Dynamics of Plasmodium vivax populations in border areas of the Greater Mekong Sub-region during malaria elimination

2020 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  

Abstract Background Countries within the Greater Mekong Sub-region (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although the malaria situation has greatly improved, malaria transmission remains at international border regions. In some areas, Plasmodium vivax has become the predominant parasite. To gain a better understanding of transmission dynamics, knowledge on the changes of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods This study investigated genetic diversity and population structures in 206 P. vivax clinical samples collected at two time points in two international border areas: the China-Myanmar border (CMB) (n=50 in 2004 and n=52 in 2016) and Thailand-Myanmar border (TMB) (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results Despite intensified control efforts, genetic diversity remained high ( H E = 0.66-0.86) and was not significantly different among the four populations ( P >0.05). Specifically, H E slightly decreased from 0.76 in 2004 to 0.66 in 2016 at the CMB and increased from 0.80 in 2012 to 0.86 in 2015 at the TMB. The proportions of polyclonal infections varied significantly among the four populations ( P < 0.05), and showed substantial decreases from 48.0% in 2004 to 23.7 at the CMB and from 40.0% in 2012 to 30.7% in 2015 at the TMB, with corresponding decreases in the multiplicity of infection. Consistent with the continuous decline of malaria incidence in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and sub-division among the four tested populations. Temporal genetic differentiation was observed at each site ( F ST = 0.081 at the CMB and F ST = 0.133 at the TMB). Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 TMB populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 TMB population was genetically distinctive, which may reflect a process of population replacement. Whereas the effective population size ( N e ) at the CMB showed a decrease from 4979 in 2004 to 3052 in 2016 with the infinite allele model, the N e at the TMB experienced an increase from 6289 to 10259. Conclusions With enhanced control efforts on malaria, P. vivax at the TMB and CMB showed considerable spatial and temporal differentiation, but the presence of large P. vivax reservoirs still sustained genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in these border areas of the GMS. Coordinated and integrated control efforts on both sides of international borders are essential to reach the goal of regional malaria elimination.

2020 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  

Abstract Background: Countries within the Greater Mekong Subregion (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although malaria situation has greatly improved, Plasmodium vivax remains at international border regions. Therefore, to gain a better understanding of transmission dynamics, knowledge on the evolution of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods: We investigated genetic diversity and population structures in 206 longitudinally collected P. vivax clinical samples in two international border areas at the China-Myanmar border (CMB, n=50 in 2004 and n=52 in 2016) and western Thailand border (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results: Despite intensified control efforts, genetic diversity in the four populations remained high (HE = 0.66-0.86). The proportions of polyclonal infections showed substantial decreases to 23.7 and 30.7% in the CMB and western Thailand, respectively, with corresponding decreases in the multiplicity of infection. Consistent with the shrinking map of malaria transmission in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting of more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and subdivision with the four tested populations. Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 Thailand populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 Thailand population was genetically distinctive, which may reflect a process of population replacement. The moderately large effective population sizes and proportions of polyclonal infections highlight the necessity of further coordinated and integrated control efforts on both sides of the borders in the pursuit of malaria elimination. Conclusions: With enhanced control efforts on malaria elimination, P. vivax population in the GMS has fragmented into a limited number of clustered foci, but the presence of large P. vivax reservoirs still sustains genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in this area.


