r P d Hy Fig. 2. Analgesics used for children with SCA admitted for acute pain crises.

Fig. 3. Adjunct pharmacotherapy co-administered to children with SCA admitted for acute pain crises.

Table 3. Adherence to the WHO medicine and dosage guidelines for pain management in children Type of analgesic

WHO recommended dosage (mg/kg)

Underdosing (%)

Overdosing (%)

Normal dosing (%)

Ibuprofen

4 - 10

-

42.9

57.1

Paracetamol

10 - 15

33.3

55.6

11.1

Pentazocine

0.5 - 1.0

-

25.0

75.0

SAJCH

NOVEMBER 2015 Vol. 9 No. 4

121

The assessment of pain in the SCA patients on the day of admission, using the visual analogue scale, showed that 75% had a moderate pain score of 5 to 8. Following this assessment, a detailed pain management plan, including pharmacological and non-pharmacological inter­ ventions, can be formulated and implemented. However, a lack of detailed pain assessment by the physicians attending to the SCA patient on admission may compromise adequate and appropriate pain management.

Non-pharmacological approaches for the treatment of pain in children include psychological strategies, education and parental support. For SCA children in pain crises, cognitive-behavioural therapy interventions, which decrease anxiety and distress, are known to be quite effective.[21] The objective of non-pharmacological therapies is to provide responses that may help children master a distressing situation, ideally in a manner consistent with their basic coping strategies. Most of these techniques take time to learn and master, so simple distraction techniques that divert attention away from painful stimuli, or positive incentive techniques that provide a small reward such as prizes for attempts at mastery of their responses, can be effective for children with mild pain. Fluid therapy and prayers were the only non-pharmacological therapies used in the patients in this study. While the former was prescribed and administered by physicians, the latter was provided by the parents of the SCA patients. The role of prayer in alleviating pain in children has not been proven scientifically, while fluid therapy tends to decrease the cellular sickle cell (HbSS) concentration by causing hypotonic swelling of erythrocytes and decreased sickling.[6,10] Antibiotics, either in combination or as a single medicine, were used in ~60% of the patients; cefuroxime, a first-generation cephalosporin was the most frequently used. These medicines were used empirically for treating presumptive sepsis and in line with the recommended guidelines for pain management in SCA.[10] In a landmark study of 30 participating centres,[22] specific causes of pain were identified in 38% of patients, and were infections in 29% of cases. Infections were equally distributed between bacterial, viral, mycoplasma and chlamydial infections, suggesting potential treatment with macrolide and cephalosporin antibiotics. A painful vaso-occlusive crisis may also be associated with fever. Since increased susceptibility to both Gram-positive and Gram-negative organisms characterises this patient cohort, infection and vaso-occlusion might coexist, such that rigorous assessment and initiation of empirical antibiotic treatment is routine, pending the time of availability of culture results.[22] Treating infection alone is known to significantly decrease pain in SCA patients.[23] Analgesics, either in combinations or as a single medicine, were prescribed for almost all the SCA patients during admission for pain crises. Paracetamol and ibuprofen are the medicines of choice recommended by the WHO in the first step of management of mild pain in children.[9] This may be the reason why paracetamol was prescribed for 75% of the patients in our study. However, the majority of the patients were assessed by the researchers to have moderate pain, which requires a stronger and more effective analgesic than the paracetamol administered for first-line pain relief to the patients.

This would suggest inadequate treatment of pain in SCA children.

Moderate or severe pain requires the use of a stronger opioid analgesic. Morphine is the medicine of choice for this kind of pain, although other opioids can be considered and made available to ensure an alternative to morphine in cases of unpleasant sideeffects. [9] Unfortunately, despite the moderate nature of the pain experienced by our patients, morphine and its derivatives – except pentazocine and hydromorphone – were rarely prescribed. This may be due to the problem of unavailability and high cost. It may also be related to certain misconceptions surrounding pain management in children, which can lead to poor treatment outcomes.[9,10] Such misconceptions include the myth that infants and children do not 122

SAJCH

feel pain or suffer less than adults, fears of respiratory depression or other adverse effects of analgesic medications, and the belief that preventing pain in children takes too much time and effort.

Most of the pain medications were administered intramuscularly which is contrary to all guidelines on pain management in children.

This is poor practice and should be discouraged. It is therefore imperative to adopt a multidisciplinary approach to managing pain in Nigerian children, which should involve a paediatric clinical pharmacologist with a bias for pain management. Where this expertise is scarce, guidelines for pain management and judicious analgesic use should be developed and properly implemented in our hospitals.

Underdosing (33.3%) and overdosing (55.6%) with paracetamol was observed in the present study. However, with pentazocine (25.0%) and ibuprofen (42.9%), only overdosing errors were observed. While paracetamol underdosing could result in poor pain control in SCA children, overdose could cause supratherapeutic toxicity.[24] Children may be at risk of gastrointestinal bleeding, impaired liver and renal function, and metabolic disorders following ibuprofen overdose.[25] However, none of the patients manifested any of these adverse events during the study.

Antimalarial drugs and hydroxyurea are among the adjunct treatments received by the patients. Patients with SCA are more vulnerable to malaria because of their weakened immunity. Malaria, like infection, can produce fever, which is associated with a painful vaso-occlusive crisis.[10] Treating malaria fever will, to an extent, indirectly reduce vaso-occlusive painful crises. This justifies the need for antimalarial use by SCA patients.

This study was characterised by some limitations, such as the use of a small sample size. Biases can result from data obtained from a small sample size; therefore, caution is required in interpreting our results. The study was limited to a single centre in Nigeria. Different results may be obtained if a similar study was conducted in other centres. It is, therefore, difficult to generalise our results. Thus, a multicentre study is required to give a true picture of acute pain management in SCA children in Nigeria.

Conclusion

SCA children admitted for acute pain were managed suboptimally with analgesics. The percentage compliance to the WHO analgesic dosing guidelines varied with different types of analgesics, especially with paracetamol. Overdosing errors were more prevalent than underdosing errors with the three most frequently used analgesics in this study. Educational intervention as well as training and retraining of the physicians involved in pain management of children with SCA is recommended as a means of improving acute pain management.

References 1. Bunn FH. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997;33(11):762-769.

2. World Health Organization (WHO). Fact Sheet No. 308, 2011. Sickle-cell disease and other haemoglobin disorders. http://www.who.int/mediacentre/ factsheets/fs308/en/ (accessed 4 January 2015).

3. Edwards CL, Scales MT, Loughlin C, et al. A brief review of the pathophysiology, associated pain, and psychosocial issues in sickle cell disease. Int J Behav Med 2005;12(3):171-179. [http://dx.doi.org/10.1207/s15327558ijbm1203_6] 4. Elander J, Lusher J, Bevan D, et al. Pain management and symptoms of substance dependence among patients with sickle cell disease. Soc Sci Med 2003;57(9):1683-1696. [http://dx.doi.org/10.1016/S0277-9536 (02)00553-1] 5. Ballas SK. Sickle cell disease: Clinical management. Baillieres Clin Haematol 1998;11(1):185-214.

6. Okpala I, Thomas V, Westerdale N, et al. The comprehensive care of sickle cell disease. Eur J Haematol 2002;68(3):157-162. [http://dx.doi.org/10.1034/j.16000609.2002.01523.x] 7. Todd KH, Ducharme J, Choiniere M, et al. Pain in the emergency department: Results of the pain and emergency medicine initiative (PEMI) multicentre study. J Pain 2007;8(6):460-466. [http://dx.doi.org/10.1016/j.jpain.2006.12.005] 8. Hofmann M, de Montalembert M, Beauquier-Maccota B, et al. Posttraumatic stress disorder in children affected by sickle-cell disease and their parents. Am J Haematol 2007;82(2):171-172. [http://dx.doi.org/10.1002/ajh.20722]

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9. World Health Organization (WHO). WHO guidelines on the pharmacological treatment of persistent pain in children with medical illnesses. WHO 2012. http:// whqlibdoc.who.int/publications/2012/9789241548120_Guidelines.pdf?ua=1 (accessed 2 March 2015).

10. Rees DC, Olujohungbe AD, Parker NE, et al. Guidelines for the management of the acute painful crisis in sickle cell disease. Br J Haematol 2003;120(5):744-752.

11. Marlowe KF, Chicella MF. Treatment of sickle cell pain. Pharmacotherapy 2002;22(4):484-491. [http://dx.doi.org/10.1592/phco.22.7.484.33675] 12. Zempsky WT. Evaluation and treatment of sickle cell pain in the emergency department: Paths to a better future. Clin Pediatr Emerg Med 2010;11(4):265273. [http://dx.doi.org/10.1016/j.cpem.2010.09.002] 13. The Federal Ministry of Health, Nigeria. Standard Treatment Guidelines, Nigeria, 2008. http://apps.who.int/medicinedocs/documents/s17035e/s17035e. pdf (accessed 27 February 2015) 14. Jacob E, The American Pain Society. Pain management in sickle cell disease.

Pain Manag Nurs 2001;2(4):121-131.

15. Thomas VJ, Taylor LM. The psychosocial experience of people with sickle cell disease and its impact on quality of life: Qualitative findings from focus groups. Br J Health Psychol 2002;7(Part 3):345-363. [http://dx.doi. org/10.1348/135910702760213724] 16. Todd KH, Green C, Bonham VL, et al. Sickle cell disease related pain: Crisis and conflict. J Pain 2006;7(7):453-458. [http://dx.doi.org/10.1016/j. jpain.2006.05.004]

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17. National Population Commission. 2006 Population and Housing Census of the Federal Republic of Nigeria. National and State Population and Housing Tables.

Priority Tables, Volume 1. http://www.population.gov.ng/images/Priority%20 Tables%20Volume%20I-update.pdf (accessed 17 January 2015).

18. Wong-Baker Faces Foundation. Wong-Baker FACES Pain Rating Scale. http:// wongbakerfaces.org/ (accessed 2 December 2014).

19. Drugs.com. Drug dosage. http://www.drugs.com/dosage/ (accessed 2 December 2014).

20. Oshikoya KA, Ojo OI. Medication errors in paediatric outpatient prescriptions of a teaching hospital in Nigeria. Nig Q J Hosp Med 2007;17(2):74-78.

21. Haywood C, Beach MC, Lanzktron S, et al. A systematic review of barriers and interventions to improve appropriate use of therapies for sickle cell disease. J Nat Med Assoc 2009;101(10):1022-1033.

22. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. N Engl J Med 2000;342(25):1855-1865. [http://dx.doi.org/10.1056/NEJM200006223422502] 23. Benjamin L, Swinson G, Nagel R. Sickle cell anaemia day hospital: An approach for management of uncomplicated painful crisis. Blood 2000;95(4):1130-1136.

24. Daly FF, Oâ&#x20AC;&#x2122;Malley GF, Heard K, et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med 2004;44(4):393-398. [http://dx.doi.org/10.1016/S0196064404005244] 25. Drugs.com. Ibuprofen side effects. http://www.drugs.com/sfx/ibuprofen-sideeffects.html (accessed 2 December 2014).

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ARTICLE

Factors associated with bacteraemia in febrile, nonneonatal children <5 years old at the paediatric outpatient clinic of the University of Port Harcourt Teaching Hospital, Nigeria U C Onubogu,1 MBBS, FWACP; I C Anochie,2 MBBS, FWACP 1 2

raithwaite Memorial Specialist Hospital, Port Harcourt, Rivers State, Nigeria B University of Port Harcourt Teaching Hospital, Port Harcourt, Rivers State, Nigeria

Corresponding author: U C Onubogu (utchayonubogu@yahoo.co.uk) Background. Fever is one of the most common presenting symptoms in the emergency room. Bacteraemia can be a cause of febrile illness in children and can have a fatal outcome if untreated. Therefore, it is important to identify factors associated with bacteraemia in febrile children in order to aid its early diagnosis and prompt treatment.

Objectives. To determine the factors associated with bacteraemia among febrile, non-neonatal, under-five children seen in the Children’s Clinic of the University of Port Harcourt Teaching Hospital, Nigeria.

Methods. Febrile children aged 29 days - 59 months who presented at the outpatient clinic and whose parents gave consent were recruited between September 2010 and January 2011. Information on their age, gender, weight, symptoms, physical examination and blood culture results was collected and analysed.

Results. A total of 362 children were studied. The prevalence rate of bacteraemia was 11.5% and 22.2% in moderately and severely malnourished children, respectively (p=0.010). Children with systemic inflammatory response syndrome (SIRS) had the highest bacteraemia prevalence rate (66.7%; p<0.001), while children with focal infection and children with fever without other symptoms or signs had bacteraemia rates of 7.1% and 3.7%, respectively. There was no significant relationship between the magnitude of fever and bacteraemia (p>0.050).

Conclusion. Blood cultures should be performed in febrile children who are malnourished or who have SIRS. Antibiotics should also be commenced while blood culture results are awaited.

S Afr J Child Health 2015;9(4):124-126. DOI:10.7196/SAJCH.2015.v9i4.890

Fever is one of the most common presenting symptoms in the emergency room, accounting for 20% of paediatric emergency room visits.[1] By 2 years of age, the average child would have had an average of 4 - 6 febrile episodes.[2,3] Self-limiting viral illnesses have been reported to be the most common cause of fever with no other symptom or sign in young children.[2,4] However, a febrile child with bacteraemia needs to be identified and treated in order to prevent progression to focal infection and sepsis, which can be fatal.

Bacteraemia can present with fever as the only symptom; it can also present with focal infections, or as systemic infection causing sepsis.

According to the International Paediatric Sepsis Consensus (IPSC) conference, a systemic inflammatory response syndrome (SIRS) resulting from an infection can be identified in the paediatric age group when two of the following criteria are met (one of which must be abnormal temperature or abnormal leukocyte count): (i) core temperature of >38.5°C or <36°C; (ii) heart rate >2SD (standard deviations) above normal for age; (iii) respiratory rate >2SD above normal for age; (iv) leukocyte count elevated or depressed for age.[5] Factors that increase the likelihood of bacteraemia in febrile child­ren include toxicity, hyperpyrexia and malnutrition.[2,6-8] Baraff et al.[2] described a toxic child as one who is ill-looking, with signs of poor perfusion (cool, mottled skin or capillary refill >2 seconds), hypo- or hyperventilation, cyanosis and making poor eye contact.

