Dataset Information

Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico.

ABSTRACT:

Background

In southern Mexico, malaria transmission is low, seasonal, and persistent. Because many patients are affected by two or more malaria episodes caused by Plasmodium vivax, we carried out a study to determine the timing, frequency, and genetic identity of recurrent malaria episodes in the region between 1998 and 2008.

Methods

Symptomatic patients with more than one P. vivax infection were followed up, and blood samples were collected from primary and recurrent infections. DNA extracted from infected blood samples was analyzed for restriction fragment length polymorphism (RFLP) in genes encoding csp and msp3?, as well as size variation in seven microsatellites.

Results

One hundred and forty six parasite samples were collected from 70 patients; of these, 65 patients had one recurrent infection, four had two, and one had three recurrent infections. The majority of recurrent infections occurred within one year of the primary infection, some of which were genetically homologous to the primary infection. As the genetic diversity in the background population was high, the probability of homologous re-infection was low and the homologous recurrences likely reflected relapses. These homologous recurrent infections generally had short (< 6 months) or long (6-12 months) intervals between the primary (PI) and recurrent (RI) infections; whereas infections containing heterologous genotypes had relatively longer intervals. The epidemiological data indicate that heterologous recurrences could be either relapse or re-infections.

Conclusions

Genetic and temporal analysis of P. vivax recurrence patterns in southern Mexico indicated that relapses play an important role in initiating malaria transmission each season. The manifestation of these infections during the active transmission season allowed the propagation of diverse hypnozoite genotypes. Both short- and long-interval relapses have contributed to parasite persistence and must be considered as targets of treatment for malaria elimination programs in the region to be successful.

SUBMITTER: Gonzalez-Ceron L

PROVIDER: S-EPMC3637411 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Publications

Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico.

Gonzalez-Ceron Lilia L Mu Jianbing J Santillán Frida F Joy Deirdre D Sandoval Marco A MA Camas Gerardo G Su Xinzhuan X Choy Elena V EV Torreblanca Rene R

Parasites & vectors 20130418

<h4>Background</h4>In southern Mexico, malaria transmission is low, seasonal, and persistent. Because many patients are affected by two or more malaria episodes caused by Plasmodium vivax, we carried out a study to determine the timing, frequency, and genetic identity of recurrent malaria episodes in the region between 1998 and 2008.<h4>Methods</h4>Symptomatic patients with more than one P. vivax infection were followed up, and blood samples were collected from primary and recurrent infections. ...[more]

PMID: 23597046

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Project description:BackgroundChina has reached important milestones in the elimination of malaria. However, the numbers of imported recurrent cases of Plasmodium vivax and P. ovale are gradually increasing, which increases the risk of malaria re-establishment in locations where Anopheles mosquitoes exist. The aim of this study is to characterize the epidemiological profiles of imported recurrent P. vivax and P. ovale cases, quantifying the recurrence burden and guiding the development of appropriate public health intervention strategies.MethodsIndividual-level data of imported recurrent P. vivax and P. ovale cases were collected from 2013 to 2020 in China via the Parasitic Diseases Information Reporting Management System. Demographic characteristics, temporal and spatial distributions, and the interval from previous infection to recurrence were analyzed by SAS, ArcGIS and GraphPad Prism software, respectively, to explore the epidemiological profiles of imported recurrent cases.ResultsA total of 307 imported recurrent cases, including 179 P. vivax and 128 P. ovale cases, were recorded. The majority of cases occurred in males (P. vivax 91.1%, P. ovale 93.8%) and migrant workers (P. vivax 43.2%, P. ovale 44.7%). Individuals aged 30-39 years had the highest P. vivax and P. ovale recurrent infection rates, respectively. The number of imported recurrent cases of infection by these two malaria species increased from 2013 to 2018, and P. vivax infection showed well-defined seasonality, with two peaks in February and June, respectively. More than 90% of patients with recurrent cases did not receive radical treatment for previous infection. Most imported recurrent P. vivax cases were reported in Yunnan Province and were imported from Myanmar, Ethiopia, and Pakistan, while most recurrent P. ovale cases were reported in southern China and primarily imported from Cameroon, Ghana, and Nigeria. The intervals from previous malaria infection to recurrence among different continents were significantly different (P = 0.0016) for P. vivax malaria but not for P. ovale malaria (P = 0.2373).ConclusionsThe large number of imported recurrent cases has been a major challenge in the prevention of malaria re-establishment in China. This study provides evidence to guide the development of appropriate public health intervention strategies for imported recurrent P. vivax and P. ovale cases.

