PDF(Sci-hub)
Abstract：
BACKGROUND: The reservoir of Plasmodium infection in humans has traditionally been defined by blood slide positivity. This study was designed to characterize the local reservoir of infection in relation to the diverse var genes that encode the major surface antigen of Plasmodium falciparum blood stages and underlie the parasite\'s ability to establish chronic infection and transmit from human to mosquito.
RESULTS: We investigated the molecular epidemiology of the var multigene family at local sites in Gabon, Senegal and Kenya which differ in parasite prevalence and transmission intensity. 1839 distinct var gene types were defined by sequencing DBLα domains in the three sites. Only 76 (4.1%) var types were found in more than one population indicating spatial heterogeneity in var types across the African continent. The majority of var types appeared only once in the population sample. Non-parametric statistical estimators predict in each population at minimum five to seven thousand distinct var types. Similar diversity of var types was seen in sites with different parasite prevalences.
CONCLUSIONS: Var population genomics provides new insights into the epidemiology of P. falciparum in Africa where malaria has never been conquered. In particular, we have described the extensive reservoir of infection in local African sites and discovered a unique var population structure that can facilitate superinfection through minimal overlap in var repertoires among parasite genomes. Our findings show that var typing as a molecular surveillance system defines the extent of genetic complexity in the reservoir of infection to complement measures of malaria prevalence. The observed small scale spatial diversity of var genes suggests that var genetics could greatly inform current malaria mapping approaches and predict complex malaria population dynamics due to the import of var types to areas where no widespread pre-existing immunity in the population exists.
RESULTS: We investigated the molecular epidemiology of the var multigene family at local sites in Gabon, Senegal and Kenya which differ in parasite prevalence and transmission intensity. 1839 distinct var gene types were defined by sequencing DBLα domains in the three sites. Only 76 (4.1%) var types were found in more than one population indicating spatial heterogeneity in var types across the African continent. The majority of var types appeared only once in the population sample. Non-parametric statistical estimators predict in each population at minimum five to seven thousand distinct var types. Similar diversity of var types was seen in sites with different parasite prevalences.
CONCLUSIONS: Var population genomics provides new insights into the epidemiology of P. falciparum in Africa where malaria has never been conquered. In particular, we have described the extensive reservoir of infection in local African sites and discovered a unique var population structure that can facilitate superinfection through minimal overlap in var repertoires among parasite genomes. Our findings show that var typing as a molecular surveillance system defines the extent of genetic complexity in the reservoir of infection to complement measures of malaria prevalence. The observed small scale spatial diversity of var genes suggests that var genetics could greatly inform current malaria mapping approaches and predict complex malaria population dynamics due to the import of var types to areas where no widespread pre-existing immunity in the population exists.
摘要：
背景：人类疟原虫感染的储库传统上是通过血载玻片阳性来定义的。本研究旨在描述与编码恶性疟原虫血液阶段主要表面抗原的不同var基因相关的感染局部库，并作为寄生虫建立慢性感染并从人传播到蚊子的能力的基础。
结果：我们调查了加蓬当地的var多基因家族的分子流行病学，塞内加尔和肯尼亚的寄生虫患病率和传播强度不同。通过对三个位点中的DBLα结构域进行测序来定义1839种不同的var基因类型。在一个以上的种群中仅发现76种（4.1％）var类型，表明整个非洲大陆的var类型具有空间异质性。大多数var类型在总体样本中仅出现一次。非参数统计估计器在每个种群中预测至少五到七千种不同的var类型。在寄生虫流行率不同的地点发现了相似的var类型。
结论：Var人口基因组学为非洲疟疾从未被征服的恶性疟原虫的流行病学提供了新的见解。特别是,我们已经描述了非洲当地地区的广泛感染库，并发现了独特的var种群结构，该结构可以通过寄生虫基因组之间的var库的最小重叠来促进重复感染。我们的发现表明，作为分子监测系统的var分型定义了感染源中遗传复杂性的程度，以补充疟疾流行的措施。观察到的var基因的小尺度空间多样性表明，var遗传学可以为当前的疟疾作图方法提供极大的信息，并预测复杂的疟疾种群动态，因为var类型输入到人口中不存在广泛的预先存在的免疫力的地区。
结果：我们调查了加蓬当地的var多基因家族的分子流行病学，塞内加尔和肯尼亚的寄生虫患病率和传播强度不同。通过对三个位点中的DBLα结构域进行测序来定义1839种不同的var基因类型。在一个以上的种群中仅发现76种（4.1％）var类型，表明整个非洲大陆的var类型具有空间异质性。大多数var类型在总体样本中仅出现一次。非参数统计估计器在每个种群中预测至少五到七千种不同的var类型。在寄生虫流行率不同的地点发现了相似的var类型。
结论：Var人口基因组学为非洲疟疾从未被征服的恶性疟原虫的流行病学提供了新的见解。特别是,我们已经描述了非洲当地地区的广泛感染库，并发现了独特的var种群结构，该结构可以通过寄生虫基因组之间的var库的最小重叠来促进重复感染。我们的发现表明，作为分子监测系统的var分型定义了感染源中遗传复杂性的程度，以补充疟疾流行的措施。观察到的var基因的小尺度空间多样性表明，var遗传学可以为当前的疟疾作图方法提供极大的信息，并预测复杂的疟疾种群动态，因为var类型输入到人口中不存在广泛的预先存在的免疫力的地区。
