title: Low infectivity of Plasmodium falciparum gametocytes to Anopheles gambiae following treatment with sulfadoxine-pyrimethamine in Mali.
abstract: Sulfadoxine-pyrimethamine (SP) treatment increases the rate of gametocyte carriage and selects SP resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS), raising concerns of increased malaria transmission and spread of drug resistance. In a setting in Mali where SP was highly efficacious, we measured the prevalence of DHFR and DHPS mutations in P. falciparum infections with microscopy-detected gametocytes following SP treatment, and used direct feeding to assess infectivity to Anopheles gambiae sensu lato. Children and young adults presenting with uncomplicated malaria were treated with SP or chloroquine and followed for 28 days. Gametocyte carriage peaked at 67% 1 week after treatment with a single dose of SP. Those post-SP gametocytes carried significantly more DHFR and DHPS mutations than pre-treatment asexual parasites from the same population. Only 0.5% of 1728 mosquitoes fed on SP-treated gametocyte carriers developed oocysts, while 11% of 198 mosquitoes fed on chloroquine-treated gametocyte carriers were positive for oocysts. This study shows that in an area of high SP efficacy, although SP treatment sharply increased gametocyte carriage, the infectiousness of these gametocytes to the vector may be very low. Accurate and robust methods for measuring infectivity are needed to guide malaria control interventions that affect transmission.
authors.affiliation: Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, University of Bamako, P.O. Box 1805, Point G, Bamako, Mali.
authors.forename: Abdoul H
authors.initials: AH
authors.lastname: Beavogui
authors.forename: Abdoulaye A
authors.initials: AA
authors.lastname: Djimde
authors.forename: Aric
authors.initials: A
authors.lastname: Gregson
authors.forename: Abdoulaye M
authors.initials: AM
authors.lastname: Toure
authors.forename: Adama
authors.initials: A
authors.lastname: Dao
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Dinkorma
authors.initials: D
authors.lastname: Ouologuem
authors.forename: Bakary
authors.initials: B
authors.lastname: Fofana
authors.forename: Adama
authors.initials: A
authors.lastname: Sacko
authors.forename: Mamadou
authors.initials: M
authors.lastname: Tekete
authors.forename: Aminatou
authors.initials: A
authors.lastname: Kone
authors.forename: Oumou
authors.initials: O
authors.lastname: Niare
authors.forename: Mamadou
authors.initials: M
authors.lastname: Wele
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
authors.forename: Stephane
authors.initials: S
authors.lastname: Picot
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000962:Antimalarials / Q000627:therapeutic use*; D004094:Dihydropteroate Synthase / Q000235:genetics / Q000378:metabolism; D004338:Drug Combinations; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000453:epidemiology; D008302:Mali / Q000453:epidemiology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D011739:Pyrimethamine / Q000627:therapeutic use*; D013413:Sulfadoxine / Q000627:therapeutic use*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase; D011739:Pyrimethamine
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