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• Both artemisinin-piperaquine and artemether-lumefantrine maintained high efficacy during the treatment of falciparum malaria in Grande Comore island. • Artemisinin-piperaquine in combination with anti-gametocyte treatment is recommended for rapidly increasing the killing effect of the malaria gametocyte in areas with a high rate of carrying. • Asymptomatic parasitaemia infections bring new challenges for malaria control in Comoros. Malaria significantly rebounded in 2018 in the Comoros; this created an urgent need to conduct clinical trials to investigate the effectiveness of artemisinin and its derivatives. An open-label, non-randomised controlled trial of artemisinin-piperaquine (AP) and artemether-lumefantrine (AL) was conducted in Grande Comore island from June 2019 to January 2020. A total of 238 uncomplicated falciparum malaria cases were enrolled and divided 1:1 into two treatments. The primary endpoint was the 42-day adequate clinical and parasitological responses (ACPR). Secondary endpoints were parasitaemia and fever clearance at day 3, gametocytes and tolerability. The 42-day ACPR before and after PCR correction were 91.43% (95% CI 83.93–95.76%) and 98.06% (95% CI 92.48–99.66%) for AP treatment, respectively, and 96.00% (95% CI 88.17–98.14%) and 98.97% (95% CI 93.58–99.95%) for AL treatment, respectively. Complete clearance of the parasitaemia and fever for both groups was detected on day 3. Gametocytes disappeared on day 21 in the AP group and on day 2 in AL group. Specifically, the adverse reactions were mild in both groups. It was found that AP and AL maintained their high efficacy and tolerance in the Comoros. Nonetheless, asymptomatic malaria infections bring new challenges to malaria control. [ABSTRACT FROM AUTHOR]

Background: Malaria is still one of the serious public health problems in Grande Comore Island, although the number of annual cases has been greatly reduced in recent years. A better understanding of malaria parasite population diversity and transmission dynamics is critical for assessing the effectiveness of malaria control measures. The objective of this study is to investigate temporal changes in genetic diversity of Plasmodium falciparum populations and multiplicity of infection (MOI) in Grande Comore 10 years after introduction of ACT., Methods: A total of 232 P. falciparum clinical isolates were collected from the Grande Comore Island during two sampling periods (118 for 2006‒2007 group, and 114 for 2013‒2016 group). Parasite isolates were characterized for genetic diversity and complexity of infection by genotyping polymorphic regions in merozoite surface protein gene 1 (msp-1), msp-2, and msp-3 using nested PCR and DNA sequencing., Results: Three msp-1 alleles (K1, MAD20, and RO33), two msp-2 alleles (FC27 and 3D7), and two msp-3 alleles (K1 and 3D7) were detected in parasites of both sampling periods. The RO33 allele of msp-1 (84.8%), 3D7 allele of msp-2 (90.8%), and K1 allele of msp-3 (66.7%) were the predominant allelic types in isolates from 2006-2007 group. In contrast, the RO33 allele of msp-1 (63.4%), FC27 allele of msp-2 (91.1%), and 3D7 allele of msp-3 (53.5%) were the most prevalent among isolates from the 2013-2016 group. Compared with the 2006‒2007 group, polyclonal infection rates of msp-1 (from 76.7 to 29.1%, P < 0.01) and msp-2 (from 62.4 to 28.3%, P < 0.01) allelic types were significantly decreased in those from 2013‒2016 group. Similarly, the MOIs for both msp-1 and msp-2 were higher in P. falciparum isolates in the 2006-2007 group than those in 2013-2016 group (MOI = 3.11 vs 1.63 for msp-1; MOI = 2.75 vs 1.35 for msp-2). DNA sequencing analyses also revealed reduced numbers of distinct sequence variants in the three genes from 2006‒2007 to 2013‒2016: msp-1, from 32 to 23 (about 28% decline); msp-2 from 29 to 21 (about 28% decline), and msp-3 from 11 to 3 (about 72% decline)., Conclusions: The present data showed dramatic reduction in genetic diversity and MOI among Grande Comore P. falciparum populations over the course of the study, suggesting a trend of decreasing malaria transmission intensity and genetic diversity in Grande Comore Island. These data provide valuable information for surveillance of P. falciparum infection and for assessing the appropriateness of the current malarial control strategies in the endemic area.