Studies have shown that children <3 months who are not toxic have a 1.2 - 2% risk of bacteraemia compared with toxic infants, who have a 10 - 11% risk.[2] In children between 3 and 36 months, the risk of bacteraemia is higher (10 - 90%) in those who are toxic.[2,3] 124

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The prevalence of bacteraemia correlates with the height of fever.[9] Children with temperatures of 39°C have a 4.3% chance of having bacteraemia while those with temperatures of 40°C have ~4 - 17% chance of having bacteraemia.[9] In a study involving febrile children ≤2 years old who were seen in an ambulatory clinic, bacteraemia was present only if the rectal temperature was ≥38.9°C.[10] Alpern et al.[6] showed that children with a temperature ≥40°C were 2.6 times more likely to have bacteraemia than if they had a lower temperature.

Immune function starts to deteriorate when weight loss exceeds 15%.[11] Undernutrition based on protein energy malnutrition greatly increases susceptibility to major human infectious diseases in lowincome countries, particularly in children. In South Africa (SA), Reed et al.[7] documented that the incidence of bacteraemia in malnourished children with any form of malnutrition was 9.6%, 11.8% in severely malnourished children and 5.6% in stunted children.

Berkowitz[8] also found the incidence of bacteraemia among severely malnourished SA children to be 8.9% compared with 4.8% among well-nourished children in the same study population.

Identifying factors associated with bacteraemia in febrile children will help in early diagnosis and treatment of bacteraemia, which will decrease childhood morbidity and mortality. The condition would also assist in rationalising antibiotic use, so as to prevent overprescription of broad-spectrum antibiotics.

Objectives

To determine the factors associated with bacteraemia among febrile, non-neonatal, under-5 children in the Children’s Clinic of the University of Port Harcourt Teaching Hospital (UPTH), and to determine the

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relationship between the severity of fever and bacteraemia among the study population.

Methods

Ethical clearance for the study was obtained from the Ethics Committee of the UPTH. Signed or thumb-printed written informed consent was obtained from parents/guardians of each child, after adequate explanation.

A sample size of 362 was calculated using a bacteraemia prevalence rate of 38.2%.[12] This was a prospective study done in the Children’s Outpatient Clinic of UPTH from 14 September 2010 to 4 January 2011. UPTH is a tertiary health institution located in Port Harcourt, a cosmopolitan city in southern Nigeria. The hospital serves as a referral centre for patients within and outside its locality.

Children aged 29 days - <60 months with axillary temperature ≥37.5°C and whose parents or guardians gave informed consent were eligible for inclusion in the study. Participants were recruited prospectively until the calculated sample size was reached. Standardised tempera­ ture and weight measurements were taken, using mercury thermometers (Hospital and Home Care LTD, UK), one infant weighing scale (Waymaster, England) and one weighing scale for older children (Ocean Med England model RGZ-160, UK). Those who had taken antibiotics or unidentified drugs within 3 days of presenting to the clinic were excluded.

Participants’ respiratory and heart rates were counted over 1 minute while they were at rest.

Their parents or guardians were interviewed, and a physical examination was carried out on the children. Age, gender, weight, symptoms and physical examination results were entered into a standardised data collection form. Blood culture was done under sterile conditions for all the patients. Paired blood culture bottles were obtained from each patient, one for anaerobic organisms and one for aerobic organisms.

All bottles were subcultured daily for up to 7 days. Colonies on the plates were identified by morphology, Gram stain and biochemical tests (coagulase, oxidase, catalase). Bacteraemia was considered positive if blood culture yielded growth of any organism within the 7 days’ incubation period, except if isolates were deemed to be likely contaminants (coagulasenegative Staphylococcus and Bacillus spp.). Blood cultures were considered negative if no growth was detected during the incubation period.

Nutritional status was determined using World Health Organization growth charts, and analysed as weight-for-age z-scores (WAZ). Based on their clinical presentations, participants were categorised into three groups as follows: (i) febrile children with no other symptoms or signs (FWS); (ii) febrile children with localised symptoms or signs (focal infection); or (iii) febrile children with SIRS (heart and respiratory rates >2SD). The data were collected and analysed using Epi Info

version 3.5.1 (Centers for Disease Control and Prevention, USA). Statistical analysis was also done using the χ2 test and Fisher’s exact test.

Statistical significance was set at p<0.05.

Results

A total of 438 febrile children aged 29 days to <5 years presented to the Children’s Outpatient Clinic at UPTH during clinic hours, over the 15-week study period. Seventy-four (16.9%)

children who had taken antibiotics within 3 days of presenting to the clinic and 2 (0.5%) children whose parents did not give consent were excluded, leaving 362 febrile children included in the study. There were 186 (51.4%) males and 176 (48.6%) females, and the median age was 18 (interquartile range (IQR) 9 - 28) months. A total of 285 (78.7%) children had normal nutritional status (WAZ –2 - 2). The median WAZ was –0.28 (IQR –1.3 - 0.7). The mean (SD) axillary

Table 1. Weight-for-age classification of children with bacteraemia WAZ

Negative culture, n (%)

Positive culture, n (%)

Total, n (%)

p-value

Above normal (≥+2)

22 (91.7)

2 (8.3)

24 (6.6)

1.000*

Normal (>–2 - <+2)

264 (92.6)

21 (7.4)

285 (78.7)

0.058

Moderate malnutrition (–3 - –2)

23 (88.5)

3 (11.5)

26 (7.2)

0.490*

Severe malnutrition (<–3)

21 (77.8)

6 (22.2)

27 (7.5)

0.010

Total

330 (91.2)

32 (8.8)

362 (100)

*Fisher exact p-values.

Table 2. Prevalence of bacteraemia according to clinical presentation Clinical presentation

Total, n Positive culture, n (%) Negative culture, n (%) (100%)

p-value*

FWS

1 (3.7)

26 (96.3)

27

0.492

Focal infection

23 (7.1)

300 (92.9)

323

0.004

Diarrhoea

4 (9.3)†

39 (90.7)†

43

-

†

†

Pneumonia

2 (5.3)

36 (94.7)

38

-

URTI

11 (7.9)†

129 (92.1)†

140

-

†

†

Tonsillitis

2 (4.3)

44 (95.7)

46

-

Others

4 (7.0)†

53 (93.0)†

57

-

SIRS

8 (66.7)

4 (33.3)

12

<0.001

Total

32 (8.8)

330 (91.2)

362

-

URTI = upper respiratory tract infection. *Fisher exact p-value. †

Percentages represent proportions with positive and negative cultures by clinical syndrome.

Table 3. Temperature pattern among children with bacteraemia Temperature (°C)

Positive culture, n (%)

Negative culture, n (%)

Total, n (100%)

p-value

37.5 - 38.0

18 (9.4)

173 (90.6)

191

0.679

>38.0 - 38.5

6 (7.4)

75 (92.6)

81

0.606

>38.5 - 39.0

4 (9.8)

37 (90.2)

41

0.772*

>39.0 - 39.5

3 (9.4)

29 (90.6)

32

0.754*

>39.5 - 40.0

0 (0)

9 (100)

9

1.000*

>40.0

1 (12.5)

7 (87.5)

8

0.527*

Total

32 (8.8)

330 (91.2)

362

*Fisher exact p-value.

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temperature of the study population was 38.2°C (0.6°C) (range 37.5 40.8°C). Twenty-seven (7.5%) children presented with isolated fever, 323 (89.2%) presented with focal infection, and SIRS occurred in 12 (3.3%).

Overall, 32 (8.8%) children had positive blood cultures and organisms isolated, including Staphylococcus aureus 18 (56.5%), Pseudomonas aeruginosa 5 (15.6%), Escherichia coli 4 (12.5%), Klebsiella spp. 3 (9.4%), Proteus spp. and Streptococcus spp. 1 (3.1%). The prevalence rate of bacteraemia increased with poor nutritional status and was significantly higher (p=0.01) in severely malnourished children (Table 1).

Children with SIRS had the highest bacteraemia prevalence rate (66.7%), while children with FWS had the lowest (3.7%) (Table 2).

The difference in their prevalence rates was statistically significant (p<0.001).

Children with temperature >40°C (hyperpyrexia) had the highest prevalence of bacteraemia (12.5%). The observed relationship between fever and presence of bacteraemia was not statistically significant (Table 3).

Discussion

The prevalence of bacteraemia in our cohort of under-5 febrile children increased significantly with decreasing weight for age, similar to findings noted by Berkowitz.[8] He reported a bacteraemia prevalence of 8.3% among severely malnourished hospitalised SA children, compared with 4.8% among their well-nourished counterparts. Reed et al.[7] also reported a bacteraemia incidence rate of 9.6% in all malnourished children, and 11% in those with severe malnutrition in a rural SA cohort.

In Kenya, Berkley et al.[13] found that bacteraemia was significantly associated with malnutrition in children, particularly in those who were severely malnourished. It has been noted that with malnutrition, there is diminished lymphocyte, macrophage and granulocyte function. In malnutrition, there is also reduced complement activity and antibody response to infection, predisposing to infection.

The prevalence of bacteraemia in our cohort increased significantly, from a low rate (3.7%) in those with FWS, to the highest rate (66.7%) among those with SIRS. The low blood culture yield among FWS in this study may suggest a viral illness, which has been reported to be the most common cause of fever with no other symptoms or signs in young children.[2,4] The 3.7% prevalence rate of bacteraemia that we observed in FWS in this study is similar to the 3% reported

by Bandyopadhyay et al.[14] in Wisconsin. A lower prevalence rate (1.9%) of bacteraemia among FWS was reported by Alpern et al.[6] in Philadelphia. The lower rate described in the latter study[6] could be due to their exclusion of children with underlying medical illness who were more likely to have bacteraemia, unlike the present study that included such children. Children with underlying medical conditions such as HIV, renal failure, congenital heart disease and sickle cell anaemia are at higher risk of bacterial infection.

Investigators in Brazil reported that 64% of paediatric patients with SIRS have an infection.[15] The Brazilian study differed from ours in that it was carried out in an intensive care unit where critically ill patients were more likely to be admitted; furthermore, they used at least two of the IPSC-recommended variables (clinical and/or laboratory) to make a diagnosis of SIRS. We used three clinical variables (fever, heart rate and respiratory rate) to meet the IPSC criteria for SIRS. This was done in order to maximise the use of the IPSC guidelines for diagnosing SIRS in a resource-poor setting where laboratory tests are not as freely available. It is interesting that we used the IPSC guidelines to diagnose SIRS in an outpatient clinic setting using clinical parameters that are easily available at first consultation of these patients. There is limited literature on the prevalence of sepsis in paediatric patients with SIRS as diagnosed in the outpatient setting.

In our study, children with hyperpyrexia (temperature >40°C) had the highest prevalence rate (12.5%) of bacteraemia. However, there was no statistically significant difference in the prevalence rate when compared with those with lower temperatures. This was also found 126

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by King et al.[16] and Yarden-Bilavsky et al.,[17] both of whom evaluated hospitalised febrile infants. In contrast, Bonadio et al.[18] reported that the rate of serious bacterial infection increased in direct proportion to the degree of fever, being 3.2%, 5.2% and 26% at temperatures of 38.1 38.9°C, 39.0 - 39.9°C and >40.0°C, respectively, among febrile infants seen in an outpatient clinic in Wisconsin. However, they acknowledged that the predictive value of hyperpyrexia in identifying individual infants with serious bacterial infection is low. Stanley et al.[19] also reported a high (38%) prevalence of bacterial infection among children with temperatures >40°C when compared with those with lower temperatures. Hyperpyrexia, especially in young infants, is known to be a risk factor for bacterial infection when assessing febrile children.[20]

Conclusion

In view of the high prevalence rate of bacteraemia among febrile, non-neonatal, under-5 children with SIRS and malnutrition, it is recommended that blood culture should be done for all such children when they are evaluated in outpatient departments. These children warrant hospitalisation and treatment with broad-spectrum antibiotic cover to treat presumed bacterial sepsis.

Acknowledgements. The authors would like to acknowledge the technical support provided by Mrs Nkereawaji Josiah, the laboratory scientist.

References 1. Graneto JW. Emergent management of pediatric patients with fever. 30 January 2014. http://emedicine.medscape.com/article/801598-overview (accessed 8 January 2015).

2. Baraff LJ, Bass JW, Fleisher GR, et al. Practice guideline for the management of infants and children 0 to 36 months of age with fever without source. Ann Emerg Med 1993;22(7):1198-1210.

3. Baraff LJ. Management of infants and children 3 to 36 months of age with fever without source. Pediatr Ann 1993;22(8):497-498.

4. Jaskiewicz JA, McCarthy CA. Evaluation and management of the febrile infant 60 days of age or younger. Pediatr Ann 1993;22(8):477-480.

5. Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International sepsis definition conference. Crit Care Med 2003;31(4):12501256. [http://dx.doi.org/10.1097/01.CCM.0000050454.01978.3B] 6. Alpern ER, Alessandrini EA, Bell LM, Shaw KN, McGowan KL. Occult bacteraemia from a paediatric emergency department: Current prevalence, time to detection and outcome. Pediatrics 2000;106(3):505-511.

7. Reed RP, Wegerhoff FO, Rothberg AD. Bacteraemia in malnourished rural African children. Ann Trop Paediatr 1996;16(1):61-68.

8. Berkowitz F. Bacteraemia in hospitalized black South African children: A oneyear study emphasizing nosocomial bacteraemia and bacteraemia in severely malnourished children. Am J Dis Child 1984;138(6):551-556.

9. Givens TG. Fever caused by occult infections in the 3-to-36-month-old child.

Pediatric Emergency Medicine Practice. EBMedicine.net 2007;4(7):1-20.

10. McCarthy PL, Dolan TF. Hyperpyrexia in children: Eight-year emergency room experience. Am J Dis Child 1976;130(8):849-851.

11. Joanna O, Zbigniew K, Małgorzata R, et al. The effect of surgical and nutritional treatment on activation parameters of peripheral blood T lymphocytes in stomach cancer patients in postoperative period. Pol Merkur Lekarski 2008;24(141):231-236.

12. Ayoola OO, Adeyemo AA, Osinusi K. Concurrent bacteraemia and malaria in febrile Nigerian infants. Trop Doc 2005;35(1):34-36.

13. Berkley JA, Lowe BS, Mwangi I, et al. Bacteraemia among children admitted to a rural hospital in Kenya. N Engl J Med 2005;352(1):39-47. [http://dx.doi. org/10.1056/NEJMoa040275] 14. Bandyopadhyay S, Bergholte J, Blackwell C, Friedlander J, Hennes H. Risk of serious bacterial infection in children with fever without a source in the posthaemophilus influenzae era when antibiotics are reserved for culture-proven bacteraemia. Arch Pediatr Adolesc Med 2002;156(5):512-517.