2019 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  

Abstract BackgroundCountries within the Greater Mekong Subregion (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although malaria situation has greatly improved, Plasmodium vivax remains at international border regions. Therefore, to gain a better understanding of transmission dynamics, knowledge on the evolution of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. MethodsWe investigated genetic diversity and population structures in 206 longitudinally collected P. vivax clinical samples in two international border areas at the China-Myanmar border (CMB, n=50 in 2004 and n=52 in 2016) and western Thailand border (n=50 in 2012 and n=54 in 2015). Parasites were genotyped using 10 microsatellite markers. ResultsDespite intensified control efforts, genetic diversity in the four populations remained high (HE = 0.66-0.86). The proportions of polyclonal infections showed substantial decreases to 23.7 and 30.7% in the CMB and western Thailand, respectively, with corresponding decreases in the multiplicity of infection. Consistent with the shrinking map of malaria transmission in the GMS over time, there were also increases in multilocus linkage disequilibrium, suggesting of more fragmented and increasingly inbred parasite populations. There were considerable genetic differentiation and subdivision with the four tested populations. Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB with the 2016 CMB and 2012 Thailand populations, suggesting some of these parasites had shared ancestry. In contrast, the 2015 Thailand population was genetically distinctive, which may reflect a process of population replacement. The moderately large effective population sizes and proportions of polyclonal infections highlight the necessity of further coordinated and integrated control efforts on both sides of the borders in the pursuit of malaria elimination. ConclusionsWith enhanced control efforts on malaria elimination, P. vivax population in the GMS has fragmented into a limited number of clustered foci, but the presence of large P. vivax reservoirs still sustains genetic diversity and transmission. These findings provide new insights into P. vivax transmission dynamics and population structure in this area.


2021 ◽  
Vol 12 ◽  
Author(s):  
Tian-Qi Shi ◽  
Hai-Mo Shen ◽  
Shen-Bo Chen ◽  
Kokouvi Kassegne ◽  
Yan-Bing Cui ◽  
...  

Malaria incidence has declined dramatically over the past decade and China was certified malaria-free in 2021. However, the presence of malaria in border areas and the importation of cases of malaria parasites are major challenges for the consolidation of the achievements made by China. Plasmodium vivax Duffy binding protein (PvDBP) performs a significant role in erythrocyte invasion, and is considered a promising P. vivax vaccine. However, the highly polymorphic region of PvDBP (PvDBP-II) impedes the development of blood-stage vaccine against P. vivax. In this study, we investigated the genetic diversity and natural selection of PvDBP-II among 124 P. vivax isolates collected from the China-Myanmar border (CMB) in Yunnan Province, China, during 2009–2011. To compare genetic diversity, natural selection, and population structure with CMB isolates, 85 pvdbp-II sequences of eastern Myanmar isolates were obtained from GenBank. In addition, global sequences of pvdbp-II were retrieved from GenBank to establish genetic differentiation relationships and networks with the CMB isolates. In total, 22 single nucleotide polymorphisms reflected in 20 non-synonymous and two synonymous mutations were identified. The overall nucleotide diversity of PvDBP-II from the 124 CMB isolates was 0.0059 with 21 haplotypes identified (Hd = 0.91). The high ratio of non-synonymous to synonymous mutations suggests that PvDBP-II had evolved under positive selection. Population structure analysis of the CMB and eastern Myanmar isolates were optimally grouped into five sub-populations (K = 5). Polymorphisms of PvDBP-II display that CMB isolates were genetically diverse. Mutation, recombination, and positive selection promote polymorphism of PvDBP-II of P. vivax population. Although low-level genetic differentiation in eastern Myanmar was identified along with the more effective malaria control measures, the complexity of population structure in malaria parasites has maintained. In conclusion, findings from this study advance knowledge of the understanding of the dynamic of P. vivax population, which will contribute to guiding the rational design of a PvDBP-II based vaccine.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  

2020 ◽  
Vol 14 (12) ◽  
pp. e0008962
Author(s):  
Lucas E. Buyon ◽  
Ana Maria Santamaria ◽  
Angela M. Early ◽  
Mario Quijada ◽  
Itza Barahona ◽  
...  

