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Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Honduras
Lopez Ana,Ortiz Andres,Coello Jorge,Sosa-Ochoa Wilfredo
Malaria Journal , 2012, DOI: 10.1186/1475-2875-11-391
Abstract: Background Understanding the population structure of Plasmodium species through genetic diversity studies can assist in the design of more effective malaria control strategies, particularly in vaccine development. Central America is an area where malaria is a public health problem, but little is known about the genetic diversity of the parasite’s circulating species. This study aimed to investigate the allelic frequency and molecular diversity of five surface antigens in field isolates from Honduras. Methods Five molecular markers were analysed to determine the genotypes of Plasmodium vivax and Plasmodium falciparum from endemic areas in Honduras. Genetic diversity of ama-1, msp-1 and csp was investigated for P. vivax, and msp-1 and msp-2 for P. falciparum. Allelic frequencies were calculated and sequence analysis performed. Results and conclusion A high genetic diversity was observed within Plasmodium isolates from Honduras. A different number of genotypes were elucidated: 41 (n = 77) for pvama-1; 23 (n = 84) for pvcsp; and 23 (n = 35) for pfmsp-1. Pvcsp sequences showed VK210 as the only subtype present in Honduran isolates. Pvmsp-1 (F2) was the most polymorphic marker for P. vivax isolates while pvama-1 was least variable. All three allelic families described for pfmsp-1 (n = 30) block 2 (K1, MAD20, and RO33), and both allelic families described for the central domain of pfmsp-2 (n = 11) (3D7 and FC27) were detected. However, K1 and 3D7 allelic families were predominant. All markers were randomly distributed across the country and no geographic correlation was found. To date, this is the most complete report on molecular characterization of P. vivax and P. falciparum field isolates in Honduras with regards to genetic diversity. These results indicate that P. vivax and P. falciparum parasite populations are highly diverse in Honduras despite the low level of transmission.
The genetic diversity of Plasmodium vivax: a review
Souza-Neiras, Wanessa Christina de;Melo, Luciane Moreno Storti de;Machado, Ricardo Luiz Dantas;
Memórias do Instituto Oswaldo Cruz , 2007, DOI: 10.1590/S0074-02762007000300002
Abstract: the genetic diversity of plasmodium vivax has been investigated in several malaria-endemic areas, including the brazilian amazon region, where this is currently the most prevalent species causing malaria in humans. this review summarizes current views on the use of molecular markers to examine p. vivax populations, with a focus on studies performed in brazilian research laboratories. we emphasize the importance of phylogenetic studies on this parasite and discuss the perspectives created by our increasing understanding of genetic diversity and population structure of this parasite for the development of new control strategies, including vaccines, and more effective drugs for the treatment of p. vivax malaria.
Neutral Polymorphisms in Putative Housekeeping Genes and Tandem Repeats Unravels the Population Genetics and Evolutionary History of Plasmodium vivax in India  [PDF]
Surendra K. Prajapati ,Hema Joshi,Jane M. Carlton,M. Alam Rizvi
PLOS Neglected Tropical Diseases , 2013, DOI: 10.1371/journal.pntd.0002425
Abstract: The evolutionary history and age of Plasmodium vivax has been inferred as both recent and ancient by several studies, mainly using mitochondrial genome diversity. Here we address the age of P. vivax on the Indian subcontinent using selectively neutral housekeeping genes and tandem repeat loci. Analysis of ten housekeeping genes revealed a substantial number of SNPs (n = 75) from 100 P. vivax isolates collected from five geographical regions of India. Neutrality tests showed a majority of the housekeeping genes were selectively neutral, confirming the suitability of housekeeping genes for inferring the evolutionary history of P. vivax. In addition, a genetic differentiation test using housekeeping gene polymorphism data showed a lack of geographical structuring between the five regions of India. The coalescence analysis of the time to the most recent common ancestor estimate yielded an ancient TMRCA (232,228 to 303,030 years) and long-term population history (79,235 to 104,008) of extant P. vivax on the Indian subcontinent. Analysis of 18 tandem repeat loci polymorphisms showed substantial allelic diversity and heterozygosity per locus, and analysis of potential bottlenecks revealed the signature of a stable P. vivax population, further corroborating our ancient age estimates. For the first time we report a comparable evolutionary history of P. vivax inferred by nuclear genetic markers (putative housekeeping genes) to that inferred from mitochondrial genome diversity.
