No Clinical or Molecular Evidence of Plasmodium falciparum Resistance to Artesunate–Mefloquine in Northwestern Brazil

• Published in: The American journal of tropical medicine and hygiene Vol. 95; no. 1; pp. 148 - 154
• Main Authors: Ladeia-Andrade, Simone, de Melo, Gladson Naber P., de Souza-Lima, Rita de Cássia, Salla, Laís C., Bastos, Melissa S., Rodrigues, Priscila T., Luz, Francisco das Chagas O., Ferreira, Marcelo U.
• Format: Journal Article
• Language: English
• Published: United States The American Society of Tropical Medicine and Hygiene 06.07.2016
• Subjects: Adolescent; Adult; Aged; Antimalarials - therapeutic use; Artemisinins - therapeutic use; Brazil; Child; Child, Preschool; DNA, Protozoan - isolation & purification; Dose-Response Relationship, Drug; Drug Combinations; Fever - drug therapy; Follow-Up Studies; Humans; Malaria, Falciparum - drug therapy; Mefloquine - therapeutic use; Middle Aged; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; Parasitemia - drug therapy; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Treatment Outcome; Young Adult; ASW, Brazil
• ISSN: 0002-9637; 1476-1645; 1476-1645
• DOI: 10.4269/ajtmh.16-0017

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).