Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.
Developing sero-diagnostic tests to facilitate Plasmodium vivax Serological Test-and-Treat approaches: modeling the balance between public health impact and overtreatment.
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DOI：
10.1186/s12916-022-02285-5
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发表时间：
2022-03-18
期刊：
影响因子：
9.3
通讯作者：
White MT
中科院分区：
文献类型：
--
作者：
Obadia T;Nekkab N;Robinson LJ;Drakeley C;Mueller I;White MT
消灭间日疟原虫需要瞄准隐藏的肝脏阶段催眠虫库。这就需要新的干预措施来平衡减少间日疟传播的益处和用可能诱导溶血的药物过度治疗某些个体的风险。通过测量一组间日疟原虫抗原的抗体，血清学检测和治疗策略（PvSeroTAT）可以识别近期血液阶段感染的个体，这些个体可能携带催眠虫，并将其作为根治的目标。这提供了一种潜在的解决方案，以选择性地治疗间日疟原虫水库与8-氨基喹啉。 PvSeroTAT可以以约80%的灵敏度和特异性识别可能的催眠虫携带者。将诊断试验的灵敏度和特异性（范围为50-100%）纳入间日疟传播的数学模型，以探讨它们如何影响涉及杀催眠虫方案的不同PvSeroTAT策略的风险和获益。风险被衡量为过度治疗率和效益作为减少社区层面的间日疟传播。在诊断灵敏度和特异性的广泛组合中，PvSeroTAT比血液阶段质量筛查和治疗策略有效得多，仅略低于质量药物给药。决定PvSeroTAT策略获益的关键测试特征是诊断灵敏度，较高的值导致更多的催眠子携带者得到有效治疗，间日疟传播减少更多。风险的关键决定因素是诊断特异性：较高的特异性确保了较低比例的未感染个体不必要地接受伯氨喹治疗。这些关系在中度和低度传播环境中均保持（qPCR流行率10%和2%）。提高治疗功效和依从性可以部分弥补较低的测试性能。多轮PvSeroTAT与较低性能的测试可能会导致类似或更高的减少间日疟传播比更少的轮与较高性能的测试，虽然有较高的过度治疗率。在目前的性能下，预计PvSeroTAT是一种安全有效的选择，可靶向催眠虫储库消除间日疟。间日疟原虫血清诊断测试应旨在实现高性能和现场易用性。因此，为这种发展提供信息的目标产品概况应反映影响、过度治疗和方案实施的便利性之间的权衡。在线版本包含补充材料，可通过10.1186/s12916-022-02285-5获得。
Eliminating Plasmodium vivax will require targeting the hidden liver-stage reservoir of hypnozoites. This necessitates new interventions balancing the benefit of reducing vivax transmission against the risk of over-treating some individuals with drugs which may induce haemolysis. By measuring antibodies to a panel of vivax antigens, a strategy of serological-testing-and-treatment (PvSeroTAT) can identify individuals with recent blood-stage infections who are likely to carry hypnozoites and target them for radical cure. This provides a potential solution to selectively treat the vivax reservoir with 8-aminoquinolines. PvSeroTAT can identify likely hypnozoite carriers with ~80% sensitivity and specificity. Diagnostic test sensitivities and specificities ranging 50–100% were incorporated into a mathematical model of vivax transmission to explore how they affect the risks and benefits of different PvSeroTAT strategies involving hypnozoiticidal regimens. Risk was measured as the rate of overtreatment and benefit as reduction of community-level vivax transmission. Across a wide range of combinations of diagnostic sensitivity and specificity, PvSeroTAT was substantially more effective than bloodstage mass screen and treat strategies and only marginally less effective than mass drug administration. The key test characteristic determining of the benefit of PvSeroTAT strategies is diagnostic sensitivity, with higher values leading to more hypnozoite carriers effectively treated and greater reductions in vivax transmission. The key determinant of risk is diagnostic specificity: higher specificity ensures that a lower proportion of uninfected individuals are unnecessarily treated with primaquine. These relationships are maintained in both moderate and low transmission settings (qPCR prevalence 10% and 2%). Increased treatment efficacy and adherence can partially compensate for lower test performance. Multiple rounds of PvSeroTAT with a lower performing test may lead to similar or higher reductions in vivax transmission than fewer rounds with a higher performing test, albeit with higher rate of overtreatment. At current performance, PvSeroTAT is predicted to be a safe and efficacious option for targeting the hypnozoite reservoir towards vivax elimination. P. vivax sero-diagnostic tests should aim for both high performance and ease of use in the field. The target product profiles informing such development should thus reflect the trade-offs between impact, overtreatment, and ease of programmatic implementation. The online version contains supplementary material available at 10.1186/s12916-022-02285-5.
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影响因子：
3.8
作者：
Rosado J;White MT;Longley RJ;Lacerda M;Monteiro W;Brewster J;Sattabongkot J;Guzman-Guzman M;Llanos-Cuentas A;Vinetz JM;Gamboa D;Mueller I
通讯作者：
Mueller I
影响因子：
4.5
作者：
Kheang, Soy Ty;Sovannaroth, Siv;Kak, Neeraj
通讯作者：
Kak, Neeraj
影响因子：
7.7
作者：
White MT;Karl S;Battle KE;Hay SI;Mueller I;Ghani AC
通讯作者：
Ghani AC
影响因子：
16.6
作者：
White MT;Walker P;Karl S;Hetzel MW;Freeman T;Waltmann A;Laman M;Robinson LJ;Ghani A;Mueller I
通讯作者：
Mueller I
影响因子：
3.8
作者：
Satyagraha AW;Sadhewa A;Baramuli V;Elvira R;Ridenour C;Elyazar I;Noviyanti R;Coutrier FN;Harahap AR;Baird JK
通讯作者：
Baird JK