15. Carvalho PR, Feldens L, Seitz EE, Rocha T, Soledade M, Trotta A. Prevalence of systemic inflammatory syndromes at a tertiary pediatric intensive care unit. J Pediatr (Rio J) 2005;81(2):143-148.

16. King JC Jr, Berman ED, Wright PF. Evaluation of fever in infants less than 8 weeks old. South Med J 1987;80(8):948-952.

17. Yarden-Bilavsky H, Bilavsky E, Amir J, Ashkenazi S, Livni G. Relationship between fever magnitude and serious bacterial infections in febrile infants less than two-months-old. Harefuah 2009;148(11):752-755.

18. Bonadio WA, Romine K, Gyuro J. Relationship of fever magnitude to rate of serious bacterial infections in neonates. J Pediatr 1990;116(5):733-735.

19. Stanley R, Pagon Z, Bachur R. Hyperpyrexia among infants younger than 3 months. Pediatr Emerg Care 2005;21(5):291-294.

20. Lee GM, Harper MB. Risk of bacteraemia for febrile young children in the post-Haemophilus influenzae type B era. Arch Pediatr Adolesc Med 1998;152(7):624-628.

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ARTICLE

Persistent and new-onset anaemia in children aged 6 - 8 years from KwaZulu-Natal Province, South Africa T P Gwetu,1 MB ChB, MPH; M Chhagan,1 FCPaed (SA), PhD; M Craib,1 MB ChB; M Taylor,1 PhD; S Kauchali,1,2 FCPaed (SA), MS, MPhil (Epidemiology) Department of Public Health Medicine, School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 2 Department of Paediatrics and Child Health, School of Nursing and Public Health, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa 1

Corresponding author: T P Gwetu (tgwetu@gmail.com)

Background. Anaemia impairs normal development in children and has wide-ranging social and economic implications. Existing anaemia control strategies primarily target anaemia in infancy. The contribution, however, of anaemia in preschool- and school-aged children as well as its long-term effects has not been extensively evaluated.

Objectives. To determine the prevalence of anaemia in the same children on two occasions at least 18 months apart.

Method. We carried out a longitudinal study in a rural community of KwaZulu-Natal, South Africa. Haemoglobin (Hb) levels were measured using the HaemoCue at baseline when the children were aged 4 - 6 years, and the follow-up assessment was done at age 6 8 years. HIV screening and helminth testing was offered to all the children.

Results. Hb levels at both baseline and follow-up were available for 181 children. The baseline anaemia prevalence was 56.9% (mean Hb 11.2, standard deviation (SD) 1.14) and at follow-up the anaemia prevalence was 41.9% (mean Hb 11.7, SD 1.19). There were 21/180 (11.7%) children with new-onset anaemia at follow-up, while anaemia from baseline persisted in 43/103 (41.8%).

Conclusions. The findings suggest a high burden of anaemia in these school-aged children, which might be reduced with early interventions.

Interventions targeting screening and management of anaemia, chronic infections and nutritional deficiencies are recommended.

S Afr J Child Health 2015;9(4):127-129. DOI:10.7196/SAJCH.2015.v9i4.929

Anaemia impairs normal development in children and is implicated as both a cause and an effect of adverse social and economic family circumstances.[1] Global estimates of childhood anaemia indicate that 293.1 million children aged <5 years are anaemic worldwide, with 28.5% of these living in sub-Saharan Africa.[2] This high anaemia burden among children of sub-Saharan Africa is generally attributed to poverty, communicable diseases, food insecurity, HIV and other associated concerns such as access to healthcare and sanitation.[3] In South Africa (SA), where poor nutrition, poverty and poor parental education are prevalent, the implications are severe for children’s future and for national development.

Existing global solution strategies to control anaemia in early childhood such as micronutrient supplementation and breastfeeding support have been successful, though associated with questionable sustainability in terms of protecting children from developing anaemia after infancy.[3] A significant proportion of anaemia in school-aged children is attributed to iron deficiency. [2] Subclinical iron deficiency is even more common and has comparable developmental consequences. In the present study, anaemia was used as an indicator of deprived nutrition and poor health status. This study was conducted in a rural community from KwaZulu-Natal (KZN) province where the children are disadvantaged by poor socioeconomic circumstances. Although the association between anaemia and poverty has been described by various researchers,[1,3] the natural history of anaemia associated with poor social environments in young children is not yet well described.

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Methods

Study population

This was a longitudinal survey in KZN. This research was an ancillary study to a larger cohort study investigating the health and psychosocial needs of children. The parent study enrolled 1 787 children aged 4 - 6 years identified in a door-to-door survey in the Valley of a Thousand Hills. The current study was conducted when these children were undergoing follow-up assessments at ages of between 6 and 8 years. A total of 184 consecutive children over a 4-month period were invited to join this study.

Diagnostic testing

Haemoglobin (Hb) determination by HaemoCue (Angelholm, Sweden) was conducted by a clinician. Anaemia was defined using Hb levels. The World Health Organization (WHO)-recommended cut-offs were used to classify anaemia severity. Children aged up to 59 months had an Hb cut-off of 11.0 g/dL, and 11.5 g/dL was applied for children 5 - 11 years old. Children aged up to 59 months had anaemia categorised as mild for Hb levels 10.0 - 10.9 g/dL, moderate 7.0 - 9.9 g/dL and severe <7.0 g/dL, while for children 5 - 11 years of age anaemia was classified as mild with Hb levels 11.0 - 11.4 g/dL, moderate 8.0 - 10.9 g/dL and severe <8.0 g/dL[4] Stool and urine samples were collected and sent for microscopy at a local academic hospital. All caregivers and children were offered voluntary HIV counselling and testing.

Analysis of time and treatment effects on anaemia

This exploratory analysis utilised Hb measurements from two time-points: the baseline at enrolment into the parent study; and at

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follow-up, which occurred at least 18 months later. The two Hb measurements were used to determine the Hb trend over time.

We assessed within-group differences for participants who had anaemia at these two time-points. Individual analyses were carried out for all the study participants. Parasitic infections were referred to as severe if the child had the presence of symptoms such as diarrhoea, abdominal pain and blood in stool. Asymptomatic cases were documented as mild.

Statistical analyses

SPSS version 22 software (IBM, USA) was used for data entry and analysis.

The distribution of anaemia, and effect of infection and treatment were assessed using descriptive statistics and graphical plots. Characteristics of the children in each defined group were compared using Student’s t-test and χ2 tests as appropriate.

Ethical review

This research study was approved by the Uni­ versity of KZN Biomedical Research Ethics Committee. Informed consent was obtained from the children’s caregivers before enrolment. All children with Hb <10 g/dL were referred for clinical intervention.

Results

Population characteristics

Hb levels at both baseline and follow-up were available for 181 of 184 (98.4%) participants.

At baseline, the children were aged 47 77 months (standard deviation (SD) 0.58) and at follow-up 72 - 102 months (SD 0.55).

The study group comprised more males (109/184 (59.2%)) than females. All children were asymptomatic for anaemia.

children with anaemia at baseline, 14/103 (13.6%) were found to have lower Hb levels at follow-up, with one child who initially had Hb 11.1 g/dL present with severe anaemia (Hb 6.6 g/dL) at follow-up.

At baseline, 27/103 (26.2%) children with Hb <10 g/dL were referred for clinical inter­vention at their local clinic. At follow-up, 18/27 (66.7%) children were still anaemic, although 23/27 (85.2%) had improved Hb levels. Of the children with persistent anaemia, 7/27 (25.9%) continued to have Hb levels <10 g/dL despite referral for clinical management.

Clinical factors

HIV infection A total of 168/181 (92.8%) children were tested for HIV at baseline and 3/168 (1.8%) were HIV-positive. Two of these children had mild anaemia at baseline. A non-significant increased uptake for HIV testing was seen at follow-up (179/181 (98.9%)), with 5/179 (2.8%) children testing positive for HIV infection. HIV-positive children had a trend towards lower Hb (11.22 g/dL, SD 0.81) than HIV-negative children (12.19 g/dL, SD 1.19) children (95% CI –4.27 - –1.32). At followup, all five HIV-infected children were anaemic with an Hb range of 8.0 - 11.4 g/dL: 2 mild, 2 moderate and 1 severe anaemia.

Parasitic infection A total of 52/181 (28.7%) children had a history of expelled worms prior to the assessment. Of these, 49 (94.2%) had mild asymptomatic infections and 2/52 (3.8%)

Anaemia profile

At baseline, the prevalence of anaemia was 103/181 (56.9%). Among the anaemic, 2/103 (1.9%) children had severe anaemia, 62/103 (60.2%) moderate and 39/103 (37.9%) mild.

A significant declining trend was seen at follow-up, with an anaemia prevalence of 76/181 (42%), with 1/76 (1.3%) severe anaemia, 45/76 (59.2%) moderate and 30/76 (39.5%) mild (p=0.002). Generally, there was a trend towards a higher mean Hb with time for all children (Table 1). The mean (SD) Hb at follow-up (11.7 (1.19) g/dL) was higher than at baseline (11.2 (1.14 g/dL) (95% confidence interval (CI) –0.71 - –0.23)). Of the non-anaemic children at baseline, 21/78 (26.9%) were anaemic at follow-up. Among the anaemic children at baseline, 43/103 (41.8%) were still anaemic at follow-up. The two children who had severe anaemia at baseline did not have anaemia at follow-up.

Of the 62 with moderate anaemia at baseline, 27/62 (43.6%) persisted with anaemia. Of the 128

had severe symptomatic infections. The age of the children at the time of expelling the worms ranged from 7 to 60 months, with a mean (SD) age of 31 (13.1) months. A total of 107/181 (59.1%) participants had received deworming treatments within the past 12 months. Of these, 37/107 (34.6%) were anaemic at follow-up. A total of 178/181 (98.3%) urine and stool samples were tested for parasitic infection in the second survey.

Microscopy was positive for parasites in 43/178 (24.2%) children, although only 31/178 (17.4%) had pathological infection. Pathogens identified were Ascaris lumbricoides (10/31 (32.3%)), Giardia lamblia (18/31 (54.8%)), Blastocystis hominis (1/31 (3.2%)), Enterobius vermicularis (2/31 (6.5%)), Trichuris trichiura (1/31 (3.2%)), Entamoeba coli (8/31 (25.8%)) and Schistosoma haematobium (3/31 (9.4%)).

Of the children with parasitic infection, 14/31 (45.2%) had anaemia compared with 31/147 (21.1%) without helminth infection. Anaemia trends for individual pathogens were Ascaris spp. (3/10 (30.0%)), S. haematobium (1/3 (33.3%)), G. lamblia (9/18 (50.0%)), E. coli 4/8 (50.0%) and B. hominis 0/1. The contribution of parasite infestation to anaemia was statistically significant (p=0.03). Deworming had a significant effect on anaemia at followup (p=0.01).

Exploratory analysis of the trend in anaemia and haemoglobin over time There was no statistical difference in anaemia between those who had been referred for treatment and those who had not (Table 2). The

Table 1. Change in haemoglobin levels according to anaemia presence at baseline n

Mean change in Hb g/dL between followup and baseline, mean (95% CI)

p-value

Anaemic at baseline

103

0.47 (0.18 - 0.75)

0.002

Non-anaemic at baseline

78

0.40 (0.12 - 0.69)

0.006

All participants

181

0.47 (0.23 - 0.72)

0.000

Table 2. Children with anaemia at baseline and at follow-up stratified according to HIV status and treatment arm Participants with anaemia, n (%) n

Baseline

Follow-up

p-value

HIV-infected

5

3 (60.00)

5 (100)

0.13

HIV-uninfected

179

100 (55.87)

71 (39.66)

0.00

Dewormed

107

55 (51.40)

37 (34.60)

0.01

Not dewormed

74

48 (64.86)

39 (52.70)

0.07

Treatment received

103

27 (26.21)

10 (9.71)

0.19

No treatment received

76

76 (73.8%)

45 (43.69)

0.13

HIV status

Parasitic infection

Anaemia status

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researchers did not explore the differences between HIV-infected children because of the small sample size. Children who received deworming treat­ ment had a trend towards higher mean increase in Hb compared with children who did not receive deworming treatment. The mean difference between baseline and follow-up Hb levels for children who had been referred for treatment was 2.4 g/dL (95% CI 1.86 - 2.88) while the mean difference in Hb levels for those who had not received treatment was 0.7 g/ dL (0.39 - 1.07). This difference was clinically significant (p<0.005).

Discussion

The prevalence of anaemia in this study population was high: 57.2% at baseline and 42.2% at follow-up. The researchers suggest that the high anaemia burden among this study population could be attributed to high levels of poverty, food insecurity and infectious diseases in the community. Anaemia persisted in 41.8% of children who were found to be anaemic at baseline. Moreover, over a quarter of initially non-anaemic children (26.9%) developed anaemia (based on WHO criteria) over the 2-year interval. Concern regarding this high anaemia burden in school-aged children remains owing to the commonly asymptomatic nature of anaemia and the inadequate treatment rates for those children who do seek healthcare. This study found evidence to suggest that deworming has a beneficial effect on anaemia prevention, while clinical interventions to treat anaemia in earlier childhood may not prevent anaemia in later childhood.

It is thought that the anaemia was related to iron deficiency and exacerbated by infections. This high prevalence of anaemia in schoolaged children highlights the need to consider additional strategies for anaemia control for this population.

The WHO, which compiled a systematic review of country-level data from 1993 to 2005, estimated a global anaemia prevalence of 25.4% (305 million children) among school-age children.[5] Very few data were available on school-aged children in most African countries, including SA. For this global database to achieve maximum potential, investigations need to be carried out and additional information gathered on Hb levels in schoolaged children. The prevalence findings from this study were in stark contrast to the recent 2013 SANHANES-1[6] report, which described a very low anaemia prevalence of 10.5% in children up to 14 years old. However, the findings from the present study are more comparable with earlier national surveys[7,8] and local studies,[9,10] which reported anaemia prevalence ranging from 16.5 to 33%. The ages of children assessed, methods of determining Hb concentration and anaemia Hb-level cut-offs varied from those used in this current study. Hence, the outcomes on anaemia prevalence need to be compared with caution.

Although studies implementing micronutrient supplementation in early childhood as a primary prevention strategy have been encouraging, the findings from this study suggest that this strategy may not prevent anaemia in later childhood. The variety of treatments received and duration of treatment make comparisons challenging. Several studies have reported difficulties in finding adequate evidence to detect significant effects and the few trials available provided limited evidence of benefit.[11,12] Anaemia burden was high among children with HIV and parasitic infections. This identifies these groups for targeted interventions.

