scholarly journals Evolution of Plasmodium vivax populations in border areas of the Greater Mekong Subregion during malaria elimination

2020 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Scale Up ◽  
Transmission Dynamics ◽  
Clinical Samples ◽  
Effective Population ◽  
Border Areas ◽  
Greater Mekong Subregion ◽  
International Border

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.

scholarly journals Evolution of Plasmodium vivax populations in border areas of the Greater Mekong Subregion during malaria elimination

2019 ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Scale Up ◽  
Transmission Dynamics ◽  
Clinical Samples ◽  
Effective Population ◽  
Border Areas ◽  
Greater Mekong Subregion ◽  
International Border

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.

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 ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Genetic Differentiation ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Malaria Incidence ◽  
Scale Up ◽  
Transmission Dynamics ◽  
Clinical Samples ◽  
Border Areas ◽  
International Border

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.

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

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuling Li ◽  
Yubing Hu ◽  
Yan Zhao ◽  
Qinghui Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Border Areas

scholarly journals The Sri Lankan paradox: high genetic diversity in Plasmodium vivax populations despite decreasing levels of malaria transmission

Parasitology ◽  
2014 ◽  
Vol 141 (7) ◽  
pp. 880-890 ◽  
Author(s):  
SHARMINI GUNAWARDENA ◽  
MARCELO U. FERREIRA ◽  
G. M. G. KAPILANANDA ◽  
DYANN F. WIRTH ◽  
NADIRA D. KARUNAWEERA
Keyword(s):  
Genetic Diversity ◽  
Sri Lanka ◽  
Plasmodium Vivax ◽  
Malaria Transmission ◽  
Population Size ◽  
Effective Population Size ◽  
Allele Frequency Distribution ◽  
Effective Population ◽  
High Genetic Diversity ◽  
Mode Shift

SUMMARYHere we examined whether the recent dramatic decline in malaria transmission in Sri Lanka led to a major bottleneck in the local Plasmodium vivax population, with a substantial decrease in the effective population size. To this end, we typed 14 highly polymorphic microsatellite markers in 185 P. vivax patient isolates collected from 13 districts in Sri Lanka over a period of 5 years (2003–2007). Overall, we found a high degree of polymorphism, with 184 unique haplotypes (12–46 alleles per locus) and average genetic diversity (expected heterozygosity) of 0·8744. Almost 69% (n = 127) isolates had multiple-clone infections (MCI). Significant spatial and temporal differentiation (FST = 0·04–0·25; P⩽0·0009) between populations was observed. The effective population size was relatively high but showed a decline from 2003–4 to 2006–7 periods (estimated as 45 661 to 22 896 or 10 513 to 7057, depending on the underlying model used). We used three approaches – namely, mode-shift in allele frequency distribution, detection of heterozygote excess and the M-ratio statistics – to test for evidence of a recent population bottleneck but only the low values of M-ratio statistics (ranging between 0·15–0·33, mean 0·26) were suggestive of such a bottleneck. The persistence of high genetic diversity and high proportion of MCI, with little change in effective population size, despite the collapse in demographic population size of P. vivax in Sri Lanka indicates the importance of maintaining stringent control and surveillance measures to prevent resurgence.

scholarly journals Genetic diversity, natural selection and haplotype grouping of Plasmodium vivax Duffy-binding protein genes from eastern and western Myanmar borders

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yubing Hu ◽  
Lin Wang ◽  
Huguette Gaelle Ngassa Mbenda ◽  
Myat Thu Soe ◽  
Chunyun Yu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Natural Selection ◽  
Genetic Differentiation ◽  
Plasmodium Vivax ◽  
Binding Protein ◽  
Duffy Binding Protein ◽  
High Genetic Diversity ◽  
Low Level ◽  
Malaria Epidemiology ◽  
Greater Mekong Subregion

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.

scholarly journals A retrospective analysis of malaria epidemiological characteristics in Yingjiang County on the China–Myanmar border

