Experimental determination of the force of malaria infection reveals a non-linear relationship to mosquito sporozoite loads.

Maya Aleshnick,Photini Sinnis,Gibran Nasir,Vitaly V Ganusov,Gayane Yenokyan,Tim J.C. Anderson

doi:10.1371/journal.ppat.1008181

Maya Aleshnick, Photini Sinnis + Show 4 more

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https://doi.org/10.1371/journal.ppat.1008181

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Abstract

Plasmodium sporozoites are the infective stage of the malaria parasite. Though this is a bottleneck for the parasite, the quantitative dynamics of transmission, from mosquito inoculation of sporozoites to patent blood-stage infection in the mammalian host, are poorly understood. Here we utilize a rodent model to determine the probability of malaria infection after infectious mosquito bite, and consider the impact of mosquito parasite load, blood-meal acquisition, probe-time, and probe location, on infection probability. We found that infection likelihood correlates with mosquito sporozoite load and, to a lesser degree, the duration of probing, and is not dependent upon the mosquito's ability to find blood. The relationship between sporozoite load and infection probability is non-linear and can be described by a set of models that include a threshold, with mosquitoes harboring over 10,000 salivary gland sporozoites being significantly more likely to initiate a malaria infection. Overall, our data suggest that the small subset of highly infected mosquitoes may contribute disproportionally to malaria transmission in the field and that quantifying mosquito sporozoite loads could aid in predicting the force of infection in different transmission settings.

Highlights

Malaria remains one of the most important infectious diseases in the world, responsible for approximately 200 million cases and 500,000 deaths annually [1], with the majority of deaths occurring in young children in sub-Saharan Africa
In this study, using a rodent model of malaria, we found that the majority of infective bites do not result in malaria infection
We found that the bites of mosquitoes with heavy parasite burdens are significantly more likely to result in blood stage infection

Summary

Introduction

Malaria remains one of the most important infectious diseases in the world, responsible for approximately 200 million cases and 500,000 deaths annually [1], with the majority of deaths occurring in young children in sub-Saharan Africa. From there sporozoites enter the blood circulation and travel to the liver where they invade hepatocytes and divide into thousands of hepatic merozoites (reviewed in [5, 6]) These liver stage parasites initiate the blood stage of infection, where iterative rounds of replication lead to high parasite numbers and clinical symptoms. The pre-erythrocytic stage of infection is not associated with clinical symptoms and is characterized by low parasite numbers whose goal it is to gain a foothold in the mammalian host That this process is not always successful has been known for some time [7], it has been difficult to establish a more quantitative foundation of this transmission bottleneck [8]

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