Institute of Tropical Medicine, Eberhard Karls University Tübingen, Tübingen, Germany.
Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné, Gabon; Centre for Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; German Center for Infection Research, Partner Site Hamburg-Borstel-Lübeck-Riems, Germany.
Int J Infect Dis. 2024 Jun;143:107013. doi: 10.1016/j.ijid.2024.107013. Epub 2024 Mar 16.
We investigated the diversity and dynamics of Plasmodium infection in serially collected samples from asymptomatic participants of a clinical trial assessing the efficacy and safety of ivermectin in Gabon. We checked whether the baseline sample reflected the P. falciparum genotype and Plasmodium species diversity seen over 7 days of follow-up.
Blood samples were collected at inclusion, every 8 hours until hour 72, daily until day 7, and on day 14. Plasmodium species was determined by qPCR and pfmsp1 length polymorphism was assessed for P. falciparum genotyping.
In 17/48 (35%) individuals, all pfmsp1 genotypes identified during the assessed period were detected at baseline; in 31/48 (65%), new genotypes were found during follow-up. Additional sampling at hour 24 allowed the identification of all genotypes seen over 7 days in 50% of the individuals. Ivermectin did not impact the genotype dynamics. Mixed Plasmodium spp. infections were detected in 28/49 (57%) individuals at baseline, and detection of non-falciparum infections during follow-up varied.
Our results reveal complex intra-host dynamics of P. falciparum genotypes and Plasmodium species and underscore the importance of serial sampling in clinical trials for antimalarial drugs with asymptomatically P. falciparum-infected individuals. This might allow a more accurate identification of genotypes in multiple infections, impacting the assessment of drug efficacy.
我们调查了在加蓬进行的评估伊维菌素疗效和安全性的临床试验中，无症状参与者连续采集样本中疟原虫感染的多样性和动态变化。我们检查了基线样本是否反映了在 7 天随访期间观察到的恶性疟原虫基因型和疟原虫物种多样性。
在纳入时、每 8 小时采集一次血液样本，直至第 72 小时，每天采集一次直至第 7 天，然后在第 14 天采集。通过 qPCR 确定疟原虫物种，评估恶性疟原虫 pfmsp1 长度多态性进行基因分型。
在 17/48（35%）个体中，在评估期间发现的所有 pfmsp1 基因型均在基线时被检测到；在 31/48（65%）个体中，在随访期间发现了新的基因型。在第 24 小时进行额外的采样，使得在 50%的个体中能够识别出在 7 天内观察到的所有基因型。伊维菌素对基因型动态没有影响。在基线时，28/49（57%）个体中检测到混合疟原虫感染，在随访期间检测到非恶性疟原虫感染的情况各不相同。
我们的研究结果揭示了恶性疟原虫基因型和疟原虫物种在宿主内的复杂动态变化，并强调了在无症状恶性疟原虫感染个体中进行临床试验时，连续采样对评估抗疟药物疗效的重要性。这可能会更准确地识别多重感染中的基因型，从而影响药物疗效的评估。
