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August 2015, VOLUME 08, ISSUE 08
THE OFFICIAL NEWSLETTER OF THE SRI LANKA MEDICAL ASSOCIATION
Cover Story...
Page 04, 06, 07
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SLMA President-Elect 2016
Winners of Prizes and Awards
SLMA Banquet
Melioidosis in Sri Lanka
3D View of Dengue
Medicines for Children in Sri Lanka
www.slma.lk
office@slma.lk
www.slma.lk/publications/newsletter/
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CONTENTS Page No.
Cover Story SLMA Banquet
SLMANEWS
THE OFFICIAL NEWSLETTER OF THE SRI LANKA MEDICAL ASSOCIATION
August 2015, Volume 8, issue 08
04, 06, 07
SLMA News Editorial Committee-2015 Editor-In-Chief: Prof. Sharmini Gunawardena
News
Committee:
President's message Winners of Prizes and Awards SLMA Banquet
02 03, 04
04, 06, 07
Melioidosis in Sri Lanka
08, 09, 10
3D View of Dengue
Medicines for Children in Sri Lanka
Events
12, 14, 16 18, 20, 22
SLMA President-Elect 2016
02
Doctors' Wives Association
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Dr. Amaya Ellawala Dr. Iyanthi Abeyewickreme Prof. Deepika Fernando Dr. Sarath Gamini De Silva
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Official Newsletter of The Sri Lanka Medical Association. Tele: +94 112 693324 E mail: office@slma.lk
Professor Jennifer Perera MBBS, MD (Col), MBA(Wales), PgDip MedEd (Dundee), PgDip Women’s Studies(Col). President, Sri Lanka Medical Association, No 6, Wijerama Mawatha, Colombo 7, Sri Lanka.
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PRESIDENT’S MESSAGE
August 2015
Dear Colleagues, The feedback I received from all quarters suggested that the 128th Anniversary International Medical Congress was a success. However, we stepped back and looked at the congress proceedings and related events to ensure that we do not repeat any mistakes during 2016. The post congress review enlightened us on how we could do things better next year. Post congress documentation is very important, as it allows us to refer back to our notes as memories fall short and people move on, and for others to take over. I am very grateful to those who conducted the review of activities related to the walk and run, pre and post congress workshops, doctors’ concert, the banquet, the orations, and the main congress related activities. At the congress many important research areas were highlighted during the free paper and poster sessions. We plan to discuss the relevant research findings with the Ministry of Health, for furthering of locally relevant research areas and / or their implementation. Many articles based on different congress symposia are in preparation for circulation through the monthly newsletter for the benefit of those who could not make it to the congress. Nirogi, has been our flagship project, which has been working towards reducing the incidence of diabetes and related complications through engagement of all stakeholder groups including the community. The SLMA with the Nirogi team renewed their partnership with DSI, through the re-
launch of the diabetic shoe. Both the Nirogi team and DSI are taking steps to popularize the ‘Nirogi’ diabetic shoe among both doctors and patients through awareness programmes. At the same time, based on consumer feedback DSI have plans to improve the cosmetic appearance of the shoe and to produce more variety in order to cater to the needs of all social classes. The Organisation of Professional Associations (OPA) is holding their annual scientific sessions on the 21st and 22nd of September 2015 at Hotel Galadari, Colombo. The SLMA is an active and long standing member of this association. The OPA conducts numerous update symposiums on nationally relevant issues and voice their opinion on many important professional and national issues of the country. Many SLMA members have held the distinguished post of President of the OPA. All members of the SLMA are cordially invited to attend the annual scientific sessions of the OPA. We are in the process of organising the annual cricket encounter with lawyers and would like to invite members who would be willing to play for the SLMA team to come forward. I am sure this year, too, the SLMA will emerge as winners. It is important to engage in social activities with other professional organizations, as this will promote and foster camaraderie which is important to achieve common goals that are nationally relevant. This type of activity in addition provides a vent to release our day to
To All Members of the SLMA Sri Lanka Medical Association President-Elect 2016
Applications are called for the Post of President-Elect, Sri Lanka Medical Association (SLMA), for the year 2016. Please indicate the role played in the SLMA and other professional bodies/institutions in your application. Applications close on 30th September 2015. Please forward applications to Dr. J. B. Peiris, Past Presidents’ Representative in the Council, via email to jbpeiris@hotmail.com.
