Dataset Information

Genetic diversity of MSP1 Block 2 of Plasmodium vivax isolates from Manaus (central Brazilian Amazon).

ABSTRACT: The diversity of MSP1 in both Plasmodium falciparum and P. vivax is presumed be associated to parasite immune evasion. In this study, we assessed genetic diversity of the most variable domain of vaccine candidate N-terminal PvMSP1 (Block 2) in field isolates of Manaus. Forty-seven blood samples the polymorphism of PvMSP1 Block 2 generates four fragment sizes. In twenty-eight of them, sequencing indicated seven haplotypes of PvMSP1 Block 2 circulating among field isolates. Evidence of striking exchanges was observed with two stretches flanking the repeat region and two predicted recombination sites were described. Single nucleotide polymorphisms determined with concurrent infections per patient indicated that nonsynonymous substitutions occurred preferentially in the repeat-rich regions which also were predicted as B-cell epitopes. The comprehensive understanding of the genetic diversity of the promising Block 2 associated with clinical immunity and a reduced risk of infection by Plasmodium vivax would be important for the rationale of malaria vaccine designs.

SUBMITTER: Soares LA

PROVIDER: S-EPMC3987980 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Genetic diversity of MSP1 Block 2 of Plasmodium vivax isolates from Manaus (central Brazilian Amazon).

Soares Leidiane Amorim LA Evangelista Janaína J Orlandi Patricia Puccinelli PP Almeida Maria Edilene ME de Sousa Luciana Pereira LP Chaves Yury Y Barbosa-Filho Roberto R Lacerda Marcus Vinícius MV Mariuba Luis André LA Nogueira Paulo Afonso PA Nogueira Paulo Afonso PA

Journal of immunology research 20140227

The diversity of MSP1 in both Plasmodium falciparum and P. vivax is presumed be associated to parasite immune evasion. In this study, we assessed genetic diversity of the most variable domain of vaccine candidate N-terminal PvMSP1 (Block 2) in field isolates of Manaus. Forty-seven blood samples the polymorphism of PvMSP1 Block 2 generates four fragment sizes. In twenty-eight of them, sequencing indicated seven haplotypes of PvMSP1 Block 2 circulating among field isolates. Evidence of striking ex ...[more]

PMID: 24741614

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Project description:BackgroundChloroquine (CQ) and primaquine (PQ) are still the drugs of choice to treat Plasmodium vivax malaria in many endemic areas, Brazil included. There is in vivo evidence for the P. vivax resistance to CQ in the Brazilian Amazon, where the increase in the proportion of P. vivax malaria parallels the increase of unusual clinical complications related to this species. In this study, in vitro CQ and mefloquine (MQ)-susceptibility of P. vivax isolates from the Western Brazilian Amazon was tested using the double-site enzyme-linked lactate dehydrogenase immunodetection (DELI) assay.MethodsA total of 112 P. vivax isolates were tested in vitro for CQ-susceptibility and out of these 47 were also tested for MQ-susceptibility. The DELI assay was used to detect P. vivax growth at 48-hour short-term culture in isolates with ring stages ranging from 50 to %. Each isolate was tested in triplicate and geometric means of IC50's was obtained. Nineteen isolates were genetically characterized for pvdhfr, pvmrp1, pvmdr1 and pvdhps candidate genes likely related to CQ resistance (10 with IC50<40 nM and 9 with IC50 >100 nM).ResultsTwelve out of 112 isolates were considered resistant to CQ, resulting in 10.7% (IC95% 5.0-16.4), while 3 out of 47 (6.4%; IC95% 0.0-12.8) were resistant to MQ. A discrete correlation was observed between IC50's of CQ and MQ (Spearman=0.294; p=0.045). For pvdhps gene, a non-synonymous mutation was found at codon 382 (S→C) in 5/8 CQ-sensitive samples and 1/9 CQ-resistant samples (p=0.027). The other molecular markers were not associated to CQ-susceptibility.ConclusionsIn vitro CQ-resistance estimated in this study, estimated by the DELI test, was very similar to that observed in clinical trials, suggesting that in vitro procedures developed by capable local laboratories are useful in the surveillance of CQ-resistance in the Amazon; concurrent Amazon P. vivax strains with both CQ and MQ resistance may be common; and a non-synonymous mutation at pvdhps codon 382 (S→C) was associated to in vitro susceptibility to CQ, needing further studies to be confirmed.

