Epidemiological consequences of reproductive senescence in a long-lived vector

采采蝇通过一次传染性叮咬将单细胞寄生虫——锥虫——传播给牲畜。一旦感染，牲畜就会患上非洲动物锥虫病（AAT），这是一种致命的疾病，每年导致1- 200万头牛死亡，并使撒哈拉以南非洲每年损失30 - 50亿美元的农业潜力。控制这种疾病的战略是由描述采采蝇和宿主之间寄生虫传播率和采采蝇数量变化的数学模型提供的。昆虫传播致病寄生虫的能力的一个关键方面是它的寿命和对感染的易感性。对于许多动物来说，寿命和对感染的易感性受到个体母亲的投资的影响。由于采采蝇不同寻常的生殖生物学特性，这种母性效应可能对它们非常重要。与大多数其他昆虫不同，雌性采采蝇会怀孕、产奶并产下比母亲重的幼虫。采采蝇在田间可存活6个月以上，雌性每10天产1只幼虫。个体苍蝇与其母亲之间的密切联系表明，母亲对采采蝇的寿命和免疫力以及寄生虫传播将有显著的影响。然而，锥虫病的模型是以人类疟疾的Ross-Macdonald模型为基础的，并且没有考虑母体在采采蝇种群动态或流行病学中的作用，因为疟疾蚊子——像大多数其他媒介一样——通过产卵繁殖。该项目将调查采采蝇中母体投资如何随年龄和营养变化，对后代生存和传播锥虫能力的影响，以及这些过程对采采蝇种群和疾病传播动态的贡献。我们将在实验室（使用利物浦热带医学院的一大群苍蝇）和在实地（使用在津巴布韦自然栖息地使用创新采样方法捕获的估计年龄的苍蝇）对采采蝇进行平行观察。我们将通过实验来控制雌性动物的营养状况，并通过阻止雌性动物在年老之前交配来衡量生殖成本，以评估晚年生殖产出的下降（如人类所报道的）是否反映了资源的枯竭或作为生殖副产品的损害的积累。我们将开发新的进化模型，以了解这些模式是否代表了适应策略，以最大化一生中产生的后代总数，生理上的限制，或这些过程的组合。我们将跟踪不同年龄和营养状况的母亲所生的后代，以测试年龄较大或营养紧张的母亲所生的后代是否更有可能早逝或感染锥虫。我们还将测试母亲对儿子的影响是否比女儿更强。最后，我们将利用这些实验观察和进化模型的见解来改进预测采采传播疾病的流行病学模型。这些疾病可能以低流行率和媒介密度持续存在，只有在控制努力放松或适宜新的生境时才会突然爆发。我们的新模型将用于预测母亲在帮助采采蝇种群在人类相关和环境变化的影响下持续生存或转移范围方面的作用。这些模型的准确性将根据有关采采蝇的分布和丰度、其宿主和疾病流行的现有数据进行验证。

Tsetse flies transmit single-celled parasites - trypanosomes - to livestock with a single infectious bite. Once infected, the animal develops animal African trypanosomiasis (AAT), a fatal disease which kills 1-2 million cattle and costs sub-Saharan Africa 3-5 billion USD in lost agricultural potential each year. Strategies to control this disease are informed by mathematical models describing rates of parasite transmission between tsetse and hosts and changes in the numbers of tsetse. A crucial aspect of an insect's ability to transmit a disease-causing parasite is its longevity and susceptibility to infection. For a wide variety of animals, longevity and susceptibility to infection are affected by the investment made by an individual's mother. This maternal effect is likely to be very important for tsetse because of their unusual reproductive biology. Unlike most other insects, female tsetse get pregnant, lactate and give birth to live young, which weigh more than the mother. Tsetse can survive over six months in the field with females producing a single larva every ~10 days. The close link between an individual fly and its mother suggests that there will be a marked maternal effect on tsetse longevity and immunity and hence parasite transmission. Models for trypanosomiasis are based on the Ross-Macdonald model for human malaria, however, and do not consider the role of maternal investment in tsetse population dynamics or epidemiology as malaria mosquitoes - like most other vectors - reproduce through egg laying.This project will investigate how maternal investment changes with age and nutrition in tsetse, the consequences for offspring survival and ability to spread trypanosomes, and the contribution of these processes to tsetse population and disease transmission dynamics. We will conduct parallel observations of tsetse in the laboratory - using a large colony of flies at the Liverpool School of Tropical Medicine - and in the field, using flies of estimated age caught using an innovative sampling method in their natural habitat in Zimbabwe. We will experimentally manipulate nutrition in females and measure the costs of reproduction by preventing females from mating until they are older, to assess whether late-life declines in reproductive output (such as those reported in humans) reflect depleted resources or build-up of damage as a by-product of reproduction. We will develop new evolutionary models to understand whether such patterns represent adaptive strategies to maximize the total number of offspring produced in a lifetime, constraints due to physiology, or a combination of these processes.We will follow offspring born to mothers of varying age and nutritional state to test whether offspring born to older or nutritionally stressed mothers are more likely to die young or become infected by trypanosomes. We will also test whether maternal effects are stronger in sons than daughters. Finally, we will use insights from these experimental observations and evolutionary models to improve epidemiological models predicting the spread of tsetse-borne diseases. These diseases can persist at low prevalence and vector density, only to flare up when control efforts are relaxed or new habitats become suitable. Our new models will be used to predict the role of mothers in helping tsetse populations to persist or shift range as a result of human-related and environmental change. The accuracy of these models will be validated against existing data on the distribution and abundance of tsetse, their hosts and disease prevalence.