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day stresses while providing room for building relationships both among SLMA members and other professional bodies. Preparations are being made to hold the annual career guidance seminar for young graduates. This seminar, which has had wide participation in the past, will be held at the SLMA auditorium on Sunday, the 4th of October 2015. Representatives of all colleges and associations will present the scope of different specialties and update the participants on the current status of their respective specialties in Sri Lanka as well as overseas. The much looked forward to SLMA Foundation Sessions are due to be held at Anuradhapura from 28th – 30th October 2015. A very good programme with the participation of overseas experts is being organized and we will keep you informed of the progress. Please keep the dates free. All in all we are having yet another busy month organizing these future events. My request to both the council and members is to join in these activities and contribute while enjoying what they have to offer. Professor Jennifer Perera
SLMANEWS
August 2015
WINNERS OF PRIZES AND AWARDS 128TH ANNIVERSARY INTERNATIONAL MEDICAL CONGRESS OF THE SLMA E M WIJERAMA PRIZE
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OP056: A randomized control study of audio versus visual distraction to reduce patient discomfort during colonoscopy De Silva AP , Nandamuni Y , Rajapakshe NN1, Nanayakkara S1, Perera KR2, Kodisinghe SK2, Subasinghe SKC2,Niriella M. A1, Dassanayake AS1, Pathmeswaran A1, De Silva HJ1 1
1
Medical Research Institute, Sri Lanka
SIR NICHOLAS ATTYGALLE PRIZE OP030: Effectiveness of a lifestyle modification programme in reducing cardiometabolic risk markers in urban Sri Lankan women with prediabetes Waidyatilaka PHIU1, de Silva A2, Lanerolle P1, Wickremasinghe R3, Atukorala S1
University Medical Unit, Colombo North Teaching Hospital, Ragama, Sri Lanka
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S E SENEVIRATNA PRIZE
2
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OP026: Bullying in schools among early adolescents in Galenbindunuweva educational zone: prevalence, types, common responses and effectiveness of a health promotion intervention Jayasinghe VPKK1, Perera KMN2, Guruge GND1 Health Promotion Division, Biological Department, Faculty of Applied Sciences, Rajarata University of Sri Lanka
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Department of Public Health, Faculty of Medicine, University of Kelaniya
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H K T FERNANDO PRIZE OP070: An investigation of food borne outbreak among army soldiers in four military establishments in North Central Province Kothalawala M1, Subasinghe SMA2, Hewavitharana SP3, Kannangara KMM4, Pathirage MVSC5 1
Teaching Hospital Kandy, Sri Lanka
District General Hospital Polonnaruwa, Sri Lanka
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3
MOH Hingurakgoda, Sri Lanka
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Military Hospital, Sri Lanka
Department of Chemistry, Faculty of Science, University of Colombo, Sri Lanka.
1
Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka
1
RS1
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Sri Lanka. Department of Physiology, Faculty of Medicine, University of Colombo, Sri Lanka. Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka,
Department of Surgery, Faculty of Medicine, University of Colombo, Sri Lanka
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Department of Pathology, Faculty of Medicine, University of Colombo, Sri Lanka
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Molecular Medicine Unit, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
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SIR FRANK GUNASEKERA PRIZE FOR THE BEST PAPER IN COMMUNITY MEDICINE AND TUBERCULOSIS None qualify
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WILSON PEIRIS PRIZE OP041: Randomised, single blind clinical trial on intramuscular long acting ACTH versus oral prednisolone for long term control of epileptic spasms Wanigasinghe J1, Arambepola C1, SriRanganathan S1, Sumanasena S1, Mohumdirum E1, Attanapola G1 1
University of Colombo
DAPHNE ATTYGALLE PRIZE FOR THE BEST PAPER IN CANCER PP050: Development of modified mismatch PCR-RFLP to screen mutations in codon 12 and 13 of K-ras gene of colorectal (CRC) patients in Sri Lanka Dhilhani MFF , De Zoysa MIM , Chandrasekharam NV1, Gunawardene YINS 4, Lokuhetti MDS3, Dassanayake 1
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KUMARADASA RAJASURIYA PRIZE FOR THE BEST PAPER IN TROPICAL MEDICINE OP008: A diagnostic model for Leptospirosis for use in resource limited settings Rajapakse S1, Weeratunga PN1, Rodrigo C1, Sriharan S1, Niloofa MJR2, Fernando N2, de Silva HJ3, Karunanayake L4, Premawansa S5, Handunnetti S2 Tropical Medicine Research Unit, Department of Clinical Medicine, Faculty of Medicine, University of Colombo, Sri Lanka.
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Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka.
2
Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
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Department of Bacteriology, Medical Research Institute, Colombo, Sri Lanka.
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Department of Zoology, University of Colombo, Sri Lanka.
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Contd. on page 4
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August 2015 Contd. from page 3
Winners of... SPECIAL PRIZE IN CARDIOLOGY OP032: The immediate outcome of intravenous Enoxaparin followed by subcutaneous Enoxaparin versus only subcutaneous Enoxaparin as adjunctive therapy for fibrinolysis in ST-elevated myocardial infarction in patients admitted to emergency treatment unit at teaching hospital Batticaloa Arulnithy K1, Hewarathna UI2, Narayanapillai S1, Santhavani T S1, Sivapramyan A1, Ladahumanan D1 Department of cardiology, Teaching Hospital, Batticaloa
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Department of cardiology, Teaching Hospital, Kandy
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S RAMACHANDRAN PRIZE FOR THE BEST PAPER IN NEPHROLOGY
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PP046: Urine micro albumin/creatinine ratio in wistar rats given unboiled and boiled water collected from dug wells in high disease prevalent areas for CKDU in North Central Province (NCP) and water from low disease prevalent Huruluwewa area in NCP
SLMA PRIZE FOR THE BEST POSTER
Thammitiyagodage MG1, Gunatillake MM1, Karunakaran R1, Kumara WGSS1, Galhena BP2, Thabrew MI3 1
Medical Research Institute, Sri Lanka
Department of Biochemistry and Clinical Chemistry, Faculty of Medicine, Kelaniya, Sri Lanka
2
Institute of Biochemistry, Molecular Biology and Biotechnology, University of Colombo, Sri Lanka
PP095: Impact of a ward-based clinical pharmacy service in reducing drug-related hospital re-admissions in patients with chronic noncommunicable diseases: evidence from a controlled trial in Sri Lanka Shanika LGT1, Wijekoon N2, Jayamanne S1,2, Coombes J1, Mamunuwa N1, Dawson A1, De Silva HA2 South Asian Clinical Toxicology Research Collaboration
1
Faculty of Medicine, University of Kelaniya
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SLMA BANQUET
The SLMA banquet held at the Galadari Hotel, Colombo, on the 8th of July 2015 provided a grand finale for the 128th Anniversary International Medical Congress. Contd. on page 6
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August 2015
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Contd. from page 4
SLMA Banquet...
