Below is the link to a booklet which summarises much of the latest research on child health in developing countries: evidence derived from all the randomized trials published over the last year.
RCTs in child health in developing countries 2014-2015 http://www.ichrc.org/sites/default/files/RCTs%20in%20child%20health%20in%20developing%20countries%202014-2015-2.pdf
The aim is to make this information widely available to paediatricians, child health nurses, midwives, researchers, students and administrators in places where up-to-date health information is hard to find. We hope it will be helpful in reviewing treatment guidelines and clinical and public health approaches, and in teaching about paediatrics and evidence-based medicine.
This year there were 245 publications from randomised or controlled trials, more than in any previous year.
A brief summary of some of the important results in 2014-15:
- In a high-mortality setting in Kenya where co-morbidities are common, among children with non-severe pneumonia, oral amoxicillin was non-inferior to intravenous benzylpenicillin, and failure rates at day 14 were 13.5 and 16.8% respectively. In Brazil oral amocycillin given 2 times per day was as effective as 3 times per day in treating non-severe pneumonia with treatment failure rates of 23% and 22% respectively.
- Children in African hospitals with severe anaemia were more likely to die in the first 24 hours (case fatality rate 13%) than those with mild or moderate anaemia (7-8%). Children with severe anaemia who were not transfused at 2.5 hours had a much higher risk of dying than those who received blood early.
- For Indian children with central nervous system infections managed in an intensive care unit, the targeting of a cerebral perfusion pressure >60mmHg using fluid boluses, and dopamine / noradrenaline, resulted in lower mortality and less neuro-disability than a strategy aiming to keep intracranial pressure <20 mmHg with osmotherapy while ensuring a normal blood pressure.
- In over 1000 Colombian children in the second year of life, a weekly home visiting program where play was taught over 18 months improved cognitive scores and receptive language. Micronutrient supplementation had no effect on developmental outcomes in this trial.
- In rural children in India, Pakistan and Zambia, an early developmental intervention taught to parents over 3 years improved cognitive abilities regardless of the type of development risk the child faced
- Using a test of “intestinal permeability”, the lactulose: mannitol urinary excretion test, among children at risk of environmental enteropathy, zinc or albendazole reduced the apparent progression of intestinal permeability
- Among 50 Indian children with type-1 diabetes and ketoacidosis, use of insulin infusion at 0.05 U/kg/hour was associated with equal resolution of acidosis and ketosis, with lower risk of hypoglycaemia than the standard infusion of 0.1 U/kg/hour.
- Among African children with prolonged convulsions use of intra-rectal diazepam was more effective in controlling seizures than sublingual lorazepam.
- Among Indian children with infantile spasms, use of high-dose prednisolone (4mg/kg/day) was more effective than 2mg/kg/day in leading to cessation of spasms by 2 weeks
- In 80 rural villages, India’s “total sanitation campaign”, designed to end the practice of open defecation by provision of individual household latrines, reduced open defecation by 10% and improved sanitation facilities by 19%. These are modest early gains, as yet insufficient to achieve measurable child health outcomes, but would be expected to grow over time.
- And this year…an RCT of soap! In Bangladesh, use of soapy water (30g powdered detergent in 1.5 L water) or bar soap, scrubbing hands for 15 seconds were both more effective in reducing coliforms than scrubbing with plain water!
- In adolescents and adults in sub-Saharan Africa with HIV and first-line treatment failure, use of a nucleoside reverse-transcriptase inhibitor was more effective as a ritonivir-boosted protease inhibitor (lopinavir-ritonavir), and as effective as combined NRTI and lopinavir-ritonavir, in achieving good HIV control (no stage 4 events, CD4>250, viral load<10,000 copies /ml at 96 weeks of observation).
- In HIV exposed, uninfected infants in Kenya and South Africa, not breast-feeding was associated with a significantly increased risk of serious infectious events in the first 3 months of life.
- In Zimbabwe, Nigeria, Malawi and South Africa, trials of the implementation of “Option B+”, which provides all HIV-infected pregnant and breast-feeding women with lifelong combination ART, have been planned and are underway.
