Attached is a booklet which summarizes some of the latest research on child health in developing countries: evidence derived from all the randomized trials published over the last year. The aim is to make this information widely available to pediatricians, child health nurses, midwives, researchers, students and policy makers in places where up-to-date health information is hard to find. It is hoped that such information will be helpful in reviewing treatment guidelines, clinical practice and public health approaches, and in teaching about paediatrics and evidence-based medicine.
This year 4 trials reported significant reductions in child mortality:
- In India a program of Integrated Management of Maternal, Neonatal and Child Health reduced neonatal and infant mortality. In this program community health workers were trained to conduct postnatal home visits and women's group meetings, where physicians, nurses, and community health workers were trained to treat or refer sick newborns and children. Supply of drugs and supervision were strengthened.
- In rural Pakistan application of 4% chlorhexidine to the umbilical cord reduced neonatal mortality and omphalitis.
- In Uganda a trial of zinc in the treatment of severe pneumonia showed a significant reduction in deaths in the zinc treated group. This is the first trial of zinc treatment in pneumonia with the power to show a mortality difference. The effect was especially strong in children with HIV. Two other trials this year ├ö├ç├┤ from India and Nepal - did not show a significant beneficial effect of zinc on resolution of pneumonia signs.
- In Bangladesh, antenatal treatment of pregnant women from poor communities with multiple micronutrients, including iron and folic acid combined with early food supplementation decreased the risk of mortality in their children.
*Other important outcomes from studies in 2010-11 include:
- In South Africa, extended nevirapine during breast-feeding significantly reduced the risk of HIV infection: 1.1% (95% CI 0├ö├ç├│3-1├ö├ç├│8) of infants who received extended nevirapine developed HIV-1 between 6 weeks and 6 months compared with 2├ö├ç├│4% (1├ö├ç├│3-3├ö├ç├│6) of infants who only received nevirapine for the first 6 weeks of life. However in a trial in
Ethiopia, children who received nevirapine for 6 weeks and had prophylaxis failure - i.e. they developed HIV - had a higher risk of resistant strains of HIV.
In the Americas, post-natal treatment with zidovudine for 6 weeks plus three doses of nevirapine during the first 8 days of life, or zidovudine for 6 weeks plus nelfinavir and lamivudine for 2 weeks was more effective than zidovudine for 6 weeks at reducing parent-to-child transmission of HIV in mothers who did not receive ART during pregnancy.
In 6 African countries initiation of HIV treatment in childrenwho had no prior exposure to nevirapine, ART with zidovudine,lamivudine, and ├ö├ç├┐ritonavir-boosted lopinavir├ö├ç├û resulted in lower virological failure than zidovudine, lamivudine and nevirapine. Nevirapine resistance was a common feature of treatment failure.
In 7 African countries in a phase III trial the RTS,S/AS01 malaria vaccine provided protection against both clinical and severe malaria in African children, with vaccine efficacies of 50% for first episode of malaria, and 35% against severe malaria. Another study from 3 African countries in a phase II trial showed similar efficacy (53% and 59%) against the first episode of malaria and all malaria episodes, respectively, when children were followed up at 19 months. A third study of seroresponse in children in Mozambique showed protective anti-circumsporozoite antibodies at 42 months. The RTS,S/AS02 vaccine also induced high levels of anti-hepatitis B surface antigen antibodies.
In a meta-analysis of 7 trials in malaria endemic countriesin West Africa involving 12,000 children, intermittent preventative therapy of malaria (IPTc) during the malaria season prevented approximately three quarters of all clinical malaria episodes and a similar proportion of severe malaria episodes. These effects remain present even where insecticide treated net (ITN) usage is high.
In Mali, a program for intermittent preventative treatment of malaria along with routine vaccines increased vaccine coverage. In Ghana health care delivery costs were less and coverage was the slightly higher when IPTi was delivered by village health workers, compared with when IPTi was delivered by clinic or outreach EPI nurses.
In a large study in Uganda involving over 100,000 children with suspected malaria, use of rapid diagnostic tests (RDT), compared with presumptive diagnosis, significantly reduced the prescribing of artemether-lumefantrine. However 23% of children with negative RDT were still prescribed antimalarials. Compared with microscopy, RDTs reduced waiting time and were considered more convenient for patients and health workers.
