Addition of artesunate to chloroquine for treatment of Plasmodium falciparum malaria in Gambian children causes a significant but short‐lived reduction in infectiousness for mosquitoes

• Published in: Tropical medicine & international health 2004-01, Vol.9 (1), p.53-61
• Main Authors: Drakeley, Christopher J., Jawara, Musa, Targett, Geoffrey A. T., Walraven, Gijs, Obisike, Uche, Coleman, Rosalind, Pinder, Margaret, Sutherland, Colin J.
• Format: Article
• Language: English
• Subjects: Acute Disease; Age Factors; Animals; Anopheles - parasitology; Anopheles gambiae; Antimalarials - therapeutic use; Artemisinins - therapeutic use; artesunate; Biological and medical sciences; Child; Child, Preschool; chloroquine; Chloroquine - therapeutic use; combination therapy; Drug Resistance; Drug Therapy, Combination; Female; Gambia; gametocytes; Human protozoal diseases; Humans; Infant; Infectious diseases; infectivity; Malaria; Malaria, Falciparum - drug therapy; Malaria, Falciparum - transmission; Medical sciences; Parasitemia - drug therapy; Parasitic diseases; Plasmodium falciparum; Plasmodium falciparum - isolation & purification; Prevalence; Protozoal diseases; Sesquiterpenes - therapeutic use; The Gambia; Treatment Failure
• ISSN: 1360-2276; 1365-3156
• DOI: 10.1046/j.1365-3156.2003.01169.x

Summary Objectives  Combination therapy using existing anti‐malarials together with artesunate (AS) has been advocated as a method to slow the spread of drug resistance. We assessed the effect on Plasmodium falciparum transmissibility of the addition of AS to chloroquine (CQ) in an area of The Gambia where resistance to CQ is increasing. Methods  Gambian children with acute uncomplicated P. falciparum malaria were treated with either CQ monotherapy (n = 120) or the combination of CQ plus three doses of AS (CQ/AS; n = 352). Post‐treatment sexual‐stage parasitaemia was assessed during a 4‐week follow‐up period. Experimental infections of Anopheles gambiae s.s. mosquitoes were performed with blood from patients who were carrying gametocytes 7 days after starting treatment (n = 69). Results  The addition of AS significantly reduced post‐treatment prevalence and mean density of gametocytes in the first 14 days (day 7: 43.7%vs. 12.4%, 62.4/μl vs. 6.2/μl; day 14: 32.9%vs. 3.7%; 21.9/μl vs. 5.2/μl; CQ vs. CQ/AS), although by day 28 the benefits of the combination were substantially less marked (40.5%vs. 21.8%; 23.0/μl vs. 63.1/μl; CQ vs. CQ/AS). The duration of gametocyte carriage over the study period was significantly lower in the CQ/AS group (5.2 days vs. 1.5 days; CQ vs. CQ/AS). The estimated infectious proportion of children at day 7 was also lower in the combination group (19.2%vs. 3.4%; CQ vs. CQ/AS), as were the proportion of mosquitoes infected and mean oocyst density (11.5%vs. 0.9%; 0.3 vs. 0.01; CQ vs. CQ/AS). Treatment failure was associated with threefold and twofold higher gametocyte carriage rates during follow‐up in CQ and CQ/AS groups, respectively (P