Strategies to increase uptake of HIV testing by caregivers need to be endorsed. The uptake for HIV testing (98.9%) was higher than that reported by another local study (41.0%).[13] Public health campaigns are needed to encourage HIV testing for children. Parents who miss the opportunity during pregnancy may be offered routine systematic testing of their children at later ages. Parasitic infestation was found in 17.7% children and contributed significantly to anaemia presence (p=0.03). The re-infection rate following treatment was 24.3%. The pathogens identified were comparable with other local studies, which reported variable parasitic infection of T. trichiura (53.9 - 86.2%), A. lumbricoides (19.4 - 85%), hookworm (20 SAJCH

83.2%) and S. haematobium (24.5%).[14-16] The KZN helminth control programme is school based. By this age, a large proportion of the children are already affected by anaemia, hence the guidelines may require refinement in order to optimise benefits.

Recommendations

Global complementary efforts are necessary to promote good nutritional status and reduce common infections in children. Chronic anaemia, including iron depletion and anaemia of inflammation, needs to be addressed. The appropriate execution of the Integrated Management of Childhood Illness programme is expected to result in better case identification and management for children with anaemia. The Expanded Programme on Immunization (EPI) has also achieved good national coverage and may be an effective vehicle for the provision of interventions for controlling anaemia and infections in children up to school age. Interventions providing dietary support need to be complemented with attempts to increase screening and treatment for anaemia, helminth infection and HIV in children at risk. Long-term interventions and policies that target individual, community and national levels are needed, recognising the effect of different cultural practices and financial restrictions.

References

1. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW. Poorer behavioural and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Paediatrics 2000;105(4):E51.

2. World Health Organization (WHO). Worldwide prevalence of anaemia 1993 - 2005: WHO global database on anaemia. Geneva: WHO, 2008. http:// whqlibdoc.who.int/publications/2008/9789241596657_eng.pdf (accessed 21 January 2015).

3. Soares Magalhães RJ, Clements ACA. Spatial heterogeneity of haemoglobin concentration in preschool-age children in sub-Saharan Africa. Bull World Health Organ 2011;89(6):459-468. [http://dx.doi.org/10.2471/BLT.10.083568] 4. WHO. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Vitamin and Mineral Nutrition Information System.

Geneva: WHO, 2011. http://www.who.int/vmnis/indicators/Hemoglobin.pdf (accessed 21 January 2015).

5. De Benoist B, McLean E, Egli I, Cogswell M, eds. Worldwide prevalence of anaemia 1993 - 2005. In: WHO Global Database on Anaemia. Geneva; WHO, 2008.

6. Shisana O, Labadarios D, Rehle T, et al. South African National Health and Nutrition Examination Survey (SANHANES-1), 2013. Cape Town: HSRC Press, 2013.

7. Labadarios D, van Middelkoop A. Children Aged 6 - 71 Months in South Africa, 1994: Their Anthropometric, Vitamin A, Iron and Coverage Status.

Technical report. Johannesburg, South African Vitamin A Consultative Group, 1995. http://www.sahealthinfo.org/nutrition/vitamina.htm (accessed 21 January 2015) 8. Labadarios D, Swart R, Maunder EMW, et al. National Food Consumption Survey - Fortification Baseline (NFCS-FB-I) South Africa, 2005. S Afr J Clin Nutr 2008;21(3):56.

9. Oelofse A, Faber M, Benadé JG, Benadé AJ, Kenoyer DG. The nutritional status of a rural community in KwaZulu-Natal, South Africa: The Ndunakazi project.

Cent Afr J Med 1999;45(1):14-19.

10. Faber M, Jogessar VB, Benade AJS. Nutritional status and dietary intakes of children aged 2 - 5 years and their caregivers in a rural South African community. Int J Food Sci Nutr 2001;52(5):401-411.

11. Chhagan MK, van den Broeck J, Luabeya KA, Mpontshane N, Tomkins A, Bennish ML. Effect on longitudinal growth and anaemia of zinc or multiple micronutrients added to vitamin A: A randomized controlled trial in children aged 6 - 24 months. BMC Public Health 2010;10:145.

12. Geltman PL, Meyers AF, Mehta SD, et al. Daily multivitamins with iron to prevent anemia in high-risk infants: A randomized clinical trial. Pediatrics 2004;114(1):86. [http://dx.doi.org/10.1542/peds.114.1.86] 13. Chhagan MK, Kauchali S, Arpadi SM. Failure to test children of HIV-infected mothers in South Africa: Implications for HIV testing strategies for preschool children. Trop Med Int Health 2011;16(12):1490-1494. [http://dx.doi.org/10.11 11/j.1365-3156.2011.02872] 14. Jinabhai CC, Taylor M, Coutsoudis A, Coovadia HM, Tomkins AM, Sullivan KR. Epidemiology of helminth infections: Implications for parasite control programmes, a South African perspective. Public Health Nutr 2001;4(6):12111219.

15. Saathoff E, Olsen A, Kvalsvig JD, Appleton CC. Patterns of geohelminth infection, impact of albendazole treatment and re-infection after treatment in schoolchildren from rural KwaZulu-Natal/South-Africa. BMC Infect Dis 2004;4:27. [http://dx.doi.org/10.1186/1471-2334-4-27] 16. Appleton CC, Mosala TI, Levin J, Olsen A. Geohelminth infection and reinfection after chemotherapy among slum-dwelling children in Durban, South Africa. Ann Trop Med Parasitol 2009;103(3):249-261. [http://dx.doi. org/10.1179/136485909X398212]

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ARTICLE

The effect of lactose-free formula feeds on growth responses among severely malnourished HIVinfected children in Durban, South Africa E Binka,1 MD; D Montoya-Fontalvo,1 MD; M Healy,1 MD; M Sobieszczyk,1 MD, MPH; P LaRussa,1 MD; R Bobat,2 MB ChB, FCPaed, MD; M Archary,2 MB ChB, DCH (SA), FCPaeds, Paeds ID (SA) 1 2

epartment of Medicine, Columbia University College of Physicians and Surgeons, Columbia University, New York, USA D Paediatric Infectious Diseases Unit, Department of Paediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa

Corresponding author: M Archary (archary@ukzn.ac.za) Background. The co-occurrence of HIV infection and severe malnutrition contributes to high rates of morbidity and mortality among children in resource-limited settings. Lactose-free, ready-to-use therapeutic feeds (RUTFs) may be most appropriate in this population because of underlying mucosal damage secondary to inflammation and infection.

Objectives. To describe the effect of lactose-free RUTFs on the growth parameters of severely malnourished HIV-infected children in Durban, South Africa (SA).

Methods. This was a prospective, observational study of nutritional recovery in HIV-infected, severely malnourished children, aged 6 months to 5 years, who received lactose-free RUTFs following admission to King Edward VIII Hospital in Durban, SA. The primary outcome was nutritional recovery, defined as 15% weight gain from enrolment to end of study. Secondary outcomes included z-scores for weight-for-height, weight-for-age, height-for-age, triceps skinfold thickness (SFT) and subscapular SFT calculated at baseline and 7, 14, 30 and 45 days after admission. Univariate analysis was done to compare outcomes among antiretroviral therapy (ART)-naive and ARTexperienced children; the effect of ART on nutritional recovery was evaluated in a logistic regression model.

Results. A significant improvement in most nutritional parameters was found at 45 days; 59% of children attained nutritional recovery.

There was no significant difference in the proportion of children reaching recovery based on ART status at admission (p=0.08).

Conclusion. Lactose-free formula feeds may be an effective strategy for nutritional rehabilitation of severely malnourished and HIVinfected children in resource-limited settings. It remains to be determined how ART initiation affects nutritional recovery in these children.

S Afr J Child Health 2015;9(4):130-132. DOI:10.7196/SAJCH.2015.v9i4.814

Severe acute malnutrition (SAM) affects 13 million child­ ren under the age of 5 years and leads to 1 - 2 million preventable paediatric deaths annually.[1] The World Health Organization (WHO) defines SAM as the presence of at least one of: (i) weight-for-height more than 70% below the age-specific median or three or more standard deviations (SDs) below the mean in a normally distributed population; (ii) mid-upper arm circumference <115 mm; or (iii) the presence of bilateral lower extremity pitting oedema of nutritional origin.[2,3] In developing countries, there is often an overlap between HIV infection and malnutrition. The prevalence of SAM is approximately three-fold higher in HIV-infected than HIV-uninfected children,[4] and SAM is often the precipitating event that prompts healthcareseeking behaviour among HIV-infected children. Co-occurrence of SAM and HIV increases morbidity, including stunted physical and cognitive development, and mortality.[5,6] The WHO recommends the use of two specific formula diets as treatment for SAM: the F-75 (75 kcal-th or 315 kJ/100 mL) during the initial phase of treatment and the F-100 (100 kcal- th or 420 kJ/100 mL) during the rehabilitation phase after the child’s appetite has returned. [2] Countries such as South Africa (SA) have developed local, ready-to-use therapeutic feeds (RUTFs) similar in nutritional composition to the WHO-recommended F-100 formula. Unlike the F-100, RUTFs are not water based, thus minimising potential contamination or barriers associated with water acquisition. [6,7] Furthermore, the WHO-recommended feeds used to treat SAM are high in lactose and may not be optimal for HIV-infected children who tend to present with diarrhoea and malabsorption. Few studies have investigated the effect of the local 130

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and lactose-free RUTFs on the growth responses and nutritional recovery of severely malnourished HIV-infected children.[8] Our study describes the effect of a lactose-free RUTF on growth responses of severely malnourished HIV-infected children in Durban, SA.

Methods Patients

Children admitted to the King Edward VIII Hospital paediatric wards were screened during two time periods: between February and March 2011 and between December 2011 and April 2012. Those who were 6 months - 5 years of age, confirmed by HIV DNA polymerase chain reaction or HIV ELISA to be HIV-infected, and met the WHO definition of SAM, were eligible for enrolment in this prospective, observational study. Antiretroviral (ARV) therapy (ART)-experienced children were defined as children who reported taking ARVs at the time of admission; ART-naive children were defined as children who were not taking ARVs at admission. All patients were fed with an age-appropriate, lactose-free RUTF based on the postadmission day (Table 1).

Study procedures

Parents and guardians were approached to obtain written informed consent. The consent form was read to them in English or IsiZulu with the use of a translator. Measurements of weight, height, and biceps, triceps, subscapular and mid-thigh skinfold thickness (SFT), and demographic and pertinent clinical information were obtained at baseline and at days 7, 14, 30 and 45 post enrolment.

SFT measurements were done with a Harpenden Skinfold Caliper (Baty International, UK). The study was approved by the Institutional Review Board of Columbia University and the Biomedical Research

NOVEMBER 2015 Vol. 9 No. 4

Ethics Committee at the University of KwaZulu-Natal, as well as by the hospital management.

Statistical analysis

Indices of growth response and recovery were calculated using the WHO Anthro software (version 3.2.2). Z-scores for weight-­for-height (WHZ), weight-for-age (WAZ), height-for-age (HAZ), triceps SFT (TSZ) and subscapular SFT (SSZ) were calculated at baseline and at follow-up days 7, 14, 30 and 45. Nutritional recovery was defined as ≥15% weight gain from enrolment through to end of study period or by day 45. Data were captured in Microsoft Access (USA). A binary logistic regression model was applied to data, including age, gender, CD4 cell count and percentage, baseline weight, ART status at baseline, presence of pedal oedema and WHZ >70% as independent variables.

Analysis was performed using SPSS version 19 (IBM, USA).

Results

Baseline demographics of participants are shown in Table 2. Sixteen of 30 children had CD4% available at baseline. Of these, 12 (75%) were severely immunosuppressed (CD4% <15%). Of 30 children, eight had HIV-1 viral loads available at baseline; median log10 HIV- 1 RNA was 6.3 (interquartile range (IQR) 5.7 - 6.9). Fifteen out of 30 children (50.0%) were on ARVs at enrolment.

Table 1. SAM refeeding protocol Days post admission

Energy (kcal/kg)

Protein (g/kg)

1-2

33 - 37

1.0

3-4

50 - 56

1.5

5-6

67 - 74

2.0

7

83 - 93

2.5

>7

100 - 112

3.0

Table 2. Baseline demographics and growth parameters in 30 HIV-positive children before starting treatment with a ready-to-use lactose formula feed Variable

HIV-positive (n=30)

Age (months), mean (SD, IQR)

16.1 (12.0, 7.6 - 18.9)

Gender (male), % (n)

46.7 (14)

CD4%, mean (SD) (n=16)

14.1 (11.2)

CD4 <15%, % (n)

75 (12)

HIV-1 RNA, log10 median (IQR) (n=8)

6.3 (5.7 - 6.9)

Weight (kg), mean (SD)

6.2 (1.5)

Height (cm), mean (SD)

69.2 (7.8)

Duration of follow-up (days), median (IQR) (n=28)

44.0 (27 - 45)

On ART* at study start, % (n)

50 (15)

Time on ART at study start (months), median (IQR) (n=9)

2.0 (1.5 - 3)

WAZ, mean (SD) WHZ, mean (SD)

Baseline growth parameters for participants are shown in Table 2.

Mean baseline growth parameters indicated that the children were severely malnourished: mean (SD) WAZ –3.97 (1.0), mean WHZ –3.27 (1.1), mean TSZ –3.08 (1.2) and mean SSZ –3.95 (1.7). Twentyfour of 30 had a WHZ <70% of the median, suggesting that this was more of an acute presentation of severe malnutrition rather than a chronic state where stunting would be more prevalent. Baseline comorbidities are shown in Table 3.

Twenty-two of the 30 children had evaluations through to study end at day 45. Three died of opportunistic infections and five were lost to follow-up. Of the study subjects, 59.0% (n=13) attained nutritional recovery while 41.0% (n=9) remained malnourished. There was a significant improvement from baseline to day 45 (n=22 patients) in WAZ (1.34 (1.90), p=0.003), TSZ (1.43 (1.60), p=0.0005) and SSZ (2.02 (2.50), p=0.001), a trend to significance for WHZ (0.95 (2.20), p=0.060) and a statistically insignificant improvement for HAZ (0.76 (0.50), p=0.100). The mean rate of weight gain was 3.5 (6.9) g/kg/day but increased to 4.7 (5.0) g/kg/day after excluding the three deceased.