Project description:BACKGROUND:Parasite genetic diversity and multiplicity of infection (MOI) affect clinical outcomes, response to drug treatment and naturally-acquired or vaccine-induced immunity. Traditional methods often underestimate the frequency and diversity of multiclonal infections due to technical sensitivity and specificity. Next-generation sequencing techniques provide a novel opportunity to study complexity of parasite populations and molecular epidemiology. METHODS:Symptomatic and asymptomatic Plasmodium vivax samples were collected from health centres/hospitals and schools, respectively, from 2011 to 2015 in Ethiopia. Similarly, both symptomatic and asymptomatic Plasmodium falciparum samples were collected, respectively, from hospitals and schools in 2005 and 2015 in Kenya. Finger-pricked blood samples were collected and dried on filter paper. Long amplicon (> 400 bp) deep sequencing of merozoite surface protein 1 (msp1) gene was conducted to determine multiplicity and molecular epidemiology of P. vivax and P. falciparum infections. The results were compared with those based on short amplicon (117 bp) deep sequencing. RESULTS:A total of 139 P. vivax and 222 P. falciparum samples were pyro-sequenced for pvmsp1 and pfmsp1, yielding a total of 21 P. vivax and 99 P. falciparum predominant haplotypes. The average MOI for P. vivax and P. falciparum were 2.16 and 2.68, respectively, which were significantly higher than that of microsatellite markers and short amplicon (117 bp) deep sequencing. Multiclonal infections were detected in 62.2% of the samples for P. vivax and 74.8% of the samples for P. falciparum. Four out of the five subjects with recurrent P. vivax malaria were found to be a relapse 44-65 days after clearance of parasites. No difference was observed in MOI among P. vivax patients of different symptoms, ages and genders. Similar patterns were also observed in P. falciparum except for one study site in Kenyan lowland areas with significantly higher MOI. CONCLUSIONS:The study used a novel method to evaluate Plasmodium MOI and molecular epidemiological patterns by long amplicon ultra-deep sequencing. The complexity of infections were similar among age groups, symptoms, genders, transmission settings (spatial heterogeneity), as well as over years (pre- vs. post-scale-up interventions). This study demonstrated that long amplicon deep sequencing is a useful tool to investigate multiplicity and molecular epidemiology of Plasmodium parasite infections.

Project description:Mexico advanced to the pre-elimination phase in 2009 due to a significant reduction in malaria cases, and since 2000, Plasmodium vivax is the only species transmitted. During the last two decades, malaria transmission has been mostly local and isolated to a few regions. It is important to gain further insights into the impact of control measures on the parasite population structure. Hence, the aim of the current study was to determine detailed changes in P. vivax genetic diversity and population structure based on analysing the gene that encodes the apical membrane antigen 1 (pvama1). This analysis covered from control to pre-elimination (1993-2011) in a hypo-endemic region in southern Mexico.The 213 pvama1 I-II sequences presently analysed were grouped into six periods of three years each. They showed low genetic diversity, with 15 haplotypes resolved. Among the DNA sequences, there was a gradual decrease in genetic diversity, the number of mixed genotype infections and the intensity of positive selection, in agreement with the parallel decline in malaria cases. At the same time, linkage disequilibrium (R2) increased. The three-dimensional haplotype network revealed that pvama1 I-II haplotypes were separated by 1-11 mutational steps, and between one another by 0-3 unsampled haplotypes. In the temporal network, seven haplotypes were detected in at least two of the six-time layers, and only four distinct haplotypes were evidenced in the pre-elimination phase. Structure analysis indicated that three subpopulations fluctuated over time. Only 8.5% of the samples had mixed ancestry. In the pre-elimination phase, subpopulation P1 was drastically reduced, and the admixture was absent.The results suggest that P. vivax in southern Mexico evolved based on local adaptation into three "pseudoclonal" subpopulations that diversified at the regional level and persisted over time, although with varying frequency. Control measures and climate events influenced the number of malaria cases and the genetic structure. The sharp decrease in parasite diversity and other related genetic parameters during the pre-elimination phase suggests that malaria elimination is possible in the near future. These results are useful for epidemiological surveillance.

