Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study.
Tracking antimalarial drug resistance using mosquito blood meals: a cross-sectional study.
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DOI：
10.1016/s2666-5247(23)00063-0
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发表时间：
2023-06
期刊：
影响因子：
38.2
通讯作者：
Parikh, Sunil
中科院分区：
文献类型：
--
作者：
Ehrlich, Hanna Y.;Some, Fabrice;Bazie, Thomas;Ebou, Catherine Neya;Dembele, Estelle Lotio;Balma, Richard;Goodwin, Justin;Wade, Martina;Bei, Amy K.;Ouedraogo, Jean-Bosco;Foy, Brian;Dabire, Roch K.;Parikh, Sunil
需要建立覆盖广泛地域的强有力的监测系统，以发现非洲大陆抗疟药物抗药性的报告并作出反应。我们的目的是评估使用吸血蚊子（xenomonitoring）进行快速监测的实用性和可行性的分子标记与耐药性在人群中。我们在2018年10月10日至2019年9月17日期间在布基纳法索西南部的两个雨季和临时旱季进行了三次横断面调查。我们收集了人类血液样本和居住在七个村庄区域的家庭集群中的吸血蚊子。采用超灵敏定量PCR对样本进行恶性疟原虫评估，对两个药物敏感性降低的标志物pfmdr1 256 A>T（Asn 86 Tyr）和pfcrt 227 A>C（Lys 76 Thr）进行基因分型，并对四个克隆性标志物进行测序。我们使用10%的等效性界限评估统计等效性。我们在1483份人类血液样本中发现了551例感染（平均感染复数[MOI] 1.94，SD 1.47），在2151份蚊子血餐中发现了346例感染（平均MOI 2.2，SD 1.67）。pfmdr1 Asn86 Tyr在人类样本中的频率在调查1中为4%，在调查2中为2%，在调查3中为12%，在蚊子血餐中的频率在调查1中为3%，在调查2中为0%，在调查3中为8%。在耐受性为0.10的范围内，调查1和2中的宿主间频率在统计学上相等（p<0.0001），但调查3中的宿主间频率不同（p= 0.062）。pfcrt Lys76Thr的频率在调查1中为16%，在调查2中为55%，在调查3中为11%，在调查1中为40%，在调查2中为72%，在调查3中为13%，并且宿主间频率仅在调查3中相等（p= 0.032），耐受性为0.10。在模拟中，蚊子的多种但非偏好的进食行为降低了宿主之间频率估计的准确性，特别是对于以较高频率循环的标记。蚊子血粉和人类中的分子标记物表现出类似的时间趋势，但在所有情况下，频率在统计上并不相等。需要做更多的工作来确定差异的经验和实用阈值。在监测不足的地区，异种监测可能是一种有效的工具，可以迅速提供关于新出现的抗疟药物耐药性的信息。国家过敏和传染病研究所。
Strong surveillance systems with wide geographic coverage are needed to detect and respond to reports of antimalarial drug resistance on the African continent. We aimed to assess the utility and feasibility of using blood-fed mosquitos (xenomonitoring) to conduct rapid surveillance of molecular markers associated with resistance in human populations. We conducted three cross-sectional surveys in two rainy seasons and the interim dry season in southwest Burkina Faso between Oct 10, 2018, and Sept 17, 2019. We collected human blood samples and blood-fed mosquitos residing in household clusters across seven village sectors. Samples were assessed for Plasmodium falciparum with ultrasensitive quantitative PCR, genotyped for two markers of reduced drug susceptibility, pfmdr1 256A>T (Asn86Tyr) and pfcrt 227A>C (Lys76Thr), and sequenced for four markers of clonality. We assessed statistical equivalence using a 10% margin of equivalence. We identified 551 infections in 1483 human blood samples (mean multiplicity of infection [MOI] 1·94, SD 1·47) and 346 infections in 2151 mosquito blood meals (mean MOI 2·2, SD 1·67). The frequency of pfmdr1 Asn86Tyr was 4% in survey 1, 2% in survey 2, and 12% in survey 3 in human samples, and 3% in survey 1, 0% in survey 2, and 8% in survey 3 in mosquito blood meals, and inter-host frequencies were statistically equivalent in surveys 1 and 2 (p<0·0001) but not Survey 3 (p=0·062) within a tolerability of 0·10. The frequency of pfcrt Lys76Thr was 16% in survey 1, 55% in survey 2, and 11% in survey 3 in humans and 40% in survey 1, 72% in survey 2, and 13% in survey 3 in mosquitos, and inter-host frequencies were equivalent in survey 3 only (p=0·032) within a tolerability of 0·10. In simulations, multiple but not preferential feeding behaviour in mosquitos reduced the accuracy of frequency estimates between hosts, particularly for markers circulating at higher frequencies. Molecular markers in mosquito blood meals and in humans exhibited similar temporal trends but frequencies were not statistically equivalent in all scenarios. More work is needed to determine empirical and pragmatic thresholds of difference. Xenomonitoring might be an efficient tool to provide rapid information on emerging antimalarial resistance in regions with insufficient surveillance. National Institute of Allergy and Infectious Diseases.
影响因子：
3
作者：
Mharakurwa S;Sialumano M;Liu K;Scott A;Thuma P
通讯作者：
Thuma P