A comparison of baseline characteristics and clinical outcomes between ART-experienced and ART-naive children at the start of the study showed no significant differences (Table 4). However, in univariate analysis, ART-naive children had a slightly higher likelihood of reaching nutritional recovery at day 45 (60% v. 40%; p=0.08) than children who were ART-experienced. In logistic regression analysis, being ART-naive at presentation was associated with nutritional recovery at day 45 (OR 2.25, p=0.465), although this was not statistically significant (Table 5). Demographic factors, baseline weight, and CD4 cell percentage were not associated with nutritional recovery at day 45.

Discussion

Current WHO guidelines for the treatment of SAM do not make specific formula recommendations for refeeding children who are both severely malnourished and HIV-infected. With HIV infection, there is mucosal damage secondary to infection or inflammation leading to chronic diarrhoea, protein-losing enteropathy, carbo­ hydrate deficiencies and fat malabsorption.[7] Therefore, lactose-free formulas may be appropriate alternatives for refeeding regimens in this population. Our results showed that HIV-infected children on lactosefree RUTFs gained an average of 3.5 g/kg/day. This figure is similar to the average weight gain of severely malnourished children known to be HIV-infected in previous studies of lactose-containing formulas recommended by the WHO. Ndekha et al.[9] and Sandige et al.[10] studied children in Malawi who were severely malnourished and HIVinfected; both studies reported an average weight gain of 3.1 (2.7) g/kg/ day and 3.6 (4.7) g/kg/day, respectively. Our study showed that children refed with lactose-free RUTF gained weight in a similar fashion.

However, our study was limited owing to policies of the institution that did not make it possible to directly compare lactose-free with lactoseTable 3. Baseline comorbidities in 30 HIV-positive children Comorbidity

HIV-positive, % (n) (N=30)

Diarrhoea

23 (7)

Pulmonary tuberculosis

17 (5)

–3.97 (1.0)

Abdominal tuberculosis

3 (1)

–3.27 (1.1)

Urinary tract infection

3 (1)

Mid-upper arm circumference (<115 mm), n (%)

28.0 (93.3)

Pneumonia

13 (4)

TSZ, mean (SD)

–3.08 (1.2)

Dermatitis

13 (4)

SSZ, mean (SD)

–3.95 (1.7)

Oral thrush

13 (4)

Cytomegalovirus

3 (1)

Toxoplasmosis

3 (1)

*Children <3 years were on abacavir, lamivudine and lopinavir/ritonavir. Children >3 years were on abacavir, lamivudine and efavirenz.

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131

ART-experienced (N=15)

ART-naive (N=15)

p-value

types of formulas in promoting nutritional recovery and explore how the timing of ART initiation with respect to acute refeeding affects nutritional recovery in these children.

Age (months), mean (SD, IQR)

17.6 (11.9, 9.4 - 21.9)

14.7 (12.3, 7 - 17)

0.56

References

CD4 (%), mean (SD)

20.66 (13.64) (n=9)

9.03 (5.24) (n=7)

0.34

HIV-1 viral load, mean (SD)

5.7 (2.1) (n=5)

6.1 (0.6) (n=3)

0.73

Weight (kg), mean (SD)

6.6 (1.7)

5.7 (1.3)

0.15

Proportion reaching nutritional recovery (%)

40

60

0.08

Rate of weight gain (g/ kg/ day), mean (SD)

2.63 (2.7)

4.39 (9.4)

0.49

Change in WHZ, mean (SD)

–0.54 (4.1)

1.45 (0.22)

0.12

Change in WAZ, mean (SD)

0.13 (2.2)

1.29 (1.7)

0.19

Change in HAZ, mean(SD)

0.64 (1.2)

0.93 (0.9)

0.53

Table 4. A comparison of baseline characteristics and clinical outcomes in ARTexperienced and ART-naive children receiving ready-to-use lactose-free formula feeds Baseline characteristics

End of study outcomes (day 45)

Table 5. Logistic regression model* evaluating effect of concurrent ART on nutritional recovery at 45 days ART at baseline

Univariate OR (95% CI)

p-value

Multivariate OR (95% CI)

p-value

Yes

0.44 (0.10 - 1.920

0.465

0.54 (0.08 - 3.89)

0.54

No

2.25 (0.52 - 9.70)

Ref

1.86 (0.26 - 13.40)

Ref

*Logistic regression model included age, gender, CD4 cell count, CD4%, baseline weight, baseline ART status, presence of pedal oedema and WHZ>70% (independent variables), and nutritional recovery (dependent variable).

containing formulas. We were also limited by our inability to confirm the presence of lactose maldigestion in our patients at presentation.

The WHO recommends that the minimum rate of weight gain at the end of a nutritional rehabilitation period should be 5.0 g/kg/ day.

After excluding values for the deceased children, our mean weight gain increased to 4.7 g/kg/day, approaching WHO-expected rates. This occurred despite the expectation that severely malnourished children who are HIV-infected should gain less weight or gain less rapidly than a normally distributed population, given the malabsorptive state and mucosal damage created by HIV infection.

Even when using high-energy RUTFs to manage SAM in HIV-infected children, mortality rates of ~38% at 4 - 6 weeks are too high.[11] Our mortality rates were slightly lower.

At the end of our 45-day study period, three patients had died (10% of our study population).

Although the use of RUTF diets has been shown to lead to significant and sustained weight gain in HIV-infected children, this improvement has not always been associated with recovery in CD4 cell count or improvement in survival. [11,12] One major limitation of our study was that we were not able to track the changes in CD4 cell count and percentage in our patients to determine if there was any association between nutritional recovery and improvement in CD4 cell count or percentage.

We compared the baseline characteristics and clinical outcomes of children on ART and those not on ART prior to the study. We observed no statistically significant differences between the two groups, although this may be due to our small sample size. We also investigated the effect of concurrent ART use on attaining nutritional recovery using a multivariate logistic regression model. Based on this model, being ART-naive during acute illness may have been associated with nutritional recovery, although this result did not reach statistical significance. We hypothesise that the acute state of severe malnutrition and the concurrent use of ART with associated gastrointestinal side-effects could compound the malabsorptive state in the gastrointestinal tracts of these children, leading to suboptimal absorption of nutrients and ART. Other studies have shown that early initiation of ART leads to improved nutritional status in HIV-infected children.[13-15] Further research needs to be conducted to determine the right timing for initiation of ART in severely malnourished and HIV-infected children.

Conclusion

Lactose-free formula feeds may be an effective strategy for nutritional rehabilitation of severely malnourished and HIV-infected children in resource-limited settings. Future studies should directly compare the effectiveness of both

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1. Collins S, Dent N, Binns P, Bahwere P, Sadler K, Hallam A. Management of severe acute malnutrition in children. Lancet 2006;368(9551):1992-2000. [http://dx.doi.org/10.1016/S0140-6736(06)694439] 2. World Health Organization. Management of severe malnutrition: A manual for physicians and other senior health workers. Geneva: World Health Organization, 1999.

3. World Health Organization/World Food Pro­ gramme/United Nations System Standing Committee on Nutrition/United Nations Children’s Fund.

Community-based management of severe acute malnutrition. Geneva/Rome/Geneva/New York: World Health Organization/World Food Programme/ United Nations System Standing Committee on Nutrition/United Nations Children’s Fund, 2007.

4. Prendergast A, Bwakura-Dangarembizi MF, Cook AD, et al. Hospitalization for severe malnutrition among HIV-infected children starting antiretroviral therapy. AIDS 2011;25(7):951-956. [http://dx.doi. org/10.1097/QAD.0b013e328345e56b] 5. Chinkhumba J, Tomkins A, Banda T, Mkangama C, Fergusson P. The impact of HIV on mortality during in-patient rehabilitation of severely malnourished children in Malawi. Trans R Soc Trop Med Hyg 2008;102(7):639-644. [http:// dx.doi.org/10.1016/j.trstmh.2009.04.02] 6. Miller T, Orav EK, Martin SR, Cooper ER, McIntosh K, Winter HS. Malnutrition and carbohydrate malabsorption in children with vertically transmitted human immunodeficiency virus 1 infection.

Gastroenterol 1991;100(5):1296-1302.

7. Hendricks KM. Ready-to-use therapeutic food for prevention of childhood undernutrition. Nutr Rev 2010;68(7):429-435. [http://dx.doi.org/10.1111/ j.1753-4887.2010.00302.x] 8. Biggs C. Clinical dietetic practice in the treatment of severe acute malnutrition in a high HIV setting.

J Hum Nutr Diet 2013;26(2):175-181. [http:// dx.doi.org/10.1111/jhn.12003] 9. Ndekha MJ, Manary MJ, Ashorn P, Briend A. Home-based therapy with ready-to-use therapeutic food is of benefit to malnourished, HIV-infected Malawian children. Acta Paediatr 2005;94(2):222-225.

10. Sandige H, Ndekha MJ, Briend A, Ashorn P, Manaray MJ. Home-based treatment of mal­ nourished Malawian children with locally prod­ uced or imported ready-to-use food. J Pediatr Gastroenterol Nutr 2004;39(2):141-146.

11. Heikens GT, Bunn J, Amadi B, et al. Case management of HIV-infected severely malnourished children: Challenges in the area of highest prevalence.

Lancet 2008;371(9620):1305-1307. [http://dx.doi. org/10.1016/S0140-6736(08)60565-6] 12. Rollins NC, van den Broeck J, Kindra G, Pent M, Kasambira T, Bennish ML. The effect of nutritional support on weight gain of HIVinfected children with prolonged diarrhoea. Acta Paediatr 2007;96(1):62-68.

13. Kim MH, Cox C, Dave A, et al. Prompt initiation of ART with therapeutic food is associated with improved outcomes in HIV-infected Malawian children with malnutrition. Acquir Immune Defic Syndr 2012;59(2):173-176. [http://dx.doi. org/10.1097/QAI.0b013e3182405f8f] 14. Sutcliffe CG, van Dijk JH, Munsanje B, et al. Weight and height z-scores improve after initiating ART among HIV-infected children in rural Zambia: A cohort study. BMC Infect Dis 2011;11(1):54. [http:// dx.doi.org/10.1186/1471-2334-11-54] 15. Weigel R, Phiri S, Chiputula F, et al. Growth response to antiretroviral treatment in HIV-infected children: A cohort study from Lilongwe, Malawi. Trop Med Int Health 2010;15(8):934-944. [http://dx.doi. org/10.1111/j.1365-3156.2010.02561.x ]

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REVIEW

Audit of feeding practices in the neonatal wards at the Charlotte Maxeke Johannesburg Academic Hospital L Sepeng,1 MB ChB; D E Ballot,2 MB BCh, FCPaed (SA), PhD 1

Department of Paediatrics and Child Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Department of Paediatrics and Child Health, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg, South Africa

2

Corresponding author: L Sepeng (mntungwasazy@gmail.com)

Background. Breastfeeding is the preferred choice of infant feeding. The Baby-Friendly Hospital Initiative (BFHI) is a ten-step plan to help establish successful breastfeeding and is adapted by public sector hospitals in Gauteng. Despite this, rates of breastfeeding in sick and preterm neonates remain low.

Objective. To determine feeding practices of neonates in the neonatal wards of the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) on discharge.

Methods. A retrospective review of the CMJAH neonatal database of feeding choices of neonates discharged from the CMJAH neonatal unit between 1 January 2013 and 30 April 2013 was conducted.

Results. The records of 404 neonates were studied. A total of 98 (24%) were very low birth weight (VLBW) (<1 500 g), while 306 (75.7%) were >1 500 g or more. Only 94 (23.2%) were discharged on exclusive breastmilk, 232 (57.4%) were discharged on exclusive formula milk and 78 (19.3%) babies were discharged on mixed feeds (both formula milk and breastmilk). Significant variables associated with feeding choices were HIV exposure, perinatal asphyxia and resuscitation at birth and, particularly in the VLBW group, necrotising enterocolitis was found to be statistically significant.

Conclusion. Despite the fact that the CMJAH was involved in the BFHI, rates of exclusive breastfeeding were still low. This needs to be urgently addressed with employment of lactation consultants and improved counselling of mothers exposed to HIV on the importance and benefits of breastfeeding.

S Afr J Child Health 2015;9(4):133-136. DOI:10.7196/SAJCH.2015.v9i4.895

Human milk is uniquely composed to meet the needs of the human infant, and has been established as the ‘optimal form’ of nutrition for neonates.[1] It contains 0.8 - 0.9% protein, 4.5% fat, 7.15% carbohydrates and 0.2% ash (minerals). There is a high concentration of lactose, which is an excellent source of carbohydrates, and the fat fraction contains specific triglycerides of palmitic and oleic acid (O-P-O triglycerides) and a large quantity of lipids with trans bonds, which are considered to have health benefits. The principal proteins are casein, α-lactalbumin, lactferrin, IgA, lysozyme and serum albumin.[2] Breastfeeding delivers immunological advantages to the infant: bifido and lactobacillus bacteria in the breastfed neonate’s gastrointestinal system produces lactate and acetate, which lowers pH. The low pH and other substances excreted by these bacteria inhibit the growth of some Gram-positive and Gram-negative bacteria. Bacteria found in breastmilk also detoxify ammonia and other amines; they activate the immune system and thus help fight bacteria that cause disease. Breastfeeding is a significant protector against diarrhoeal disease, respiratory disease and other infections. It tends to result in better nutritional outcomes, including protecting against obesity in overfed populations and against wasting in underfed populations.

It has beneficial effects on cognitive functioning and psychosocial development.[2] Breastfeeding has also been shown to reduce the incidence of necrotising enterocolitis (NEC) in preterm infants.[1] The Baby-Friendly Hospital Initiative[3] (BFHI) is a 10-step plan to help establish successful breastfeeding, and has been adapted by public sector hospitals in Gauteng. Despite this, rates of breastfeeding in the neonatal unit at the Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) are unacceptably low. Possible reasons for this may include reluctance among the staff to promote breastfeeding to SAJCH

HIV-positive mothers, lack of dedicated lactation counsellors and a lack of facilities for breastfeeding mothers to live in the hospital.

A number of studies have been done on infant feeding in South Africa (SA), the majority conducted in the KwaZulu-Natal (KZN) [4-9] and Western Cape[10-11] provinces. In the Gauteng province,[11] the study on feeding was done with relation to prevention of mother-tochild transmission (PMTCT) in the preterm infant.