Project description:Reported malaria cases in the Americas had been reduced to about one-half million by 2012. To advance towards elimination of this disease, it is necessary to gain insights into how the malaria parasite is evolving, including the emergence, spread and persistence of new haplotypes in affected regions. In here, the genetic diversity of the three major P. vivax merozoite genes was analyzed.From P. vivax-infected blood samples obtained in southern Mexico (SMX) during 2006-2007, nucleotide sequences were achieved for: the 42 kDa carboxyl fragment of the merozoite surface protein-1 (msp1 42 ), domains I-II of the apical membrane antigen-1 (ama1 I-II ), and domain II of the Duffy binding protein (dbp II ). Gene polymorphism was examined and haplotype networks were developed to depict parasite relationships in SMX. Then genetic diversity, recombination and natural selection were analyzed and the degree of differentiation was determined as FST values.The diversity of P. vivax merozoite genes in SMX was less than that of parasites from other geographic origins, with dbp II ?<?ama1 I-II ?<?msp1 42 . Ama1 I-II and msp1 42 exposed the more numerous haplotypes exclusive to SMX. While, all dbp II haplotypes from SMX were separated from one to three mutational steps, the networks of ama1 I-II and msp1 42 were more complex; loops and numerous mutational steps were evidenced, likely due to recombination. Sings of local diversification were more evident for msp1 42 . Sixteen combined haplotypes were determined; one of these haplotypes not detected in 2006 was highly frequent in 2007. The Rm value was higher for msp1 42 than for ama1 I-II, being insignificant for dbp II . The dN-dS value was highly significant for ama1 I-II and lesser so for dbp II . The F ST values were higher for dbp II than msp1 42 , and very low for ama1 I-II .In SMX, P. vivax ama1 I-II , dbp II and msp1 42 demonstrated limited diversity, and exhibited a differentiated parasite population. The results suggest that differential intensities of selective forces are operating on these gene fragments, and probably related to their timing, length of exposure and function during reticulocyte adhesion and invasion. Therefore, these finding are essential for mono and multivalent vaccine development and for epidemiological surveillance.

Project description:BACKGROUND:Plasmodium vivax poses a significant challenge to malaria elimination due to its ability to cause relapsed infections from reactivation of dormant liver parasites called hypnozoites. We analyzed 69 P. vivax whole genome sequences obtained from subjects residing in three different villages along the Peruvian Amazon. This included 23 paired P. vivax samples from subjects who experienced recurrent P. vivax parasitemia following observed treatment with chloroquine and primaquine. METHODS:Genomic DNA was extracted from whole blood samples collected from subjects. P. vivax DNA was enriched using selective whole genome amplification and whole genome sequencing. We used single nucleotide polymorphisms (SNPs) from the core P. vivax genome to determine characteristics of the parasite population using discriminant analysis of principal components, maximum likelihood estimation of individual ancestries, and phylogenetic analysis. We estimated the relatedness of the paired samples by calculating the number of segregating sites and using a hidden Markov model approach to estimate identity by descent. RESULTS:We present a comprehensive dataset of population genetics of Plasmodium vivax in the Peruvian Amazonian. We define the parasite population structure in this region and demonstrate a novel method for distinguishing homologous relapses from reinfections or heterologous relapses with improved accuracy. The parasite population in this area was quite diverse with an estimated five subpopulations and evidence of a highly heterogeneous ancestry of some of the isolates, similar to previous analyses of P. vivax in this region. Pairwise comparison of recurrent infections determined that there were 12 homologous relapses and 3 likely heterologous relapses with highly related parasites. To the best of our knowledge, this is the first large-scale study to evaluate recurrent P. vivax infections using whole genome sequencing. CONCLUSIONS:Whole genome sequencing is a high-resolution tool that can identify P. vivax homologous relapses with increased sensitivity, while also providing data about drug resistance and parasite population genetics. This information is important for evaluating the efficacy of known and novel antirelapse medications in endemic areas and thus advancing the campaign to eliminate malaria.

Dataset Information

Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico.

Background

Methods

Results

Conclusions

Publications

Molecular and epidemiological characterization of Plasmodium vivax recurrent infections in southern Mexico.

Similar Datasets

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