Malaria incidence in Panama has plateaued in recent years in spite of elimination efforts, with almost all cases caused by Plasmodium vivax. Notwithstanding, overall malaria prevalence remains low (fewer than 1 case per 1000 persons). We used selective whole genome amplification to sequence 59 P. vivax samples from Panama. The P. vivax samples were collected from two periods (2007–2009 and 2017–2019) to study the population structure and transmission dynamics of the parasite. Imported cases resulting from increased levels of human migration could threaten malaria elimination prospects, and four of the samples evaluated came from individuals with travel history. We explored patterns of recent common ancestry among the samples and observed that a highly genetically related lineage (termed CL1) was dominant among the samples (47 out of 59 samples with good sequencing coverage), spanning the entire period of the collection (2007–2019) and all regions of the country. We also found a second, smaller clonal lineage (termed CL2) of four parasites collected between 2017 and 2019. To explore the regional context of Panamanian P. vivax we conducted principal components analysis and constructed a neighbor-joining tree using these samples and samples collected worldwide from a previous study. Three of the four samples with travel history clustered with samples collected from their suspected country of origin (consistent with importation), while one appears to have been a result of local transmission. The small number of Panamanian P. vivax samples not belonging to either CL1 or CL2 clustered with samples collected from Colombia, suggesting they represent the genetically similar ancestral P. vivax population in Panama or were recently imported from Colombia. The low diversity we observe in Panama indicates that this parasite population has been previously subject to a severe bottleneck and may be eligible for elimination. Additionally, while we confirmed that P. vivax is imported to Panama from diverse geographic locations, the lack of impact from imported cases on the overall parasite population genomic profile suggests that onward transmission from such cases is limited and that imported cases may not presently pose a major barrier to elimination.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yubing Hu ◽  
Lin Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
Myat Thu Soe ◽  
Chunyun Yu ◽  
...  

Abstract Background Merozoite proteins of the malaria parasites involved in the invasion of red blood cells are selected by host immunity and their diversity is greatly influenced by changes in malaria epidemiology. In the Greater Mekong Subregion (GMS), malaria transmission is concentrated along the international borders and there have been major changes in malaria epidemiology with Plasmodium vivax becoming the dominant species in many regions. Here, we aimed to evaluate the genetic diversity of P. vivax Duffy-binding protein gene domain II (pvdbp-II) in isolates from the eastern and western borders of Myanmar, and compared it with that from global P. vivax populations. Methods pvdbp-II sequences were obtained from 85 and 82 clinical P. vivax isolates from the eastern and western Myanmar borders, respectively. In addition, 504 pvdbp-II sequences from nine P. vivax populations of the world were retrieved from GenBank and used for comparative analysis of genetic diversity, recombination and population structure of the parasite population. Results The nucleotide diversity of the pvdbp-II sequences from the Myanmar border parasite isolates was not uniform, with the highest diversity located between nucleotides 1078 and 1332. Western Myanmar isolates had a unique R391C mutation. Evidence of positive natural selection was detected in pvdbp-II gene in P. vivax isolates from the eastern Myanmar area. P. vivax parasite populations in the GMS, including those from the eastern, western, and central Myanmar as well as Thailand showed low-level genetic differentiation (FST, 0.000–0.099). Population genetic structure analysis of the pvdbp-II sequences showed a division of the GMS populations into four genetic clusters. A total of 60 PvDBP-II haplotypes were identified in 210 sequences from the GMS populations. Among the epitopes in PvDBP-II, high genetic diversity was found in epitopes 45 (379-SIFGT(D/G)(E/K)(K/N)AQQ(R/H)(R/C)KQ-393, π = 0.029) and Ia (416-G(N/K)F(I/M)WICK(L/I)-424], Ib [482-KSYD(Q/E)WITR-490, π = 0.028) in P. vivax populations from the eastern and western borders of Myanmar. Conclusions The pvdbp-II gene is genetically diverse in the eastern and western Myanmar border P. vivax populations. Positive natural selection and recombination occurred in pvdbp-II gene. Low-level genetic differentiation was identified, suggesting extensive gene flow of the P. vivax populations in the GMS. These results can help understand the evolution of the P. vivax populations in the course of regional malaria elimination and guide the design of PvDBP-II-based vaccine.


