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Genetic diversity in merozoite surface protein-1 and 2 among Plasmodium falciparum isolates from malarious districts of tribal dominant state of Jharkhand, India.

ABSTRACT: INTRODUCTION: The genetic make-up of malaria parasite is potent for understanding the parasite virulence, designing antimalarial vaccine and evaluating the impact of malaria control measures. There is a paucity of information on genetic structure of Plasmodium falciparum in Jharkhand, India where malaria is rampant and this study aimed to establish molecular characterization of P. falciparum field isolates from Jharkhand measured with two highly polymorphic genetic markers, i.e. the merozoite surface proteins (MSPs) 1 and 2. METHODS: The genetic diversity of P. falciparum population from low transmission area, Ranchi, Bokaro and Hazaribagh and highly malarious area, Latehar and Palamau districts of Jharkhand were evaluated by polymerase chain reaction-sequencing analyzing msp-1 and msp-2 genes to explore the genetic structure of parasite from this understudied region. RESULTS: A total of 134 P. falciparum isolates were analyzed by polymorphic regions of msp-1 and msp-2 and classified according to prevalence of allelic families. The majority of patients from all the five sites had mean monoclonal infections of 67·1 and 60·4% of P. falciparum for msp-1 and msp-2, respectively, whereas, mean multiple genotypes of 32·8 and 39·5% for msp-1 and msp-2, respectively. Interestingly, we observed higher multiclonal infection in low transmission area as compared to highly malarious area in the case of msp-1 genotypes, whereas in msp-2 higher multiclonal infection was observed in highly malarious area compared to low transmission area. The overall multiplicities of infection of msp-1 and msp-2 were 1·38 and 1·39, respectively. CONCLUSION: This is the first report on molecular characterization of P. falciparum field isolates from Jharkhand. The genetic diversity and allelic distribution found in this study is somewhat similar to other reports from India and Southeast Asian countries. However, P. falciparum infection can be highly complex and diverse in these disease-endemic regions of Jharkhand, suggesting continual genetic mixing that could have significant implications for the use of antimalarial drugs and vaccines.

SUBMITTER: Hussain MM

PROVIDER: S-EPMC4089806 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Genetic diversity in merozoite surface protein-1 and 2 among Plasmodium falciparum isolates from malarious districts of tribal dominant state of Jharkhand, India.

Hussain M M MM Sohail M M Kumar R R Branch O H OH Adak T T Raziuddin M M

Annals of tropical medicine and parasitology 20111201 8

<h4>Introduction</h4>The genetic make-up of malaria parasite is potent for understanding the parasite virulence, designing antimalarial vaccine and evaluating the impact of malaria control measures. There is a paucity of information on genetic structure of Plasmodium falciparum in Jharkhand, India where malaria is rampant and this study aimed to establish molecular characterization of P. falciparum field isolates from Jharkhand measured with two highly polymorphic genetic markers, i.e. the mero ...[more]

PMID: 22325817

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Project description:BackgroundPlasmodium falciparum merozoite surface protein-3 (PfMSP-3) is a target of naturally acquired immunity against P. falciparum infection and is a promising vaccine candidate because of its critical role in the erythrocyte invasion of the parasite. Understanding the genetic diversity of pfmsp-3 is important for recognizing genetic nature and evolutionary aspect of the gene in the natural P. falciparum population and for designing an effective vaccine based on the antigen.MethodsBlood samples collected from P. falciparum-infected patients in Naung Cho and Pyin Oo Lwin, Myanmar, in 2015 were used in this study. The pfmsp-3 was amplified by polymerase chain reaction, cloned, and sequenced. Genetic polymorphism and natural selection of Myanmar pfmsp-3 were analysed using the programs DNASTAR, MEGA6, and DnaSP 5.10.00. Genetic diversity and natural selection of the global pfmsp-3 were also comparatively analysed.ResultsMyanmar pfmsp-3 displayed 2 different alleles, 3D7 and K1. The 3D7 allelic type was predominant in the population, but genetic polymorphism was less diverse than for the K1 allelic type. Polymorphic characters in both allelic types were caused by amino acid substitutions, insertions, and deletions. Amino acid substitutions were mainly occurred at the alanine heptad repeat domains, whereas most insertions and deletions were found at the glutamate rich domain. Overall patterns of amino acid polymorphisms detected in Myanmar pfmsp-3 were similar in the global pfmsp-3 population, but novel amino acid changes were observed in Myanmar pfmsp-3 with low frequencies. Complicated patterns of natural selection and recombination events were predicted in the global pfmsp-3, which may act as major driving forces to maintain and generate genetic diversity of the global pfmsp-3 population.ConclusionGlobal pfmsp-3 revealed genetic polymorphisms, suggesting that the functional and structural consequences of the polymorphisms should be considered in designing a vaccine based on PfMSP-3. Further examination of genetic diversity of pfmsp-3 in the global P. falciparum population is necessary to gain in-depth insight for the population structure and evolutionary aspect of global pfmsp-3.