Several studies in KZN have looked at the beneficial effects of human milk on decreasing rates of paediatric infections such as NEC and sepsis.[4-8] The objective was to look at the feasibility of providing donor breastmilk to neonates in a resource-limited neonatal premature unit. It was found that staff attitudes influenced the uptake of donor breastmilk.[4,6,7] Studies in HIV-positive mothers showed that those neonates who were exclusively breastfed showed significantly lower rates of diarrhoeal diseases and had lower rates of hospitalisation. In addition, there was an association with better developmental scores and growth parameters during long-term follow-up, and mothers who exclusively breastfed had lower rates of postnatal depression.[8] In the Western Cape, Goga et al.[9,10] conducted a prospective obser­vation study between HIV-exposed neonates and unexposed neonates between the ages of 6 and 9 months. They concluded that HIV-positive mothers were more diligent with good feeding practices and this was mainly owing to good PMTCT counselling sites, emphasising the importance of the presence of an encouraging health worker.

Goga et al.[10] also looked at three districts that were part of a trial and which reflected different socioeconomic conditions: rural-urban prevalence and HIV prevalence rates were considered. They found that there were still barriers to exclusive breastfeeding and that

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measures should be put into place to reduce or even break these barriers.

The objective of the current study was to audit feeding choices in babies discharged from the neonatal unit at CMJAH.

Table 1. Characteristics of feeds (for whole group) Feeds, n (%)

Methods

The CMJAH neonatal unit prospectively collects information upon discharge of neonates for clinical audit. The data are entered into a database managed by Research Electronic Data Capture (REDCAP), hosted by the University of the Witwatersrand.[12] The current study is a review of the neonatal database. Babies who had been admitted to the CMJAH neonatal unit within 72 hours of birth and who were discharged from hospital between 1 January and 30 April 2014 were enrolled; those who died or were transferred to other hospitals were excluded.

Babies who were admitted to the neonatal intensive care unit (NICU) were excluded from the study as these were the sickest neonates and this may have negatively affected mothers’ ability to establish breastfeeding. There was no sleep-in facility available for breastfeeding mothers with sick newborn or preterm neonates.

The only such facility was the Kangaroo Mother Care (KMC) unit, which has 15 beds, where mothers of preterm neonates approaching discharge could do continuous KMC. Mothers were counselled as to the benefits of breastfeeding by attending staff, but formula milk was provided to those neonates whose mothers chose not to breastfeed.

There was no donor breastmilk available and no dedicated lactation counsellors in the neonatal ward during the study period. The variables found to be statistically significant were defined as follows: resuscitation – all neonates who received bag-mask ventilation, chest compressions, resuscitative drugs or intubation; and NEC – Bell stages 2 and 3.

Statistical analysis

Data were described using standard statis­ tical methods using SPSS version 21 (IBM, USA). Continuous variables were normally distributed, so mean and standard deviation (SD) were used as measures of central tendency. Categorical data were described using frequencies and percentages.

Babies were divided into groups according to feeding choice: breastmilk only; formula milk only; or mixed feeds. They were also grouped by birth weight: <1 500 g and ≥1 500 g. These groups (feeding choice and birth weight) were compared using χ2 analysis for categorical variables and unpaired tests for continuous variables. Logistic regression was also done using the method of feeds as the multinomial variable against the various demographic and clinical characteristics as input variables. Those variables with a

Variables

Breastmilk only

Formula only

Breastmilk and formula (mixed)

p-value

Inborn

78 (22.5)

197 (56.8)

72 (20.7)

0.738

Para 1

32 (24.1)

69 (51.9)

32 (24.1)

0.719

Gravida 1

23 (19.5)

68 (57.6)

27 (22.9)

0.322

Attended antenatal care

81 (24.3)

188 (56.3)

65 (19.5)

0.830

Teenage mothers

0

6 (66.7)

3 (33.3)

0.497

Caesarean section

52 (21.3)

142 (58.2)

50 (20.5)

0.765

HIV-positive

12 (10.6)

95 (84.1)

6 (5.3)

<0.001

Anti-tuberculosis treatment

0

4 (80)

1 (20)

0.440

Early sepsis

2 (25.0)

3 (37.5)

3 (37.5)

0.601

Late sepsis

2 (13.3)

12 (80.0)

1 (6.7)

0.403

Resuscitation

19 (17.6)

74 (68.50

15 (13.9)

0.024

Respiratory pathology

34 (21.7)

83 (60.55)

25 (18.25)

0.210

Birth asphyxia

7 (31.8)

13 (59.1)

2 (9.1)

0.040

Patent ductus arteriosus 1 (10)

8 (80)

1 (10)

0.177

NEC

2 (66.7)

1 (33.3)

0

0.448

NCPAP

26 (23)

70 (61.9)

17 (15.0)

0.194

Birth defect

4 (57.1)

1 (14.3)

2 (28.6)

0.050

NCPAP = nasal continuous positive airway pressure.

p-value <0.1 on univariate analysis were included.

If the infant required non-invasive ventila­ tion by means of continuous positive airway pressure, the date of initiation and date of being weaned off were recorded, as during this time initiation of feeds would be delayed. Variables which were similar in nature were grouped together to facilitate analysis (e.g. hyaline membrane disease and transient tachypnoea of the newborn were classified as respiratory illness).

Results

A total of 404 neonates were enrolled. Out of the group, 197 (48.8%) were female and 207 (51.2%) were male. The mean birth weight was 3 372 g. Of the 404 infants studied, 98 (24.0%) were very low birth weight (VLBW) and 306 (75.7%) were >1 500 g at birth. Only 94/404 (23.2%) of the total group were discharged on exclusive breastmilk, 78 (19.3%) were discharged on mixed feeding (both formula and breastmilk) and 232 (57.4%) neonates were discharged on exclusive formula milk.

Various factors postulated to affect feeding choice are compared in Table 1. Significant factors found were HIV-exposed neonates, neonates who had birth asphyxia post delivery and required resuscitation, and in the VLBW group, NEC was also found to be statistically significant (Table 2).

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Discussion

Breastfeeding rates in the CMJAH neonatal unit remain unacceptably low: 42.5% of all babies discharged from the unit received breastmilk, but only 23.2% of neonates were discharged on exclusive breastmilk.

Irrespective of birth weight, the preferred method of feed was still formula feeds (57.4%).

The most significant factors associated with feeding choice in the whole group were: birth asphyxia (p<0.040), maternal HIV status (p<0.001) and resuscitation (p<0.024).

In the VLBW group, NEC was found be significant (p<0.024). It is surprising that the lack of breastfeeding was not different between VLBW and bigger neonates (Table 3), as establishing breastfeeding in sick preterm neonates is more challenging than in bigger, healthier neonates.

The reasons for the very low rate of breastfeeding were not evaluated in the present study, but may relate to the fact that there was no dedicated lactation counsellor assigned to the neonatal ward and no donor breastmilk available during the study period.

Establishing breastfeeding in sick and preterm neonates in a busy, understaffed neonatal unit is more effort than formula feeding, and adequate support in terms of education, dedicated staff and donor breastmilk is essential. There was also no sleep-in facility for breastfeeding mothers

NOVEMBER 2015 Vol. 9 No. 4

Table 2. Characteristics of feeds in VLBW Feeds, n (%) Variables

Breastmilk

Formula milk

Breastmilk and formula

p-value

Inborn

19 (21.6)

53 (60.2)

16 (18.2)

0.744

Para 1

19 (25.0)

16 (53.3)

8 (26.7)

0.298

Gravida 1

4 (14.3)

15 (65.2)

6 (21.4)

0.135

Attended antenatal care

19 (25.0)

43 (56.6)

14 (18.4)

0.180

Caesarean section

15 (23.1)

39 (60.0)

11 (16.9)

0.856

Teenage mothers

0

2 (66.7)

1 (33.3)

0.155

HIV-positive

3 (9.4)

27 (84.4)

2 (6.3)

0.011

Anti-tuberculosis treatment

0

2 (100)

0

0.673

Early sepsis

0

1 (100)

0

0.726

Late sepsis

1 (7.7)

11 (84.6)

1 (7.7)

0.177

Cranial sonar

6 (13.0)

30 (65.2)

10 (27.1)

0.350

Resuscitation

2 (7.7)

20 (76.9)

4 (15.4)

0.099

Respiratory pathology

18 (20.0)

53 (61.6)

15 (17.4)

0.949

Birth asphyxia

-

-

-

-

Patent ductus arteriosus

0

8 (80.0)

2 (20.0)

0.367

NEC

2 (100)

0

0

0.024

NCPAP

9 (16.1)

36 (64.3)

11 (19.6)

0.106

Birth defect

0

2 (100)

0

0.524

Table 3. Characteristics of feeds in babies >1 500 g

Study limitations

This was a retrospective study confined to evaluating the type of feeding on discharge from the CMJAH neonatal unit. Feeding choice is a complex, multifactorial issue, and many of the possible factors involved could not be investigated (as outlined above). A prospective study including various staff and maternal factors that influence feeding choice should be conducted in the unit, therefore further prospective research study is needed.

Conclusion

Feeds, n (%) Variables

Breastmilk

Formula milk

Breastmilk and formula

p-value

Inborn

59 (22.8)

143 (55.2)

57 (22.0)

0.714

Para 1

26 (25.0)

53 (51.0)

25 (24.0)

0.842

Gravida 1

19 (21.1)

50 (55.6)

21 (23.3)

0.907

Attended antenatal care

62 (23.8)

146 (55.9)

53 (20.3)

0.991

Caesarean section

36 (20.1)

102 (57.0)

41 (22.9)

0.128

Teenage mothers

0

4 (66.7)

2 (33.3)

0.383

HIV-positive

9 (11.1)

68 (84.0)

4 (4.9)

0.000

Antituberculosis treatment

0

2 (66.7)

1 (33.3)

0.635

Early sepsis

2 (28.6)

2 (28.6)

3 (42.9)

0.476

Late sepsis

1 (25.0)

2 (50.0)

1 (25.0)

0.949

Cranial sonar

2 (25.0)

2 (25.0)

4 (50.0)

0.123

Resuscitation

17 (20.5)

54 (65.1)

12 (14.5)

0.125

Respiratory pathology

22 (22.25)

55 (58.1)

19 (19.65)

0.743

Birth asphyxia

8 (36.4)

8 (36.4)

6 (27.3)

0.154

Patent ductus arteriosus

2 (50.0)

2 (50.0)

0

0.367

Necrotising enterocolitis

0

1 (100)

0

0.815

NCPAP

9 (19.1)

28 (59.6)

10 (21.3)

0.712

Birth defect

0

8 (84.3)

2 (28.6)

0.079

SAJCH

with sick neonates. Many of the mothers live far away and transport is expensive.

CMJAH is a tertiary obstetric referral centre and many of the mothers are ill at the time of delivery. The majority of babies requiring admission are delivered by emergency caesarean section, most often owing to pregnancy-induced hypertension.

Establishing breastfeeding is more difficult in these circumstances.

It is more challenging to latch a newborn within an hour of birth and discuss feeding choices with an ill mother. The strong association with maternal HIV exposure and lack of breastfeeding may reflect reluctance on the part of health workers to promote breast足 feeding in HIV-infected mothers. It may also reflect a lag in implementing a change in the feeding policy (HIV-infected mothers were provided with formula in Gauteng until early 2012). Ongoing education and training of health workers in the BFHI and provincial feeding policies is crucial.

NOVEMBER 2015 Vol. 9 No. 4

Despite the fact that CMJAH is involved in the BFHI, the rates of exclusive breastfeeding were still low. Reasons for this were not studied but could include inadequate education of healthcare workers, lack of lactation counsellors, maternal illness, lack of sleep-in facilities and no donor breastmilk.

Maternal factors, including previous breast足 feeding experience, socioeconomic status, atten足dance at antenatal clinics and level of edu足 cation, would also influence feeding choices, but these were beyond the scope of this study. Establishing breastfeeding in sick neonates requires a team approach with dedicated counsellors and ongoing training of healthcare workers.

References 1. Kuhn L, Aldrovandi G. Survival and health benefits versus artificial feeding in neonates of HIV-infected women: Developing versus developed world. Clin Perinatol 2010;37(4):843862. [http://dx.doi.org/10.1016/j.clp.2010.08.011] 2. Precht D, Molkentin J. C18:1, C18:2 and C8:3 trans and cis fatty acid isomers including conjugated cis delta 9, trans delta 11 linoleic acid (CLA) as well as total fat composition of German human milk lipids. Nahrung 1999;43(4):233-244. [http://dx.doi.org/10.1002/ (SICI)1521-3803(19990801)43:4&lt;233::AIDFOOD233&gt;3.0.CO;2-B]

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3. Merewood A, Phillip BL, Chawla N, Cimo S. The Baby-Friendly Hospital Initiative increases breastfeeding rates in a US neonatal intensive care unit. J Hum Lact 2003;19(2):166-171.

4. Coutscoudis I, Adhikari M, Nair N, Coutscoudis A. Feasibility and safety of setting up a donor breastmilk bank in a neonatal prem unit in a resource limited setting: An observational, longitudinal cohort study. BMC Public Health 2011;11:356. [http://dx.doi.org/10.1186/1471-2458-11-356] 5. Coutscoudis I, Petrites A, Coutscoudis A. Acceptability of donated breastmilk in a resource limited South Africa setting. Int Breastfeed J 2011;6:3-4358-6-3. [http://dx.doi.org/10.1186/1746-4358-6-3] 6. Bland RM, Little KE, Coovadia HM, Coutscoudis A, Rollins NC, Newell ML. Intervention to promote exclusive breast-feeding for the first 6 months of life in a high HIV prevalence area. AIDS 2008;22(7):883-891. [http://dx.doi. org/10.1097/QAD.0b013e3282f768de] 7. Bobat R, Moodley D, Coutscoudis A, Coovadia HM. Breastfeeding by HIV-1infected women and outcome in their neonates: A cohort study from Durban, South Africa. AIDS 1997;11(13):1627-1633.

8. Kindra G, Coutscoudis A, Esposito F, Esterhuzen T. Breastfeeding in HIV exposed neonates significantly improves child health: A prospective study.

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Matern Child Health J 2012;16(3):632-640. [http://dx.doi.org/10.1007/s10995011-0795-8] 9. Goga AE, van Wyk B, Doherty T, et al. Infant feeding practices at routine PMTCT sites, South Africa: Results of a prospective observational study amongst HIV exposed and unexposed neonates: Birth to 9 months. Int Breastfeed J 2012;7:4. [http://dx.doi.org/10.1186/17464358-7-4] 10. Goga AE, van Wyk B, Doherty T, et al. Operational effectiveness of guidelines on complete breast-feeding cessation to reduce mother-to-child transmission of HIV: Results from a prospective observational cohort study at routine prevention of mother-to-child transmission sites, South Africa. J Acquir Immune Defic Syndr 2009;50(5):521-528.