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fang Huang ◽  
Shi-Gang Li ◽  
Peng Tian ◽  
Xiang-Rui Guo ◽  
Zhi-Gui Xia ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Retrospective Analysis ◽  
Malaria Elimination ◽  
Case Detection ◽  
Migrant Population ◽  
Predominant Species ◽  
Surveillance And Response ◽  
Response Systems ◽  
Border Areas ◽  
Epidemiological Characteristics

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.

scholarly journals Identification, Mapping, and Genetic Diversity of Novel Conserved Cross-Species Epitopes of RhopH2 in Plasmodium knowlesi With Plasmodium vivax

2022 ◽  
Vol 11 ◽  
Author(s):  
Md Atique Ahmed ◽  
Gauspasha Yusuf Deshmukh ◽  
Rehan Haider Zaidi ◽  
Ahmed Saif ◽  
Mohammed Abdulrahman Alshahrani ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Vivax ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Epitope Prediction ◽  
Purifying Selection ◽  
Peninsular Malaysia ◽  
Health Concern ◽  
Clinical Samples

Malaria is a major public health concern, and any tangible intervention during the pre-elimination phase can result in a significant reduction in infection rates. Recent studies have reported that antigens producing cross-protective immunity can play an important role as vaccines and halt malaria transmission in different endemic regions. In this study, we studied the genetic diversity, natural selection, and discovered novel conserved epitopes of a high molecular weight rhoptry protein 2 (RhopH2) in clinical samples of Plasmodium knowlesi and Plasmodium vivax cross-protective domains, which has been proven to produce cross-protective immunity in both species. We found low levels of nucleotide diversity (P. knowlesi; π ~ 0.0093, SNPs = 49 and P. vivax π ~ 0.0014, SNPs = 23) in P. knowlesi (n = 40) and P. vivax (n = 65) samples in the PkRhopH2 cross-protective domain. Strong purifying selection was observed for both species (P. knowlesi; dS - dN = 2.41, p &lt; 0.009, P. vivax; dS - dN = 1.58, p &lt; 0.050). In silico epitope prediction in P. knowlesi identified 10 potential epitopes, of which 7 epitopes were 100% conserved within clinical samples. Of these epitopes, an epitope with 10 amino acids (QNSKHFKKEK) was found to be fully conserved within all P. knowlesi and P. vivax clinical samples and 80%–90% conservation within simian malaria ortholog species, i.e., P. coatneyi and P. cynomolgi. Phylogenetic analysis of the PkRhopH2 cross-protective domain showed geographical clustering, and three subpopulations of P. knowlesi were identified of which two subpopulations originated from Sarawak, Malaysian Borneo, and one comprised only the laboratory lines from Peninsular Malaysia. This study suggests that RhopH2 could be an excellent target for cross-protective vaccine development with potential for outwitting strain as well as species-specific immunity. However, more detailed studies on genetic diversity using more clinical samples from both species as well as the functional role of antibodies specific to the novel conserved epitope identified in this study can be explored for protection against infection.

scholarly journals Estimated impact of tafenoquine for Plasmodium vivax control and elimination in Brazil: A modelling study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (4) ◽  
pp. e1003535
Author(s):  
Narimane Nekkab ◽  
Raquel Lana ◽  
Marcus Lacerda ◽  
Thomas Obadia ◽  
André Siqueira ◽  
...  
Keyword(s):  
Case Management ◽  
Plasmodium Vivax ◽  
Malaria Elimination ◽  
Population Level ◽  
Transmission Dynamics ◽  
Radical Cure ◽  
Treatment Pathways ◽  
The Impact ◽  
Modelling Study ◽  
Clinical Cases

