# Investigating the Mechanisms Underlying Mosquito Infectiousness in Malaria

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $163,750

## Abstract

Project Summary
Malaria continues to have a huge toll on morbidity and mortality in the world, responsible for over
600,000 deaths annually. The transmission stages are bottlenecks for the parasite and thus critical
stages for intervention, particularly when aiming for elimination. Using the rodent model
Plasmodium yoelli, we recently found that salivary gland sporozoite load of a biting mosquito
strongly correlates with infection likelihood, with highly infected mosquitoes being 7.5 times more
likely to initiate an infection. Importantly, the likelihood of achieving secondary infections rapidly
rises at salivary gland sporozoite densities >10,000 that represent a small proportion of field-
caught mosquitoes. These data challenge the assumption that all infected mosquitoes are
equal, a belief that underlies epidemiological models of transmission and impacts malaria
elimination strategies. In this proposal we will determine the mechanisms underlying the
increased infectious potential of highly infected mosquitoes, comparing the quantity of sporozoites
inoculated by mosquitoes harboring high and low numbers of sporozoites, as well as the quality of
sporozoites in these two groups. In Aim 1 we will determine the inocula associated with low- and
high-infected mosquitoes using both rodent malaria parasites and the human parasite P.
falciparum. In Aim 2, we will compare sporozoites from mosquitoes with low and high infections
using infection assays, intravital imaging, and single-cell RNA-Seq analysis. Overall these
experiments will fill crucial knowledge gaps on parasite transmission probability that will greatly
improve our understanding of parasite biology and epidemiology.

## Key facts

- **NIH application ID:** 10887802
- **Project number:** 1R21AI178535-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Photini Sinnis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,750
- **Award type:** 1
- **Project period:** 2024-06-06 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887802

## Citation

> US National Institutes of Health, RePORTER application 10887802, Investigating the Mechanisms Underlying Mosquito Infectiousness in Malaria (1R21AI178535-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10887802. Licensed CC0.

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