Contd. on page 7
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August 2015
Contd. from page 6
SLMA Banquet...
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August 2015
MELIOIDOSIS IN SRI LANKA Dr. Enoka Corea Senior Lecturer, Department of Microbiology, Faculty of Medicine, University of Colombo Tel: 0777808439 e-mail: enokacorea@hotmail.com
What is melioidosis?
Melioidosis is a tropical infection caused by the saprophytic soil bacterium Burkholderia pseudomallei. It is found in the tropics between 20°N and 20°S of the equator. While it is considered an uncommon infection in most of this region, in high endemic areas such as Thailand, Malaysia and Northern Australia it is a significant cause of community-acquired pneumonia and sepsis. Its apparent rarity in other tropical regions may be due to lack of clinical awareness and microbiology services.
How is infection acquired?
Infection is acquired accidentally, during occupational, recreational or lifestyle exposure to soil, mud or water containing the bacterium. B. pseudomallei enters the body by percutaneous inoculation, inhalation or ingestion. Initial infection following exposure may be asymptomatic and the bacterium may remain dormant for many months, years or even decades before activation in a fulminant form. However, in most cases, the incubation period varies from a few days to weeks.
Are there any risk factors for melioidosis?
B. pseudomallei is an opportunistic pathogen, and though clinical disease is seen in healthy individuals it is more common in persons with chronic comorbidity, particularly uncontrolled diabetes mellitus. Other risk factors include renal or liver disease, alcoholism, chronic lung disease and thalassaemia.
What are the common presentations? Melioidosis may involve any system
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and is often multifocal. Clinical presentation ranges from severe to mild and from acute to chronic. Typical presentations include fulminant septicaemia, severe community acquired pneumonia or lung abscess, single or multiple abscesses of the superficial or deep tissues including liver, splenic, and cerebral abscess, musculoskeletal disease such as abscess of the psoas muscle, septic arthritis or osteomyelitis, skin infection, genitourinary infection and lymphnode suppuration. Patients often have multifocal involvement, with combinations of the above presentations, with or without blood stream infection. Less common presentations include brain stem encephalitis, prostatitis and parotitis. Melioidosis is one of the differential diagnoses of tuberculosis. Relapses after apparent cure are characteristic and a history of recurring infection may be elicited.
Does it occur in outbreaks? Melioidosis is usually sporadic, in keeping with the accidental and opportunistic nature of the infection, with a sharp increase in the number of cases during the rainy season. Case clusters may be seen after severe weather events, probably due to aerosolisation of bacteria and increased inhalation risk. Case clusters were reported in many countries following the 2004 Indian Ocean tsunami. A few point source outbreaks due to untreated natural water sources and nosocomial outbreaks have been described in Australia.
What is the mortality of melioidosis? Melioidosis is a potentially fatal infection and mortality can be as high as 50%. However early diagnosis and appropriate treatment reduce morbidity and mortality considerably.
Is melioidosis found in Sri Lanka? Between 1927 and 2006 only three cases of indigenous transmission of melioidosis were reported. How-
ever, after 2006 more than 80 culture proven cases and a large number of cases diagnosed by high antibody titres have been identified. B. pseudomallei appears to be ubiquitous in soil in Sri Lanka and cases of melioidosis have been reported from all provinces. Genotyping of strains show that the bacterium is an established endemic pathogen in Sri Lanka and that the emergence of melioidosis in the recent past is not due to recent introduction.
What are the geographic and demographic features of patients with melioidosis in Sri Lanka? Most cases are seen in rice growing areas and it seems to be less common in rubber and tea growing districts. Infection occurs in all age groups, including children, and in both sexes, though the highest incidence is seen in middle aged males. Persons with occupational exposure to soil, such as farmers and cultivators and house or road construction workers, are at special risk, as are persons in the police and defence forces. However, it is clear that the majority of the Sri Lankan population is exposed to risk, as even areas classified as ‘urban’ are contiguous with cultivated lands and most of the population is directly or indirectly engaged in cultivating food crops for commercial or domestic use. The custom of walking barefoot and of using natural sources of water for drinking and bathing may also contribute to an increased risk of infection. The rapidly increasing incidence of diabetes is likely to result in an increase in clinical disease in the future.
Is there a seasonal trend in incidence? Melioidosis occurs throughout the year but incidence appears to increase with the onset of the monsoon rains, especially the north east monsoon. The peak number of cases occurs about 1-2 months after the peak rainfall. Contd. on page 9
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Contd. from page 8
Melioidosis in... How can we make the diagnosis? As the clinical presentation and baseline laboratory tests in melioidosis are non-specific and may mimic many other infectious diseases, the diagnosis of melioidosis can only be established by the microbiology laboratory. This is best achieved by isolation of the pathogen from patient specimens. B. pseudomallei is not fastidious and is easily isolated on all common culture media used in a clinical microbiology laboratory. Specimens for culture include blood, pus from abscesses, sputum, urine and infected tissues. Specimens from sterile sites should be inoculated into an enrichment medium such as brain heart infusion broth and incubated for up to 2 weeks. Although selective media are described for selective isolation of B. pseudomallei they do not increase the yield from sterile sites and may not be cost effective for use on specimens from non-sterile sites.
