Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya.
Malar J. 2021 Sep 17;20(1):371. doi: 10.1186/s12936-021-03905-w.
Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission.
In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals.
The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR.
This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.
随着越来越多的国家接近消除疟疾，疟疾发病率的进一步降低需要识别和治疗携带引起疟疾传播的蚊媒感染疟原虫配子体的无症状个体。在现场调查中评估总寄生虫血症和配子体血症之间的关系，可以深入了解使用敏感的分子方法检测低密度无症状恶性疟原虫感染是否足以检测到大多数具有潜在传播能力的感染个体。
在肯尼亚西部三个社区（Ajigo、Webuye 和 Kapsisywa-Kipsamoite）的横断面调查中，对 1354 名健康儿童和成年人进行了无症状恶性疟原虫感染筛查，采用快速诊断检测、血涂片和针对基因组 DNA 中 varATS 基因的干血斑定量 PCR 检测。还开发了一种针对女性和男性配子体基因（pfs25、pfs230p）、一种转录模式仅限于无性血期的基因（piesp2）和人类 GAPDH 的多重定量逆转录酶 PCR 检测方法，以确定寄生虫血症个体中的总寄生虫和配子体密度。
在 Ajigo（42%），随后是 Webuye（10%），检测到 varATS 可检测的无症状感染的流行率最高。在 Kapsisywa 仅检测到两个感染。在 Kipsamoite 未检测到感染。在所有社区中，11-15 岁的儿童占总感染和亚微观无症状感染的最大比例。在年龄较小的群体中，大多数感染可通过显微镜检测到，而 68%的无症状感染成年人（>21 岁）有亚微观寄生虫血症。与基于 varATS 的检测相比，piesp2 衍生的寄生虫密度与显微镜确定的寄生虫密度相关性较差。一般来说，随着 varATS 衍生的总寄生虫血症的增加，男性和女性配子体血症也随之增加。具有传播潜力的个体中，有相当大的比例（41.7%）的 qPCR 估计寄生虫密度低于显微镜检测的下限，但高于 varATS qPCR 的检测下限。
本研究评估了具有不同传播强度的三个社区的寄生虫血症和配子体血症，结果表明在恶性疟原虫无症状携带者中存在大量亚潜伏感染的传染源。需要进行实验研究以确定像 Ajigo 和 Webuye 这样的社区中的低密度感染是否对疟疾传播有重大贡献。
