The Lancet: Monthly drug during rainy season prevents malaria deaths in children, as experts call for wide roll-out across West and Central Africa
- Seasonal Malaria Chemoprevention (SMC) has previously been shown to significantly reduce malaria cases among children
- The new study is the first evidence of impact on malaria deaths in children – in The Gambia hospital deaths due to malaria during the rainy season reduced by 57% and in Burkina Faso, death rates reduced by 42%
- The cost was estimated at US$3.63 per child to cover four months of treatments, as authors call for a wide roll-out across West and Central Africa
- Programs have already been set up in 13 countries reaching 22 million children in 2019, but a remaining 8 million children still lack access to SMC
- In the study, there were low levels of drug resistance to seasonal treatment, so continued molecular monitoring will be needed to provide early warning of loss of effectiveness
Tablets are given once a month for the four-month rainy season help to prevent children from dying from malaria and can be delivered effectively to large areas of west and central Africa, according to a new study published in The Lancet journal.
Malaria was responsible for 643,000 deaths globally in 2019, with over half of these (356,000) in children under 5 years, with the vast majority of deaths in West and Central Africa.
In the sub-Sahel region of Africa (from southern Senegal and northern Guinea to Chad and northern Cameroon), seasonal malaria chemoprevention (SMC) is given to children monthly, during the rainy season, the time of year when most cases of childhood disease and deaths occur. The tablets are given over three days – two are taken on the first day, one on the second and one on the third. It has been shown in clinical trials to reduce the incidence of malaria, including severe malaria, by 75% .
The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project aimed to evaluate the safety and effectiveness of SMC at scale, the costs of delivery, cost-effectiveness, and effects on drug resistance, during 2015 and 2016 in seven countries (Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria).
Professor Paul Milligan, of the London School of Hygiene & Tropical Medicine, UK, a corresponding author of the study, said: “This evaluation of the scaling-up of SMC implementation provides the first evidence of an impact in reducing malaria deaths in children. The project increased demand for SMC drugs, which in turn encouraged drug manufacturers to increase capacity and develop child-friendly formulations.
There are now programs in 13 countries, reaching about 22 million children in 2019. However, there is still a gap of around eight million children who live in areas suitable for SMC but are being missed, and delivery needs to be optimized to ensure high levels of coverage in all regions. These gaps must urgently be closed – while SMC does not provide complete protection, it should be made available alongside other measures to reduce the thousands of unnecessary child deaths from malaria every year.”
SMC involves a combination of the antimalarials sulfadoxine-pyrimethamine with amodiaquine, given in tablet form once every month during the four-month rainy season by community health workers.
Over the study period, SMC reduced malaria deaths in children during the rainy season by 42% in Burkina Faso and 57% in The Gambia. The incidence of severe malaria disease was reduced in The Gambia by 55% during 2015 and 2016 and by 27% in Burkina Faso in 2015 (data for 2016 was not available). Across all seven countries, outpatient malaria cases reduced, ranging from a 25% reduction in Nigeria in 2016 to 59% in The Gambia in 2016.
In the study, each monthly treatment gave a high degree of personal protection for four weeks, reducing malaria incidence by over 80% during this time. Protection then drops rapidly, with the drug reducing malaria incidence by 61% during the 29 to 42 days after treatment. Therefore, the treatments should be strictly 28 days apart to maintain high levels of protection, the authors suggest.
Over 12 million monthly SMC treatments were administered in 2015 to a target population of over 3.6 million children, and 25 million SMC treatments were administered in 2016 to a target population of 7.6 million children. In 2015, 86% of children received at least one treatment while 55% received all four treatments. On average 76% of children received the treatment each month. Similar numbers received treatment in 2016. In both years, coverage varied across the seven countries. Door-to-door delivery was found to be the most effective method of reaching children, especially in the poorest areas.
In addition to monitoring effectiveness, the researchers also looked at drug resistance before and after the project, by testing blood samples from children who had received the treatment as well as from people aged between 10 and 30 years old, who had not received the treatment, for molecular markers of parasite resistance to sulfadoxine-pyrimethamine and amodiaquine.
Low levels of drug resistance were reported in the study. The combination of mutations associated with resistance to amodiaquine, was found at a prevalence of 1·3% in 2016 and 0·5% in 2018 in children and, in 0·7% in 2016 and 0·4% in 2018 in individuals aged 10–30 years. The prevalence of the quintuple mutation associated with resistance to sulfadoxine–pyrimethamine was 0·4% in 2016 and 0·7% in 2018 in children, and in the 10-30 age group was 0·2% in 2016 and 1·0% in 2018. The authors say that while these are low levels of resistance, there is some selection for resistance to sulfadoxine-pyrimethamine, and resistance should be carefully monitored across all regions where SMC is used to be able to quickly identify if the drug’s effectiveness is threatened.
Safety monitoring through the national pharmacovigilance system in each country within the study was improved to ensure the drug remained safe when administered on a large scale. Severe adverse reactions were uncommon, which was in line with previous clinical trials. In 779 individual case safety reports related to SMC treatment that were available to the study, including cases of rash and gastrointestinal disorders, there were 36 serious adverse drug reactions, but all these children recovered, and no cases of severe skin reactions were reported in the study.
Yacine Djibo, Executive Director of Speak Up Africa and an author on the study, added: “Despite the challenges of delivering monthly treatments door to door, high coverage can be achieved, reducing the unacceptable child death rate associated with malaria. These findings should support efforts to sustain high levels of coverage of SMC and it is very encouraging to see that since the end of ACCESS-SMC, project countries have successfully transitioned to other sources of funding, and more countries have started seasonal malaria chemoprevention programs.”
James Tibenderana, technical director at Malaria Consortium and an author on the study, added: “The impact of SMC could be increased by further adapting delivery approaches, and, in some areas, increasing the number of monthly cycles to five in some regions could also help ensure children are protected throughout the high-risk period. Additionally, molecular monitoring is needed to show any resistance to the treatment, and safety monitoring should continue to ensure treatment remains safe.”
In a linked comment, Elizabeth Ashley of the Lao-Oxford-Mahosot Hospital, Laos, and Adoke Yeka of Makerere University, Uganda, wrote: “The scale-up of SMC is an instructive success story. Recently completed research and future research will define the relative roles of SMC and the malaria vaccine in areas with seasonal transmission. Optimal approaches will also be determined to expand SMC beyond the current recommendations, increase coverage and adherence, provide optimal timing of the intervention in different areas, and develop simpler regimens with new drugs for prevention that are unrelated to those used for treatment.”
The Lancet: Monthly drug/The Lancet: Monthly drug /The Lancet: Monthly drug /The Lancet: Monthly drug
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