Adapted from: Pitman MC, Luck T, Marshall CS, Anstey NM, Ward L, Currie BJ (2015) Intravenous Therapy Duration and Outcomes in Melioidosis: A New Treatment Paradigm. PLoS Negl Trop Dis 9(3):e0003586. doi:10.1371/journal.pntd.0003586
How do I treat melioidosis? There are well established antibiotic treatment guidelines for the treatment of melioidosis (see tables below). Treatment comprises an early phase of acute treatment with parenteral antibiotics such as ceftazidime OR imipenem OR meropenem, with additional adjunct therapy with oral cotrimoxazole for deep seated focal involvement. Duration of the intensive phase ranges from 2-8 weeks. This is
Adapted from: Inglis Timothy J.J., Rolim Dionne B., Rodriguez Jorge L.N. Clinical guideline for diagnosis and management of melioidosis. Rev. Inst. Med. Trop. S. Paulo 2010; 48 (1): 1-4.
followed by 3-5 months of eradication therapy using a combination of any two of oral cotrimoxazole, doxycycline or amoxicillin / clavulanic acid. (See tables below for recommended antibiotics and duration of therapy).
How is B. pseudomallei identified in the laboratory? Colony appearance on blood and MacConkey agar, Gram stain morphology, oxidase reaction and a typical antibiotic sensitivity profile are sufficient for presumptive identification of B. pseudomallei in the clinical microbiology laboratory. Growth on most media occurs after overnight incubation in ambient air at 37째C. Colonies at 24 hours are usually pin point in size. After 48 hours colonies are larger (2mm) and circular with an entire edge. On blood agar, the well is usually chalky white with a metallic sheen and shows underlying beta haemolysis. The culture has a characteristic earthy odour. After further incubation the colonies become umbonate and then acquire a concentric appearance (Figure 1). Wrinkling, if it occurs at all, is seen only after 5-7 days of incubation at room temperature. On MacConkey agar colonies are pin point in size and have a nonlactose fermenting appearance at 24 hours, changing to dark pink (similar to lactose fermenting bacteria) at 48 hours (Figure 2). Contd. on page 10
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August 2015 Contd. from page 9
Melioidosis in... Some strains give rise to colonies with varying morphology and may be dismissed as mixed cultures. A minority of strains differ considerably from the typical one described and can appear serous to frankly mucoid. These strains give a non-lactose fermenting appearance on MacConkey agar. On Gram stain, the bacterium is a Gram negative bacillus showing a characteristic ‘safety-pin’ appearance (Figure 3), due to lack of stain uptake in the centre of the bacterium caused by inclusions of beta hydroxyl butyrate. The isolate is oxidase positive, which may be more apparent if the test is done with a sweep from the well than from an isolated colony. It is important to perform the oxidase test even in cultures that appear lactose fermenting on MacConkey agar, or B. pseudomallei may be missed. The typical antibiotic sensitivity pattern of resistance to gentamicin, polymyxin and colistin and sensitivity to coamoxyclav may be demonstrated using the disc susceptibility testing method. A vancomycin disc could be included if it is necessary to exclude the possibility of the isolate being a spore bearer. Commercial identification systems such as API20NE or Rapid ID NE often misidentify B. pseudomallei and are unreliable. Definitive identification requires PCR amplification and detection of genes specific to B. pseudomallei. The detection of two separate genes is recommended. This facility is available in Sri Lanka.
What are the pitfalls and dangers in the laboratory diagnosis of melioidosis? Unfamiliarity of laboratory personnel with this bacterium may lead to misidentification of B. pseudomallei as a Pseudomonas sp., E. coli or coliform. Isolates may be discarded as insignificant contaminants, especially if found in mixed culture in specimens from non-sterile sites. Pellicle forming iso-
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lates in blood culture broths may be dismissed as sporing contaminants. Laboratory acquired infection has been well documented, usually through exposure to aerosols. Once a culture is suspected to be B. pseudomallei, further handling should be done in a Class II safety cabinet. Presumptive isolates could be sent to the reference laboratory c/o Dr. Enoka Corea, Microbiology Department, Faculty of Medicine, University of Colombo, for definitive identification by PCR.
considered an endemic disease, with more than one hundred culture and antibody proven cases diagnosed since 2006. It is widely distributed throughout the island and affects all age groups. Mortality has dropped from 50% to around 20% during this period. It should be included in the differential diagnosis of febrile illness in Sri Lanka and suspected cases referred to a clinical microbiologist for microbiology laboratory support for definitive diagnosis.
Is there an antibody test for melioidosis? Antibodies to B. pseudomallei are detected using the indirect haemagglutination assay (IHA). Antigen for the test is made in-house, from local strains. While the IHA titre of infected persons and exposed persons may overlap, it is useful to support a clinical diagnosis in patients where culture is not possible, due to prior antibiotic treatment or inaccessibility of specimens. A single low titre of up to 1:160, may be seen in acute infection but may also represent environmental exposure to B. pseudomallei. High titres (≥1:320) are likely to depict acute infection. Antibody tests may be negative early in acute infection, therefore a negative test does not exclude infection. A blood sample of around 2ml of blood taken in a plain bottle may be sent to the reference laboratory c/o Dr. Enoka Corea, Microbiology Department, Faculty of Medicine, University of Colombo, for antibody testing. If there is any delay it is preferable that serum should be sent after separation.