Project description:BackgroundAnti-malarial drug resistance continues to be a leading threat to malaria control efforts and calls for continued monitoring of waning efficacy of artemisinin-based combination therapy (ACT). Artesunate + sulfadoxine/pyrimethamine (AS + SP) is used for the treatment of uncomplicated Plasmodium falciparum malaria in India. However, resistance against AS + SP is emerged in northeastern states. Therefore, artemether-lumefantrine (AL) is the recommended first line treatment for falciparum malaria in north eastern states. This study investigates the therapeutic efficacy and safety of AL for the treatment of uncomplicated falciparum malaria in three malaria-endemic states in India. The data generated through this study will benefit the immediate implementation of second-line ACT as and when required.MethodsThis was a one-arm prospective evaluation of clinical and parasitological responses for uncomplicated falciparum malaria using WHO protocol. Patients diagnosed with uncomplicated mono P. falciparum infection were administered six-dose regimen of AL over 3 days and subsequent follow-up was carried out up to 28 days. Molecular markers msp-1 and msp-2 were used to differentiate recrudescence and re-infection and K13 propeller gene was amplified and sequenced covering the codon 450-680.ResultsA total of 402 eligible patients were enrolled in the study from all four sites. Overall, adequate clinical and parasitological response (ACPR) was 98 % without PCR correction and 99 % with PCR correction. At three study sites, ACPR rates were 100 %, while at Bastar, cure rate was 92.5 % on day 28. No early treatment failure was found. The PCR-corrected endpoint finding confirmed that one late clinical failure (LCF) and two late parasitological failures (LPF) were recrudescences. The PCR corrected cure rate was 96.5 %. The mean fever clearance time was 27.2 h ± 8.2 (24-48 h) and the mean parasite clearance time was 30.1 h ± 11.0 (24-72 h). Additionally, no adverse event was recorded. Analysis of total 186 samples revealed a mutation in the k13 gene along with non-synonymous mutation at codon M579T in three (1.6 %) samples.ConclusionAL is an efficacious drug for the treatment of uncomplicated falciparum malaria. However, regular monitoring of AL is required in view of malaria elimination initiatives, which will be largely dependent on therapeutic interventions, regular surveillance and targeted vector control.

