Last Updated: 19/02/2020

What are we missing? Malaria infection, disease and transmission in school-age children

Objectives

To define the age distribution of Plasmodium infection using the most sensitive assays; Measure the risk of developing symptomatic malaria disease after detecting Plasmodium infections below the limit of detection by rapid diagnostic test; Estimate the cumulative risk of gametocytemia in sub-RDT infections in school children.

Principal Investigators / Focal Persons

Lauren Cohee

Rationale and Abstract

Despite widespread access to malaria control interventions, the prevalence of malaria remains high in Malawi. According to the 2014 Malaria Indicator Survey, 33% of children under the age of five in Malawi have Plasmodium infections detected by microscopy. This is an increase from 28% in 2012. There has been good uptake of current control measures including long-lasting insecticide-treated nets, intermittent preventive treatment of malaria during pregnancy, and malaria case management using both rapid diagnostic tests (RDTs) and effective anti-malarial chemotherapy. These interventions have been successful in reducing the burden of malaria in other sub-Saharan African countries, but the results have been modest in Malawi.

Malaria in Malawi is recalcitrant to the interventions that have decreased malaria burden in neighbouring countries. The reasons remain unknown. We have found that school-age children have higher prevalence of Plasmodium infection than younger children and adults. In a series of community-based, cross-sectional surveys we conducted over the last three years in southern Malawi, we determined prevalence of malaria infection detected by microscopy and PCR as well as molecular detection of gametocytes in all age groups. We observed that school-age children (5-15 year olds) have higher prevalence of PCR-detected Plasmodium infection (24%) than both younger children (10%) and adults (10%) (p<0.001). We hypothesize that school-age children bear a disproportionate burden of Plasmodium infection and that interventions targeting this population will improve the health of this population. While infection in school-age children is generally not associated with fatal malaria disease, infections in this age group exacerbate anemia, lead to absenteeism, and cause decreased cognitive function.

We also found that school-age children had the highest rates of infections containing gametocytes, the stage of the malaria parasite responsible for transmission. Although a complete characterization of the transmission potential of an individual or a defined population is complex, the presence of gametocytes is often used as a surrogate measure. Gametocytes are present in the peripheral blood in some but not all people with Plasmodium infections. They represent a small portion of the total parasite abundance in humans and are not distributed equally among all infected people.4 Our findings of high prevalence of infection and increased rates of gametocytes within those infections lead us to believe that school-age children are at underappreciated risk of the adverse effects of malaria infection and play a significant role in the transmission of malaria in Malawi. 

Several questions remain in determining the potential effectiveness of school-based interventions:

1. Are school-age children truly the largest reservoir of Plasmodium infections?

Our studies and others have shown the parasite density is inversely related to age and adults often have the lowest density malaria infections. It is possible that if the limit of detection were lower than our standard PCR, adults may have the same overall burden of infection as school-age children. Our lab has developed an ultra-sensitive PCR technique that has a limit of detection 100 fold lower than our traditional PCR (Adams, submitted). This technique will allow us to more thoroughly evaluate the burden of Plasmodium infection in different age groups.

2. When targeting malaria control and elimination efforts to school age children, should interventions be based on screening test results or should all children be treated without testing?

Two types of chemotherapeutic interventions in schools are: screen and treat interventions—which usually rely on the results of RDTs and only treat individuals with positive tests—and mass treatment in which malaria diagnostic tests are not done and all individuals are treated. One potential reason for the failure of prior screen and treat based interventions either in schools or in the community is that RDTs are not a sensitive enough screening tool. Molecular methods can detect lower density infections than RDTs, referred to here as sub-RDT infections. However, neither the clinical relevance nor the contribution to transmission of these sub-RDT infections is known. Understanding the contribution of sub-RDT infections to subsequent development of disease and transmission is critical to the development of future malaria control interventions.

Study Design

The present proposal is designed to use samples collected in our on-going school- and community-based surveys to determine the burden of sub-RDT infections as detected by both traditional qPCR and ultra sensitive PCR and follow school-age children with these infections longitudinally. We will use these data to estimate the risk of malaria infection, disease and the transmission of these individuals over time. We will be able to compare the dynamics of these infections between seasons and in different transmission settings. These results will allow us to estimate the differential impact of mass treatment versus screen and treat interventions on both disease and transmission.

Date

Jan 2016 — May 2018

Total Project Funding

$130,000

Funding Details
Burroughs Wellcome Fund, United States

Burroughs Wellcome Fund-ASTMH Postdoctoral Fellowship in Tropical Infectious Diseases
Project Site

Malawi
United States

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