Assessing the daily natural history of asymptomatic Plasmodium infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study.

Assessing the daily natural history of asymptomatic Plasmodium infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study.
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DOI:
10.1016/s2666-5247(23)00262-8
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发表时间:
2024-01
期刊:
影响因子:
38.2
通讯作者:
Murphy, Sean C.
Murphy, Sean C.
中科院分区:
生物学1区
文献类型:
--
作者:
Hergott, Dianna E. B.;Owalla, Tonny J.;Staubus, Weston J.;Seilie, Annette M.;Chavtur, Chris;Balkus, Jennifer E.;Apio, Bernadette;Lema, Jimmy;Cemeri, Barbara;Akileng, Andrew;Chang, Ming;Egwang, Thomas G.;Murphy, Sean C.

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低密度无症状疟原虫感染在流行地区流行,但对其自然历史知之甚少。这些感染的轨迹及其波动到无法检测到的密度的倾向会影响临床试验和实地研究的检测。我们的目标是对高传播地区29天内这些感染的自然病史进行分类。在这项纵向队列研究中,我们在乌干达Katakwi地区招募了健康、无疟疾症状、不发烧的成年人(18-59岁)和年龄较大的儿童(8-17岁),他们在快速诊断测试中疟原虫感染呈阴性。参与者被要求每天自行收集一个干血点(DBS),最多持续29天。我们排除了怀孕或服用抗疟疾药物的人。在每周的门诊访问中,工作人员收集了DBS和4ml静脉血样本。我们采用疟原虫18S rRNA定量RT-PCR (qRT-PCR)分析DBSs。我们根据感染类型将DBS分为阴性、恶性疟原虫、非恶性疟原虫或混合感染。我们绘制了每个参与者随时间的感染类型,并将感染轨迹分为阴性、新感染、清除感染、慢性感染或不确定感染。为了估计单时间点采样的效果,我们计算了每个研究日的每日患病率,并估计了如果减少采样频率,在我们的人群中将检测到的感染数量。在2021年4月9日至5月20日期间,128名研究参与者(40名男性成人,60名女性成人,12名男性儿童和16名女性儿童)收集了3577份DBSs。2287例(64%)DBSs为阴性,751例(21%)为恶性疟原虫阳性,507例(14%)为非恶性疟原虫阳性,32例(1%)为混合感染。人群中每日疟原虫流行率从基线时的45.3% (95% CI 36.6 - 54.1)到第24天的30.3%(21.9 - 38.6)不等。每隔一天采样可检出39例恶性疟原虫中37例(95%)和41例非恶性疟原虫感染中35例(85%),而每周采样可检出35例(90%)恶性疟原虫感染和31例(76%)非恶性疟原虫感染。在低密度无症状疟原虫感染中,寄生虫的动态和种类是高度可变的。每隔一天或每3天采样检测到的感染比例与每日采样相似,而每周一次或更少频率的检测可能会错误分类多达三分之一的感染。即使使用高度敏感的诊断方法,单时间点测试也可能对个体的真实感染状态进行错误分类。美国国立卫生研究院和比尔及梅林达·盖茨基金会。
Low-density asymptomatic Plasmodium infections are prevalent in endemic areas, but little is known about their natural history. The trajectories of these infections and their propensity to fluctuate to undetectable densities can affect detection in clinical trials and field studies. We aimed to classify the natural history of these infections in a high transmission area over 29 days. In this longitudinal cohort study, we enrolled healthy, malaria-asymptomatic, afebrile, adults (age 18–59 years) and older children (age 8–17 years) in Katakwi District, Uganda, who were negative for Plasmodium infection on rapid diagnostic tests. Participants were instructed to self-collect one dried blood spot (DBS) per day for a maximum of 29 days. We excluded people if they were pregnant or taking antimalarials. During weekly clinic visits, staff collected a DBS and a 4 mL sample of venous blood. We analysed DBSs by Plasmodium 18S rRNA quantitative RT-PCR (qRT-PCR). We classified DBS by infection type as negative, P falciparum, non-P falciparum, or mixed. We plotted infection type over time for each participant and categorised trajectories as negative, new, cleared, chronic, or indeterminate infections. To estimate the effect of single timepoint sampling, we calculated the daily prevalence for each study day and estimated the number of infections that would have been detected in our population if sampling frequency was reduced. Between April 9 and May 20, 2021, 3577 DBSs were collected by 128 (40 male adults, 60 female adults, 12 male children, and 16 female children) study participants. 2287 (64%) DBSs were categorised as negative, 751 (21%) as positive for P falciparum, 507 (14%) as positive for non-P falciparum, and 32 (1%) as mixed infections. Daily Plasmodium prevalence in the population ranged from 45·3% (95% CI 36·6–54·1) at baseline to 30·3% (21·9–38·6) on day 24. 37 (95%) of 39 P falciparum and 35 (85%) of 41 non-P falciparum infections would have been detected with every other day sampling, whereas, with weekly sampling, 35 (90%) P falciparum infections and 31 (76%) non-P falciparum infections would have been detected. Parasite dynamics and species are highly variable among low-density asymptomatic Plasmodium infections. Sampling every other day or every 3 days detected a similar proportion of infections as daily sampling, whereas testing once per week or even less frequently could misclassify up to a third of the infections. Even using highly sensitive diagnostics, single timepoint testing might misclassify the true infection status of an individual. US National Institutes of Health and Bill and Melinda Gates Foundation.
DOI: 10.1186/s12936-021-03907-8
发表时间: 2021-10-07
期刊: Malaria journal
影响因子: 3
作者:
Chang M;Johnston S;Seilie AM;Hergott D;Murphy SC
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DOI: 10.1186/s12936-022-04239-x
发表时间: 2022-07-14
期刊: MALARIA JOURNAL
影响因子: 3
作者:
Hergott, Dianna E. B.;Owalla, Tonny J.;Balkus, Jennifer E.;Apio, Bernadette;Lema, Jimmy;Cemeri, Barbara;Akileng, Andrew;Seilie, Annette M.;Chavtur, Chris;Staubus, Weston;Chang, Ming;Egwang, Thomas G.;Murphy, Sean C.
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DOI: 10.3389/fimmu.2022.1003452
发表时间: 2022
影响因子: 7.3
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DOI: 10.1186/s12936-022-04076-y
发表时间: 2022-03-18
期刊: Malaria journal
影响因子: 3
作者:
Abidha CA;Amoako YA;Nyamekye RK;Bedu-Addo G;Grziwotz F;Mockenhaupt FP;Telschow A;Danquah I
通讯作者: Danquah I