Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.

Effect of intermittent treatment with amodiaquine on anaemia and malarial fevers in infants in Tanzania: a randomised placebo-controlled trial.

BACKGROUND: Malaria is a major cause of infant morbidity and mortality in sub-Saharan Africa, and is often complicated by severe anaemia. Resistance of Plasmodium falciparum to most affordable antimalarial drugs is an impediment to intermittent chemotherapy. We investigated the effect of presumptive intermittent treatment with amodiaquine and daily iron supplementation in infants on malarial fevers and anaemia, in a holoendemic area of Tanzania where malaria is largely resistant to chloroquine and sulfadoxine/ pyrimethamine. METHODS: 291 infants aged 12-16 weeks who attended three clinics were randomised to receive amodiaquine, iron supplementation, amodiaquine plus iron supplementation, or placebo. Over 6 months, we gave amodiaquine three times with intervals of 60 days; oral iron supplementation was given daily. Malarial fevers and anaemia were monitored at bimonthly treatment visits and by self-reporting to health centres. FINDINGS: The protective efficacy of intermittent amodiaquine treatment in prevention of malarial fevers and anaemia was 64.7% (95% CI, 42.4-77.2) and 67.0% (95% CI, 34.5-83.4), respectively. Protective efficacy was similar in the group receiving amodiaquine plus iron supplementation. Infants receiving iron supplementation only were partly protected against anaemia (protective efficacy 59.8%; 95% CI, 23.4-78.9), but not against malarial fevers. 4 months' follow-up did not show rebound morbidity. We noted no haematological or clinical adverse effects. INTERPRETATION: Presumptive intermittent treatment for malaria with amodiaquine reduced malarial fevers and anaemia in infants, in an area with high resistance to other antimalarials. Intermittent treatment strategies for malaria in highly endemic areas could be of great benefit to public health.