Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, 110122, Liaoning, China.
Emergency Department, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, Liaoning, China.
Malar J. 2020 Apr 8;19(1):145. doi: 10.1186/s12936-020-03221-9.
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.
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.
Despite intensified control efforts, genetic diversity remained high (H = 0.66-0.86) and was not significantly different among the four populations (P > 0.05). Specifically, H 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 = 0.081 at the CMB and F = 0.133 at the TMB). Various degrees of clustering were evident between the older parasite samples collected in 2004 at the CMB and 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) at the CMB showed a decrease from 4979 in 2004 to 3052 in 2016 with the infinite allele model, the N at the TMB experienced an increase from 6289 to 10,259.
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.
东南亚大湄公河次区域（GMS）国家承诺到 2030 年消除疟疾。尽管疟疾情况已大大改善，但疟疾仍在国际边境地区传播。在某些地区，间日疟原虫已成为主要寄生虫。为了更好地了解传播动态，了解控制干预措施扩大后间日疟原虫种群的变化将指导更有效的有针对性的控制工作。
本研究调查了在两个国际边境地区（中国-缅甸边境（CMB）（2004 年 n=50，2016 年 n=52）和泰国-缅甸边境（TMB）（2012 年 n=50，2015 年 n=54））采集的 206 例间日疟原虫临床样本的遗传多样性和种群结构。寄生虫使用 10 个微卫星标记进行基因分型。
尽管控制工作力度加大，但遗传多样性仍然很高（H=0.66-0.86），四个种群之间没有显著差异（P>0.05）。具体来说，CMB 的 H 值从 2004 年的 0.76 略微下降到 2016 年的 0.66，而 TMB 的 H 值从 2012 年的 0.80 增加到 2015 年的 0.86。四个种群中多克隆感染的比例差异显著（P<0.05），CMB 从 2004 年的 48.0%降至 2016 年的 23.7%，TMB 从 2012 年的 40.0%降至 2015 年的 30.7%，感染倍数相应下降。与大湄公河次区域疟疾发病率随时间持续下降一致，多基因座连锁不平衡也有所增加，表明寄生虫种群更加碎片化和日益近亲繁殖。四个检测种群之间存在相当大的遗传分化和细分。每个地点都观察到时间遗传分化（CMB 处 F=0.081，TMB 处 F=0.133）。2004 年老的寄生虫样本与 2016 年 CMB 和 2012 年 TMB 种群之间存在相当程度的聚类，这表明其中一些寄生虫具有共同的祖先。相比之下，2015 年 TMB 种群具有独特的遗传特征，这可能反映了种群更替的过程。而 CMB 的有效种群数量（N）从 2004 年的 4979 下降到 2016 年的 3052，而无限等位基因模型的 N 在 TMB 经历了从 6289 到 10259 的增加。
随着疟疾控制工作的加强，TMB 和 CMB 的间日疟原虫表现出相当大的空间和时间分化，但大量间日疟原虫储存仍然维持着遗传多样性和传播。这些发现为大湄公河次区域这些边境地区间日疟原虫传播动态和种群结构提供了新的见解。在国际边境两侧协调和综合控制工作对于实现区域消除疟疾的目标至关重要。
