Malaria transmission can change rapidly and vary dramatically over small spatial scales. The result is that current maps of malaria epidemiology do not reflect recent changes and have poor predictive capacity at the level of individual communities. Current measures of community exposure to P. falciparum - principally the entomological inoculation rate and parasite rate - have several limitations. Assays of antimalarial antibodies, which can be performed using dried blood spots collected in the field, have recently been shown to provide robust estimates of a community's average exposure to parasites over the prior years. Such assays offer the promise of obtaining frequent, high coverage data on exposure at low cost. However, these assays need to be further refined to reflect dynamic changes in exposure that may occur with implementation of control efforts and to reflect heterogeneity in exposure over small spatial scales. In addition, changes in a population's exposure and therefore immune protection alter the relationship between exposure and disease in a complicated fashion. Assays designed to assess immunologic protection directly would help predict the impact of changing transmission on the burden of disease. In response to the need for better tools to measure exposure and the relationship between exposure and disease, the specific aims of research project 3 are: 1) to characterize the individual-level relationships between P. falciparum exposure, the immune response, and protection from infection and disease in Ugandan cohorts, 2) to develop and validate mmunologic assays for estimating the population-level dynamics of exposure to P. falciparum in surveillance studies performed throughout Uganda, and 3) to develop and validate immunologic assays for estimating the population-level dynamics of disease in response to changing P. falciparum exposure in surveillance studies performed throughout Uganda. Using data and specimens from existing cohorts, laboratory and statistical methods will be optimized to provide immunologic assessments of prior exposure and protection from infection and disease. Immunologic assays will then be translated to the population level and prospectively validated using surveillance data and filter paper blood samples collected at multiples sites in Uganda.

Public Health Relevance

Obtaining standard metrics for assessing malaria exposure and the relationship between exposure and disease requires surveillance that is expensive and time consuming, and therefore only performed sporadically. Immunologic assays using blood collected on dried blood spots provide a potentially costeffective and robust method for improving malaria surveillance.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Yeka, Adoke; Kigozi, Ruth; Conrad, Melissa D et al. (2016) Artesunate/Amodiaquine Versus Artemether/Lumefantrine for the Treatment of Uncomplicated Malaria in Uganda: A Randomized Trial. J Infect Dis 213:1134-42
Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J et al. (2016) Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination. Trans R Soc Trop Med Hyg 110:107-17
Sullivan, Richard T; Ssewanyana, Isaac; Wamala, Samuel et al. (2016) B cell sub-types following acute malaria and associations with clinical immunity. Malar J 15:139
Zhao, Xia; Smith, David L; Tatem, Andrew J (2016) Exploring the spatiotemporal drivers of malaria elimination in Europe. Malar J 15:122
Huber, John H; Johnston, Geoffrey L; Greenhouse, Bryan et al. (2016) Quantitative, model-based estimates of variability in the generation and serial intervals of Plasmodium falciparum malaria. Malar J 15:490
Donnelly, Martin J; Isaacs, Alison T; Weetman, David (2016) Identification, Validation, and Application of Molecular Diagnostics for Insecticide Resistance in Malaria Vectors. Trends Parasitol 32:197-206
Farrington, Lila A; Jagannathan, Prasanna; McIntyre, Tara I et al. (2016) Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood. J Infect Dis 213:1483-90
Alegana, Victor A; Atkinson, Peter M; Lourenço, Christopher et al. (2016) Advances in mapping malaria for elimination: fine resolution modelling of Plasmodium falciparum incidence. Sci Rep 6:29628
Odorizzi, Pamela M; Feeney, Margaret E (2016) Impact of In Utero Exposure to Malaria on Fetal T Cell Immunity. Trends Mol Med 22:877-888
Ruktanonchai, Nick W; DeLeenheer, Patrick; Tatem, Andrew J et al. (2016) Identifying Malaria Transmission Foci for Elimination Using Human Mobility Data. PLoS Comput Biol 12:e1004846

Showing the most recent 10 out of 122 publications