title: Molecular epidemiology of Plasmodium vivax in the State of Amazonas, Brazil.
abstract: Over the past 2 decades, the Amazon region of Brazil has experienced reemergence of Plasmodium vivax malaria, with reported occurrence of severe disease. The frequency and manifestations of this severe disease are unlike previous clinical experience. The hypothesis has been raised that the occurrence of severe disease may relate to the emergence of a variant form of the parasite. To test this hypothesis, we conducted a retrospective cohort study of P. vivax strains in the State of Amazonas. We determined nucleic acid sequences of segments of three genes, the 18S SSUrRNA Type A gene, the circumsporozoite surface protein (CSP) gene and the MSP-1 gene. Sequences were determined for parasites infecting 11 hospitalized (Inpatients) and 21 non-hospitalized (Outpatients) patients. We observed two common polymorphisms in the 18S SSUrRNA Type A gene; a thymidine (T)/adenine (A) polymorphism at residue 117 was significantly more common in the Inpatient group (p<0.05). Types of variation in the CSP gene included the numbers of repeat nonapeptide segments, alanine/aspartic acid polymorphism at position 5 of the nonapeptide repeat, and sporadic mutations. Alanine was more common as the fifth residue of the nonapeptide repeat in Inpatients and in strains causing second infections (both, p<0.05). Synonymous substitutions of the common repeat sequence occurred frequently in codons 1, 2, and 7, while the mutations at codon 5 were always non-synonymous, indicating that variation at codon 5 reflected selective pressure. Among MSP-1 gene sequences, recombination among progenitor strains, related to the Salvador I and Belém strains, was the main source of diversity. Phylogenetic analyses that incorporated sequence data for all three genes tested did not reveal clustering of sequences from inpatients. Our data do not affirm that the hypothesis that severe P. vivax disease in Amazonas is related to emergence of a new variant, but do suggest that variation in the fifth position of the CSP gene nonapeptide repeat may relate to disease manifestations.
authors.affiliation: Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road Room A3079, Bethesda, MD, USA. particiadantas@hotmail.com
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Santos-Ciminera
authors.forename: Maria das Graças C
authors.initials: Md
authors.lastname: Alecrim
authors.forename: Donald R
authors.initials: DR
authors.lastname: Roberts
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Quinnan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001938:Brazil / Q000453:epidemiology; D016054:DNA, Protozoan / Q000032:analysis / Q000302:isolation & purification; D014644:Genetic Variation; D006801:Humans; D016780:Malaria, Vivax / Q000453:epidemiology* / Q000469:parasitology / Q000503:physiopathology; D020066:Merozoite Surface Protein 1 / Q000235:genetics; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D010966:Plasmodium vivax / Q000235:genetics* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics; D012337:RNA, Ribosomal, 18S / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D016054:DNA, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D012337:RNA, Ribosomal, 18S; C041595:circumsporozoite protein, Protozoan