Intermittent preventive treatment for malaria in children living in areas with seasonal transmission (original) (raw)
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PLoS ONE, 2011
Background: Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention. Methods: An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3-59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted. Results: On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67-4.02) and 3.45 (95%CI; 3.29-3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04-1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79-0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb,8 g/dL), wasting, stunting, or of being underweight in children differed between treatment arms. Conclusion: IPT with SP+AQ was associated with a small increase in the incidence of clinical malaria in the subsequent malaria transmission season.
PLoS Medicine, 2014
Background: Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children. . 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were ill. Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%-67%, p,0.001) for DP, 28% (95% CI, 7%-44%, p = 0.01) for TS, and 7% for SP (95% CI, 219% to 28%, p = 0.57). PQ levels were below the detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.
Intermittent preventive antimalarial treatment to children (IPTc): firebreak or fire trap?
Trends in Parasitology, 2008
Plasmodium falciparum kills about a million African children every year. Trials of malaria chemoprophylaxis in endemic settings have shown the potential of antimalarial drugs to protect children from malaria episodes and death. 1 However, several studies have documented an increase in the incidence of clinical malaria in children after prophylaxis stopped-the socalled rebound effect. 1 In a safety and efficacy trial of intermittent antimalarial preventive treatment in infants, 2 we have reported that sulfadoxinepyrimethamine delivered at the time of routine vaccinations reduced the incidence of clinical malaria by 59% (95% CI 41-72), and halved the incidence of severe anaemia (defined by a packed cell volume Ͻ25%) in the first year of life. Here, we present analyses of extended follow-up to assess the possibility of a rebound effect after this treatment.
PLOS One, 2011
Background: Intermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by .80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.
A Randomized Controlled Trial of Extended Intermittent Preventive Antimalarial Treatment in Infants
Clinical Infectious Diseases, 2007
Background. Intermittent preventive antimalarial treatment in infants (IPTi) with sulfadoxine-pyrimethamine reduces falciparum malaria and anemia but has not been evaluated in areas with intense perennial malaria transmission. It is unknown whether an additional treatment in the second year of life prolongs protection. Methods. A randomized, double-blinded, placebo-controlled trial with administration of sulfadoxine-pyrimethamine therapy at 3, 9, and 15 months of age was conducted with 1070 children in an area in Ghana where malaria is holoendemic. Participants were monitored for 21 months after recruitment through active follow-up visits and passive case detection. The primary end point was malaria incidence, and additional outcome measures were anemia, outpatient visits, hospital admissions, and mortality. Stratified analyses for 6-month periods after each treatment were performed. Results. Protective efficacy against malaria episodes was 20% (95% confidence interval [CI], 11%-29%). The frequency of malaria episodes was reduced after the first 2 sulfadoxine-pyrimethamine applications (protective efficacy, 23% [95% CI, 6%-36%] after the first dose and 17% [95% CI, 1%-30%] after the second dose). After the third treatment at month 15, however, no protection was achieved. Protection against the first or single anemia episode was only significant after the first IPTi dose (protective efficacy, 30%; 95% CI, 5%-49%). The number of anemia episodes increased after the last IPTi dose (protective efficacy, Ϫ24%; 95% CI, Ϫ50% to Ϫ2%). Conclusion. In an area of intense perennial malaria transmission, sulfadoxine-pyrimethamine-based IPTi conferred considerably lower protection than reported in areas where the disease is moderately or seasonally endemic. Protective efficacy is age-dependent, and extension of IPTi into the second year of life does not provide any benefit.