Microsatellite analysis reveals connectivity among geographically distant transmission zones of Plasmodium vivax in the Peruvian Amazon: A critical barrier to regional malaria elimination
Microsatellite analysis reveals connectivity among geographically distant transmission zones of Plasmodium vivax in the Peruvian Amazon: A critical barrier to regional malaria elimination
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DOI：
10.1371/journal.pntd.0007876
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发表时间：
2019-11-01
影响因子：
3.8
通讯作者：
Gamboa, Dionicia
中科院分区：
文献类型：
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作者：
Manrique, Paulo;Miranda-Alban, Julio;Gamboa, Dionicia
尽管秘鲁政府几十年来为消除疟疾做出了努力，但间日疟原虫仍然是该国公共卫生决策者面临的挑战。其发病率分布不均，加上其复杂的传播模式，使得基于全球信息的控制措施无效，而全球信息缺乏充分了解传播的必要细节。从这个意义上说，群体遗传工具可以补充目前的监测。这项研究描述了2012年9月至2015年3月在三个地理上遥远的定居点，位于秘鲁亚马逊的Cahuide（CAH），Lupuna（LUP）和Santa Emilia（STE）的遗传多样性和种群结构。在3264例间日疟原虫单一感染中，共对777例进行了基因分型。在所研究的地区中，LUP显示19.7%的多克隆感染，其遗传多样性（H-exp）为0.544。时间分析显示，自2013年3月以来，多克隆感染和H-exp显著增加，并引入和持续存在新的寄生虫种群。在STE中，40.1%的感染是多克隆的，H-exp = 0.596。与其他两个地区相比，还发现存在四个没有克隆扩张信号的遗传簇，并且感染的寄生虫密度较低。2012年CAH至少存在四个寄生虫种群，2014年6月后，疟疾病例从213例减少到61例，同时多克隆感染减少（从0.286到0.18），和可变的H-exp。强烈的基因流信号存在于研究领域和广泛的地理分布的高度多样化的寄生虫populationsoffered. This研究表明，疟疾寄生虫的人类水库的运动连接地理上遥远的疟疾传播地区在秘鲁亚马逊。维持高水平的寄生虫遗传多样性，通过人类的流动性是一个关键的障碍，消除疟疾在该region.Author摘要间日疟原虫传播是异质性和不连续的秘鲁亚马逊。造成这种异质性的因素包括但不限于环境、公共政策以及寄生虫、病媒和人类活动的特征。所有这些因素使间日疟原虫的传播对干预措施具有弹性。为了实现控制和局部消除的目标，间日疟原虫监测必须告知这些因素如何维持疾病传播，以便集中和同步控制策略。在这项研究中，我们在位于秘鲁亚马逊的Cahuide，Lupuna和Santa Emilia地区实施了分子监测，并辅以群体遗传工具。特别是，我们描述了2012年9月至2015年3月期间这些地点的传播和寄生虫遗传变异。寄生虫多样性的变化，广泛的地理分布的寄生虫亚群和引入一个新的寄生虫克隆或亚群在Lupuna在本研究中记录表明，不同的流行地区之间的连接，可能是由于人类的流动性，维持疾病传播的区域阻碍了控制措施的成功。在设计当前控制策略时必须考虑这些信息。
Despite efforts made over decades by the Peruvian government to eliminate malaria, Plasmodium vivax remains a challenge for public health decision-makers in the country. The uneven distribution of its incidence, plus its complex pattern of dispersion, has made ineffective control measures based on global information that lack the necessary detail to understand transmission fully. In this sense, population genetic tools can complement current surveillance. This study describes the genetic diversity and population structure from September 2012 to March 2015 in three geographically distant settlements, Cahuide (CAH), Lupuna (LUP) and Santa Emilia (STE), located in the Peruvian Amazon. A total 777 P. vivax mono-infections, out of 3264, were genotyped. Among study areas, LUP showed 19.7% of polyclonal infections, and its genetic diversity (H-exp) was 0.544. Temporal analysis showed a significant increment of polyclonal infections and H-exp, and the introduction and persistence of a new parasite population since March 2013. In STE, 40.1% of infections were polyclonal, with H-exp = 0.596. The presence of four genetic clusters without signals of clonal expansion and infections with lower parasite densities compared against the other two areas were also found. At least four parasite populations were present in CAH in 2012, where, after June 2014, malaria cases decreased from 213 to 61, concomitant with a decrease in polyclonal infections (from 0.286 to 0.18), and expectedly variable H-exp. Strong signals of gene flow were present in the study areas and wide geographic distribution of highly diverse parasite populations were found. This study suggests that movement of malaria parasites by human reservoirs connects geographically distant malaria transmission areas in the Peruvian Amazon. The maintenance of high levels of parasite genetic diversity through human mobility is a critical barrier to malaria elimination in this region.Author summary Plasmodium vivax transmission is heterogeneous and discontinuous in the Peruvian Amazon. Such heterogeneity is the result of factors that include, but are not restricted to, the environment, public policies, and characteristics of the parasite, the vector, and human activities. All these factors make P. vivax transmission resilient to interventions. In order to achieve the goals of control and local elimination, P. vivax surveillance must inform how those factors sustain disease transmission in order to focalize and synchronize control strategies. In this study, we implemented molecular surveillance complemented with population genetic tools in the areas of Cahuide, Lupuna, and Santa Emilia located in the Peruvian Amazon. In particular, we characterize the transmission and the parasite genetic variation in these sites from September 2012 to March 2015. The changes in parasite diversity, the wide geographic dispersion of parasite subpopulation and the introduction of a new parasite clone or subpopulation in Lupuna documented in this study suggest that connectivity among the different endemic areas, likely due to human mobility, sustains disease transmission in the region hindering the success of control measures. This information must be considered in the design of current control strategies.