SummaryBackgroundArtemether–lumefantrine and artesunate–amodiaquine are used as first-line artemisinin-based combination therapies (ACTs) in west Africa. Pyronaridine–artesunate and dihydroartemisinin–piperaquine are potentially useful for diversification of ACTs in this region, but further safety and efficacy data are required on malaria retreatment.MethodsWe did a randomised, multicentre, open-label, longitudinal, controlled phase 3b/4 clinical trial at seven tertiary centres in Burkina Faso, Guinea, and Mali. Eligible participants for first malaria episode and all retreatment episodes were adults and children aged 6 months and older with microscopically confirmed Plasmodium spp malaria (>0 to <200 000 parasites per μL of blood) and fever or history of fever in the previous 24 h. Individuals with severe or complicated malaria, an alanine aminotransferase concentration of more than twice the upper limit of normal, or a QTc greater than 450 ms were excluded. Using a randomisation list for each site, masked using sealed envelopes, participants were assigned to either pyronaridine–artesunate or dihydroartemisinin–piperaquine versus either artesunate–amodiaquine or artemether–lumefantrine. Block sizes were two or four if two treatments were allocated, and three or six if three treatments were allocated. Microscopists doing the parasitological assessments were masked to treatment allocation. All treatments were once-daily or twice-daily tablets or granules given orally and dosed by bodyweight over 3 days at the study centre. Patients were followed up as outpatients up to day 42, receiving clinical assessments on days 0, 1, 2, 3, 7, 14, 21, 28, 35, and 42. Two primary outcomes were compared for non-inferiority: the 2-year incidence rate of all microscopically confirmed, complicated and uncomplicated malaria episodes in patients in the intention-to-treat population (ITT; non-inferiority margin 20%); and adequate clinical and parasitological response (ACPR) in uncomplicated malaria across all episodes (unadjusted and PCR-adjusted for Plasmodium falciparum and unadjusted for other Plasmodium spp) in the per-protocol population on days 28 and 42 (non-inferiority margin 5%). Safety was assessed in all participants who received one dose of study drug. This study is registered at the Pan African Clinical Trials Registry (PACTR201105000286876).FindingsBetween Oct 24, 2011, and Feb 1, 2016, we assigned 4710 eligible participants to the different treatment strategies: 1342 to pyronaridine–artesunate, 967 to artemether–lumefantrine, 1061 to artesunate–amodiaquine, and 1340 to dihydroartemisinin–piperaquine. The 2-year malaria incidence rate in the ITT population was non-inferior for pyronaridine–artesunate versus artemether–lumefantrine (1·77, 95% CI 1·63–1·93 vs 1·87, 1·72–2·03; rate ratio [RR] 1·05, 95% CI 0·94–1·17); and versus artesunate–amodiaquine (1·39, 95% CI 1·22–1·59 vs 1·35, 1·18–1·54; RR 0·97, 0·87–1·07). Similarly, this endpoint was non-inferior for dihydroartemisinin–piperaquine versus artemether–lumefantrine (1·16...
BackgroundSeasonal malaria chemoprevention (SMC) with sulphadoxine-pyrimethamine (SP) plus amodiaquine (AQ) is being scaled up in Sahelian countries of West Africa. However, the potential development of Plasmodium falciparum resistance to the respective component drugs is a major concern.MethodsTwo cross-sectional surveys were conducted before (August 2012) and after (June 2014) a pilot implementation of SMC in Koutiala, Mali. Children aged 3–59 months received 7 rounds of curative doses of SP plus AQ over two malaria seasons. Genotypes of P. falciparum Pfdhfr codons 51, 59 and 108; Pfdhps codons 437 and 540, Pfcrt codon 76 and Pfmdr1codon 86 were analyzed by PCR on DNA from samples collected before and after SMC, and in non-SMC patient population as controls (November 2014).ResultsIn the SMC population 191/662 (28.9%) and 85/670 (12.7%) of children were P. falciparum positive by microscopy and were included in the molecular analysis before (2012) and after SMC implementation (2014), respectively. In the non-SMC patient population 220/310 (71%) were successfully PCR analyzed. In the SMC children, the prevalence of all molecular markers of SP resistance increased significantly after SMC including the Pfdhfr-dhps quintuple mutant genotype, which was 1.6% before but 7.1% after SMC (p = 0.02). The prevalence of Pfmdr1-86Y significantly decreased from 26.7% to 15.3% (p = 0.04) while no significant change was seen for Pfcrt 76T. In 2014, prevalence of all molecular markers of SP resistance were significantly higher among SMC children compared to the non-SMC population patient (p < 0.01). No Pfdhfr-164 mutation was found neither at baseline nor post SMC.ConclusionSMC increased the prevalence of molecular markers of P. falciparum resistance to SP in the treated children. However, there was no significant increase of these markers of resistance in the general parasite population after 2 years and 7 rounds of SMC.
Background Artisanal mining creates enabling breeding ground for the vector of malaria parasites. There is paucity of data on the effects of artisanal mining on malaria. This study assessed burden of malaria and caregivers’ health-seeking behaviour for children under five in artisanal mining communities in East Akim District in Ghana. Methods A cross-sectional study involving caregivers and their children under five was conducted in three artisanal mining communities in the East Akim District in Ghana. Caregivers were interviewed using a structured questionnaire. Finger prick blood samples were collected and analysed for haemoglobin concentration using a rapid diagnostic test, and thick and thin blood smears were analysed to confirm the presence of malaria parasites. Results Of the 372 children under 5 years included in the study, 197 (53.1%) were male, with a mean age (± SD) of 23.0 ± 12.7 months. The proportion of children with malaria (Plasmodium falciparum and P. malariae) was 98.1% and 1.9%, respectively, whilst the proportion with anaemia (Hb < 11.0 g/dl) was 39.5% (n = 147). Almost all caregivers were female (98.9%), and 28.6% (n = 106) did not have access to any malaria control information. Caregivers associated malaria infection with mosquito bites (68.3%, n = 254) and poor sanitation (21.2%, n = 79). Malaria in children under five was significantly associated with anaemia (OR 11.07, 95% CI 6.59–18.68, n = 111/160, 69.4%; P < 0.0001), residing close to stagnant water (≤ 25 m) from an artisanal mining site (AOR 2.91, 95% CI 1.47–5.76, P = 0.002) and caregiver age younger than 30 years (OR 0.44, 95% CI 0.208–0.917, n = 162, 43.55%, P = 0.001). Conclusions There is a high burden of malaria and anaemia among children under five in artisanal mining communities of the East Akim District, and far higher than in non-artisanal mining sites. Interventions are needed to effectively regulate mining activities in these communities, and strengthen malaria control and health education campaigns to curtail the high malaria burden and improve health-seeking behaviour. Graphical abstract
A recent randomised controlled trial, WANECAM, conducted at seven centres in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting sub-microscopic parasitaemia by qPCR at 72h post-treatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and compared treatment outcomes for this group to those with complete parasite clearance by 72h. Among 547 evaluable patients, 17.7% had qPCR-detectable parasitaemia at 72h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72h were significantly more likely to have microscopically-detectable recurrent Plasmodium falciparum parasitaemia by day 42 than those receiving other regimens, and experienced on average a shorter time-interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.