Monitoring the Efficacy of Chloroquine-Primaquine Therapy for Uncomplicated Plasmodium vivax Malaria in the Main Transmission Hot Spot of Brazil.

Autor:	Ladeia-Andrade S; Laboratory of Parasitic Diseases, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil sladeia@ioc.fiocruz.br muferrei@usp.br., Menezes MJ; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., de Sousa TN; Malaria Laboratory, René Rachou Research Center, Fiocruz, Belo Horizonte, Brazil., Silvino ACR; Malaria Laboratory, René Rachou Research Center, Fiocruz, Belo Horizonte, Brazil., de Carvalho JF Jr; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Salla LC; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Nery OA; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., de Melo GNP; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Corder RM; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Rodrigues PT; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil., Ferreira MU; Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil sladeia@ioc.fiocruz.br muferrei@usp.br.
Jazyk:	angličtina
Zdroj:	Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Apr 25; Vol. 63 (5). Date of Electronic Publication: 2019 Apr 25 (Print Publication: 2019).
DOI:	10.1128/AAC.01965-18
Abstrakt:	Emerging Plasmodium vivax resistance to chloroquine (CQ) may undermine malaria elimination efforts in South America. CQ-resistant P. vivax has been found in the major port city of Manaus but not in the main malaria hot spots across the Amazon Basin of Brazil, where CQ is routinely coadministered with primaquine (PQ) for radical cure of vivax malaria. Here we randomly assigned 204 uncomplicated vivax malaria patients from Juruá Valley, northwestern Brazil, to receive either sequential (arm 1) or concomitant (arm 2) CQ-PQ treatment. Because PQ may synergize the blood schizontocidal effect of CQ and mask low-level CQ resistance, we monitored CQ-only efficacy in arm 1 subjects, who had PQ administered only at the end of the 28-day follow-up. We found adequate clinical and parasitological responses in all subjects assigned to arm 2. However, 2.2% of arm 1 patients had microscopy-detected parasite recrudescences at day 28. When PCR-detected parasitemias at day 28 were considered, response rates decreased to 92.1% and 98.8% in arms 1 and 2, respectively. Therapeutic CQ levels were documented in 6 of 8 recurrences, consistent with true CQ resistance in vivo In contrast, ex vivo assays provided no evidence of CQ resistance in 49 local P. vivax isolates analyzed. CQ-PQ coadministration was not found to potentiate the antirelapse efficacy of PQ over 180 days of surveillance; however, we suggest that larger studies are needed to examine whether and how CQ-PQ interactions, e.g., CQ-mediated inhibition of PQ metabolism, modulate radical cure efficacy in different P. vivax -infected populations. (This study has been registered at ClinicalTrials.gov under identifier NCT02691910.). (Copyright © 2019 American Society for Microbiology.)
Databáze:	MEDLINE
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