Genotyping of Plasmodium vivax Reveals Both Short and Long Latency Relapse Patterns in Kolkata  [PDF]
Jung-Ryong Kim, Amitabha Nandy, Ardhendu Kumar Maji, Manjulika Addy, Arjen M. Dondorp, Nicholas P. J. Day, Sasithon Pukrittayakamee, Nicholas J. White, Mallika Imwong
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039645
Abstract: Background The Plasmodium vivax that was once prevalent in temperate climatic zones typically had an interval between primary infection and first relapse of 7–10 months, whereas in tropical areas P.vivax infections relapse frequently at intervals of 3–6 weeks. Defining the epidemiology of these two phenotypes from temporal patterns of illness in endemic areas is difficult or impossible, particularly if they overlap. Methods A prospective open label comparison of chloroquine (CQ) alone versus CQ plus unobserved primaquine for either 5 days or 14 days was conducted in patients presenting with acute vivax malaria in Kolkata. Patients were followed for 15 months and primary and recurrent infections were genotyped using three polymorphic antigen and up to 8 microsatellite markers. Results 151 patients were enrolled of whom 47 (31%) had subsequent recurrent infections. Recurrence proportions were similar in the three treatment groups. Parasite genotyping revealed discrete temporal patterns of recurrence allowing differentiation of probable relapse from newly acquired infections. This suggested that 32 of the 47 recurrences were probable relapses of which 22 (69%) were genetically homologous. The majority (81%) of probable relapses occurred within three months (16 homologous, 10 heterologous) and six genetically homologous relapses (19%) were of the long latency (8–10 month interval) phenotype. Conclusions With long follow-up to assess temporal patterns of vivax malaria recurrence, genotyping of P.vivax can be used to assess relapse rates. A 14 day unobserved course of primaquine did not prevent relapse. Genotyping indicates that long latency P.vivax is prevalent in West Bengal, and that the first relapses after long latent periods are genetically homologous. Trial Registration Controlled-Trials.com ISRCTN14027467
Genetic diversity of Plasmodium vivax and Plasmodium falciparum in Kohat District, Pakistan
Khatoon, Lubna;Khan, Inam Ullah;Shah, Shahid Ali;Jan, Muhammad Ishtiaq;Ullah, Farhat;Malik, Salman Akbar;
Brazilian Journal of Infectious Diseases , 2012, DOI: 10.1590/S1413-86702012000200014
Abstract: malaria is one of the serious diseases threatening human health in pakistan and contributes to a large proportion of the total malaria deaths in south asia. however, little is known about the nature and extent of genetic diversity of the malarial parasites circulating in pakistan. this study was designed to assess the infection status of plasmodium and the genetic diversity of plasmodium vivax and plasmodium falciparum by analyzing msp-3α, msp-3β and msp-1, msp-2 genes respectively using allele specific nested pcr and rflp assays. for this purpose, 130 field isolates were collected from the individuals who exhibited clinical symptoms associated with malaria in the kohat region of khyber pakhtoonkhwa (kpk), pakistan. among 130 blood samples collected, p. vivax was detected in 105/130 (80.8%) and p. falciparum in 21/130 (16.2%). mixed infections with both parasites were detected in 4/130 (3%) of the isolates. a large number of distinguishable alleles were found for msp genetic markers: 10 alleles for msp-3α and seven for msp-3β with one mixed infection in case of msp-3β. the genotyping of p. falciparum showed that k1+mad20 mixed genotype was dominant in msp-1 and fc27 in msp-2. the results collectively suggest that p. vivax and p. falciparum populations in this region are highly polymorphic and mixed infections are prevalent.
Molecular markers and genetic diversity of Plasmodium vivax
Brito, Cristiana Ferreira Alves de;Ferreira, Marcelo Urbano;
Memórias do Instituto Oswaldo Cruz , 2011, DOI: 10.1590/S0074-02762011000900003
Abstract: enhanced understanding of the transmission dynamics and population genetics for plasmodium vivax is crucial in predicting the emergence and spread of novel parasite phenotypes with major public health implications, such as new relapsing patterns, drug resistance and increased virulence. suitable molecular markers are required for these population genetic studies. here, we focus on two groups of molecular markers that are commonly used to analyse natural populations of p. vivax. we use markers under selective pressure, for instance, antigen-coding polymorphic genes, and markers that are not under strong natural selection, such as most minisatellite and microsatellite loci. first, we review data obtained using genes encoding for p. vivax antigens: circumsporozoite protein, merozoite surface proteins 1 and 3α, apical membrane antigen 1 and duffy binding antigen. we next address neutral or nearly neutral molecular markers, especially microsatellite loci, providing a complete list of markers that have already been used in p. vivax populations studies. we also analyse the microsatellite loci identified in the p. vivax genome project. finally, we discuss some practical uses for p. vivax genotyping, for example, detecting multiple-clone infections and tracking the geographic origin of isolates.
