Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria

African Journal of Laboratory Medicine ISSN: (Online) 2225-2010, (Print) 2225-2002 Page 1 of 6 Original Research Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria Authors: Dinkorma T. Ouologuem1 Cheick O. Kone1 Bakary Fofana1 Bakary Sidibe1 Amadou H. Togo1 Demba Dembele1 Sekou Toure1 Sekou Koumare1 Ousmane Toure1 Issaka Sagara1 Abdoulaye Toure1 Adama Dao1 Ogobara K. Doumbo1† Abdoulaye A. Djimde1 Affiliations: 1 Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, University of Science, Techniques and Technologies of Bamako, Bamako, Mali Corresponding author: Abdoulaye Djimde, Dates: Received: 02 Feb. 2018 Accepted: 30 Sept. 2018 Published: 06 Dec. 2018 How to cite this article: Ouologuem DT, Kone CO, Fofana B, et al. Differential infectivity of gametocytes after artemisinin-based combination therapy of uncomplicated falciparum malaria. Afr J Lab Med. 2018;7(2), a784. https://doi. org/10.4102/ajlm.v7i2.784 Note: †, 1956-2018 Copyright: © 2018. The Authors. Licensee: AOSIS. This work is licensed under the Creative Commons Attribution License. Read online: Scan this QR code with your smart phone or mobile device to read online. Background: Most malaria-endemic countries use artemisinin-based combination therapy (ACT) as their first-line treatment. ACTs are known to be highly effective on asexual stages of the malaria parasite. Malaria transmission and the spread of resistant parasites depend on the infectivity of gametocytes. The effect of the current ACT regimens on gametocyte infectivity is unclear. Objectives: This study aimed to determine the infectivity of gametocytes to Anopheles gambiae following ACT treatment in the field. Methods: During a randomised controlled trial in Bougoula-Hameau, Mali, conducted from July 2005 to July 2007, volunteers with uncomplicated malaria were randomised to receive artemether-lumefantrine, artesunate-amodiaquine, or artesunate-sulfadoxine/ pyrimethamine. Volunteers were followed for 28 days, and gametocyte carriage was assessed. Direct skin feeding assays were performed on gametocyte carriers before and after ACT administration. Results: Following artemether-lumefantrine treatment, gametocyte carriage decreased steadily from Day 0 to Day 21 post-treatment initiation. In contrast, for the artesunateamodiaquine and artesunate-sulfadoxine/pyrimethamine arms, gametocyte carriage increased on Day 3 and remained constant until Day 7 before decreasing afterward. Mosquito feeding assays showed that artemether-lumefantrine and artesunate-amodiaquine significantly increased gametocyte infectivity to Anopheles gambiae sensu lato (s.l.) (p < 10−4), whereas artesunate-sulfadoxine/pyrimethamine decreased gametocyte infectivity in this setting (p = 0.03). Conclusion: Different ACT regimens could lead to gametocyte populations with different capacity to infect the Anopheles vector. Frequent assessment of the effect of antimalarials on gametocytogenesis and gametocyte infectivity may be required for the full assessment of treatment efficacy, the potential for spread of drug resistance and malaria transmission in the field. Background Malaria is still a major public health problem in numerous parts of the world. Malaria still affects 216 000 million individuals each year with 445 000 deaths worldwide.1 The global agenda for malaria elimination and eradication may never succeed without a thorough understanding of gametocyte biology and the true effect of the various interventions on malaria transmission. Gametocyte development and viability are essential for the perpetuation of Plasmodium life cycle by enabling both transmission from the human host to the mosquito vector2,3 and the spread of resistant parasites. Plasmodium gametocyte development within the human host is a tedious process involving the differentiation from asexual to sexual forms to accommodate metabolic requirements, environmental changes and sexual reproduction.4,5 Plasmodium gametocytes are conventionally classified into five distinct stages (stages I–V) but only the immature stage I gametocytes and the mature stage V gametocytes are detectable in the peripheral blood of a malaria-infected patient.6,7 The other stages (stage II, III, IV) are sequestered in the bone marrow and possibly other internal organs.6,8,9 Gametocytes do not cause any symptoms in the infected human host, but the presence of competent circulating gametocytes and their duration in the bloodstream, which varies from 3 to 4 weeks,10 are directly responsible for malaria parasite transmission to the Anopheles vector.11 However, gametocytogenesis and gametocyte transmission to the mosquito vector constitute a population bottleneck in the Plasmodium life cycle as only a minute number of parasites enter the http://www.ajlmonline.org Open Access Page 2 of 6 Original Research mosquito bloodmeal and gut.12 Monitoring the density and infectiousness of circulating gametocytes is necessary for a better assessment of malaria transmission in endemic areas. Bamako (No 05-20 dated 22 June 2005). Each participant (or legal guardian for minors) gave fully informed written consent before enrolment. Gametocyte development within the human host is influenced by various factors, including host and parasite genetic factors, immune response, mosquitoes’ gut microbiota and the exposure to antimalarial drugs.13,14,15 Several clinical and in vitro studies reveal that most antimalarial drugs currently in use can promote or impair gametocytogenesis and to some extent affect sexual reproduction within the mosquito vector.16 The 8-aminoquinoline primaquine is presently the only clinically used antimalarial drug displaying potent activity against all Plasmodium species and gametocyte stages,16 but its side effects on glucose-6phosphate dehydrogenase-deficient individuals hinder its use in large-scale elimination strategies.17,18 The 4-aminoquinoline chloroquine was shown to increase the production of fully competent gametocytes both in vitro and in vivo.19,20 In contrast atovaquone, artemisinin and the antifolates (sulfadoxine and pyrimethamine) have been shown to impair gametocyte development and infectivity.20,21,22,23,24 The gametocyte developmental stages affected by antimalarial drugs is poorly understood. The antimalarial treatment represents a stress factor that triggers differentiation of the asexual form into the gametocytes.25,26 This process may be more prevalent with drug-resistant parasites compared to sensitive ones.27 Hence, the selective pressure exerted by the antimalarial drugs on the parasite may contribute to the spread of resistant parasites through the development and transmission of drug-resistant gametocytes.28 Therefore it becomes essential to assess the emergence of resistant strains and the impact of treatment on gametocytogenesis and gametocyte infectivity. Study sites Artemisinin-based combinatio (...truncated)