title: No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate-Mefloquine in Northwestern Brazil.
abstract: We evaluated the clinical efficacy of artesunate-mefloquine (ASMQ) fixed-dose combination to treat uncomplicated malaria in Juruá Valley, the main Plasmodium falciparum transmission hotspot in Brazil. Between November 2010 and February 2013, we enrolled 162 patients aged 4-73 years, with fever or a history of fever, and a single-species P. falciparum infection confirmed by microscopy and polymerase chain reaction (PCR). All 154 patients who completed the 42-day follow-up presented an adequate clinical and parasitologic response. ASMQ was well tolerated and no adverse event caused treatment interruption. Gametocytes were detected in 46.3% patients; 35.2% had gametocytes at enrollment, whereas others developed patent gametocytemia 1-14 days after starting ASMQ. By day 3 of treatment, all subjects had cleared asexual parasitemia, but parasite DNA remained PCR detectable in 37.6% of them. Day-3 PCR positivity was associated with prolonged gametocyte carriage. We found no molecular evidence of resistance to either MQ (pfmdr1 gene amplification) or AS (mutations in selected kelch13 gene domains known to be associated with AS resistance) in the local P. falciparum population. These results strongly support the use of ASMQ as a first-line regimen to treat uncomplicated P. falciparum malaria in northwestern Brazil, but underscore the need for gametocytocidal drugs to reduce the transmission potential of ASMQ-treated patients (ClinicalTrials.gov number NCT01144702).
authors.affiliation: Laboratory of Parasitic Diseases, Oswaldo Cruz Institute/Oswaldo Cruz Foundation (Fiocruz), Rio de Janeiro, Brazil. Amazonian Malaria Initiative/Amazon Network for the Surveillance of Antimalarial Drug Resistance, Ministry of Health of Brazil, Cruzeiro do Sul, Brazil.
authors.forename: Simone
authors.initials: S
authors.lastname: Ladeia-Andrade
authors.affiliation: Amazonian Malaria Initiative/Amazon Network for the Surveillance of Antimalarial Drug Resistance, Ministry of Health of Brazil, Cruzeiro do Sul, Brazil.
authors.forename: Gladson Naber P
authors.initials: GN
authors.lastname: de Melo
authors.affiliation: Amazonian Malaria Initiative/Amazon Network for the Surveillance of Antimalarial Drug Resistance, Ministry of Health of Brazil, Cruzeiro do Sul, Brazil.
authors.forename: Rita de Cássia
authors.initials: Rde C
authors.lastname: de Souza-Lima
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Laís C
authors.initials: LC
authors.lastname: Salla
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Bastos
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Priscila T
authors.initials: PT
authors.lastname: Rodrigues
authors.affiliation: Center for Tropical Medicine, University of Brasília, Brasília, Brazil.
authors.forename: Francisco das Chagas O
authors.initials: Fd
authors.lastname: Luz
authors.affiliation: Amazonian Malaria Initiative/Amazon Network for the Surveillance of Antimalarial Drug Resistance, Ministry of Health of Brazil, Cruzeiro do Sul, Brazil. Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. muferrei@usp.br.
authors.forename: Marcelo U
authors.initials: MU
authors.lastname: Ferreira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D016054:DNA, Protozoan / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005334:Fever / Q000188:drug therapy; D005500:Follow-Up Studies; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015767:Mefloquine / Q000627:therapeutic use*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D018512:Parasitemia / Q000188:drug therapy; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; D016054:DNA, Protozoan; D004338:Drug Combinations; D015767:Mefloquine; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513498:Mdr1 protein, Plasmodium falciparum