- In Cameroon, mobile-phone text messaging and phone call reminders increased attendance for HIV exposed or infected children.
- A controlled trial of wearing shoes failed to reduce hookworm, because those in the control arm also acquired shoes! Wearing shoes in either arm was associated with a lower risk of hookworm infectio
- Among children in Tanzania infected with Trichuris trichura, the use of albendazole and oxantel pamoate, or albendazole and ivermectin, were more effective than the albendazole and mebendazole, or mebendazole alone
- In India, a large trial of Integrated Management of Neonatal and Childhood Illness reduced inequity in post-neonatal mortality; that is the effect on child survival beyond the neonatal period was greatest in those from poorer families. Living within areas where IMNCI was introduced was associated with increased care seeking for neonatal illness, diarrhoea and pneumonia, and a greater chance of being breast fed for 6 months.
- Among hospitalised Indian children receiving IV fluids, with severe pneumonia or central nervous system infections, use of an isotonic fluid reduced the risk of hyponatraemia compared with use of a hypotonic fluid.
- In Ghana, providing rapid diagnostic tests for malaria along with realistic training markedly increased the prescription of rational therapy, and in Camaroon use of RDTs reduced the costs of health care in a study which helped define the best type of health worker training
- A meta-analysis of trials of intermittent preventative therapy for malaria on the effect on anaemia showed a modest protective effect only
- Among children in Malawi treated for malaria with chloroquine-azithromycin, the incidence of subsequent respiratory and gastrointestinal infections was lower than those treated with chloroquine alone.
- Among Ugandan children the use of dihydroartemisinin-piperaquine compared with artemether-lumefantrine reduced the risk of recurrent malaria and hospitalisations over the 84 days of follow-up.
- Among children with sickle-cell disease, malaria parasite clearance was slower than for children without SCD when treated with artemisinin-based therapies.
- In a large meta-analysis of severe malaria, arthemeter was probably less effective in reducing mortality than artesunate, although there are limited direct comparison trials.
- Among children with vivax malaria in Peru, 7 days of primaquine was as effective in preventing relapses as 14 days of primaquine
- In a large cluster RCT of community-based treatment of moderate malnutrition in Burkina Faso, the giving of locally produced ready-to-use supplemental feeds resulted in better weight gain than merely counselling parents about appropriate foods.
- In Kenya, Mozambique and Tanzania, mothers receiving intermittent preventative therapy for malaria with mefloquine had significantly lower rates of malarial parasitaemia, placental malaria and non-obstetric hospital admissions than mothers receiving placebo, but those who received mefloquine had higher rates of perinatal mother-to-child transmission of HIV. This was an exploratory finding with potential confounding, but requires further investigation.
- In Malawi, a large trial of maternal nutrient supplementation with lipid-based nutrient supplementation failed to show improved birth size or child growth in the first 18 months of life. However in another large trial in Ghana, birth weight was greater (+85g) and risk of low birth weight less with lipid-based nutrient supplementation.
- In Argentina, a trial of delayed cord clamping showed that it was just as effective if the baby is nursed on the mother’s abdomen immediately after birth as if the baby is held at the level of the placenta. That is, there is no detrimental effect on blood transfer from placental to baby of immediate skin-to-skin contact with the mother (despite the baby being higher). In India, umbilical cord milking (a quicker process that may be done in emergency situations) resulted in no different haemoglobin or serum ferritin than delayed cord clamping for 60-90 seconds.
- In a large trial in rural Tanzania, home-based counselling of newborn care practices by volunteers improved several practices, including clean cord care and exclusive breast-feeding
- In India, the routine use of antibiotics to babies born through meconium stained amniotic fluid did not reduce the risk of sepsis
- In 6 countries in South America, Asia and Africa, a trial of antenatal steroids fopr pregnant women at risk of preterm birth did not reduce mortality in those who delivered preterm, but increased neonatal and maternal sepsis and increased overall neonatal mortality.