Genetic diversity of Plasmodium vivax isolates from Azerbaijan
Marie Leclerc, Michela Menegon, Alexandra Cligny, Jean Noyer, Suleyman Mammadov, Namig Aliyev, Elkhan Gasimov, Giancarlo Majori, Carlo Severini
Malaria Journal , 2004, DOI: 10.1186/1475-2875-3-40
Abstract: Thirty-six P. vivax isolates from Central Azerbaijan were characterized by analysing the genetic polymorphism of the circumsporozoite protein (CSP) and the merozoite surface protein 1 (MSP-1) genes, using PCR amplifications and amplicons sequencing.Analysis of CSP sequences showed that all the processed isolates belong to the VK 210 type, with variations in the alternation of alanine residue (A) or aspartic acid residue (D) in the repeat motif GDRA(A/D)GQPA along the sequence. As far as MSP-1 genotyping is concerned, it was found that the majority of isolates analysed belong to Belem and Sal I types. Five recombinant isolates were also identified. Combined analysis with the two genetic markers allowed the identification of 19 plasmodial sub-types.The results obtained in the present study indicate that there are several P. vivax clones circulating in Azerbaijan and, consequently, a careful malaria surveillance could be of paramount importance to identify, at early stage, the occurrence of possible P. vivax malaria outbreaks.Plasmodium vivax is the most widely distributed human parasite, with an estimated burden of 70–80 million cases annually [1]. In some parts of the world (Asia, South America), it is the most prevalent form of the four human malarial parasites. Although it causes a less severe disease than Plasmodium falciparum, being rarely lethal, P. vivax affects the working capacity of the population and the lack of efficient drug distribution favors the onset of drug resistant strains [2,3]. Imported malaria is an increasing health problem in Western Europe, where about 6,500 cases are reported annually in Germany, France, Italy and the United Kingdom [4]. Although P. falciparum infections account for the majority of cases (64%), P. vivax is responsible for an additional 23% [4]. Presence in this area of residual anopheline populations susceptible to P. vivax infection represents a permanent risk for the occurrence of P. vivax indigenous malaria cases, as rece
Recent increase of genetic diversity in Plasmodium vivax population in the Republic of Korea
Hajime Honma, Jung-Yeon Kim, Nirianne MQ Palacpac, Toshihiro Mita, Wonja Lee, Toshihiro Horii, Kazuyuki Tanabe
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-257
Abstract: Sequences for 13 microsatellite loci distributed across the twelve chromosomes of P. vivax were obtained from 58 South Korean isolates collected during two sampling periods, namely 1997-2000 and 2007. The sequences were used for the analysis of expected heterozygosity and multilocus genotype diversity. Population structure was evaluated using STRUCTURE version 2.3.2. Linkage disequilibrium was also analysed to investigate the extent of outbreeding in the P. vivax population.Mean expected heterozygosity significantly increased from 0.382 in 1997-2000 to 0.545 in 2007 (P < 0.05). The number of multilocus genotypes was 7 and 27; and genotype diversity was statistically significant (P < 0.01) at 0.661 and 0.995 in 1997-2000 and 2007, respectively. Analysis by STRUCTURE showed a more complex population structure in 2007 than in 1997-2000. Linkage disequilibrium between 13 microsatellites, although significant in both time points, was notably lower in 2007.The present microsatellite analysis clearly showed recent increase of genetic diversity and recent relaxation of the strong population structure observed in 1997-2000. These results suggest that multiple genotypes not present previously recently migrated into South Korea, accompanied by substantial outbreeding between different genotypes.Of the five human malaria parasites, Plasmodium vivax is the most prevalent in Asia, Melanesia, the Middle East, South and Central America, accounting for 70-80 million cases annually [1], with 2.6 billion people at risk of infection [2]. Despite modest gains in Plasmodium falciparum control, the global burden of P. vivax remains underestimated [3] and emergence of drug resistant P. vivax makes the control of vivax malaria more difficult than before [4,5]. In the Republic of Korea (South Korea), vivax malaria was eradicated once in the late 1970s [6]. However, indigenous malaria has reemerged since the first infection of a soldier who had never been abroad was confirmed in 1993 in the D