Figure 1. Colony appearance on blood agar after 3-4 days
Figure 2. Lactose-fermenting appearance on MacConkey agar after 3-4 days
Conclusion Melioidosis is no longer an ‘emerging’ infection in Sri Lanka but can be
Figure 3. ‘Safety pin’ appearance on Gram stain
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August 2015
“3D VIEW OF DENGUE:
Diversity, Developments and Determination to Control”
A
symposium on the above topic was jointly organized by the Expert Committee on Communicable Diseases of the SLMA and the National Dengue Control Unit of the Ministry of Health and Indigenous Medicine. It was held on 18th June 2015 from 11.30am to 1.30pm at the Auditorium of the Sri Lanka Medical Association in Colombo. Dr. Ananda Wijewickrama, Consultant Physician of the Infectious Diseases Hospital at Angoda enlightened the audience on “Dealing with serious or unusual presentations of dengue in adults”. Dr. Shanthini Ganeshan, Consultant Paediatrician at the Infectious Diseases Hospital, Angoda, highlighted issues related to “Dealing with serious or unusual presentations of dengue in children”. Dr. Neelika Malavige, Senior Lecturer and Immunologist; Director, Centre for Dengue Research; Head / Department of Microbiology, University of Sri Jayewardenepura, Nugegoda, spoke on the “Recent advances in therapeutic options available for dengue: progress, obstacles and optimism”. Dr. Hasitha Tissera, Consultant Epidemiologist and Head, National Dengue Control Programme, Ministry of Health, Sri Lanka, discussed the “Obstacles in socio-ecological and biological aspects of dengue control in Sri Lanka”. Dr. Prasad Liyanage, Regional Epidemiologist, Kalutara District, highlighted the importance of the “Voice of those who are in the field: bridging the gap between policy makers and
those who are in action”. SSP Quintus Raymond, Director, Environment Protection Division of the Police, due to speak on “Environmental policing and dengue control: lessons to be learned” was unable to attend the symposium due to ill health.
Lanka. Therefore, in order to reduce morbidity associated with dengue and to reduce the burden to the economies of developing countries, it is crucial to develop new therapeutic options for better management of dengue infections.
Abstracts of some of these lectures are given below.
The three main groups of drugs that have been developed or undergone clinical trials are those that inhibit or reduce viral replication (antivirals), modulate the immune response (immunomodulators) and drugs that prevent the vascular leak. Among the main groups of antiviral drugs that have been developed and tested, iminosugars and cholesterol reducing drugs are currently leading with some undergoing phase I and phase II clinical trials. In mice models, cholesterol lowering drugs such as lovastatin have shown to reduce viraemia and improve survival rates. Some of the antivirals that were used for similar viruses such as dengue have been shown to have a low safety profile in dengue.
Recent advances in therapeutic options available for dengue: progress, obstacles and optimism Dr. Neelika Malavige, MBBS (Col.), MRCP (UK), DPhil (Oxon), FRCP (Lond), FRCPath Senior Lecturer and Immunologist; Director, Centre for Dengue Research; Head/ Department of Microbiology, University of Sri Jayewardenepura, Nugegoda Sri Lanka has been severely affected by regular epidemics of dengue for the past three decades. Although the case fatality rates have now almost dropped to 0.2% due to tremendous effort taken by the clinicians and the Epidemiology Unit of Sri Lanka, dengue still causes a significant burden to resource poor countries such as Sri
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Among the immunomodulatory drugs steroids have been most extensively studied.
Contd. on page 14
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August 2015 Contd. from page 12
3D view of... A large double blind, randomised, placebo controlled trial using both high dose and low dose steroids showed that use of steroid had no effect on any of the clinical outcomes. This study revealed that none of the immune parameters or the concentrations of inflammatory cytokines were different in the three groups (high dose and low dose steroids and the placebo). Another case control study using dexamethasone also showed that the use of steroids had no effect on thrombocytopenia or the duration of illness. We have mainly focused our research on mediators that result in vascular leak in dengue and have found that platelet activating factor (PAF) was significantly elevated and was associated with vascular leak in acute dengue. We also found that another mediator, Sphingosine 1-phosphate, which is associated with vascular integrity and reversed the effects of PAF was significantly reduced in dengue. Based on our findings we are in the process of recruiting patients for a randomised, placebo controlled trial with a PAF antagonist (high dose and low dose).
Obstacles in socio-ecological and biological aspects of dengue control in Sri Lanka Dr. Hasitha Tissera MBBS (Hons.), MSc., MD (Community Medicine) Epidemiology Unit / National Dengue Control Unit, Ministry of Health Many people infected with dengue virus develop no symptoms at all. Others develop dengue fever, which is a “flu-like� illness that is not life threatening. A minority of infected people develop a severe life threatening form of the disease known as dengue haemorrhagic fever (DHF). Typically less than five to ten percent of people infected with dengue viruses develop DHF. Although scientists are still far from understanding why only some dengue infections lead to haemorrhagic disease, it is clear that factors such as age of the person and previous exposure to dengue infections increase risk of severe disease. Dengue viruses are transmitted throughout the year in many parts of the Island, with greater intensity in more urban, densely populated cities. The Western Province contributes to over half the disease burden.