- Among very low birth weight infants in Turkey, the use of probiotics (Bifidobacterium lactis) added to expressed breast-milk reduced the risk of necrotising enterocolitis, clinical nosocomial sepsis, length of NICU stay and mortality, compared with placebo or a pre-biotic (inulin).
- In Democratic Republic of Congo, Kenya and Nigeria, the community based treatment of low risk but possible bacterial infection in newborns with simplified antibiotic regimens which included oral amoxicillin instead of injectable penicillin were no different in effect on newborn sepsis. Similarly for infants up to 3 months of age with fast breathing only, oral amoxicillin was as effective as injectable penicillin and gentamicin. Both trials were done in populations at very low risk of serious bacterial infection.
- In a large trial in 55 villages in Burkina Faso, the implementation of an agriculture, nutrition and health behaviour program run by Helen Keller International reduced wasting, diarrhoea and anaemia.
- In a large meta-analysis of 30 trials, praziquantel was the most effective drug for treating urinary schistosomiasis, however the proportion of patients cured varied from 22-83%, and trials of combination therapy with other agents is indicated. There is still no appropriate formulation of praziquantel for young children.
- In a trial of shortened tuberculosis drug regimens, use of a 4-month regimen that included moxifloxacin was significantly less effective than the standard regimen 2RHZE/4RH. At this stage shortening TB treatment to less than 6 months is not of proven efficacy.
- In Indian children with grade I-IV vesicoureteric reflux, use of antibiotic prophylaxis with trimethoprim-sufamethoxizole was associated with a greater risk of UTI, most of which were caused by TMP-SMX resistant bacteria. Children receiving antibiotic prophyxis also had a greater risk of renal scarring.
- In a study involving over 10,000 children aged 2-14 years in 5 countries in Asia, three doses of a recombinant, live, attenuated tetravalent Dengue vaccine (CYD-DTV) was 56% efficacious in preventing symptomatic, virologically confirmed dengue over 25 months of follow-up.
- A follow-up study of HPV vaccine in Taiwan showed protective antibodies for 6 years, at levels which could be expected to last at least 20 years post vaccination.
- In South Africa, influenza vaccine given to pregnant HIV-positive and HIV-negative women provided partial protection (around 50% efficacy) for them, and protection for the infants the infants were HIV-unexposed. There was no protection of giving maternal influenza vaccine to infants who were HIV-infected or exposed.
- In 11 African sites 3 doses of the RTS,S/AS01 malaria vaccine given to infants provided 40-50% protection against clinical malaria, 34% protection against severe malaria and 19% protection against all-cause hospitalisation.
- In India, giving IPV to children who have at least 6 months previously received 3 doses of OPV boosted intestinal immunity and reduced viral excretion after exposure to a test dose of bivalent OPV. This boosted intestinal immunity may be used to prevent outbreaks of poliomyelitis.
- In Indian children given rotavirus vaccine at 6, 10 and 14 weeks, protective efficacy against rotavirus gastroenteritis and severe rotavirus disease of about 50% was observed in the second year of life.
- There were several large trials of neonatal vitamin A supplementation reported on in 2014-15, finding minimal or no effect on mortality (NeoVitA trials). In one trial in India of over 40,000 newborns randomised to vitamin A 50,000 U or placebo, vitamin A showed a modest and non-significant lower mortality (-3 per 1000, 95% CI -6% to 0.1) in the first 6 months of life. In similar trials in Ghana and Tanzania involving 22,000 and 32,000 newborn infants respectively, the mortality risk was also not significantly different in the vitamin supplemented group. Bulging fontanelle was reported as an adverse effect in <1% of newborns given vitamin A. Trials from Guinea Bissau also confirmed no beneficial effect of neonatal vitamin A supplementation.
- In Indian children with acute respiratory infection, 2 weeks of prophylactic zinc supplementation reduced subsequent acute lower respiratory infections over the following 5 months of follow-up, but had no effect on all acute respiratory infections.
Please feel free to make as many copies as you like or pass this document on to anyone who may find it useful.
Prof Trevor Duke, MD FRACP
Centre for International Child Health, University of Melbourne and MCRI