Liver fluke (Opisthorchis viverrini) worm burdens and egg counts from humans in Thailand and Lao PDR

Helminth transmission and morbidity are dependent on the number of mature parasites within a host, however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per-worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini, which infects approximately ten million people across Southeast Asia, by analysing five epidemiological surveys (n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that > 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is non–linear and strongly influenced by parasite aggregation.

寄生蠕虫的传播与发病情况取决于宿主体内成熟寄生虫的数量，但多数自然感染病例无法直接观测到成虫。因此，核心挑战在于如何将粪便虫卵计数（faecal egg counts）等常规诊断手段与宿主实际的蠕虫荷量建立关联。这一关联的构建会受到两大因素的干扰：一是密度依赖性繁殖力（density-dependent fecundity）——即单条蠕虫的产卵量会因高荷量下的虫体拥挤而降低；二是寄生虫的偏态分布（skewed distribution）特征——多数寄生蠕虫聚集在少数宿主个体中。本研究以致癌性肝吸虫（carcinogenic liver fluke）麝猫后睾吸虫（Opisthorchis viverrini）为研究对象，该寄生虫在东南亚地区感染约1000万人；我们通过分析5项可采集到成虫肝吸虫的流行病学调查数据（样本量n=641）来解答上述问题。借助机理模型（mechanistic model）开展分析后，我们发现不同地理种群的寄生虫繁殖力存在差异：泰国与老挝的调查数据呈现出截然不同的产卵量与密度依赖模式。由于宿主粪便中检出虫卵的概率随宿主体内成熟寄生虫数量增加而升高，我们将诊断灵敏度（diagnostic sensitivity）量化为蠕虫荷量的函数；结果显示，在接近疾病消除的社区中，超过50%的病例会被误诊为假阴性（false negative）。最后，我们证实常规诊断检测得到的观测患病率与真实患病率之间呈非线性关系，且该关系会受到寄生虫聚集分布特征的强烈影响。