Objectives: Although the incidence of malaria is increased in women in endemic areas after delivery compared to non-pregnant women, no studies have assessed the benefit of presumptive antimalarial treatment given postpartum.
Methods: A randomised controlled trial investigating the efficacy of antimalarial treatment in preventing postpartum malaria was performed in healthy Papua New Guinea mothers immediately following delivery. Participants were randomised 1:1 to no treatment (n = 90) or artemisinin combination therapy (ACT), with further 1:1 ACT randomisation to artemether-lumefantrine (AL; n = 45) or dihydroartemisinin-piperaquine (DP; n = 45). Standardised reviews were conducted monthly for 6 months, including clinical assessment, malaria screening and haemoglobin measurement. The primary endpoint was incidence of slide-positive malaria within 6 months of delivery.
Results: Of 183 recruited participants, 151 completed study procedures and were included in per-protocol analyses (no treatment n = 71, AL n = 40, DP, n = 40). Those allocated to ACT were significantly less likely to develop slide-positive malaria during the 6-month follow-up period compared to those who were untreated (n = 17 (21%) vs n = 27 (38%); P = 0.016; hazard ratio 0.49 (95% confidence intervals 0.27-0.90). There was no significant difference in malaria incidence between the two ACT groups.
Conclusion: A treatment course of ACT at time of delivery halved the incidence of malaria infection during the first 6-month postpartum.
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http://dx.doi.org/10.1016/j.ijid.2024.107258 | DOI Listing |
Lancet Infect Dis
December 2024
MMV Medicines for Malaria Venture, Geneva, Switzerland.
Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.
Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).
Lancet Microbe
December 2024
Malaria Research and Training Centre, Faculty of Pharmacy and Faculty of Medicine and Dentistry, University of Sciences, Techniques and Technologies of Bamako, Bamako, Mali.
Background: Triple artemisinin-based combination therapies (TACTs) can delay the spread of antimalarial drug resistance. Artesunate-amodiaquine is widely used for uncomplicated Plasmodium falciparum malaria. We therefore aimed to determine the safety and efficacy of artemether-lumefantrine-amodiaquine and artesunate-amodiaquine with and without single low-dose primaquine for reducing gametocyte carriage and transmission to mosquitoes.
View Article and Find Full Text PDFAntimicrob Agents Chemother
December 2024
Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Praziquantel alone is insufficient for the control of schistosomiasis due to poor efficacy against juvenile worms and increasing concerns about the risk of drug resistance. We compared the efficacy and safety of praziquantel combined with four different artemisinin-based combinations to praziquantel alone in treating infection in Kenyan children. In this randomized, open-label, five-arm, head-to-head, non-inferiority trial, children (aged 9-15 years) with infection according to duplicate Kato Katz thick smears from a stool sample in the Mwea irrigation scheme of central Kenya, were enrolled.
View Article and Find Full Text PDFActa Pharmacol Sin
December 2024
Laboratory of Biochemistry, Structural and Molecular Biology, Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125, Bari, Italy.
Carnitine O-acetyltransferase (CRAT) is a crucial enzyme involved in mitochondrial energy metabolism. Alterations in CRAT activity have emerged as significant contributors to the pathogenesis of Leigh syndrome and related mitochondrial disorders. In this study we employed an integrated approach combining in silico docking analysis and virtual screening of chemical libraries with subsequent in vitro validation to identify small molecule modulators of the activity of the wild type (WT) CRAT and the p.
View Article and Find Full Text PDFJ Infect Dis
December 2024
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY 10032, USA.
Background: Piperaquine, used in combination with dihydroartemisinin, has been identified as a promising partner drug for uncomplicated treatment and chemoprevention of Plasmodium falciparum malaria in Africa. In light of the earlier spread of piperaquine resistance in Southeast Asia, mediated primarily by mutations in the drug efflux transporter PfCRT, we have explored whether PfCRT mutations would represent a probable path to piperaquine resistance becoming established in Africa.
Methods: We edited PfCRT mutations known to mediate piperaquine resistance in Southeast Asia into P.
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