In Tanzania community health workers could use RDT: no fatal or severe malaria occurred among 682 RDT negative children who were not treated with antimalarials by CHWs. This suggests that it is safe to withhold malaria treatment to RDT negative patients and that lower level health workers can make decisions based on RDT.
As has been found in studies in previous years, in a multi-country study in Africa, dihydroartemisinin-piperaquine was as effective as artemisinin-based therapy for uncomplicated P. falciparum, and resulted in a lower malaria recurrence risk.
In Lao, China, and Uganda trials of albendazole and mebendazole for the treatment of worm infestation showed that albendazole is more efficacious than mebendazole for hookworm. However single-dose albendazole had low efficacy against hookworm, and treatment daily for 3 days (in Lao and China), or 2 doses 8 hours apart (in Uganda) was better. Albendazole had lower efficacy than mebedazole against Trichuris trichiura, where 3 days of treatment (or 2 doses in the one day) was optimal for cure.
In Kenya, the combination of albendazole and di-ethyl carbamazine (DEC) was more effective than either drug alone for filariasis. This is important for mass administration programs aiming to interrupt transmission of W. ancrofti* in endemic areas.
In Columbia, oral Meltifesone given for 28 days by directly-observed treatment was shown to be as effective as antimonial drugs given by intramuscular injection daily for 20 days in the treatment of cutaneous Leishmaniasis. Meltifesone is the first oral drug to be effective against visceral or cutaneous leishmaniasis, and is good news for efforts to eradicate the disease.
In a trial involving over 66,000 people in Kolkata, India, the 2-dose killed whole-cell oral cholera vaccine provided 65% protection for at least 3 years. One case of cholera was averted for every 404 people vaccinated.
In the Gambia, the 7-valent pneumococcal conjugate vaccine showed a marked herd immunity among children in neighbouring non-vaccinated villages, with no significant serotype replacement.
In Malawi, South Africa, and Kenya, rotavirus vaccine given in the first 3 months of life remained effective against severe rotavirus diarrhoea in the second year of life. Three doses of RV vaccine in the first 3 months of life provided greater second year protection than two doses.
In *Papua New Guinea a single dose of oral azithromycin was as effective as a single injection of benzathine penicillin. This may overcome the operational difficulties associated with administering an injection, raising the prospect of tackling yaws through the mass treatment of populations at risk.
For Indian children with type I diabetes, drinking 500ml of camel milk daily improved glucose tolerance and reduced insulin requirements.
In Angola, a 12-hour infusion of cefotaxime resulted in a lower rate of the combined outcome of mortality and severe neurological sequelae in children with pneumococcal meningitis, than boluses of cefotaxime every 6 hours.
In Bangladesh simple guidelines and training on childTB case detection together with basic logistics support were integrated into the existing National TB Control Programme and markedly improved case funding for children with TB.
This is the tenth edition of this booklet. It is part of a project supported by WHO, AusAID and many international partners, which critically appraises the evidence behind WHO's treatment guidelines. Previous editions (2003-2011) and further reviews of WHO guidelines are available at www.ichrc.org.au
If you have a laser printer, the document may be printed out as a small booklet form to save trees. After clicking on ├ö├ç┬úPrint├ö├ç├ÿ go to ├ö├ç┬úProperties├ö├ç├ÿ and select: ├ö├ç┬úPrint to both sides├ö├ç├ÿ; Booklet layout ├ö├ç┬úLeft edge binding├ö├ç├ÿ; Pages per sheet ├ö├ç┬útwo pages per sheet├ö├ç├ÿ. Printing this way will use 53 sheets. Then fold the A-4 pages in half and cut down the middle to form a booklet.
*Please feel free to make as many copies as you like and to pass this document on to anyone who may find it useful.*
ProfessorTrevor Duke*, **MD**** FRACP
Centre for International Child Health
Department of Paediatrics, ****University** of **Melbourne****
Intensive Care Unit, Royal Children├ö├ç├ûs Hospital
Parkville, Vic 3052, Victoria, Australia
Adjunct Professor of Child Health
School of Medicine, University of PNG
James K Tumwine
Professor, Paediatrics and Child Health
School of Medicine, College of Health Sciences, Makerere University, at
Mulago Hospital, Kampala, Uganda
Phone: +256 414 531875
Mobile: +256 772 494120