Molecular epidemiology of Plasmodium vivax anti-folate resistance in India
Surendra K Prajapati, Hema Joshi, Vas Dev, Virendra K Dua
Malaria Journal , 2011, DOI: 10.1186/1475-2875-10-102
Abstract: Microscopically diagnosed one hundred Plasmodium vivax field isolates were collected from five widely separated geographical regions of India. Dhfr and dhps genes were PCR amplified and sequenced. Previously published mutations data were collected and analyzed using Chi square test to identify geographical cluster of mutant/wild type genotypes.Sequence analysis revealed single (S58R), double (S58R/S117N) and quadruple (F57L/S58R/T61M/S117T/) point mutations at dhfr and single (A383G) to double (A383G/A553G) mutations at dhps in P. vivax field isolates. In addition, three new mutations were also observed at dhfr. Both, dhfr and dhps genes revealed tandem repeat variations in field isolates. Dhps revealed very low mutation frequency (14.0%) compared to dhfr (50.70%). Comparative analysis revealed a progressive increase in frequency of quadruple mutant dhfr genotype (p < 0.001) within five years in north-eastern state (Kamrup, Assam). Frequency of dhfr genotypes revealed three distinct geographical clusters of wild (northern India), double mutant (southern India), and quadruple mutant (north-eastern and island regions of India) on the Indian sub-continent.Study suggests that SP may be susceptible to P. vivax in India, except Andaman and north-eastern state. The distinction of geographical regions with sensitive and resistant parasite phenotypes would be highly useful for designing and administering national anti-malarial drug policy.Malaria is a life-threatening ancient parasitic disease and causes 250-500 million clinical episodes and nearly one million deaths annually [1]. Among the five human malaria species, Plasmodium falciparum is the most severe form, causing malignant malaria globally, while Plasmodium vivax is the most widespread species outside Africa, causing huge morbidity and can be severe and fatal [2-7].The worldwide spread of chloroquine (CQ) resistant strains of P. falciparum has led to use of sulphadoxine-pyrimethamine (SP) as the first-line anti-mala
Patterns of Plasmodium vivax and Plasmodium falciparum malaria underscore importance of data collection from private health care facilities in India
Sangeeta Gupta, James T Gunter, Robert J Novak, James L Regens
Malaria Journal , 2009, DOI: 10.1186/1475-2875-8-227
Abstract: Malarial morbidity by Plasmodium species (Plasmodium falciparum, Plasmodium vivax, or Plasmodium sp.) was confirmed using microscopy and antigen tests. The influence of seasonal factors and selected patient demographics on morbidity was evaluated. The proportions of malaria cases caused by P. falciparum at the private facility were compared to data from India's National Vector Borne Disease Control Programme (NVBDCP) during the same period for the Delhi region.In New Delhi, P. faciparum was the dominant cause of cases requiring treatment in the private hospital during the period examined. The national data reported a smaller proportion of malaria cases caused by P. falciparum in the national capital region than was observed in a private facility within the region. Plasmodium vivax also caused a large proportion of the cases presenting clinically at the private hospital during the summer and monsoon seasons.The proportion of P. falciparum malaria cases tends to be greatest during the post-monsoon season while the proportion of P. vivax malaria cases tends to be greatest in the monsoon season. Private hospital data demonstrate an under-reporting of malaria case incidences in the data from India's national surveillance programme during the same period for the national capital region.Although malaria is a serious public health problem in many developing countries, estimates of the number of malaria cases and deaths frequently have lacked sufficient accuracy for establishing reliable baselines against which to evaluate the success of control measures. Three factors affect whether routinely reported malaria data accurately reflect patterns in malaria in countries with surveillance programmes, even ones that have relatively good statistical services [1]. First, information in routine surveillance systems may be incomplete. This may result in overestimates of reporting completeness thereby underestimating malaria patterns. Second, patients may use private health care facili
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