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Background: Mass administration of azithromycin for trachoma control led to a sustained reduction in all-cause mortality among Ethiopian children. Whether the addition of azithromycin to the monthly sulfadoxine-pyrimethamine plus amodiaquine used for seasonal malaria chemoprevention could reduce mortality and morbidity among African children was unclear., Methods: We randomly assigned children 3 to 59 months of age, according to household, to receive either azithromycin or placebo, together with sulfadoxine-pyrimethamine plus amodiaquine, during the annual malaria-transmission season in Burkina Faso and Mali. The drug combinations were administered in four 3-day cycles, at monthly intervals, for three successive seasons. The primary end point was death or hospital admission for at least 24 hours that was not due to trauma or elective surgery. Data were recorded by means of active and passive surveillance., Results: In July 2014, a total of 19,578 children were randomly assigned to receive seasonal malaria chemoprevention plus either azithromycin (9735 children) or placebo (9843 children); each year, children who reached 5 years of age exited the trial and new children were enrolled. In the intention-to-treat analysis, the overall number of deaths and hospital admissions during three malaria-transmission seasons was 250 in the azithromycin group and 238 in the placebo group (events per 1000 child-years at risk, 24.8 vs. 23.5; incidence rate ratio, 1.1; 95% confidence interval [CI], 0.88 to 1.3). Results were similar in the per-protocol analysis. The following events occurred less frequently with azithromycin than with placebo: gastrointestinal infections (1647 vs. 1985 episodes; incidence rate ratio, 0.85; 95% CI, 0.79 to 0.91), upper respiratory tract infections (4893 vs. 5763 episodes; incidence rate ratio, 0.85; 95% CI, 0.81 to 0.90), and nonmalarial febrile illnesses (1122 vs. 1424 episodes; incidence rate ratio, 0.79; 95% CI, 0.73 to 0.87). The prevalence of malaria parasitemia and incidence of adverse events were similar in the two groups., Conclusions: Among children in Burkina Faso and Mali, the addition of azithromycin to the antimalarial agents used for seasonal malaria chemoprevention did not result in a lower incidence of death or hospital admission that was not due to trauma or surgery than antimalarial agents plus placebo, although a lower disease burden was noted with azithromycin than with placebo. (Funded by the Joint Global Health Trials scheme; ClinicalTrials.gov number, NCT02211729.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: The efficacy of intermittent preventive treatment for malaria with sulfadoxine-pyrimethamine (IPTp-SP) in pregnancy is threatened in parts of Africa by the emergence and spread of resistance to SP. Intermittent screening with a rapid diagnostic test (RDT) and treatment of positive women (ISTp) is an alternative approach., Methods and Findings: An open, individually randomized, non-inferiority trial of IPTp-SP versus ISTp was conducted in 5,354 primi- or secundigravidae in four West African countries with a low prevalence of resistance to SP (The Gambia, Mali, Burkina Faso and Ghana). Women in the IPTp-SP group received SP on two or three occasions whilst women in the ISTp group were screened two or three times with a RDT and treated if positive for malaria with artemether-lumefantrine (AL). ISTp-AL was non-inferior to IPTp-SP in preventing low birth weight (LBW), anemia and placental malaria, the primary trial endpoints. The prevalence of LBW was 15.1% and 15.6% in the IPTp-SP and ISTp-AL groups respectively (OR = 1.03 [95% CI: 0.88, 1.22]). The mean hemoglobin concentration at the last clinic attendance before delivery was 10.97g/dL and 10.94g/dL in the IPTp-SP and ISTp-AL groups respectively (mean difference: -0.03 g/dL [95% CI: -0.13, +0.06]). Active malaria infection of the placenta was found in 24.5% and in 24.2% of women in the IPTp-SP and ISTp-AL groups respectively (OR = 0.95 [95% CI 0.81, 1.12]). More women in the ISTp-AL than in the IPTp-SP group presented with malaria parasitemia between routine antenatal clinics (310 vs 182 episodes, rate difference: 49.4 per 1,000 pregnancies [95% CI 30.5, 68.3], but the number of hospital admissions for malaria was similar in the two groups., Conclusions: Despite low levels of resistance to SP in the study areas, ISTp-AL performed as well as IPTp-SP. In the absence of an effective alternative medication to SP for IPTp, ISTp-AL is a potential alternative to IPTp in areas where SP resistance is high. It may also have a role in areas where malaria transmission is low and for the prevention of malaria in HIV positive women receiving cotrimoxazole prophylaxis in whom SP is contraindicated., Trial Registration: ClinicalTrials.gov NCT01084213 Pan African Clinical trials Registry PACT201202000272122.

The present work describes the recognition of three synthetic polypeptides encompassing the N- and C-terminal regions of the transmembrane Exp-1 protein of the parasite Plasmodium falciparum by plasma and peripheral blood mononuclear cells from naturally exposed individuals living in African endemic areas. The three polypeptides comprise the sequences 23-105, 73-162 and 101-162, and overlap at the transmembrane domain (73-105). Thus, they permitted characterization of the immune response specific to the N- and C-terminal domains in an independent fashion. Two different populations were evaluated, one in the village of Safo in Mali and the other in the villages of Somnaway, Kabortenga and Toussouktenga in Burkina Faso. Antibodies to the sequence 73-162 of Pf Exp-1 were found in 70% of adult Mali donors and in all of the donors tested from Burkina Faso. Strikingly, the N-terminal fragment Pf Exp-1 23-105 was only weakly recognized by a few donors. Evaluation of the T-cell response indicated that the peptide Pf Exp-1 23-105 was more potent than Pf Exp-1 73-162 in inducing a proliferative response. A correlation between peptide-specific interferon-gamma and interleukin-6 production and proliferation to peptide Pf Exp-1 23-105 was observed. Further studies are needed to evaluate this molecule as a vaccine candidate.