In more recent years, an increase in the number of cases has been observed during mid-year (May-July) with the south-western monsoon rains and towards the end of the year (October-January) with the north-eastern monsoon rains. Studies have demonstrated the presence of dengue virus in Colombo as far back as the 1960s. However, DHF was a rare disease in Sri Lanka in the period from 19601988. After 1989, clinicians started to observe more cases of DHF. Initially, most of the cases were reported from Colombo and other parts of the south western coastal belt. After the year 2000, the magnitude of dengue epidemics increased and the virus started to spread to other parts of the country as well. Currently DHF cases are reported from almost all districts in the Island. The years 2012 and 2014 were the worst years on record with over 44,000 (220 cases/100,000 population) and 47,000 (232 cases/100,000 population) cases of suspected dengue reported respectively. Thus, the current DHF epidemic is the continuation of a worsening, long term trend that began in the late 1980s. Contd. on page 16
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August 2015 Contd. from page 14
3D view of... It is not feasible to eradicate dengue from Sri Lanka anytime in the near future. A well-organized vector mosquito (Aedes) control programme can certainly reduce the number of infections in the community. A steady decline in positive breeding places is observed through continued source reduction campaigns as part of integrated vector management. In addition to focusing on mosquito control, dengue prevention efforts should also emphasize on accurate, early detection and treatment of DHF cases. Educating the public about symptoms of dengue illness and warning signs of severe disease and particularly young doctors about the proper diagnosis and management of DHF are effective ways to reduce deaths due to dengue. One of the long term solutions to dengue is going to be safe and effective vaccines. There are several vaccines under development or in various stages of clinical trials and we are likely to have a vaccine within the next 5 years. However, even with a potential dengue vaccine, given the complexity of dengue, it is imperative to continue scientific research that is directed at improving our understanding of this all important disease. Voice of those who are in the field: bridging the gap between policy makers and those who are in action Dr. Udaya Rathnayake1,4, Dr. Prasad Liyanage1,2, Mr. Saman Geeganage1,3 Regional Director of Health Services office, Kalutara; 2Regional Epidemiologist; 3District Supervising Public Health Inspector; 4Regional Director of Health Services, Kalutara 1
Dengue is a major public health burden in Sri Lanka. More than 60% of national dengue cases are reported from the Western Province in which Kalutara is one of the most affected districts. The magnitude of dengue epidemics have continued to increase since 2009 in this district, contributing
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on average to 5.6% of total dengue cases reported in the country. The average annual incidence rate is 151.8 per 100,000 population ranking the Kalutara district at 5th place at national level. Entomological surveys show that 89% of dengue mosquito breeding places are manmade; out of which 57% consist of domestic discarded receptacles. Religious places, schools, factories, and government institutions collectively showed a higher percentage of mosquito breeding places (25.9%) than households (3.8%). Lack of private sector contribution for notification along with delayed referral for specific treatment is a drawback. Prompt investigation of notified dengue cases and analysis of surveillance data for action need improvement. Vector surveillance should be enhanced and proper recognition and priority should be given. Diversity in interest and support given by the intersectoral agencies for vector control is a major challenge. Poorly developed solid waste management system is one of the key barriers identified in the community mobilization process towards eliminating mosquito breeding places. With the limited resources available, a strategic approach and high level of commitment is needed for the challenging task of implementing dengue control activities in field settings
while bridging gaps between policies and action. Early warning based on climate and entomology gives an additional lead time for timely preventive action. Continuous medical education and enhanced public-private partnership at every level of the health sector would improve early referral and proper case management. Evidence based, effective communication and empowerment programmes targeted at the health sector, inter-sectoral authorities and the community, are needed to build capacity and to improve the contribution of these groups. Sharing, scaling up and appraisal of the innovative effective interventions for dengue control are required for sustainability. The establishment of a solid waste management system is essential. National level re-structuring and internalization of elements of inter-sectoral collaboration for dengue control into the existing policies of local authorities, education and public administration is a felt need. Dengue vector control should be a common goal and a common policy of all stakeholder agencies.
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SLMANEWS
August 2015
Medicines for Children in Sri Lanka The State of Play
Professor Shalini Sri Ranganathan MBBS (Jaffna), MD (Paediatrics, Colombo), DCH (Colombo), MRCP (London), Dip MedTox (Cardiff), PhD (Cardiff) Professor in Pharmacology and Specialist in Paediatrics Department of Pharmacology, Faculty of Medicine, University of Colombo
Children are not small adults: Almost 100 years ago, Dr. Abraham Jacobi (1830-1919), the father of American paediatrics, had argued “Paediatrics does not deal with miniature men and women, with reduced doses and the same class of disease in smaller bodies, but has its own independent range and horizon” (1). In this context, let us critically look at certain aspects of pharmacotherapy in paediatrics in Sri Lanka.
What is special about medicines for children? Medicines are the cornerstone of pharmacotherapy. Medicines for children are not different from adult medicines, except for a few varieties that are mainly used in neonatal and metabolic disorders. However, children are not small adults, their bodies respond to medicines differently. Therefore, they need medicines tailored to their age, body weight and physiological condition. The key reasons for the varied response to medicines among children include: (1) pharmacokinetic differences, (2) pharmacodynamic disparities, (3) effects of medicines on growth and development, (4) the need for age specific dosing regimen (“one size does not fit all”), (5) pharmaceutical, financial and ethical issues in drug development, (6) lack of paediatric data leading to off label use of medicines, (7) practical difficulties in giving medicines, (8) inability of neo-
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nates and young children to express themselves regarding safety concerns and response to medicines, (9) inability to use adult formulations and (10) unproven bioavailability and poor palatability of manipulated adult tablets which are frequently given to young children. Detailed accounts of each of these factors are available in the literature. I have omitted the details as it is beyond the scope and objective of this article.
What is happening globally? Hundred years after the “eye opening” remark of Dr. Jacobi, we can observe that many initiatives are taking place globally to improve the status of paediatric medicines. The United States and the European Union (EU) can be considered as the leaders of such initiatives followed by Canada, Australia and Japan (2). These initiatives are strong, sustainable, integrated and multidisciplinary covering major dimensions in the area of paediatric medicines such as legislation, regulation, expertise development, information resources, research, education and training, prescribing and dispensing standards, formulations, access and rational use. These initiatives are designed mainly to benefit the children in their respective countries and do not extend beyond. There are few exceptions, for example, the EU funded “Global Research in Paediatrics” extends its education and training programmes beyond the EU. Similarly, the “Better Medicines for Children” project funded by the Bill and Melinda Gates Foundation and the “Make medicines child size” initiative of the World Health Organization (WHO) are some other programmes which have extended its support to developing countries as well. However, owing to the unique and inherent characteristics of healthcare structures prevailing in most of the developing countries, the benefits of such initiatives and
programmes have not yet reached the children in such countries.
