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

Abstract

SummaryIn 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.Methods2102 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.FindingsThe 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.ConclusionsMonthly 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.Trial RegistrationClinicaltrials.gov NCT00132548

Modeling the Relationship between Precipitation and Malaria Incidence in Children from a Holoendemic Area in Ghana

“…[31][32][33][34] Other studies have used geographic information systems and satellite imagery to investigate environmental factors that potentially drive the dynamics of malaria vector populations [34][35][36] and other vector-borne and zoonotic diseases such as dengue fever or hantavirus. [37][38][39] It has been shown that the efficacy of control measures such as intermittent preventive treatment (IPT) can be strongly dependent on the present malaria incidence, [40][41][42] and it can be assumed that direct and contextual effects increase with malaria risk after an intervention. The results of the present study highlight that it is feasible in holoendemic areas to predict fluctuations in the malaria incidence with information that is easy to obtain.…”

Amodiaquine Dosage and Tolerability for Intermittent Preventive Treatment To Prevent Malaria in Children

“…Amodiaquine was also given alongside artesunate in the Niakhar study, but this was apparently better tolerated than AQ with SP (14). Amodiaquine was the focus of this analysis because the recommended range for SP (between 25 mg/kg and 70 mg/kg [18]) is substantially wider than it is for amodiaquine, making it easier to dose accurately, and because in both studies SP combined with a different partner drug was well tolerated (5,14). An amodiaquine dosage of 10 mg AQ base/kg/day over 3 days is the present target when dosing by weight (21).…”

“…Sulfadoxine-pyrimethamine combined with amodiaquine (SP-AQ) has been identified as a highly efficacious regimen for treatment of malaria (4,8,11,(23)(24)(25)(26) and for IPT (5,14). However, when used for IPT in children, SP-AQ has been associated with an increased incidence of mild adverse events, particularly vomiting and fever, in the days following the IPT course (5,14).…”

“…However, when used for IPT in children, SP-AQ has been associated with an increased incidence of mild adverse events, particularly vomiting and fever, in the days following the IPT course (5,14). One answer to this problem would be to use other antimalarials as the partner drug to SP, which has been shown extensively to be safe and well tolerated when used for intermittent preventive treatment (1,6).…”

Intermittent preventive treatment for malaria in infants: a decision-support tool for sub-Saharan Africa

“…The strategy of seasonally administering intermittent preventive treatment in children aged under 5 years (IPTc) provides almost continuous chemoprophylaxis during the period of peak transmission and has proven highly effective against clinical malaria. [45][46][47][48] However, the main concern with IPTc, and with any extension of IPTi beyond infancy, is the logistical complexity of delivering treatment in a sustainable and cost-effective manner. Studies of the efficacy of IPTc indicate that the cost would be considerably higher than for IPTi, which can take advantage of the healthcare infrastructure that already exists for EPI and hence be a highly cost-effective addition to existing malaria control interventions.…”