multiple-clone activation of hypnozoites is the leading cause of relapse in plasmodium vivax infectionmultiple-clone激活hypnozoites是间日疟原虫感染复发的主要原因.pdfVIP

Multiple-Clone Activation of Hypnozoites Is the Leading Cause of Relapse in Plasmodium vivax Infection ´ 1 ˆ 2 3 1 Flavia Carolina F. de Araujo , Antonio Mauro de Rezende , Cor Jesus F. Fontes , Luzia Helena Carvalho , Cristiana F. Alves de Brito1* ´ 1 Laboratory of Malaria, Centro de Pesquisas Rene Rachou – Fiocruz Minas, Belo Horizonte, Minas Gerais, Brazil, 2 Laboratory of Cellular and Molecular Parasitology, Centro ´ ´ ´ ´ de Pesquisas Rene Rachou – Fiocruz Minas, Belo Horizonte, Minas Gerais, Brazil, 3 Hospital Universitario Julio Muller, UFMT, Cuiaba, Mato Grasso, Brazil Abstract Background: Plasmodium vivax infection is characterized by a dormant hepatic stage, the hypnozoite that is activated at varying periods of time after clearance of the primary acute blood-stage, resulting in relapse. Differentiation between treatment failure and new infections requires characterization of initial infections, relapses, and clone multiplicity in vivax malaria infections. Methodology/Principal Findings: Parasite DNA obtained from primary/relapse paired blood samples of 30 patients with P. vivax infection in Brazil was analyzed using 10 molecular markers (8 microsatellites and MSP-1 blocks 2 and 10). Cloning of PCR products and genotyping was used to identify low-frequency clones of parasites. We demonstrated a high frequency of multiple-clone infections in both primary and relapse infections. Few alleles were identified per locus, but the combination of these alleles produced many haplotypes. Consequently, the majority of parasites involved in relapse sh