Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study.
Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study.
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DOI：
10.1016/s1473-3099(21)00072-4
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发表时间：
2021-11
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影响因子：
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通讯作者：
Bousema T
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作者：
Andolina C;Rek JC;Briggs J;Okoth J;Musiime A;Ramjith J;Teyssier N;Conrad M;Nankabirwa JI;Lanke K;Rodriguez-Barraquer I;Meerstein-Kessel L;Arinaitwe E;Olwoch P;Rosenthal PJ;Kamya MR;Dorsey G;Greenhouse B;Drakeley C;Staedke SG;Bousema T
症状性疟疾病例仅占所有疟原虫属感染的一小部分。许多感染者是无症状的，持续无症状的恶性疟原虫感染在地方性环境中很常见。我们的目的是量化有症状和无症状感染的贡献，恶性疟原虫在托罗罗，乌干达的传播。我们在乌干达的托罗罗区进行了一项纵向观察性队列研究。我们从该地区随机选择的家庭中招募了所有年龄段的参与者。如果选定的家庭有不超过9名永久居民和至少两名10岁以下的成员，并且该家庭是他们的主要居住地，并且他们同意在任何发热事件时前往研究诊所并避免在研究之外使用抗疟药物，则参与者有资格参加研究。通过持续被动监测症状性感染的发生率对参与者进行随访;在基线和每4周一次的常规访视时进行常规评估（即标准化临床评价和血液样本），持续2年。分别使用定量PCR（qPCR）、定量逆转录酶PCR（qRT-PCR）和扩增子深度测序对恶性疟原虫密度、配子体密度和遗传组成进行分子测定。还进行了膜摄食测定以评估对蚊子的感染性。针对有症状感染、无症状但显微镜下检测到的感染和无症状但qPCR检测到的感染，以及年龄小于5岁、5-15岁和16岁或以上的年龄组，估计不同人群对传染性储库的贡献。在2017年10月4日至2019年10月31日期间，从80个随机选择的家庭中招募了531人，并随访了2年。在基线时，531名参与者中有28名（5.3%）通过显微镜检测到恶性疟原虫，另外64名（12.1%）通过qPCR检测到恶性疟原虫，此后恶性疟原虫数量下降。在对107只个体进行的538次蚊子喂养实验中，37404只蚊子中有446只（1.2%）被感染，蚊子感染率与配子体密度密切相关（β= 2.11，95%CI 1.62 - 2.67; p<0.0001）。考虑到感染的传播性及其相对频率，估计的人类感染宿主主要包括无症状的显微镜检测到的感染（83.8%），其次是无症状的亚显微镜感染（15.6%）和有症状的感染（0.6%）。5-15岁儿童占感染宿主的一半以上（58.7%）; 5岁以下（25.8%）和16岁或以上（15.6%）的个体贡献较少。在多次蚊子喂养试验后，446只感染蚊子中有279只（62.6%）来自4名儿童的样本。无症状感染者是疟疾传播的重要驱动因素。学龄儿童占所有蚊子感染病例的一半以上，少数无症状儿童具有高度传染性。在病媒得到有效控制的地区，针对学龄儿童采取针对人口的干预措施，可进一步减少传播。美国国立卫生研究院、比尔和梅林达·盖茨基金会以及欧洲研究理事会。
Symptomatic malaria cases reflect only a small proportion of all Plasmodium spp infections. Many infected individuals are asymptomatic, and persistent asymptomatic Plasmodium falciparum infections are common in endemic settings. We aimed to quantify the contribution of symptomatic and asymptomatic infections to P falciparum transmission in Tororo, Uganda. We did a longitudinal, observational cohort study in Tororo district, Uganda. We recruited participants of all ages from randomly selected households within this district. Participants were eligible if the selected household had no more than nine permanent residents and at least two members younger than 10 years, and the household was their primary residence, and they agreed to come to the study clinic for any fever episode and avoid antimalarial medications outside the study. Participants were followed-up by continuous passive surveillance for the incidence of symptomatic infections; routine assessments (ie, standardised clinical evaluation and blood samples) were done at baseline and at routine visits every 4 weeks for 2 years. P falciparum parasite density, gametocyte density, and genetic composition were determined molecularly using quantitative PCR (qPCR), quantitative reverse transcriptase PCR (qRT-PCR), and amplicon deep sequencing, respectively. Membrane feeding assays were also done to assess infectivity to mosquitoes. The contribution of different populations to the infectious reservoir was estimated for symptomatic infections, asymptomatic but microscopically detected infections, and asymptomatic but qPCR-detected infections; and for age groups younger than 5 years, 5–15 years, and 16 years or older. Between Oct 4, 2017, and Oct 31, 2019, 531 individuals were enrolled from 80 randomly selected households and were followed-up for 2 years. At baseline, P falciparum was detected in 28 (5·3%) of 531 participants by microscopy and an additional 64 (12·1%) by qPCR and declined thereafter. In 538 mosquito feeding experiments on 107 individuals, 446 (1·2%) of 37 404 mosquitoes became infected, with mosquito infection rates being strongly associated with gametocyte densities (β=2·11, 95% CI 1·62–2·67; p<0·0001). Considering both transmissibility of infections and their relative frequency, the estimated human infectious reservoir consisted primarily of asymptomatic microscopy-detected infections (83·8%), followed by asymptomatic submicroscopic infections (15·6%), and symptomatic infections (0·6%). Children aged 5–15 years accounted for more than half of the infectious reservoir (58·7%); individuals younger than 5 years (25·8%) and those 16 years or older (15·6%) contributed less. Samples from four children contribued to 279 (62·6%) of 446 infected mosquitoes after multiple mosquito-feeding assays. Individuals with asymptomatic infections were important drivers of malaria transmission. School-aged children contributed to more than half of all mosquito infections, with a small minority of asymptomatic children being highly infectious. Demographically targeted interventions, aimed at school-aged children, could further reduce transmission in areas under effective vector control. US National Institutes of Health, Bill & Melinda Gates Foundation, and the European Research Council.