Background Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. Methods We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. Results We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. Conclusions Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.

中文翻译：

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无症状感染的幕后黑手阻碍了被忽视的热带病的控制：模型分析

背景 被忽视的热带病导致低收入人群发病率和死亡率相当高。国际社会的努力减轻了全球负担，但传播持续存在，而且基于病例发现的干预措施很少针对无症状个体。方法 我们开发了一个通用数学模型框架，用于分析印度次大陆内脏利什曼病 (VL)、冈比亚昏睡病 (gHAT) 和恰加斯病的动态，并用它来评估后来发展为疾病的无症状者的可能贡献。有症状者）和无症状者（无症状者）维持感染。针对这三种疾病模拟了合理的干预措施，包括主动筛查、病媒控制和缩短检测时间。结果我们发现，恰加斯病毒和 gHAT 对传播的无症状贡献率较高，以及 VL 的基本繁殖数明显较高，可能会破坏长期控制。然而，治疗一些无症状的南美锥虫病和 gHAT 的能力应该会使它们更加可控，尽管由于这些疾病的动态发展缓慢而需要相对较长的时间。对于 VL，现有疗法的毒性意味着目前无法治疗无症状人群，但将症状治疗和病媒控制相结合可以快速减少传播。结论 尽管自然史存在不确定性，但似乎已经存在一个相对较好的消除 gHAT 的干预措施工具箱，并且恰加斯可能需要改进诊断及其使用，以更好地针对症状前。 VL 的情况不太清楚，可以通过额外的经验数据来改进模型预测。然而，可能必须改进干预措施才能成功消除这种疾病。