Plasmodium falciparum infection in humans and mosquitoes influence natural Anopheline biting behavior and transmission

Malaria transmission efficiency depends on the rate of vector-host contact and the effectiveness of parasite transmission during that contact. Understanding mosquito biting preferences in natural settings is crucial for targeted interventions. Previous studies have shown variability in attractiveness to mosquitoes and the influence of Plasmodium infection on mosquito biting behavior, but these often relied on experimental or short-term settings. This 15-month longitudinal study aimed to quantify variation in mosquito-human contact in a natural setting across a well-defined population, incorporating multispecies bloodmeals to understand who is bitten, who transmits to mosquitoes, and how mosquito characteristics influence biting behavior. The hypothesis was that mosquitoes exhibit biting biases towards certain human groups and that mosquito characteristics (species and P. falciparum infection status) influence this behavior.

Existing literature demonstrates high inter-individual variability in attractiveness to mosquitoes and the impact of Plasmodium infection on mosquito biting preferences. Studies in natural settings show heterogeneity in mosquito bite exposure and transmission likelihood. However, many studies lack the longitudinal scope and the inclusion of multi-source bloodmeals needed for a comprehensive understanding of transmission dynamics in natural populations. This study addresses this gap by utilizing a large, longitudinal dataset.

This study employed a 15-month community-based cohort in western Kenya, collecting indoor-resting mosquitoes weekly from 75 households. Mosquito species were identified morphologically and molecularly. Short Tandem Repeat (STR) genotyping was used to match mosquito bloodmeals to cohort participants. qPCR was used to detect P. falciparum in human blood samples and mosquito abdomens. Risk factor analysis and discrete choice models assessed mosquito biting behavior concerning parasite transmission. The maximum transmission efficiency (probability of a mosquito becoming infected after biting an infected host) was estimated. Statistical methods such as negative binomial models and discrete mixed models were used to analyze the data.

Biting rates were highly unequal; 20% of people received 86% of bites. Biting rates were significantly higher for males, children aged 5-15 years, and P. falciparum-infected individuals. School-age boys accounted for approximately 50% of bites potentially leading to onward transmission and had an entomological inoculation rate 6.4 times higher than other groups. Infectious mosquitoes were nearly 3 times more likely to bite P. falciparum-infected individuals. Infected Anopheles funestus took more multi-source bloodmeals than uninfected mosquitoes. Mosquito biting behavior was strongly associated with P. falciparum sporozoite infection, with infectious mosquitoes showing a preference for males, children, and individuals not sleeping under bed nets. The maximum transmission efficiency was estimated to be between 0.12 and 0.22. Higher sporozoite densities in mosquitoes increased the likelihood of biting infected individuals.

This study's findings demonstrate that malaria transmission is not random but influenced by both human and mosquito characteristics. The disproportionate biting of school-age boys suggests that targeting interventions towards this group could significantly impact transmission. The observation that infected mosquitoes preferentially bite infected humans suggests a potential feedback loop enhancing transmission. These results highlight the importance of considering heterogeneity in human susceptibility and mosquito behavior for accurate modeling of malaria transmission and effective intervention design.

This 15-month longitudinal study reveals non-random mosquito biting patterns influenced by both human and mosquito factors. School-age boys are disproportionately bitten and contribute to onward transmission, and infected mosquitoes preferentially bite infected individuals. These findings are crucial for developing targeted malaria interventions. Future research could investigate the underlying mechanisms driving these preferences and further refine strategies to disrupt malaria transmission.

Limitations include the inability to determine the initial feeding status of all reared mosquitoes, the relatively small sample size of reared abdomens limiting inferences about onward transmission, and potential biases in matching mosquito bloodmeals to humans. The study also assumes equal transmission efficiency and gametocyte carriage across groups, which may not be entirely accurate. Additionally, the detection of P. falciparum in mosquito head-thoraces could not definitively distinguish between sporozoites and blood-stage parasites.