基因组监测通常用于跟踪病毒和细菌病原体，例如鉴定SARS-COV-2的新变体，并将食源性疾病的暴发与特定产品和地理区域联系起来。类似的工具可以加速进步，以消除流行的被忽视的热带疾病血吸虫病但历史上一直难以发展和use for such multicellular parasites. Parasites have larger genomes and more complex life cycles than viruses and bacteria, making it more technically challenging and expensive to sequence and analyze their DNA at scale. But recent advances in sequencing technologies have made whole genome sequencing increasingly affordable for population-based studies of schistosomes and other complex parasites. These advances create new opportunities to address key threats to schistosomiasis control and tailor interventions to local contexts.
Threats to schistosomiasis control
在过去的二十年中，血吸虫病控制工作集中在通过大众药物管理（MDA）扩大治疗范围。这些计划降低了发病率和感染强度，但尚未实现世界卫生组织（WHO）的控制和消除目标。实际上，血吸虫病仍然影响全球2亿人，导致疾病和残疾破坏身体的生长，认知能力发展和劳动生产力。它在确定的脊椎动物宿主和中间蜗牛宿主之间的传播在某些地区持续存在尽管治疗计划和在其他领域重新出现以前被控制的地方。我们尚不完全理解为什么这样做。可能是动物在传输周期中起作用不足，人们的运动将寄生虫重新引入了正在进行控制工作的地方，或者MDA运动没有达到足够的人来中断传播。我们需要新的工具来填补这些空白，并解决不同的社会和环境过程如何破坏MDA计划并威胁其成功。最近评论论文概述了整个基因组方法如何揭示血吸虫病持久性和重新出现的机制。在里面，我们描述对血吸虫病控制的两个关键威胁，我们对它们的了解以及对基因组数据的周到使用如何在不同情况下与MDA一起实施的干预措施如何告知。
These threats – the contributions of non-human definitive host species to human infection and the importance of locally-acquired versus imported infections – are key to understanding the contexts in which MDA is sufficient and when additional interventions are necessary. We argue that MDA programs are likely to be sufficient only when infections are found primarily in people (with limited involvement of non-human definitive hosts) and are acquired locally (rather than imported from elsewhere). In contrast, frequent involvement of non-human definitive hosts, such as livestock or wildlife, may undermine MDA programs by allowing parasites to persist in species that are not the targets of control programs. This can be addressed by monitoring and treating relevant animal species. Similarly, the movement of infected people, animals, and snail hosts can threaten the success of MDA by introducing parasites from outside a program’s catchment area. This threat can be mitigated by supplementing MDA with environmental interventions (such as snail control and the provision water and sanitation infrastructure) to reduce exposure and contamination and the risk of re-infection after treatment.
人畜共形传播
Historically, questions related to the contributions of non-human definitive hosts and parasite importation in the transmission of schistosomiasis have been addressed with a variety of epidemiologic, ecological, and genetic methods. This work has revealed how the role of non-human definitive hosts varies across schistosome species and geographic contexts and how parasite importation can创建新的传输焦点也sustain existing foci of transmission，即使在控制努力的情况下。它还揭示了与血吸虫血吸虫病感染人类和牲畜的复合物可以彼此交配，form viable hybrids，可能使控制努力变得复杂。过去这些研究中使用的遗传工具最常使用的微卫星（MSAT），快速突变的非编码DNA的简短重复序列以及在线粒体（mtDNA）中发现的基因的测序和真核生物细胞的核糖体（rDNA），这些基因是真核生物细胞的，这些细胞是易于放大和序列，因为它们出现在数量上。
尽管MSAT和mtDNA/rDNA标记在血吸虫的遗传研究中广泛采用，但它们在可以提供的信息中受到限制。MSAT研究可以识别相关性的近似模式，但由于它们通常仅包含一些非编码DNA的小部分（代表了基因组的一小部分），所以它们并没有透露寄生虫如何适应其环境。复制和比较跨实验室的MSAT分析也很难。同样，mtDNA/rDNA标记可以用于“棒编码”或识别存在哪种螺旋体物种，但它们的变化水平相对较低，这限制了它们检测寄生虫之间相关性的能力，或者它们如何对控制努力或宿主的反应方式响应在其环境中的可用性。整个基因组测序产生更多信息，允许在精细规模上推断相关性，并使用通常更可重复的工作流程进行。
利用整个基因组方法控制血吸虫病
Whole genome approaches can overcome the limitations of older approaches in addressing both the contributions of non-human definitive hosts and parasite importation to schistosome transmission and risk. They can be used to identify transmission events between species (e.g., non-human to snail to human), and determine whether they occurred in the past, are ongoing or are shifting over time. This may be particularly important in low-transmission contexts, such as China, where control efforts that reduce prevalence in certain target species (e.g., humans) may increase the importance of other, non-target species (e.g.,啮齿动物）作为确定的主机。还可以使用整个基因组方法来推断有关血吸虫之间杂交事件的频率和时机的详细信息，以及由人，动物和蜗牛宿主运动所驱动的寄生虫引入的地理起源和目的地。
Integrating whole genome data with epidemiologic and ecological data can have an immediate impact on our scientific understanding of key threats to schistosomiasis control. The knowledge generated by these advances can support decisions about which interventions to implement alongside MDA in different contexts. But substantial challenges remain to integrating genomic workflows into surveillance systems. Using genomic data in surveillance systems on time scales relevant for operational decision-making will require investment in resources and local infrastructure in endemic regions. The good news is that costs are declining for whole genome approaches and their replicability across laboratories creates opportunities for standardization and curation of publicly available resources. It is our hope that epidemiologists and geneticists will expand collaborations to harness these increasingly available technologies to tackle the issues of schistosomiasis persistence and reemergence and accelerate progress towards elimination.
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