Intra-host dynamics of co-infecting parasite genotypes in asymptomatic malaria patients.
Intra-host dynamics of co-infecting parasite genotypes in asymptomatic malaria patients.
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DOI：
10.1016/j.meegid.2018.08.018
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Ward SA
中科院分区：
文献类型：
--
作者：
Nkhoma SC;Banda RL;Khoswe S;Dzoole-Mwale TJ;Ward SA
感染疟疾的个体通常具有遗传上不同的寄生虫基因型。我们研究了马拉维Chikhwawa疟疾传播密集地区寄生虫基因型共感染无症状成人的宿主内动态。连续7天从25名患有无症状恶性疟原虫疟疾的成年人中收集系列血液样本（5 ml），并进行分析以确定单个外周血样本是否准确捕获宿主内寄生虫多样性。还通过分离的寄生虫克隆的有限稀释克隆和SNP基因分型来分析来自三名参与者的血液样本，以检查共感染寄生虫单倍型的数量和相关性。我们观察到88%的采样个体（n = 22）中共感染寄生虫基因型的快速周转，使得感染这些个体的寄生虫的遗传组成在7天的随访过程中发生了显着变化。25个样本中有19个（76%）在基线时携带多种寄生虫基因型。对其中三个个体的系列血液样本的分析显示，它们分别具有6、12和17种不同的寄生虫单倍型。从三个广泛采样的个体中回收的寄生虫单倍型中约70%是不相关的（共享等位基因的比例<83.3%），并且被认为主要是由重复感染（通过多次蚊子叮咬接种不相关的寄生虫单倍型）引起的。其余的在半同胞水平或更高水平上相关，并被认为是通过单次蚊子叮咬的寄生虫共传播接种到个体人类宿主中的。这些发现进一步增加了越来越多的证据，表明单一血液样本很难捕获宿主内寄生虫的多样性，并强调了重复血液采样以准确捕获宿主内寄生虫生态的重要性。我们的数据还表明，寄生虫共传播在产生宿主内寄生虫多样性的高传输设置比以前假设的更明显的作用。综上所述，这些发现对了解抗药性的演变、疟疾传播、寄生虫毒力、配子体性别比例的分配和疟疾免疫力的获得具有重要意义。我们检查了来自疟疾感染个体的单个血液样本是否准确地捕获了宿主内寄生虫多样性。我们还检查了共感染寄生虫单倍型之间的亲缘关系模式，以推断疟疾传播动力学。单个样本捕获的宿主内寄生虫多样性较差，表明需要重复采样感染。即使在这种高传播区域，宿主寄生虫也具有多样性
Malaria-infected individuals often harbor mixtures of genetically distinct parasite genotypes. We studied intra-host dynamics of parasite genotypes co-infecting asymptomatic adults in an area of intense malaria transmission in Chikhwawa, Malawi. Serial blood samples (5 ml) were collected over seven consecutive days from 25 adults with asymptomatic Plasmodium falciparum malaria and analyzed to determine whether a single peripheral blood sample accurately captures within-host parasite diversity. Blood samples from three of the participants were also analyzed by limiting dilution cloning and SNP genotyping of the parasite clones isolated to examine both the number and relatedness of co-infecting parasite haplotypes. We observed rapid turnover of co-infecting parasite genotypes in 88% of the individuals sampled (n = 22) such that the genetic composition of parasites infecting these individuals changed dramatically over the course of seven days of follow up. Nineteen of the 25 individuals sampled (76%) carried multiple parasite genotypes at baseline. Analysis of serial blood samples from three of the individuals revealed that they harbored 6, 12 and 17 distinct parasite haplotypes respectively. Approximately 70% of parasite haplotypes recovered from the three extensively sampled individuals were unrelated (proportion of shared alleles <83.3%) and were deemed to have primarily arisen from superinfection (inoculation of unrelated parasite haplotypes through multiple mosquito bites). The rest were related at the half-sib level or greater and were deemed to have been inoculated into individual human hosts via parasite co-transmission from single mosquito bites. These findings add further to the growing weight of evidence indicating that a single blood sample poorly captures within-host parasite diversity and underscore the importance of repeated blood sampling to accurately capture within-host parasite ecology. Our data also demonstrate a more pronounced role for parasite co-transmission in generating within-host parasite diversity in high transmission settings than previously assumed. Taken together, these findings have important implications for understanding the evolution of drug resistance, malaria transmission, parasite virulence, allocation of gametocyte sex ratios and acquisition of malaria immunity. We examined if a single blood sample from a malaria-infected individual accurately captures within-host parasite diversity We also examined patterns of kinship between co-infecting parasite haplotypes to infer malaria transmission dynamics A single sample poorly captured within-host parasite diversity indicating the need for repeat sampling of infections Single mosquito bites played a key role in generating within-host parasite diversity even in this high transmission area
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影响因子：
15.8
作者：
Chen I;Clarke SE;Gosling R;Hamainza B;Killeen G;Magill A;O'Meara W;Price RN;Riley EM
通讯作者：
Riley EM
与柬埔寨恶性疟原虫疟疾双氢青蒿素-哌喹失败相关的遗传标记：基因型-表型关联研究。
DOI：
10.1016/s1473-3099(16)30409-1
发表时间：
2017-03
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Amato R;Lim P;Miotto O;Amaratunga C;Dek D;Pearson RD;Almagro-Garcia J;Neal AT;Sreng S;Suon S;Drury E;Jyothi D;Stalker J;Kwiatkowski DP;Fairhurst RM
通讯作者：
Fairhurst RM
影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
6.7
作者：
Abkallo HM;Tangena JA;Tang J;Kobayashi N;Inoue M;Zoungrana A;Colegrave N;Culleton R
通讯作者：
Culleton R
影响因子：
3.7
作者：
Auburn S;Campino S;Miotto O;Djimde AA;Zongo I;Manske M;Maslen G;Mangano V;Alcock D;MacInnis B;Rockett KA;Clark TG;Doumbo OK;Ouédraogo JB;Kwiatkowski DP
通讯作者：
Kwiatkowski DP