Essential medicine list for children Traditionally, the WHO supports countries to build up their own mechanisms to improve the health of their citizens. The support is mainly in the form of advocacy, technical assistance, training experts, development of policy, recommendations and guidelines and information sharing. In pharmacotherapy, a crucial public health intervention by the WHO is the publication of the model essential medicine list (EML) every two years since 1977. Essential medicines are those that satisfy the priority health care needs of the population (3). This model list is used by the member countries to develop their own national EMLs. According to Article 12 of the “International Covenant on Economics, Social and Cultural Rights”, General Comment nr 14 (May 2000), member states are obliged to provide essential drugs (medicines) as defined by the WHO action programme on essential drugs (medicines) to its citizens. (4). In simple terms, the EML can be considered as a “shopping list” because the listed medicines receive priority in procurement, supply and use of medicines to the extent that even rich countries are beginning to use the EML in their reimbursement schemes. Despite being the “gold standard”, the Model EML published by the WHO had neglected paediatric medicines until 2007, which is 30 long years since its launch. With the adoption of WHA60.20 resolution in the World Health Assembly in 2007 which urged the 193 WHO Member States to promote access to essential medicines for children (5), the WHO launched the first model EML for children in 2007 which is updated regularly every two years with the 5th revision published in April 2015. Contd. on page 20
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August 2015 Contd. from page 18
Medicines for... What is happening in Sri Lanka? Essential Medicines for children
Now let us see what is happening in Sri Lanka. We do not have a national policy framework to improve the status of paediatric medicines. We do have a national list of essential medicines, which was last updated (5th revision) in 2013/2014, but there is no separate children's list available. The paediatric strength preparations and formulations are included for most of the medicines in the main list. But the purpose of having an EML is to ensure availability of these medicines “within the context of functioning health systems at all times, in adequate amounts, in the appropriate dosage forms, with assured quality, and at a price the individual and the community can afford” (3). This purpose has not been achieved in Sri Lanka, not only for essential medicines for children, but for all essential medicines. We do not need research to substantiate this unmet basic need. All in the healthcare field are aware of this sad situation. Anyone interested can look up this reference which has documented the poor availability of key essential medicines for children in the public health sector in Sri Lanka (6). Though the EML is considered as a “shopping list”, in Sri Lanka, the majority of stakeholders are not even aware of this list. I am not sure whether the last revision of the EML was distributed to all the stakeholders. My informal discussions with house officers, medical officers, postgraduate trainees and specialists mainly in paediatrics have revealed that they are not aware of such a list. The Medical Supplies Division (MSD) uses another list to procure and supply medicines. In the last revision of the EML, attempts have been made to synchronize the EML and MSD list. We hope this attempt will have some useful impact. There is another problem: Many guidelines are being developed in Sri Lanka. The guidelines development
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committees generally look at the current evidence, but fail to look at the national EML. Lack of synchronization between the national therapeutic guidelines and national EML demonstrate lack of integration in the healthcare services. If we are not “marketing” the EML and if we are not interested in “ensuring” that the purpose of the EML is met, then I see no reason for having such a list!!
What is happening in Sri Lanka? Rational use of medicines in children
Rational use of medicines is “patients receiving medications appropriate to their needs, in doses that meet their individual requirements, for an adequate period of time, and at the lowest cost to them and their community” (7). There is nothing new here. Any patient trust that he/she will be receiving medicines based on the above principle. Patients (and public) will naturally expect that the medical education and healthcare services in this country will ensure that he/she will receive medications appropriate to his/her needs, in doses that meet his/her own individual requirements, for an adequate period of time, and at the lowest cost to them and their community. Children are not an exception. A child presenting with the first episode of wheezing does not expect that he/she will be given montelukast. A child with one day of fever does not expect to receive mefenamic acid syrup and diclofenac suppository. A child with one day of respiratory symptoms does not expect that he/she will be asked to take coamoxiclav. A child with asthma who requires prophylaxis for the first time does not expect to be given a combined steroid and long acting beta2 agonist inhaler. A child with one day history of watery diarrhoea and not dehydrated trusts that he/she will be given only oral rehydration salt with advice to his/her parents about home management of acute gastroenteritis.
But the silent majority of us know what our children are actually receiving. Children and parents trust that the children will receive medicines based on unbiased drug information coming from formularies, textbooks, and independent guidelines, and not based on biased marketing promotional tactics. But the silent majority of us know what really happens. How long can we remain silent? Don’t we need to act now?
