A Trial of the Efficacy, Safety and Impact on Drug Resistance of Four Drug Regimens for Seasonal Intermittent Preventive Treatment for Malaria in Senegalese Children

UNLABELLED: In the Sahel, most malaria deaths occur among children 1-4 years old during a short transmission season. A trial of seasonal intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) and a single dose of artesunate (AS) showed an 86% reduction in the incidence of malaria in Senegal but this may not be the optimum regimen. We compared this regimen with three alternatives. METHODS: 2102 children aged 6-59 months received either one dose of SP plus one dose of AS (SP+1AS) (the previous regimen), one dose of SP plus 3 daily doses of AS (SP+3AS), one dose of SP plus three daily doses of amodiaquine (AQ) (SP+3AQ) or 3 daily doses of AQ and AS (3AQ+3AS). Treatments were given once a month on three occasions during the malaria transmission season. The primary end point was incidence of clinical malaria. Secondary end-points were incidence of adverse events, mean haemoglobin concentration and prevalence of parasites carrying markers of resistance to SP. FINDINGS: The incidence of malaria, and the prevalence of parasitaemia at the end of the transmission season, were lowest in the group that received SP+3AQ: 10% of children in the group that received SP+1AS had malaria, compared to 9% in the SP+3AS group (hazard ratio HR 0.90, 95%CI 0.60, 1.36); 11% in the 3AQ+3AS group, HR 1.1 (0.76-1.7); and 5% in the SP+3AQ group, HR 0.50 (0.30-0.81). Mutations associated with resistance to SP were present in almost all parasites detected at the end of the transmission season, but the prevalence of Plasmodium falciparum was very low in the SP+3AQ group. CONCLUSIONS: Monthly treatment with SP+3AQ is a highly effective regimen for seasonal IPT. Choice of this regimen would minimise the spread of drug resistance and allow artemisinins to be reserved for the treatment of acute clinical malaria

Review: Intermittent preventive treatment--a new approach to the prevention of malaria in children in areas with seasonal malaria transmission.

Intermittent preventive treatment, the administration of a full course of an anti-malarial treatment to a population at risk at specified time points regardless of whether or not they are known to be infected, is now a recommended approach to the prevention of malaria in pregnancy and is being explored as a potential way of preventing malaria in infants. However, in many malaria endemic areas, the main burden of malaria is in older children and increasing use of insecticide treated bednets is likely to increase further the proportion of episodes of malaria that occur in older children. Recently, it has been shown in Senegal and in Mali that intermittent preventive treatment given to older children during the malaria transmission season can be remarkably effective in preventing malaria. This approach to malaria control is likely to be most effective in areas with a high level of malaria transmission concentrated in a short period of the year. However, several issues need to be addressed before intermittent preventive treatment in children can be advocated for use in malaria control programmes. These include: (1) determination of whether intermittent preventive treatment adds to the protection afforded by other control measures such as insecticide-treated bednets; (2) whether an effective and sustainable delivery system can be found; (3) choice of drug to be used; (4) optimum timing of drug administration; (5) the requisite interval between treatments. The potential benefits of intermittent preventive treatment in children are substantial; more research is needed to determine if this is a practical approach to malaria control

Review of intermittent preventive treatment for malaria in infants and children

Malaria is one of the greatest killers of children in the world. Treatment is available, but there are problems with affordability, availability, accessibility and increasing drug resistance. A new regime, intermittent preventive treatment in infants (IPTi) shows promise. It involves giving a treatment course of antimalarial drugs, regardless of parasitaemia, at intervals over the first year of life. The aim is to decrease the frequency of malarial illness while allowing the development of natural immunity. Its strength is that it can be linked with the childhood immunisation schedule. Early studies are encouraging, but much remains to be learned before its potential place in the prevention of malaria in children can be determined and it can safely be introduced as public policy. A review of the literature was performed in July 2006 for references relating to IPTi and other forms of personal prevention of malaria in infants and children