Project description:BackgroundPlasmodium falciparum merozoite surface protein-1 (PfMSP-1) and -2 (PfMSP-2) are major blood-stage vaccine candidate antigens. Understanding the genetic diversity of the genes, pfmsp-1 and pfmsp-2, is important for recognizing the genetic structure of P. falciparum, and the development of an effective vaccine based on the antigens. In this study, the genetic diversities of pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum were analysed.MethodsThe pfmsp-1 block 2 and pfmsp-2 block 3 regions were amplified by polymerase chain reaction from blood samples collected from Myanmar patients who were infected with P. falciparum in 2013-2015. The amplified gene fragments were cloned into a T&A vector, and sequenced. Sequence analysis of Myanmar pfmsp-1 block 2 and pfmsp-2 block 3 was performed to identify the genetic diversity of the regions. The temporal genetic changes of both pfmsp-1 and pfmsp-2 in the Myanmar P. falciparum population, as well as the polymorphic diversity in the publicly available global pfmsp-1 and pfmsp-2, were also comparatively analysed.ResultsHigh levels of genetic diversity of pfmsp-1 and pfmsp-2 were observed in the Myanmar P. falciparum isolates. Twenty-eight different alleles of pfmsp-1 (8 for K1 type, 14 for MAD20 type, and 6 for RO33 type) and 59 distinct alleles of pfmsp-2 (18 for FC27, and 41 for 3D7 type) were identified in the Myanmar P. falciparum population in amino acid level. Comparative analyses of the genetic diversity of the Myanmar pfmsp-1 and pfmsp-2 alleles in the recent (2013-2015) and past (2004-2006) Myanmar P. falciparum populations indicated the dynamic genetic expansion of the pfmsp-1 and pfmsp-2 in recent years, suggesting that a high level of genetic differentiation and recombination of the two genes may be maintained. Population genetic structure analysis of the global pfmsp-1 and pfmsp-2 also suggested that a high level of genetic diversity of the two genes was found in the global P. falciparum population.ConclusionDespite the recent remarkable decline of malaria cases, the Myanmar P. falciparum population still remains of sufficient size to allow the generation and maintenance of genetic diversity. The high level of genetic diversity of pfmsp-1 and pfmsp-2 in the global P. falciparum population emphasizes the necessity for continuous monitoring of the genetic diversity of the genes for better understanding of the genetic make-up and evolutionary aspect of the genes in the global P. falciparum population.

Project description:Indigenous food (IF) systems, derived from natural ecosystems are perceived to be sustainable and nutritionally adequate. Mundas, an indigenous tribal community in Jharkhand India, are surrounded by rich agroforestry resources, yet display high levels of malnutrition. Our study explored the food environment of Munda community, different IFs they accessed, levels of utilization of IFs in routine diets, their nutritional attributes and factors influencing IF consumption. A cross-sectional mixed-methods study was conducted in nine villages of Murhu and Torpa blocks in Khunti district, Jharkhand. Using focus group discussions and key informant interviews, we did free-listing of IFs known to the community. This was followed by enumerating preferred and little used/historically consumed IFs, along with reasons. Qualitative enquiries were recorded and transcribed verbatim; data were coded and analyzed using thematic framework approach. The listed IFs were identified through common names and photographs, and verified by ethnobotanist in the team. The nutritive values of identified IFs were searched in literature or nutritional analysis of specific plant based foods were undertaken in an accredited laboratory. The community demonstrated traditional ecological knowledge of several IFs (n = 194), which are accessed from wild, cultivated and built food environments. Taxonomic classification was available for 80% (n = 156) IFs, out of which 60 foods had nutritive values in secondary literature and 42 foods were analyzed in laboratory. Many IFs were rich in micronutrients like calcium, iron, folate, vitamin A and C. Among the listed IFs, only 45% were commonly consumed, while rest were little used/historically consumed. Factors like desirable taste, satiety, perceived nutrition benefits, adaptability to climate variability, traditional practice of food preservation and their cultural importance promoted IF consumption. However, local climatic impacts on agroforestry systems, easy access to foods bought from markets or distributed under government food security schemes, and promotion of hybrid seeds by local agricultural organizations, emerged as potential barriers. Thus, reinforcement of traditional ecological knowledge and informal food literacy, along with promotion of climate resilient attributes of IFs, can contribute to sustainable food systems in Munda community.