2019 ◽  
Vol 18 (1) ◽  
pp. 25
Author(s):  
Aja Fatimah Zohra ◽  
Samsul Anwar ◽  
Aida Fitri ◽  
Muhammad Haikal Nasution

Latar belakang: Malaria merupakan salah satu kasus penyakit yang tidak pernah hilang. World Health Organization (WHO) memperkirakan sebanyak 300 hingga 500 juta orang terinfeksi malaria tiap tahunnya dengan angka kematian berkisar antara 1,5 hingga 2,7 juta pertahun. Pemerintah melalui Rencana Pembangunan Jangka Menengah Nasional (RPJMN) tahun 2015-2019 menargetkan sebanyak 300 kabupaten/kota akan memiliki sertifikasi eliminasi malaria pada tahun 2019. Penelitian ini merupakan penelitian pendahuluan terkait dengan distribusi dan prevalensi kejadian malaria di Provinsi Aceh. Meskipun sebagian besar kabupaten/kota di Provinsi Aceh sudah memiliki sertifikat eliminasi malaria, akan tetapi sebagian wilayah masih terdapat kasus malaria yang relatif tinggi. Penelitian ini bertujuan untuk mengetahui jenis parasit plasmodium yang paling dominan menyebabkan penyakit malaria dan mengklasifikasikan wilayah Provinsi Aceh yang rentan terserang kasus malaria berdasarkan indikator Annual Parasite Incidence (API).Metode: Penelitian ini adalah penelitian analitik kuantitatif dengan pendekatan data panel. Sampel pada penelitian ini adalah kasus malaria yang terjadi di 23 kabupaten/kota di Provinsi Aceh dari tahun 2015 sampai 2018 yang bersumber dari Dinas Kesehatan Provinsi Aceh. Metode statistik yang digunakan adalah analisis non-parametrik Kruskal-Wallis test, Mann-Whitney test dan K-Means Clustering. Hasil: Terdapat tiga jenis parasit yang paling dominan menyebabkan kasus malaria di Provinsi Aceh yaitu plasmodium vivax, plasmodium falcifarum dan plasmodium knowlesi. Berdasarkan indikator Annual Parasite Incidence (API), metode K-means clustering menunjukkan bahwa Kabupaten Aceh Jaya, Kota Sabang dan Kabupaten Aceh Selatan merupakan tiga wilayah yang paling rentan untuk terserang kasus malaria di Provinsi Aceh.Simpulan: Jenis-jenis parasit penyebab kasus malaria tertinggi adalah plasmodium vivax, plasmodium falcifarum dan plasmodium knowlesi. Tiga wilayah di Provinsi Aceh yang paling rentan terserang kasus malaria berdasarkan indikator API adalah Kabupaten Aceh Jaya, Kota Sabang dan Kabupaten Aceh Selatan.ABSTRACTTitle: Classification of Aceh Province Region Based on Vulnerability Levels of Malaria Cases in 2015 - 2018Background: Malaria is a case of an emerging disease. World Health Organization (WHO) estimates that 300 to 500 million people are infected with malaria each year with mortality rate ranging from 1.5 to 2.7 million per year. The government through the National Medium Term Development Plan (RPJMN) for 2015-2019 targets as many as 300 districts/cities to have certification of malaria elimination in 2019. This is a preliminary study related to the distribution and prevalence of malaria incidence in Aceh Province. Although most districts/cities in Aceh Province have been awarded malaria elimination certificates, some regions still have relatively high cases of malaria. This study aims to determine the type of plasmodium parasite that is the most dominant cause of malaria and to classify the regions in Aceh Province that is vulnerable to malaria cases based on the Annual Parasite Incidence (API) indicator.Method: This study is a quantitative analytical research study with panel data approach. The sample in this study was malaria cases that occurred in 23 districts/cities in Aceh Province from 2015 to 2018 obtained from the Aceh Provincial Health Office. The statistical methods used in this study were the non-parametric Kruskal-Wallis test, Mann-Whitney test and K-Means Clustering analyses.Result: There are three types of parasites which are the most dominant causes of malaria cases in Aceh Province, namely plasmodium vivax, plasmodium falcifarum and plasmodium knowlesi. Based on the Annual Parasite Incidence (API) indicator, the K-means clustering method shows that Aceh Jaya District, Sabang City and South Aceh District are the three most vulnerable areas for malaria in Aceh Province.Conclusion: The types of parasites that cause the highest malaria cases are plasmodium vivax, plasmodium falcifarum and plasmodium knowlesi. Three regions in Aceh Province that are most vulnerable to malaria cases based on API indicator are Aceh Jaya District, Sabang City and South Aceh District.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Huang ◽  
Shi-Gang Li ◽  
Peng Tian ◽  
Xiang-Rui Guo ◽  
Zhi-Gui Xia ◽  
...  