What is happening in Sri Lanka? Irrational use of antibiotics in children
A large number of “not so sick” children receive medicines in non-hospital settings. Due to multiple factors, the current trend is to seek medication for children suffering from even a single day of fever, cough or common cold. I have witnessed teachers calling parents and sending children with common cold or cough back home and “admonishing” parents for not seeking treatment for their children. These children end up receiving coamoxiclav, clarithromycin, azithromycin, cefixime, cefuroxime axetil, etc. In most of these instances, antibiotics are not indicated at all. Even if antibiotics are indicated we hardly see children receiving amoxicillin, cephalexin or erythromycin. The justification given is “they are not effective”. However, when these antibiotics are prescribed to such children in public hospitals or in the private sector by the “rational” prescribers, their effectiveness has not been questioned until now. Don’t we know when it comes to antibiotics that “the more we use the more we lose? Instead, why are we exposing our children with simple illnesses to such new, expensive, second (or even third)-level, inappropriate antibiotics from day one itself, without allowing the natural defences to overcome the bug which is in most cases a virus causing self limiting illness? Don’t we need to take this case up? Contd. on page 22
077 395 1513 /
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August 2015 Contd. from page 20
Medicines for... What is happening in Sri Lanka? Paediatric formulations Young children cannot swallow tablets. Forcing very small children to swallow large tablets may cause choking and asphyxiation. Four small children died from choking on albendazole tablets during a deworming campaign in Ethiopia in 2007 (8). For small children who cannot swallow conventional tablets, there is a paradigm shift in the preferred formulation from the traditionally used liquids to flexible-solid oral formulations such as dispersible tablets (9). This shift is due to various problems encountered with liquid formulations such as logistics in transport, difficulties in getting clean water for reconstitution, lack of refrigerators to store reconstituted medications and climate in tropical countries affecting the quality of liquid formulations.
What is happening in Sri Lanka?
Firstly, we have not included these current recommendations in our EML or MSD list. Only few medicines are listed as dispersible tablets in the EML. Procurement and supply of paediatric formulations are neither prioritized nor streamlined. I have been told that 2-4 paediatric strength tablets equivalent to a single adult tablet are supplied to hospitals when there is a shortage of adult strength tablets. This depletes the paediatric strength stock of tablets and deprives children from getting what had been procured for them. Despite the shift from syrup to dispersible tablets, liquid preparations remain the preferred formulation for young children in Sri Lanka. However, availability of liquid formulations of key essential medicines for children has been reported to be poor in OPD pharmacies in the public sector in Sri Lanka (6). In the private sector, availability of liquid formulations of key essential medicines for children is very much better than that of the public sector (6). However, we witness two issues of concern: (1) Children re-
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ceiving 3-4 bottles of liquids and 3-4 sachets of powder; the medicines are not labelled, and only the person who dispensed the medicines will know the contents, and children hate these liquids and powders. (2) Children receiving prescription for 2-3 liquid formulations; in most instances such preparations will include either cefuroxime axetil or coamoxiclav syrup. Generally these liquid formulations are expensive and the majority of parents find them unaffordable, but spend their hard earned money to buy these medicines thinking it is for the benefit of their children. Epilepsy is a major chronic disease in children. Liquid formulations of carbamazepine and sodium valproate became available at the Lady Ridgeway Hospital only recently though both have been listed in our EML for some time. We have documented the difficulties parents undergo to break, cut, crush and dissolve the adult antiepileptic tablets to give to their young children (10). Effective treatment of epilepsy requires a consistent plasma steady state concentration of the antiepileptic drug and good adherence to treatment, However many young epileptic children in Sri Lanka are still receiving these manipulated adult tablets with unproven bioavailability and poor palatability. How long we are going to deny the access to suitable formulations of medicines to young children of this country? We are lagging far behind because by this time we should be promoting supply of flexible oral dosage forms for young children. Should we not start to think about the issues I have presented? Mainly the four I have described: essential medicines, rational use of medicines, irrational use of antibiotics and paediatric formulations. Can't some (or even all) of us become champions or ambassadors of paediatric medicines? What prevents us from trying to improve the status of paediatric medicines in our
country? “It is my aspiration that health will finally be seen not as a blessing to be wished for, but as a human right to be fought for.”------ (Kofi Annan, past United Nations Secretary General) (1) Halpern S A. American pediatrics: the social dynamic of professionalism, 1880– 1980. Berkeley: University of California Press, 1988:52 (2) Kalle Hoppu, Gabriel Anabwani, Facundo Garcia-Bournissen, Madlen Gazarian, Gregory L. Kearns, Hidefumi Nakamura, Robert G. Peterson, Shalini Sri Ranganathan, Saskia N. de Wildt. The status of paediatric medicines initiatives around the world-what has happened and what has not? Eur J Clin Pharmacol 2012 68:1–10 (3) World Health Organization. The Selection of essential drugs. Report of the WHO Expert Committee. Technical Report Series No 615. Geneva: WHO; 1977 (4) Office of the United Nations High Commissioner for Human Right. The right to the highest attainable standard of health (08/11/2000): General comment no 14. Available from: http://www.unhchr.ch/tbs/ doc.nsf/(symbol)/E.C.12.2000.4.En. accessed on 20th June2015 (5) World Health Assembly. Resolution WHA 60.20. Better medicines for children. Available from http://www.who.int/childmedicines/publications/WHA6020.pdf. Accessed on 20th June 2015 (6) Balasubramaniam R, Beneragama BVSH, Sri Ranganathan S. A national survey of availability of key essential medicines for children in Sri Lanka. Ceylon Medical Journal 2011; 56: 101-107 (7) World Health Organization. The rational use of drugs. Report of the Conference of Experts. Geneva: WHO; 1985 (8) World Health Organization. Promoting safety of medicines for children. World Health Organization: France; 2007 (9) WHO Report of the Informal Expert Meeting on Dosage Forms of Medicines for Children. Available form: http://www. who.int /selection_medicines /committees /expert/ 17/ application/paediatric/Dosage_form_reportDEC2008.pdf2008 (10) UL Somasiri, S Thillainathan, R Fernandopulle, S Sri Ranganathan. Antiepileptic drugs for children: Availability, suitability and acceptability. Sri Lanka Journal of Child Health, 2012; 41(1): 38-39
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THE OFFICIAL NEWSLETTER OF THE SRI LANKA MEDICAL ASSOCIATION
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