The distributions of human malaria parasite species overlap in most malarious regions of the world, and co-infections involving two or more malaria parasite species are common. Little is known about the consequences of interactions between species during co-infection for disease severity and parasite transmission success. Anti-malarial interventions can have disproportionate effects on malaria parasite species and may locally differentially reduce the number of species in circulation. Thus, it is important to have a clearer understanding of how the interactions between species affect disease and transmission dynamics. Controlled competition experiments using human malaria parasites are impossible, and thus we assessed the consequences of mixed-species infections on parasite fitness, disease severity, and transmission success using the rodent malaria parasite species Plasmodium chabaudi, Plasmodium yoelii, and Plasmodium vinckei. We compared the fitness of individual species within single species and co-infections in mice. We also assessed the disease severity of single vs. mixed infections in mice by measuring mortality rates, anemia, and weight loss. Finally, we compared the transmission success of parasites in single or mixed species infections by quantifying oocyst development in Anopheles stephensi mosquitoes. We found that co-infections of P. yoelii with either P. vinckei or P. chabaudi led to a dramatic increase in infection virulence, with 100% mortality observed in mixed species infections, compared to no mortality for P. yoelii and P. vinckei single infections, and 40% mortality for P. chabaudi single infections. The increased mortality in the mixed infections was associated with an inability to clear parasitaemia, with the non-P. yoelii parasite species persisting at higher parasite densities than in single infections. P. yoelii growth was suppressed in all mixed infections compared to single infections. Transmissibility of P. vinckei and P. chabaudi to mosquitoes was also reduced in the presence of P. yoelii in co-infections compared to single infections. The increased virulence of co-infections containing P. yoelii (reticulocyte restricted) and P. chabaudi or P. vinckei (predominantly normocyte restricted) may be due to parasite cell tropism and/or immune modulation of the host. We explain the reduction in transmission success of species in co-infections in terms of inter-species gamete incompatibility.

中文翻译：

---

在小鼠和蚊子中混合物种疟疾寄生虫共感染对疾病严重性，寄生虫适应性和传播成功的影响。

在世界上大多数疟疾流行地区，人类疟疾寄生虫物种的分布重叠，并且涉及两种或多种疟疾寄生虫物种的共同感染很常见。关于共感染期间物种之间相互作用对疾病严重性和寄生虫传播成功的后果知之甚少。抗疟疾干预措施可能对疟疾寄生虫物种产生不成比例的影响，并可能局部差异地减少流通中的物种数量。因此，重要的是要更清楚地了解物种之间的相互作用如何影响疾病和传播动力学。使用人类疟疾寄生虫进行的竞争控制实验是不可能的，因此，我们评估了混合物种感染对寄生虫适应性，疾病严重性，和传播成功，使用了啮齿动物疟原虫chabaudi疟原虫，yoelii疟原虫和vinckei疟原虫。我们比较了单个物种内单个物种和小鼠共感染的适应性。我们还通过测量死亡率，贫血和体重减轻来评估小鼠单次感染与混合感染的疾病严重程度。最后，我们通过量化斯蒂芬按蚊的卵囊发育，比较了寄生虫在单一或混合物种感染中的传播成功率。我们发现，与P. vineli和P. vinckei的无致死率相比，P。vineli和P. chabaudi的共感染会导致感染毒力的急剧增加，在混合物种感染中观察到死亡率为100％。沙门氏菌单次感染的死亡率为40％。与非P相比，混合感染中死亡率增加与无法清除寄生虫血症有关。yoelii寄生虫物种比单个感染具有更高的寄生虫密度。与单一感染相比，所有混合感染均抑制了约氏疟原虫的生长。与单一感染相比，在共感染中存在约氏疟原虫的情况下，温克氏假单胞菌和沙巴氏假单胞菌对蚊子的传染性也降低了。含有约氏疟原虫（网织红细胞限制）和沙巴氏假单胞菌或温克酵母（主要是正常细胞限制）的共感染毒力增加，可能是由于寄生虫的细胞嗜性和/或宿主的免疫调节。我们根据种间配子不相容性解释了共感染中物种传播成功的减少。