AbstractYingjiang County, which is on the China–Myanmar border, is the main focus for malaria elimination in China. The epidemiological characteristics of malaria in Yingjiang County were analysed in a retrospective analysis. A total of 895 malaria cases were reported in Yingjiang County between 2013 and 2019. The majority of cases occurred in males (70.7%) and individuals aged 19–59 years (77.3%). Plasmodium vivax was the predominant species (96.6%). The number of indigenous cases decreased gradually and since 2017, no indigenous cases have been reported. Malaria cases were mainly distributed in the southern and southwestern areas of the county; 55.6% of the indigenous cases were reported in Nabang Township, which also had the highest risk of imported malaria. The “1–3–7” approach has been implemented effectively, with 100% of cases reported within 24 h, 88.9% cases investigated and confirmed within 3 days and 98.5% of foci responded to within 7 days. Although malaria elimination has been achieved in Yingjiang County, sustaining elimination and preventing the re-establishment of malaria require the continued strengthening of case detection, surveillance and response systems targeting the migrant population in border areas.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica N. McCaffery ◽  
Balwan Singh ◽  
Douglas Nace ◽  
Alberto Moreno ◽  
Venkatachalam Udhayakumar ◽  
...  

Abstract Background As malaria incidence and transmission in a region decreases, it becomes increasingly difficult to identify areas of active transmission. Improved methods for identifying and monitoring foci of active malaria transmission are needed in areas of low parasite prevalence in order to achieve malaria elimination. Serological assays can provide population-level infection history to inform elimination campaigns. Methods A bead-based multiplex antibody detection assay was used to evaluate a chimeric Plasmodium vivax MSP1 protein (PvRMC-MSP1), designed to be broadly immunogenic for use in vaccine studies, to act as a pan-malaria serological tool based on its ability to capture IgG in plasma samples obtained from naturally exposed individuals. Samples from 236 US travellers with PCR confirmed infection status from all four major Plasmodium species infecting humans, Plasmodium falciparum (n = 181), Plasmodium vivax (n = 38), Plasmodium malariae (n = 4), and Plasmodium ovale (n = 13) were tested for IgG capture using PvRMC-MSP1 as well as the four recombinant MSP1-19 kD isoforms representative of these Plasmodium species. Results Regardless of infecting Plasmodium species, a large proportion of plasma samples from infected US travellers provided a high assay signal to the PvRMC-MSP1 chimeric protein, with 115 high responders out of 236 samples assessed (48.7%). When grouped by active infection, 38.7% P. falciparum-, 92.1% of P. vivax-, 75.0% P. malariae-, and 53.4% of P. ovale-infected individuals displayed high assay signals in response to PvRMC-MSP1. It was also determined that plasma from P. vivax-infected individuals produced increased assay signals in response to the PvRMC-MSP1 chimera as compared to the recombinant PvMSP1 for 89.5% (34 out of 38) of individuals. PvRMC-MSP1 also showed improved ability to capture IgG antibodies from P. falciparum-infected individuals when compared to the capture by recombinant PvMSP1, with high assay signals observed for 38.7% of P. falciparum-infected travellers in response to PvRMC-MSP1 IgG capture compared to just 1.1% who were high responders to capture by the recombinant PvMSP1 protein. Conclusions These results support further study of designed antigens as an approach for increasing sensitivity or broadening binding capacity to improve existing serological tools for determining population-level exposure to Plasmodium species. Including both broad-reacting and Plasmodium species-specific antigen-coated beads in an assay panel could provide a nuanced view of population-level exposure histories, an extensive IgG profile, and detailed seroestimates. A more sensitive serological tool for detection of P. vivax exposure would aid malaria elimination campaigns in co-endemic areas and regions where P. vivax is the dominant parasite.


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