11. Saloojee H, Cooper PA. Feeding of infants of HIV-positive mothers. Curr Opin Clin Nutr Metab Care 2010;13(3):336-343. [http://dx.doi.org/10.1097/ MCO.0b013e328337321a] 12. Harris PA, Taylor R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap): A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2008;42(2):377-381. [http://dx.doi.org/10.1016/j.jbi.2008.08.010]

NOVEMBER 2015 Vol. 9 No. 4

SHORT REPORT

Posterior reversible encephalopathy syndrome: Some novel associations M Nandi,1 MD; S Sarkar,2 MD; R Mondal,3 MD; T Dhibar,4 MD Pediatrics, Nil Ratan Sircar Medical College, Kolkata, India Pediatrics, Institute of Post-Graduate Medical Education and Research, Kolkata, India 3 Medical College, Kolkata, India 4 Department of Neuroradiology, Bangur Institute of Neurosciences, Kolkata, India 1 2

Corresponding author: M Nandi (madhumitabanik@rediffmail.com) Posterior reversible encephalopathy syndrome (PRES) (also called reversible posterior leukoencephalopathy syndrome) is a mostly transient and reversible neurological disorder clinically characterised by headache, seizures, blindness and altered consciousness associated with radiological abnormalities in the posterior white matter. Hypertension has been implicated as the most common association. We report four cases of PRES associated with non-hypertensive causes together with a review of the literature. Two cases occurred following cerebral anoxia due to accidental strangulation and near-drowning, respectively. The third patient, a child known to have E-β thalassaemia, presented with transient encephalopathy following blood transfusion but involving the anterior brain rather than the posterior part classically described in PRES. The fourth patient developed PRES while recovering from toxic epidermal necrolysis syndrome. None of these four cases had hypertension at any point during their illness.

S Afr J Child Health 2015;9(4):137-139. DOI:10.7196/SAJCH.2015.v9i4.934

Posterior reversible encephalopathy syndrome (PRES) is characterised by the acute onset of transient and usually reversible alteration of consciousness, seizures, headache and visual disorders, and is associated with abnormal neuroimaging findings mostly in the parieto-occipital cortex.[1] We describe four children with PRES with novel aetiological associations. The first two had hypoxia following accidental strangulation and near-drowning, respectively. The third, a thalassaemic child receiving regular blood transfusions, had PRES following one such transfusion episode. The fourth child had PRES while recovering from toxic epidermal necrolysis syndrome (TENS).

In addition, the child with thalassaemia had involvement of the anterior brain instead of the classically described posterior parts of the brain.

Case reports

Key features of the four cases are detailed in Table 1. PRES in cases 1 and 2 appears to have been precipitated by brain hypoxia, as a result of strangulation and drowning, respectively. The third child was on regular blood transfusions and PRES occurred following one such blood transfusion. The neuroradiological findings of the third child differed as she had involvement of the anterior brain rather than the more commonly reported posterior brain. The fourth child was admitted initially with a diagnosis of TENS. She had 80% involvement of the body surface area along with oral, genital and conjunctival mucosal lesions.

Hence, her SCORTEN score[2] was 4, giving her mortality risk of 58.3%.

She also developed septicaemia with blood culture growing Acinetobacter baumanii sensitive to colistin. She was on the road to recovery, having responded to intensive supportive care and IV antibiotics, when she developed features of PRES on day 12 of admission.

Discussion

PRES (also termed reversible posterior leukoencephalopathy syn­­ drome), first described in 1996, is a neurological disorder clinically charac­terised by headache, seizures, blindness and altered conscious­ ness associated with radiological features of oedema, most often involving the white matter in the posterior regions of the cerebral hemispheres. The oedema is often more pronounced bilaterally in SAJCH

the parieto-occipital regions, but may sometimes spread to the basal ganglia, brainstem and cerebellum. The oedema is usually completely reversible with resolution of clinical symptoms and radiological features. This is in contrast to changes resulting from hypoxicischaemic insults, which show permanent radiological signs. PRES was first reported by Hinchey et al.[1] in 1996 after an observational study of 15 patients. Since then, a few case reports and some case series have been published.[3-6] The most frequently implicated cause of PRES is a hypertensive crisis.

Renal failure, fluid retention, and some immunosuppressive drugs have also been reported as causes.[4] Despite an extensive search, we could not find any aetiological association of PRES with strangulation, drowning, red cell transfusion for thalassaemia or TENS. The exact pathophysiology of PRES has yet to be elucidated.

It has been postulated that the clinical features might be due to sudden disruption of the autoregulatory mechanisms of the central nervous system vasculature, resulting in endothelial dysfunction and breakdown of the blood-brain barrier. Sudden elevation of blood pressure could be one of the factors leading to this disruption.

There is a predilection for involvement of posterior circulation territories, thought to result from the relatively sparse sympathetic innervations of the vertebrobasilar circulation, but there are reports of involvement of the anterior brain, brainstem, basal ganglia, corpus callosum and cerebellum (atypical magnetic resonance imaging (MRI) findings). [1,6] The second postulated cause for PRES is a direct cytotoxic effect on the cerebrovasular endothelium.[6] We report these cases to highlight some unusual associations with this condition. The first two cases are unique as the patients had PRES following hypoxic encephalopathy. The third patient did not have any overt cerebral anoxia but had received a blood transfusion preceding this event. There are a few case series and some reports of PRES occurring after blood transfusion,[7-10] but none associated with E-β thalassaemia or with involvement of anterior regions of the brain. We suspect that a rapid transfusion may have been responsible for PRES in this case. Rapid transfusion can result in a sudden rise in total blood volume, resulting in rapid increase in cerebral blood flow. Such acutely induced cerebral hyperperfusion could exceed the capacity for cerebral autoregulation and produce vasogenic oedema

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Table 1. Details of the patients with PRES Patient 1

Patient 2

Patient 3

Patient 4

Age

7 months

3 years

5 years

4 years

Gender

Female

Male

Female

Female

Brief history

Deep unconsciousness following accidental strangulation as a result of getting accidentally stuck between the wall and the side of her bed, compressing her neck

Unconsciousness and generalised convulsions following neardrowning in a local pool

Vomiting, severe headache, aphasia and drowsiness 2 days after receiving two units of packed cells in a known case of E-βthalassaemia

Generalised maculopapular and bullous eruptions following ingestion of some antipyretics with involvement of oral, genital and conjunctival mucosa. Developed sudden-onset focal convulsion with secondary generalisation followed by headache and loss of vision on D12

Pulse rate (/min)

130

108

90

100

Respiratory rate (/min)

30

Physical findings on admission 36

22

24

Blood pressure (mmHg) 70/46

76/50

92/60

90/58

GCS

E1V1M1

E1V2M1

E3V4M5

E4V4M4

Others

Pupils bilaterally dilated and responding sluggishly

Pupils bilaterally dilated and non-reacting

Pupils normal, liver 4 cm, spleen 5 cm

Pupils dilated and reacting sluggishly (all features were at onset of neurological manifestations)

10.2

10.4

9.6

9.8

TC (/mm )

13 400

11 300

9 600

6 440

DC

N-56, L-45

N-68, L-32

N-64, L-26

N-78, L-22

Platelets (lac/mm )

1.6

1.8

2.2

2.5

Serum electrolytes, calcium, creatinine blood sugar

Within normal range

Within normal range

Within normal range

Within normal range

Chest X-ray

Patchy opacities

Normal

Normal

Normal

CSF study

No abnormality

No abnormality

No abnormality

No abnormality

Management given

ABC of resuscitation, mechanical ventilation for 10 days, mannitol for 4 days

ABC of resuscitation, mechanical ventilation for 5 days, mannitol for 3 days

IV fluids and mannitol

IV fluids, methylprednisolone during the TENs stage, IV fluids and mechanical ventilation for 4 days after neurological manifestations

Time to regain consciousness (days)

10

6

4

7

Condition on discharge

Fully conscious and breastfeeding

Conscious, orientated, seizure free but unable to see

Fully conscious

Fully conscious

Time for full recovery

One month. Achieved normal milestones of development

Vision gradually improved for 2 months

Regained speech gradually and recovered completely neurologically by 2 months

Gradual improvement in vision over 3 months

MRI findings during the acute stage

Bilateral extensive and confluent hyperintensities in the white matter, mostly in the parietal and occipital lobe, suggestive of PRES

Hyperintense signals in both parieto-occipital regions with mild diffusion restriction in T2 and flair images (Fig. 1a)

Multiple hyperintense lesions over subcortical white matter involving cerebral and cerebellar regions in T2 and flair image

Bilateral hyperintensities in both parietal and occipital lobes

Investigations Hb (g/dL) 3

3

Continued ...

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NOVEMBER 2015 Vol. 9 No. 4

Table 1 (continued). Details of the patients with PRES Patient 1

Patient 2

Patient 3

Patient 4

MRI findings after recovery (6 months after acute episode)

No abnormality

Complete disappearance of hyperintensities (Fig. 1b)

No abnormality. Complete disappearance of hyperintensities

Complete recovery. No residual abnormality

Final diagnosis

PRES due to accidental strangulation

PRES due to neardrowning

PRES following red cell transfusion in a child with thalassaemia

PRES following TENS

GCS = Glasgow Coma Scale; Hb = haemoglobin; TC = total count; DC = differential count.

Fig. 1a. Hyperintense signals in both parieto-occipital regions with mild diffusion restriction in T2 flair images of patient 2 (PRES due to near-drowning).

Fig. 1b. Complete disappearance of the hyperintensities after 6 months.

leading to PRES.[10] The fourth child had PRES while recovering from TENS. The pathophysiology behind PRES with TENS remains unknown.

Although hypertension has been implicated as the most common aetiology of PRES, blood pressure was not raised at any time during the course of illness in any of these cases.

The importance of these cases lies in the fact that although PRES is a serious life-threatening condition, it is almost always completely reversible if appropriate management is given in the acute stage.

Also, given the scores of patients given blood transfusion for thalassaemia in our regular practice, more vigilance and awareness may pick up many similar cases. Early recognition of characteristic radiological features is key to the diagnosis as clinical symptoms may be nonspecific or mimic other more common neurological illnesses.

Only long-term multicentre follow-up studies will provide more clues regarding the exact pathogenesis and non-hypertensive etiological factors involved in this condition, especially in children, in whom the physiology of cerebral circulation may be different from that of adults.

2. Bastuji-Garin S, Fouchard N, Bertocchi M, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN: A severity-of-illness score for toxic epidermal necrolysis. J Invest Dermatol 2000;115(2):149-153. [http://dx.doi.org/10.1046/j.1523-1747.2000.00061.x] 3. Moratalla MB. Posterior reversible encephalopathy syndrome. Emerg Med J 2010;27(7):547. [http://dx.doi.org/10.1136/emj.2008.069765] 4. Incecik F, Herguner MO, Altunbasak S, Erbey F, Leblebisatan G. Evaluation of nine children with reversible posterior encephalopathy syndrome. Neurol India 2009;57(4):475-478. [http://dx.doi.org/10.4103/0028-3886.55605] 5. Endo A, Fuchigami T, Hasegawa M. Posterior reversible encephalopathy syndrome in childhood: Report of four cases and review of the literature.

Pediatr Emerg Care 2012;28(2):153-157. [http://dx.doi.org/10.1097/ PEC.0b013e3182442fe8] 6. Chen TH, Lin WC, Tseng YH, Tseng CM, Chang TT, Lin TJ. Posterior reversible encephalopathy syndrome in children: Case series and systematic review. J Child Neurol 2013;28(11):1378-1386. [http://dx.doi.org/10.1177/0883073813500714] 7. Huang YC, Tsai PL, Yeh JH, Chen WH. Reversible posterior leukoencephalopathy syndrome caused by blood transfusion: A case report. Acta Neurol Taiwan 2008;17(4):258-262.

8. Khademian Z, Speller-Brown B, Nouraie SM, Minniti CP. Reversible posterior leuko-encephalopathy in children with sickle cell disease. Pediatr Blood Cancer 2009;52(3):373-375. [http://dx.doi.org/10.1002/pbc.21812] 9. Kolovou V, Zampakis P, Ginopoulou A, Varvarigou A, Kaleyias J. Reversible posterior leukoencephalopathy syndrome after blood transfusion in a pediatric patient with sickle cell disease. Pediatr Neurol 2013;49(3):213-217. [http:// dx.doi.org/10.1016/j.pediatrneurol.2013.04.024] 10. Wada K, Kano M, Machida Y, Hattori N, Miwa KH. Posterior reversible encephalopathy syndrome induced after blood transfusion for severe anemia.

Case Reports Clin Med 2013;2(5):332-334. [http://dx.doiorg/10.4236/ crcm.2013.25089]

References

1. Hinchey J, Chaves C, Appignani B, et al. A reversible leuoencephalopathy syndrome. N Engl Med J 1996;334(8):494-500. [http://dx.doi.org/10.1056/ NEJM199602223340803]

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CASE REPORT

Congenital nephrotic syndrome: A diagnostic and management dilemma R Moodley, MB ChB, FCPaed, Cert Nephrology (Paeds); E Naicker, MB ChB, DCH, FCP (Paeds), Cert Nephrology (Paeds); R Bhimma, MB ChB, DCH, FCP (Paeds), MMed, MD, Cert in Nephrology (Paeds), ISN Fellowship

Department of Paediatrics and Child Health, School of Clinical Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa Corresponding author: R Bhimma (bhimma@ukzn.ac.za) Congenital nephrotic syndrome (CNS) is characterised by heavy proteinuria, hypoproteinaemia and oedema presenting in the first 3 months of life. We present a 27-day-old female patient admitted to the Inkosi Albert Luthuli Central Hospital with CNS; one of twins and HIV exposed but uninfected. The child had a cytomegalovirus (CMV) polymerase chain reaction (PCR) positive result in the urine, confirmed on two separate occasions. The CMV PCR for qualitative testing of CMV DNA was negative and quantitative testing was not done. CMV retinitis and central nervous system involvement were absent. Despite treatment with gancyclovir, the CNS did not improve.

Further management required indomethacin followed by unilateral nephrectomy to decrease administration of albumin infusions to control oedema. Unfortunately, due to loss to follow-up, the patient demised from probable sepsis. We discuss the challenges we faced with respect to the diagnosis and management of CNS in a resource-limited setting where transplantation is not readily available.

