High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali.
High Plasmodium falciparum longitudinal prevalence is associated with high multiclonality and reduced clinical malaria risk in a seasonal transmission area of Mali.
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DOI：
10.1371/journal.pone.0170948
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Long CA
中科院分区：
文献类型：
--
作者：
Adomako-Ankomah Y;Chenoweth MS;Durfee K;Doumbia S;Konate D;Doumbouya M;Keita AS;Nikolaeva D;Tullo GS;Anderson JM;Fairhurst RM;Daniels R;Volkman SK;Diakite M;Miura K;Long CA
恶性疟原虫（Pf）持续感染和多克隆性对随后临床疟疾风险的影响已有报道，但这2个参数之间的关系及其对感染临床结局的相对影响尚不清楚。在马里的一个季节性和高传播地区进行了一项纵向队列研究，对500名1-65岁的受试者进行了为期1年的随访。每两周采集一次血样，并对疟疾病例进行诊断和治疗。通过种特异性巢式PCR评估每个个体在每个时间点的Pf感染，并计算每个人的Pf纵向患病率（PfLP，超过1年的Pf阳性样本比例）。使用24-SNP DNA条形码分析在一年内的4个时间点（两个在雨季，两个在旱季）测量Pf感染的多克隆性。PfLP与各时间点的多克隆性呈正相关（所有r≥0.36;所有P≤0.011）。当宿主因素（例如，年龄、性别）、PfLP和多克隆性（在传播季节开始时）一起进行分析，只有年龄增加和高PfLP与临床疟疾发生率降低或疟疾发作次数减少相关（对于两种结果，年龄P<0.001，PfLP P = 0.005）。当同时分析年龄、PfLP和基线Pf阳性率时，即使调整了其他两个因素，高PfLP的影响仍然显著（疟疾发生率P = 0.001，发作次数P<0.001）。除了宿主年龄和基线Pf阳性，这两者都已被报道为临床疟疾风险的重要修饰符，我们的研究结果表明，持续寄生虫携带，但不是基线多克隆性，与临床疾病的风险降低，在这一人群。我们的研究强调了在未来评估临床疟疾风险的研究中考虑重复寄生虫暴露的重要性。
The effects of persistent Plasmodium falciparum (Pf) infection and multiclonality on subsequent risk of clinical malaria have been reported, but the relationship between these 2 parameters and their relative impacts on the clinical outcome of infection are not understood. A longitudinal cohort study was conducted in a seasonal and high-transmission area of Mali, in which 500 subjects aged 1–65 years were followed for 1 year. Blood samples were collected every 2 weeks, and incident malaria cases were diagnosed and treated. Pf infection in each individual at each time point was assessed by species-specific nested-PCR, and Pf longitudinal prevalence per person (PfLP, proportion of Pf-positive samples over 1 year) was calculated. Multiclonality of Pf infection was measured using a 24-SNP DNA barcoding assay at 4 time-points (two in wet season, and two in dry season) over one year. PfLP was positively correlated with multiclonality at each time point (all r≥0.36; all P≤0.011). When host factors (e.g., age, gender), PfLP, and multiclonality (at the beginning of the transmission season) were analyzed together, only increasing age and high PfLP were associated with reduced clinical malaria occurrence or reduced number of malaria episodes (for both outcomes, P<0.001 for age, and P = 0.005 for PfLP). When age, PfLP and baseline Pf positivity were analyzed together, the effect of high PfLP remained significant even after adjusting for the other two factors (P = 0.001 for malaria occurrence and P<0.001 for number of episodes). In addition to host age and baseline Pf positivity, both of which have been reported as important modifiers of clinical malaria risk, our results demonstrate that persistent parasite carriage, but not baseline multiclonality, is associated with reduced risk of clinical disease in this population. Our study emphasizes the importance of considering repeated parasite exposure in future studies that evaluate clinical malaria risk.