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Blood levels of histamine and serotonin (5-HT) are altered in human malaria, and, at these levels, we have shown they have broad, independent effects onAnopheles stephensifollowing ingestion by this invasive mosquito. Given that histamine and 5-HT are ingested together under natural conditions and that histaminergic and serotonergic signaling are networked in other organisms, we examined effects of combinations of these biogenic amines provisioned toA. stephensiat healthy human levels (high 5-HT, low histamine) or levels associated with severe malaria (low 5-HT, high histamine). Treatments were delivered in water (priming) before feedingA. stephensionPlasmodium yoelii-infected mice or via artificial blood meal. Relative to effects of histamine and 5-HT alone, effects of biogenic amine combinations were complex. Biogenic amine treatments had the greatest impact on the first oviposition cycle, with high histamine moderating low 5-HT effects in combination. In contrast, clutch sizes were similar across combination and individual treatments. While high histamine alone increased uninfectedA. stephensiweekly lifetime blood feeding, neither combination altered this tendency relative to controls. The tendency to re-feed 2 weeks after the first blood meal was altered by combination treatments, but this depended on mode of delivery. For blood delivery, malaria-associated treatments yielded higher percentages of fed females relative to healthy-associated treatments, but the converse was true for priming. Female mosquitoes treated with the malaria-associated combination exhibited enhanced flight behavior and object inspection relative to controls and healthy combination treatment. Mosquitoes primed with the malaria-associated combination exhibited higher mean oocysts and sporozoite infection prevalence relative to the healthy combination, with high histamine having a dominant effect on these patterns. Compared with uninfectedA. stephensi, the tendency of infected mosquitoes to take a second blood meal revealed an interaction of biogenic amines with infection. We used a mathematical model to project the impacts of different levels of biogenic amines and associated changes on outbreaks in human populations. While not all outbreak parameters were impacted the same, the sum of effects suggests that histamine and 5-HT alter the likelihood of transmission by mosquitoes that feed on hosts with symptomatic malariaversusa healthy host.

 

Mosquitoes vector harmful pathogens that infect millions of people every year, and developing approaches to effectively control mosquitoes is a topic of great interest. However, the success of many control measures is highly dependent upon ecological, physiological, and life history traits of mosquito species. The behavior of mosquitoes and their potential to vector pathogens can also be impacted by these traits. One trait of interest is mosquito body mass, which depends upon many factors associated with the environment in which juvenile mosquitoes develop. Our experiments examined the impact of larval density on the body mass of Aedes aegypti mosquitoes, which are important vectors of dengue, Zika, yellow fever, and other pathogens. To investigate the interactions between the larval environment and mosquito body mass, we built a discrete time mathematical model that incorporates body mass, larval density, and food availability and fit the model to our experimental data. We considered three categories of model complexity informed by data, and selected the best model within each category using Akaike’s Information Criterion. We found that the larval environment is an important determinant of the body mass of mosquitoes upon emergence. Furthermore, we found that larval density has greater impact on body mass of adults at emergence than on development time, and that inclusion of density dependence in the survival of female aquatic stages in models is important. We discuss the implications of our results for the control of Aedes mosquitoes and on their potential to spread disease.