Background Despite recent intensification of control measures, Plasmodium vivax poses a major challenge for malaria elimination efforts. Liver-stage hypnozoite parasites that cause relapsing infections can be cleared with primaquine; however, poor treatment adherence undermines drug effectiveness. Tafenoquine, a new single-dose treatment, offers an alternative option for preventing relapses and reducing transmission. In 2018, over 237,000 cases of malaria were reported to the Brazilian health system, of which 91.5% were due to P. vivax. Methods and findings We evaluated the impact of introducing tafenoquine into case management practices on population-level transmission dynamics using a mathematical model of P. vivax transmission. The model was calibrated to reflect the transmission dynamics of P. vivax endemic settings in Brazil in 2018, informed by nationwide malaria case reporting data. Parameters for treatment pathways with chloroquine, primaquine, and tafenoquine with glucose-6-phosphate dehydrogenase deficiency (G6PDd) testing were informed by clinical trial data and the literature. We assumed 71.3% efficacy for primaquine and tafenoquine, a 66.7% adherence rate to the 7-day primaquine regimen, a mean 5.5% G6PDd prevalence, and 8.1% low metaboliser prevalence. The introduction of tafenoquine is predicted to improve effective hypnozoite clearance among P. vivax cases and reduce population-level transmission over time, with heterogeneous levels of impact across different transmission settings. According to the model, while achieving elimination in only few settings in Brazil, tafenoquine rollout in 2021 is estimated to improve the mean effective radical cure rate from 42% (95% uncertainty interval [UI] 41%–44%) to 62% (95% UI 54%–68%) among clinical cases, leading to a predicted 38% (95% UI 7%–99%) reduction in transmission and over 214,000 cumulative averted cases between 2021 and 2025. Higher impact is predicted in settings with low transmission, low pre-existing primaquine adherence, and a high proportion of cases in working-aged males. High-transmission settings with a high proportion of cases in children would benefit from a safe high-efficacy tafenoquine dose for children. Our methodological limitations include not accounting for the role of imported cases from outside the transmission setting, relying on reported clinical cases as a measurement of community-level transmission, and implementing treatment efficacy as a binary condition. Conclusions In our modelling study, we predicted that, provided there is concurrent rollout of G6PDd diagnostics, tafenoquine has the potential to reduce P. vivax transmission by improving effective radical cure through increased adherence and increased protection from new infections. While tafenoquine alone may not be sufficient for P. vivax elimination, its introduction will improve case management, prevent a substantial number of cases, and bring countries closer to achieving malaria elimination goals.

scholarly journals High Plasmodium falciparum genetic diversity and temporal stability despite control efforts in high transmission settings along the international border between Zambia and the Democratic Republic of the Congo

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Julia C. Pringle ◽  
Amy Wesolowski ◽  
Sophie Berube ◽  
Tamaki Kobayashi ◽  
Mary E. Gebhardt ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Elimination ◽  
Democratic Republic ◽  
Small Sample ◽  
Suitable Alternative ◽  
High Transmission ◽  
Republic Of The Congo ◽  
Genetic Signatures ◽  
International Border

Abstract Background While the utility of parasite genotyping for malaria elimination has been extensively documented in low to moderate transmission settings, it has been less well-characterized in holoendemic regions. High malaria burden settings have received renewed attention acknowledging their critical role in malaria elimination. Defining the role for parasite genomics in driving these high burden settings towards elimination will enhance future control programme planning. Methods Amplicon deep sequencing was used to characterize parasite population genetic diversity at polymorphic Plasmodium falciparum loci, Pfama1 and Pfcsp, at two timepoints in June–July 2016 and January–March 2017 in a high transmission region along the international border between Luapula Province, Zambia and Haut-Katanga Province, the Democratic Republic of the Congo (DRC). Results High genetic diversity was observed across both seasons and in both countries. No evidence of population structure was observed between parasite populations on either side of the border, suggesting that this region may be one contiguous transmission zone. Despite a decline in parasite prevalence at the sampling locations in Haut-Katanga Province, no genetic signatures of a population bottleneck were detected, suggesting that larger declines in transmission may be required to reduce parasite genetic diversity. Analysing rare variants may be a suitable alternative approach for detecting epidemiologically important genetic signatures in highly diverse populations; however, the challenge is distinguishing true signals from potential artifacts introduced by small sample sizes. Conclusions Continuing to explore and document the utility of various parasite genotyping approaches for understanding malaria transmission in holoendemic settings will be valuable to future control and elimination programmes, empowering evidence-based selection of tools and methods to address pertinent questions, thus enabling more efficient resource allocation.

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