Project description:BackgroundEach year, 92 million pregnant women are at risk of contracting malaria during pregnancy, with the underestimation of the mortality and morbidity burden associated with Plasmodium vivax. During pregnancy, P. vivax infection is associated with low birth weight, maternal anaemia, premature delivery, and stillbirth. In the State of Acre (Brazil), high transmission leaves pregnant women at greater risk of contracting malaria and having a greater number of recurrences. The study of genetic diversity and the association of haplotypes with adverse pregnancy effects is of great importance for the control of the disease. Here we investigate the genetic diversity of P. vivax parasites infecting pregnant women across their pregnancies.MethodsP. vivax DNA was extracted from 330 samples from 177 women followed during pregnancy, collected in the State of Acre, Brazil. All samples were negative for Plasmodium falciparum DNA. Sequence data for the Pvmsp1 gene was analysed alongside data from six microsatellite (MS) markers. Allelic frequencies, haplotype frequencies, expected heterozygosity (HE) were calculated. Whole genome sequencing (WGS) was conducted on four samples from pregnant women and phylogenetic analysis performed with other samples from South American regions.FindingsInitially, the pregnant women were stratified into two groups-1 recurrence and 2 or more recurrences-in which no differences were observed in clinical gestational outcomes or in placental histological changes between the two groups. Then we evaluated the parasites genetically. An average of 18.5 distinct alleles were found at each of the MS loci, and the HE calculated for each marker indicates a high genetic diversity occurring within the population. There was a high percentage of polyclonal infections (61.7%, 108/175), and one haplotype (H1) occurred frequently (20%), with only 9 of the haplotypes appearing in more than one patient.InterpretationMost pregnant women had polyclonal infections that could be the result of relapses and/or re-infections. The high percentage of H1 parasites, along with the low frequency of many other haplotypes are suggestive of a clonal expansion. Phylogenetic analysis shows that P. vivax population within pregnant women clustered with other Brazilian samples in the region.FundingFAPESP and CNPq - Brazil.

Project description:BACKGROUND:There is a growing body of evidence linking micronutrient deficiencies and malaria incidence arising mostly from P. falciparum endemic areas. We assessed the impact of micronutrient deficiencies on malaria incidence and vice versa in the Brazilian state of Amazonas. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated children <10 years old living in rural communities in the state of Amazonas, Brazil, from May 2010 to May 2011. All children were assessed for sociodemographic, anthropometric and laboratory parameters, including vitamin A, beta-carotene, zinc and iron serum levels at the beginning of the study (May 2010) and one year later (May 2011). Children were followed in between using passive surveillance for detection of symptomatic malaria. Those living in the study area at the completion of the observation period were reassessed for micronutrient levels. Univariate Cox-proportional Hazards models were used to assess whether micronutrient deficiencies had an impact on time to first P. vivax malaria episode. We included 95 children median age 4.8 years (interquartile range [IQR]: 2.3-6.6), mostly males (60.0%) and with high maternal illiteracy (72.6%). Vitamin A deficiencies were found in 36% of children, beta-carotene deficiency in 63%, zinc deficiency in 61% and iron deficiency in 51%. Most children (80%) had at least one intestinal parasite. During follow-up, 16 cases of vivax malaria were diagnosed amongst 13 individuals. Micronutrient deficiencies were not associated with increased malaria incidence: vitamin A deficiency [Hazard ratio (HR): 1.51; P-value: 0.45]; beta-carotene [HR: 0.47; P-value: 0.19]; zinc [HR: 1.41; P-value: 0.57] and iron [HR: 2.31; P-value: 0.16]). Upon reevaluation, children with al least one episode of malaria did not present significant changes in micronutrient levels. CONCLUSION:Micronutrient serum levels were not associated with a higher malaria incidence nor the malaria episode influenced micronutrient levels. Future studies targeting larger populations to assess micronutrients levels in P. vivax endemic areas are warranted in order to validate these results.

Dataset Information

Genetic diversity of MSP1 Block 2 of Plasmodium vivax isolates from Manaus (central Brazilian Amazon).

Publications

Genetic diversity of MSP1 Block 2 of Plasmodium vivax isolates from Manaus (central Brazilian Amazon).

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