Project description:Background & objectivesSerosurvey of COVID-19 provides a better estimation of people who have developed antibodies against the infection. Undertaking such a serosurvey in certain districts of India which are densely populated with prominent tribes can provide valuable information regarding seropravelance of SARS-CoV-2 antibodies among such indigenous populations. In this context, two rounds of population-based, cross-sectional serosurveys for SARS-CoV-2 IgG antibody were carried out in Jharkhand, a tribal-dominated State of India, to compare the seroprevalence of SARS-CoV-2 infection and to determine the associated demographic risk factors.MethodsThe surveys were carried out in June 2020 and February 2021 in ten districts of the State of Jharkhand. Blood samples were collected from the residents of the selected districts by random sampling and tested for anti-SARS-CoV-2 antibodies using an automated chemiluminescence immunoassay platform. A total of 4761 and 3855 eligible participants were included in round 1 and round 2, respectively.ResultsThe age- and gender-standardized seroprevalence for COVID-19 during round 1 was 0.54 per cent (0.36-0.80) that increased to 41.69 per cent (40.16-43.22) during round 2 with a gap of eight months in between. The seropositivity among male and female participants was 0.73 and 0.45 per cent, respectively, during the first round and 51.35 and 33.70 per cent, respectively, during the second round. During the first round, 17.37 per cent of the participants were tribal with seropositivity of 0.24 per cent (0.02-0.87), and during the second round, 21.14 per cent were tribal with seropositivity of 39.14 per cent (35.77-42.59). Compared to tribal group, non-tribal participants had an adjusted odds of 1.24 (95% confidence interval=1.04-1.48) for SARS-CoV-2 seropositivity.Interpretation & conclusionsCOVID-19 seroprevalence was found to be low during the first round (0.54%) of the survey, possibly due to the travel restrictions during lockdown better adherence to social distancing and wearing of face masks among the people. Understanding the dynamics of SARS-CoV-2 transmission and the susceptibility to infection at the individual as well as community level will inform decision and help policy makers to design and implement effective public health strategies to mitigate the pandemic in this State.

Project description:BACKGROUND: Molecular techniques have facilitated the studies on genetic diversity of Plasmodium species particularly from field isolates collected directly from patients. The msp-1 and msp-2 are highly polymorphic markers and the large allelic polymorphism has been reported in the block 2 of the msp-1 gene and the central repetitive domain (block3) of the msp-2 gene. Families differing in nucleotide sequences and in number of repetitive sequences (length variation) were used for genotyping purposes. As limited reports are available on the genetic diversity existing among Plasmodium falciparum population of India, this report evaluates the extent of genetic diversity in the field isolates of P. falciparum in eastern and north-eastern regions of India. METHODS: A study was designed to assess the diversity of msp-1 and msp-2 among the field isolates from India using allele specific nested PCR assays and sequence analysis. Field isolates were collected from five sites distributed in three states namely, Assam, West Bengal and Orissa. RESULTS: P. falciparum isolates of the study sites are highly diverse in respect of length as well as sequence motifs with prevalence of all the reported allelic families of msp-1 and msp-2. Prevalence of identical allelic composition as well as high level of sequence identity of alleles suggest a considerable amount of gene flow between the P. falciparum populations of different states. A comparatively higher proportion of multiclonal isolates as well as multiplicity of infection (MOI) was observed among isolates of highly malarious districts Karbi Anglong (Assam) and Sundergarh (Orissa). In all the five sites, R033 family of msp-1 was observed to be monomorphic with an allele size of 150/160 bp. The observed 80-90% sequence identity of Indian isolates with data of other regions suggests that Indian P. falciparum population is a mixture of different strains. CONCLUSION: The present study shows that the field isolates of eastern and north-eastern regions of India are highly diverse in respect of msp-1 (block 2) and msp-2 (central repeat region, block 3). As expected Indian isolates present a picture of diversity closer to southeast Asia, Papua New Guinea and Latin American countries, regions with low to meso-endemicity of malaria in comparison to African regions of hyper- to holo-endemicity.

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Genetic diversity in merozoite surface protein-1 and 2 among Plasmodium falciparum isolates from malarious districts of tribal dominant state of Jharkhand, India.

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Genetic diversity in merozoite surface protein-1 and 2 among Plasmodium falciparum isolates from malarious districts of tribal dominant state of Jharkhand, India.

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