A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study).
A clinical study to optimise a sand fly biting protocol for use in a controlled human infection model of cutaneous leishmaniasis (the FLYBITE study).
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DOI：
10.12688/wellcomeopenres.16870.1
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发表时间：
2021
影响因子：
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通讯作者：
Lacey CJN
中科院分区：
文献类型：
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作者：
Parkash V;Ashwin H;Sadlova J;Vojtkova B;Jones G;Martin N;Greensted E;Allgar V;Kamhawi S;Valenzuela JG;Layton AM;Jaffe CL;Volf P;Kaye PM;Lacey CJN
背景：利什曼病是一种由白蛉传播的全球性重要但被忽视的寄生虫病。随着新的候选疫苗在临床或附近，一个控制的人类挑战模型（CHIM）使用自然白蛉挑战将提供一种方法，早期评估预防效果。 研究方法：我们评估了人类志愿者暴露于两种利什曼原虫的天然载体帕帕塔西白蛉或杜博斯奇白蛉叮咬后的叮咬频率和不良反应。招募了12名健康受试者（平均年龄40.2 ± 11.8岁），他们没有前往L.主要传播白蛉的情况很普遍。参与者以1：1的比例被分配到任一媒介，并在定制的叮咬室中暴露于五只雌性白蛉30分钟。记录咬频以确认采集了血粉。使用视觉模拟量表（VAS）、临床检查和血液生化监测参与者的反应和安全性结局。随后进行了焦点小组讨论，以探讨参与者的可接受性。 结果如下：所有参与者至少有一次成功的沙蝇叮咬，没有报告任何严重不良事件，沙蝇叮咬后第21天的中位VAS评分为0-1/10。对白蛉的相应评估证实，对于每名参与者，至少1/5的白蛉成功地吸食了血粉（每名参与者的总体平均叮咬次数为3.67±1.03次）。帕帕塔斯白蛉和杜博斯白蛉对人类参与者的5只白蛉叮咬次数无显著差异（每名参与者3.3±0.81对3.00±1.27次叮咬; p=0.56）。 在两个焦点小组（每组n=5），主题相关的积极参与者报告的经验，被咬伤和整体研究，确定。 结论：这些结果验证了一个方案，实现成功的沙蝇叮咬人类是安全的，耐受性良好，可接受的参与者。 Clinicaltrials.gov注册：NCT 03999970（27/06/2019）
Background: Leishmaniasis is a globally important yet neglected parasitic disease transmitted by phlebotomine sand flies. With new candidate vaccines in or near the clinic, a controlled human challenge model (CHIM) using natural sand fly challenge would provide a method for early evaluation of prophylactic efficacy. Methods : We evaluated the biting frequency and adverse effects resulting from exposure of human volunteers to bites of either Phlebotomus papatasi or P. duboscqi, two natural vectors of Leishmania major. 12 healthy participants were recruited (mean age 40.2 ± 11.8 years) with no history of significant travel to regions where L. major-transmitting sand flies are prevalent. Participants were assigned to either vector by 1:1 allocation and exposed to five female sand flies for 30 minutes in a custom biting chamber. Bite frequency was recorded to confirm a bloodmeal was taken. Participant responses and safety outcomes were monitored using a visual analogue scale (VAS), clinical examination, and blood biochemistry. Focus groups were subsequently conducted to explore participant acceptability. Results: All participants had at least one successful sand fly bite with none reporting any serious adverse events, with median VAS scores of 0-1/10 out to day 21 post-sand fly bite. Corresponding assessment of sand flies confirmed that for each participant at least 1/5 sand flies had successfully taken a bloodmeal (overall mean 3.67±1.03 bites per participant). There was no significant difference between P. papatasi and P. duboscqi in the number of bites resulting from 5 sand flies applied to human participants (3.3±0.81 vs 3.00±1.27 bites per participant; p=0.56) . In the two focus groups (n=5 per group), themes relating to positive participant-reported experiences of being bitten and the overall study, were identified. Conclusions: These results validate a protocol for achieving successful sand fly bites in humans that is safe, well-tolerated and acceptable for participants. Clinicaltrials.gov registration: NCT03999970 (27/06/2019)