S Afr J Child Health 2015;9(4):140-141. DOI:10.7196/SAJCH.2015.v9i4.903

One of the most difficult clinical challenges in the treatment of glomerular diseases in children is the management of congenital nephrotic syndrome (CNS). This is a rare but severe disorder characterised by heavy proteinuria, hypoproteinaemia and oedema presenting in the first 3 months of life. The primary or inherited form is associated most commonly with mutations encoding one of two structured proteins of the slit diaphragm viz. nephrin (NPHS1) and podocin (NPHS2), and a transcription factor (WT1).[1] The secondary form is associated with systemic diseases, typically perinatal infections including congenital syphilis, rubella, toxoplasma, cytomegalovirus (CMV), HIV-1 and hepatitis B.[2] Other less common secondary causes include maternal lupus erythematosus, neonatal antibodies against neutral endopeptidase and drugs such as maternal steroid and chlopheniramine treatment.[3] Treatment with steroids and other immunosuppressive drugs is ineffective in inducing remission. Therefore, the objectives of therapy are to control oedema, delay progression to end-stage kidney disease, prevent and treat complications such as infections and thrombosis, and provide optimal nutrition for growth and development.

The definitive treatment is kidney transplantation once the infant is about 10 kg in weight.[3] However in resource-limited settings with numerous technical challenges and organ shortage, transplantation is not readily feasible, especially in young recipients.

We present a child with CNS in such a setting and discuss the challenges faced with respect to diagnosis and management.

Permission to publish this case as part of a larger study was obtained from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal (Ref number: BE078/13).

Case

A 27-day-old female patient was admitted to the Inkosi Albert Luthuli Central Hospital in August 2011. The child was one of dizygotic twins delivered at 31 weeks’ gestation, with an admission weight of 1.9 kg. There was no history of an enlarged placenta. The mother was infected with HIV-1; serology for syphilis was negative and alphafetoprotein was not tested. She received antiretrovirals antenatally and both infants tested negative for HIV on two separate occasions.

Ten days post delivery, twin 1 presented to a peripheral hospital with anasarca, failure to thrive and clinical sepsis. Laboratory 140

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findings showed severe hypoalbuminaemia (serum albumin 18 mg/ dL), a high urinary protein:creatinine ratio of 2.65 mg/dL/ mg/dL (reference range <2 mg/dL/mg/dL) with a normal total serum cholesterol of 4.20 mmol/L (2.75 - 4.53 mmol/L) and normal liver enzymes. Kidney function tests showed a serum urea of 4.1 mmol/L (1.1 - 9.1 mmol/L) and serum creatinine of 52 µmol/L (44 - 88 µmol/L).

Thyroid function tests were normal. Kidney ultrasound showed normalsized, hyperechoic kidneys with loss of corticomedullary differentiation.

The CMV polymerase chain reaction (PCR) was positive in the urine on two separate occasions. Cardiac echocardiogram showed peripheral pulmonary stenosis while an ophthalmology examination revealed no evidence of CMV retinitis. Cranial ultrasound did not show periventricular calcification. Open renal biopsy was unfortunately not done on the initial admission due to the child being too ill. It was assumed she had CMV-associated CNS in view of the positive CMV PCR in her urine, present before 3 weeks of age. Tests for other infections viz. syphilis, hepatitis B and C and rubella were negative. Due to lack of resources, genetic testing for candidate genes incriminated in the genetic origin of this condition was not possible.

Management included symptomatic control of oedema with albumin infusions. She was also prescribed hydrochlorthiazide, spironolactone, enalapril and a high-protein diet. Indomethacin was initially commenced at a low dose and titrated to a maximum dose.

Vitamin and iron supplementation were commenced following control of sepsis. Subsequent testing showed the child to have hyperlipidaemia (serum cholesterol 7.3 mmol/L and triglycerides 4.35 mmol/L) and hypothyroidism with a serum T4 level of 9.1 pmol/L and thyroidstimulating hormone level of 12.45 mIU/L. She was prescribed simvastatin as well as thyroxine. Anticoagulation therapy was not commenced due to the risk of bleeding, as the platelet count dropped significantly following commencement of indomethacin.

Gancyclovir was given as treatment for CMV for two weeks and she was then discharged on oral valgancyclovir. Valgancyclovir therapy was completed over a 6-month period owing to poor compliance and medication unavailability. Her nutrition was optimised, and she was referred to her base hospital for control of oedema. Weekly monitoring for neutropenia was done during the period of gancyclovir use. She required admissions two to three times a week for albumin infusions In September 2012 an open kidney biopsy showed histopathological features in keeping with the spectrum of CNS. CMV inclusions were

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not seen. She was noted to have severe acute malnutrition with failure to thrive, hepatosplenomegaly and generalised lymphadenopathy.

Screening for metabolic diseases, repeat HIV-1 PCR testing, as well as investigations for tuberculosis were negative. Repeated testing for CMV PCR on three occasions was negative.

Despite aggressive nutritional therapy and maximal medical management, she required albumin and diuretic infusions at least two to three times a week, with numerous admissions for lower respiratory tract infections, for which she was treated with bronchodilator nebulisations and intravenous antibiotics. In March 2013, she tested positive for Mycobacterium tuberculosis and received a 6-month course of anti-tuberculosis therapy.

In view of her frequent hospitalisations for control of oedema, a unilateral nephrectomy was performed in October 2013 (age 26 months) to decrease urinary protein losses. The resected left kidney showed dilated Bowman’s capsules with florid focal segmental glomerular sclerosis, global glomerulosclerosis and interstitial fibrosis.

Although the child remained mildly oedematous, her albumin and diuretic infusions decreased to not more than once weekly. Her kidney function was normal and she remained euthyroid. Serum albumin levels remained low with an average protein:creatinine ratio of 4.5 (mg/dL/ mg/dL). She remained malnourished despite attempts to optimise her nutrition. She had features of global developmental delay; with normal neuroimaging. The child was unfortunately lost to follow-up for about a year and the mother subsequently reported that the child had died, presumably from overwhelming sepsis.

Discussion

We present a case of a child with CNS, one of twins and HIV-1 exposed but not infected. The case presented both diagnostic and management challenges in a resource-limited setting. Prior to the 1990s, CNS in our region was seen almost exclusively in newborns secondary to congenital syphilis, with a gratifying response to penicillin therapy (personal communication, Adhikari). It is, however, possible that the condition was undiagnosed as it is rare and may have been mistaken for severe acute malnutrition. The latter is not uncommon in our population, where the majority of patients present from a lower socioeconomic background.

The diagnostic dilemma was whether our patient had CNS secondary to CMV or whether the presence of a positive CMV PCR in the urine at just over 3 weeks of age was a gratuitous finding.

Screening for CMV involvement of other systems was negative.

CMV PCR viral load was not done owing to cost implications.

Kidney biopsy did not demonstrate evidence of a proliferative glomerulonephritis, viral immune defects in glomerular cells, or an immune complex glomerulonephritis with IgG, IgA, C3 or CMV antigens within glomeruli. However, the biopsy was done after gancyclovir treatment. Treatment with an extended course of valganciclovir had no effect on ameliorating the disease.

CMV intrauterine infection is a well-documented cause of the secondary form of this disease. However, the causal relationship between CMV and CNS has been challenged by Frishberg et al.,[4] who reported a case of mutated podocin manifesting as CMV-associated CNS and proposed that CMV infection was only a secondary finding. Several reports have established a causal relationship between CMV and CNS. [5] In these reports, CNS was associated with extrarenal manifestations such as neurological, ophthalmological, haematological, cutaneous and pulmonary manifestations.[5] In almost all cases reported to date, CNS associated with CMV responded to treatment. This unfortunately was not the case in our patient, suggesting that CMV infection may have been an incidental finding. This is similar to the case reported by Frishberg et al.[4] in which mutated podocin-associated CNS had CMV as an incidental finding. We unfortunately could not undertake genetic testing in our patient due to lack of resources and financial constraints.

The management of CNS is extremely difficult as immuno­ suppressive agents are ineffective in alleviating proteinuria and SAJCH

inducing long-term remission. The goals of therapy in the first months of life are to control oedema, prevent progression to end-stage kidney disease, prevent and treat complications such as fluid and electrolyte disturbances, recurrent infections, thrombosis, hypothyroidism, hypertension and hypercholesterolaemia, and optimise nutrition to promote growth and development. When necessary, supplemental calcium and magnesium replacement therapy is given to keep serum levels within normal range. As our patient was able to tolerate adequate amounts of oral feeds to meet dietary requirements, an indwelling nasogastric tube or gastrostomy was not necessary.

Despite maximal antiproteinuric therapy, the patient remained highly proteinuric with failure to thrive. Ideally, bilateral nephrectomies and commencement of dialysis should have been undertaken, but given the challenges faced in our setting, a more conservative approach was adopted and a unilateral nephrectomy was performed to reduce protein losses. This decreased the frequency of albumin infusions while maintaining kidney function. It was hoped that this would allow the child to thrive and gain weight. Only if the child’s kidney function had progressed to end-stage kidney disease, would chronic dialysis and a kidney transplant have been considered once an appropriate weight was reached. Unfortunately, sepsis is a major complication of this condition; the child was lost to follow-up and most likely died from overwhelming sepsis.

The only curative treatment of CNS is kidney transplantation.

This poses major challenges in resource-limited settings owing to the enormous costs involved, technical challenges and organ shortages.

Whereas previously, CNS patients had a higher rate of kidney graft failure compared with patients undergoing transplants for other kidney diseases, particularly in younger recipients <2 years old, more recent data have shown graft survival rates of over 80%. This is similar to that obtained with other aetiologies, with 5-year patient survival of 90%.[6] Although the results of kidney transplantation in these younger patients are improving, chronic allograft nephropathy remains a major problem and a second kidney transplant is inevitable when the patients reach adulthood.[3]

Conclusion

This is the first report of a child with CNS from a resource-limited setting that presented with both a diagnostic and management challenge. Following optimal nutrition and maximum drug therapy, a unilateral nephrectomy was undertaken that ameliorated proteinuria and decreased the need for frequent albumin infusions. We advocate such an approach in a resource-limited setting where access to renal replacement therapy may not be readily available.

Acknowledgments. The authors wish to thank the Medical Manager of Inkosi Albert Luthuli Central Hospital for permission to publish, Ms Nompumelelo Ndlela for her administrative support in formatting the paper, and medical and nursing staff at the various healthcare centres who were involved in the care of the child.

References 1. Boute N, Gribouval O, Roselli S, et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000;24(4):349-354. [http://dx.doi.org/10.1038/74166] 2. Holmberg CJH, Tryggavason K, Rapola J. Congenital nephrotic syndrome.

In: Barratt TM, Harmon WE, eds. Pediatric Nephrology. 4th ed. Baltimore: Lippincott Williams & Wilkins, 1999:765-777.

3. Jalanko H. Congenital nephrotic syndrome. Pediatr Nephrol 2009;24(11):21212128. [http://dx.doi.org/10.1007/s00467-007-0633-9] 4. Frishberg Y, Rinat C, Feinstein S, Becker-Cohen R, Megged O, Schlesinger Y. Mutated podocin manifesting as CMV-associated congenital nephrotic syndrome. Pediatr Nephrol 2003;18(3):273-275.

5. Besbas N, Bayrakci U, Kale G, et al. Cytomegalovirus-related congenital nephrotic syndrome with diffuse mesangial sclerosis. Pediatr Nephrol 2006;21(5):740-742. [http://dx.doi.org/10.1007/s00467-003-1079-3] 6. Benfield MR, McDonald RA, Bartosh S, Ho PL, Harmon W. Changing trends in pediatric transplantation: 2001 Annual Report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Transplant 2003;7(4):321-335.

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CPD November 2015 The CPD programme for SAJCH is being administered by Medical Practice Consulting: CPD questionnaires must be completed online at www.mpconsulting.co.za

True (T) or False (F): Regarding the EPI and vitamin A supplementation programmes in KwaZulu-Natal 1. T he uptake of vitamin A supplementation in infants during the first year of life is as good as the uptake of the EPI programme.

2. The uptake of diphtheria and tetanus (DT) 1 and oral polio vaccine (OPV) 5 at 6 years of age was nearly 80%.

Regarding interhospital transfers of critically ill children 3. The Triage Early Warning Signs score is an age-independent scoring system to identify potentially seriously ill children.

4. Transfer times between the referring hospital and the central hospital were short – generally <3 hours.

Regarding sickle cell anaemia (SCA) 5. Sickle cell anaemia is a genetic disorder affecting the alphaglobin subunit of haemoglobin.

6. Severe pain in SCA is usually caused by vaso-occlusion of the microcirculation and tissue ischaemia.

7. Approximately half of children being treated for pain associated with SCA in a Nigerian hospital were being overdosed.

Regarding bacteraemia in young children 8. Approximately 10% of children <5 years of age admitted with pyrexia will have a positive blood culture.

9. The incidence of bacteraemia in children is unrelated to the severity of fever.

10. Bacteraemia is approximately twice as common in malnourished children as it is in children with normal nutrition.

Anaemia in primary school children in KwaZulu-Natal 11. Anaemia in prepubertal children >5 years of age is defined as Hb <11.5 g/dL. 12. Over 50% of early school-going children had anaemia.

Regarding the use of lactose-free feeds in the management of severely malnourished HIV children 13. One of the criteria used by the World Health Organization to define severe acute malnutrition in children is a weight-forheight of <–3 standard deviations below the mean.

14.

F-75 refers to a specific formula that contains more than 75 kcal/100 mL. Regarding the feeding of neonates in hospital 15. Breastfeeding results in a higher stool pH than that found in the stools of formula-fed neonates.

16. Twenty percent of preterm neonates discharged from a neonatal unit in Johannesburg were exclusively breastfed.

Regarding posterior reversible encephalopathy syndrome (PRES) 17.

PRES typically presents with altered consciousness, seizures, headaches and visual disturbances.

18. Hypertension is the most common cause of PRES. Regarding congenital nephrotic syndrome 19. Congenital nephrotic syndrome is defined as nephrotic syndrome occurring within the first 6 weeks of birth.

20. Congenital syphilis is one of the secondary causes of congenital nephrotic syndrome.

A maximum of 3 CEUs will be awarded per correctly completed test.

CPD questionnaires must be completed online via www.mpconsulting.co.za. After submission you can check the answers and print your certificate. Accreditation number: MDB015/165/02/2015(Clinical)

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