Tessema Sofonias K, Monk Stephanie L, Schultz Mark B, Tavul Livingstone, Reeder John C, Siba Peter M, Mueller Ivo, Barry Alyssa E
Division of Infection and Immunity, Walter and Eliza Hall Institute, 3052, Melbourne, Vic., Australia; Department of Medical Biology, University of Melbourne, 3052, Melbourne, Vic., Australia.
Mol Ecol. 2015 Jan;24(2):484-97. doi: 10.1111/mec.13033. Epub 2015 Jan 9.
Plasmodium falciparum malaria is a major global health problem that is being targeted for progressive elimination. Knowledge of local disease transmission patterns in endemic countries is critical to these elimination efforts. To investigate fine-scale patterns of malaria transmission, we have compared repertoires of rapidly evolving var genes in a highly endemic area. A total of 3680 high-quality DBLα-sequences were obtained from 68 P. falciparum isolates from ten villages spread over two distinct catchment areas on the north coast of Papua New Guinea (PNG). Modelling of the extent of var gene diversity in the two parasite populations predicts more than twice as many var gene alleles circulating within each catchment (Mugil = 906; Wosera = 1094) than previously recognized in PNG (Amele = 369). In addition, there were limited levels of var gene sharing between populations, consistent with local parasite population structure. Phylogeographic analyses demonstrate that while neutrally evolving microsatellite markers identified population structure only at the catchment level, var gene repertoires reveal further fine-scale geospatial clustering of parasite isolates. The clustering of parasite isolates by village in Mugil, but not in Wosera was consistent with the physical and cultural isolation of the human populations in the two catchments. The study highlights the microheterogeneity of P. falciparum transmission in highly endemic areas and demonstrates the potential of var genes as markers of local patterns of parasite population structure.
恶性疟原虫疟疾是一个重大的全球健康问题,目前正被作为逐步消除的目标。了解疟疾流行国家当地的疾病传播模式对于这些消除工作至关重要。为了调查疟疾传播的精细模式,我们比较了高流行地区快速进化的var基因库。从巴布亚新几内亚(PNG)北海岸两个不同集水区的十个村庄的68株恶性疟原虫分离株中,共获得了3680个高质量的DBLα序列。对两个寄生虫群体中var基因多样性程度的建模预测,每个集水区内循环的var基因等位基因数量(穆吉尔=906;沃塞拉=1094)是PNG此前所认识到的(阿梅莱=369)两倍多。此外,群体之间var基因共享水平有限,这与当地寄生虫群体结构一致。系统地理学分析表明,虽然中性进化的微卫星标记仅在集水区水平上识别出群体结构,但var基因库揭示了寄生虫分离株进一步的精细地理空间聚类。在穆吉尔,寄生虫分离株按村庄聚类,但在沃塞拉没有,这与两个集水区人群的物理和文化隔离一致。该研究突出了高流行地区恶性疟原虫传播的微观异质性,并证明了var基因作为当地寄生虫群体结构模式标记的潜力。