The Incidence and Differential Seasonal Patterns of Plasmodium vivax Primary Infections and Relapses in a Cohort of Children in Papua New Guinea.
The Incidence and Differential Seasonal Patterns of Plasmodium vivax Primary Infections and Relapses in a Cohort of Children in Papua New Guinea.
复制标题
DOI：
10.1371/journal.pntd.0004582
复制
发表时间：
2016-05
影响因子：
3.8
通讯作者：
Tanner M
中科院分区：
文献类型：
--
作者：
Ross A;Koepfli C;Schoepflin S;Timinao L;Siba P;Smith T;Mueller I;Felger I;Tanner M
间日疟原虫有能力在接种后数周或数月内从肝脏中的休眠寄生虫中复发，从而导致进一步的血液阶段感染和潜在的进一步传播。估计原发感染和复发引起的血液阶段感染的强度对于设计干预策略非常重要。然而，在流行情况下，它们的相对贡献尚不清楚。感染通常是无症状的，许多人患有多种感染，虽然血液样本的高分辨率基因分型可以区分个体感染，但无法识别原发感染和复发。我们开发了一个模型，并将其与巴布亚新几内亚儿童的纵向基因分型数据进行拟合，以估计间日疟原发感染和复发的发病率和季节性。这些孩子入学时年龄为 1 至 3 岁，每两个月进行一次例行调查，随访时间超过 16 个月。在例行就诊时以及孩子生病的其他时间采集血样。使用高分辨率毛细管电泳对通过显微镜或用于物种检测的分子方法呈阳性的样品进行间日疟原虫 MS16 和 msp1F3 以及恶性疟原虫 msp2 的基因分型。数据被总结为在每个常规时间点（例如001000001）成功或失败检测基因型的纵向模式。我们假设间日疟原发感染的季节性与恶性疟相似，因为它们通过相同的媒介传播，并且由于恶性疟没有复发的能力，因此可以估计季节性。研究期间发生的复发可能是研究之前发生的感染的结果：我们假设原发感染的季节性模式随着时间的推移而重复。我们整合了寄生虫学和昆虫学研究的信息，以获得估计参数的杠杆，并考虑到不完美的检测。我们估计，对于一名三岁儿童，每年间日疟原虫原发感染的强度为 11.5 (10.5, 12.3)，每次感染在 16 个月内的平均复发次数为 4.3 (4.0, 4.6)。复发高峰出现在原发感染高峰期之后的两个月内：根据季节不同，复发对血液阶段感染力的贡献在 71% 至 90% 之间。我们的估计有助于了解间日疟原虫流行病学，并对针对生命周期不同阶段的干预策略的时机产生影响。间日疟原虫是影响人类最广泛的疟疾种类。它使寄生虫能够在肝细胞中休眠，然后在数周或数月后复发，导致进一步的血液阶段感染和进一步传播。复发对控制和消除计划提出了挑战。复发对血液阶段感染的影响尚未明确。虽然基因分型可以区分个体感染，但困难在于无法区分原发感染（在传染性蚊子叮咬后不久发生）和复发。这是间日疟原虫流行病学知识的一个空白。我们开发了一个统计模型来梳理和估计原发感染和复发对血液阶段感染的影响。我们使用来自巴布亚新几内亚一组儿童的数据，其中包含基因分型的常规血液样本。研究区域同时存在间日疟和恶性疟：我们利用恶性疟的季节性来估计间日疟原发感染的季节性。我们还考虑了研究期间之前发生的感染及其随后在研究期间的复发。我们发现大约 80% 的血期感染力是由复发造成的，并且原发感染和复发具有不同的季节性模式。这些发现对于间日疟原虫的流行病学以及针对寄生虫生命周期不同阶段的干预策略的设计具有重要意义。
Plasmodium vivax has the ability to relapse from dormant parasites in the liver weeks or months after inoculation, causing further blood-stage infection and potential onward transmission. Estimates of the force of blood-stage infections arising from primary infections and relapses are important for designing intervention strategies. However, in endemic settings their relative contributions are unclear. Infections are frequently asymptomatic, many individuals harbor multiple infections, and while high-resolution genotyping of blood samples enables individual infections to be distinguished, primary infections and relapses cannot be identified. We develop a model and fit it to longitudinal genotyping data from children in Papua New Guinea to estimate the incidence and seasonality of P vivax primary infection and relapse. The children, aged one to three years at enrolment, were followed up over 16 months with routine surveys every two months. Blood samples were taken at the routine visits and at other times if the child was ill. Samples positive by microscopy or a molecular method for species detection were genotyped using high-resolution capillary electrophoresis for P vivax MS16 and msp1F3, and P falciparum msp2. The data were summarized as longitudinal patterns of success or failure to detect a genotype at each routine time-point (eg 001000001). We assume that the seasonality of P vivax primary infection is similar to that of P falciparum since they are transmitted by the same vectors and, because P falciparum does not have the ability to relapse, the seasonality can be estimated. Relapses occurring during the study period can be a consequence of infections occurring prior to the study: we assume that the seasonal pattern of primary infections repeats over time. We incorporate information from parasitological and entomology studies to gain leverage for estimating the parameters, and take imperfect detection into account. We estimate the force of P vivax primary infections to be 11.5 (10.5, 12.3) for a three-year old child per year and the mean number of relapses per infection to be 4.3 (4.0, 4.6) over 16 months. The peak incidence of relapses occurred in the two month interval following the peak interval for primary infections: the contribution to the force of blood-stage infection from relapses is between 71% and 90% depending on the season. Our estimates contribute to knowledge of the P vivax epidemiology and have implications for the timing of intervention strategies targeting different stages of the life cycle. Plasmodium vivax is the most widespread of the malaria species affecting humans. It has the ability for parasites to lie dormant in liver cells and then to relapse weeks or months later, causing further blood-stage infections and onward transmission. Relapses present a challenge to control and elimination programs. The contribution of relapses to the force of blood-stage infection is not well established. While genotyping can distinguish individual infections, the difficulty lies in the inability to distinguish primary infections (occurring shortly after an infectious mosquito bite) and relapses. This is a gap in the knowledge of the epidemiology of P vivax. We develop a statistical model to tease out and estimate the contributions of primary infections and relapses to the force of blood-stage infection. We use data from a cohort of children in Papua New Guinea with genotyped routine blood samples. The study area has both P vivax and P falciparum malaria: we use the seasonality of P falciparum to estimate the seasonality of P vivax primary infections. We also take into account infections occurring prior to the study period and their subsequent relapses during the study period. We find that approximately 80% of the force of blood-stage infection l is contributed by relapses and that primary infections and relapses have different seasonal patterns. The findings are important to the epidemiology of P vivax and for designing intervention strategies targeting different stages of the parasite life cycle.