scholarly journals Evolution of the Plasmodium vivax multidrug resistance 1 gene in the Greater Mekong Subregion during malaria elimination

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Huguette Gaelle Ngassa Mbenda ◽  
Meilian Wang ◽  
Jian Guo ◽  
Faiza Amber Siddiqui ◽  
Yue Hu ◽  
...  
2008 ◽  
Vol 52 (7) ◽  
pp. 2657-2659 ◽  
Author(s):  
Mallika Imwong ◽  
Sasithon Pukrittayakamee ◽  
Wirichada Pongtavornpinyo ◽  
Supatchara Nakeesathit ◽  
Shalini Nair ◽  
...  

ABSTRACT Plasmodium vivax mdr1 gene amplification, quantified by real-time PCR, was significantly more common on the western Thailand border (6 of 66 samples), where mefloquine pressure has been intense, than elsewhere in southeast Asia (3 of 149; P = 0.02). Five coding mutations in pvmdr1, independent of gene amplification, were also found.


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.


2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Fredy E. Villena ◽  
Jorge L. Maguiña ◽  
Meddly L. Santolalla ◽  
Edwar Pozo ◽  
Carola J. Salas ◽  
...  

Abstract Background The high incidence of Plasmodium vivax infections associated with clinical severity and the emergence of chloroquine (CQ) resistance has posed a challenge to control efforts aimed at eliminating this disease. Despite conflicting evidence regarding the role of mutations of P. vivax multidrug resistance 1 gene (pvmdr1) in drug resistance, this gene can be a tool for molecular surveillance due to its variability and spatial patterns. Methods Blood samples were collected from studies conducted between 2006 and 2015 in the Northern and Southern Amazon Basin and the North Coast of Peru. Thick and thin blood smears were prepared for malaria diagnosis by microscopy and PCR was performed for detection of P. vivax monoinfections. The pvmdr1 gene was subsequently sequenced and the genetic data was used for haplotype and diversity analysis. Results A total of 550 positive P. vivax samples were sequenced; 445 from the Northern Amazon Basin, 48 from the Southern Amazon Basin and 57 from the North Coast. Eight non-synonymous mutations and three synonymous mutations were analysed in 4,395 bp of pvmdr1. Amino acid changes at positions 976F and 1076L were detected in the Northern Amazon Basin (12.8%) and the Southern Amazon Basin (4.2%) with fluctuations in the prevalence of both mutations in the Northern Amazon Basin during the course of the study that seemed to correspond with a malaria control programme implemented in the region. A total of 13 pvmdr1 haplotypes with non-synonymous mutations were estimated in Peru and an overall nucleotide diversity of π = 0.00054. The Northern Amazon Basin was the most diverse region (π = 0.00055) followed by the Southern Amazon and the North Coast (π = 0.00035 and π = 0.00014, respectively). Conclusion This study showed a high variability in the frequencies of the 976F and 1076L polymorphisms in the Northern Amazon Basin between 2006 and 2015. The low and heterogeneous diversity of pvmdr1 found in this study underscores the need for additional research that can elucidate the role of this gene on P. vivax drug resistance as well as in vitro and clinical data that can clarify the extend of CQ resistance in Peru.


2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Emilie Faway ◽  
Lise Musset ◽  
Stéphane Pelleau ◽  
Béatrice Volney ◽  
Jessica Casteras ◽  
...  

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.


2018 ◽  
Vol 64 ◽  
pp. 168-177 ◽  
Author(s):  
Veerayuth Kittichai ◽  
Wang Nguitragool ◽  
Huguette Gaelle Ngassa Mbenda ◽  
Jetsumon Sattabongkot ◽  
Liwang Cui

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shwe Sin Kyaw ◽  
Gilles Delmas ◽  
Tom L. Drake ◽  
Olivier Celhay ◽  
Wirichada Pan-ngum ◽  
...  

Abstract Background Mass drug administration (MDA) has received growing interest to accelerate the elimination of multi-drug resistant malaria in the Greater Mekong Subregion. Targeted MDA, sometimes referred to as focal MDA, is the practice of delivering MDA to high incidence subpopulations only, rather than the entire population. The potential effectiveness of delivering targeted MDA was demonstrated in a recent intervention in Kayin State, Myanmar. Policymakers and funders need to know what resources are required if MDA, targeted or otherwise, is to be included in elimination packages beyond existing malaria interventions. This study aims to estimate the programmatic cost and the unit cost of targeted MDA in Kayin State, Myanmar. Methods We used financial data from a malaria elimination initiative, conducted in Kayin State, to estimate the programmatic costs of the targeted MDA component using a micro-costing approach. Three activities (community engagement, identification of villages for targeted MDA, and conducting mass treatment in target villages) were evaluated. We then estimated the programmatic costs of implementing targeted MDA to support P. falciparum malaria elimination in Kayin State. A costing tool was developed to aid future analyses. Results The cost of delivering targeted MDA within an integrated malaria elimination initiative in eastern Kayin State was approximately US$ 910,000. The cost per person reached, distributed among those in targeted and non-targeted villages, for the MDA component was US$ 2.5. Conclusion This cost analysis can assist policymakers in determining the resources required to clear malaria parasite reservoirs. The analysis demonstrated the value of using financial data from research activities to predict programmatic implementation costs of targeting MDA to different numbers of target villages.


2007 ◽  
Vol 68 (1) ◽  
pp. 95-100 ◽  
Author(s):  
Shinobu Matsuura ◽  
Hisao Koto ◽  
Kaori Ide ◽  
Yasuhito Fujino ◽  
Asuka Setoguchi-Mukai ◽  
...  

Autoimmunity ◽  
2016 ◽  
Vol 49 (7) ◽  
pp. 486-495 ◽  
Author(s):  
Wenjie Liu ◽  
Huiyuan Li ◽  
Donglei Zhang ◽  
Mingen Lv ◽  
Yang Li ◽  
...  

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