Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda
Principal Investigator: Grant Dorsey, M.D.
Lead Institution: University of California, San Francisco
Award date: original award in 2010; renewed in 2017
- Epidemiology: Moses R. Kamya, Makerere University and Infectious Diseases Research Collaboration (IDRC), Uganda
- Resistance: Samuel Nsobya, Makerere University and IDRC, Uganda
- Transmission: Sarah Staedke, London School of Hygiene and Tropical Medicine, U.K.
- Infectious Diseases Research Collaboration (IDRC), Kampala, Uganda
- Makerere University College of Health Sciences, Kampala, Uganda
- Liverpool School of Tropical Medicine, Liverpool, UK
- London School of Hygiene and Tropical Medicine, London, UK
- Radboud Institute for Health Sciences, Netherlands
- Stanford University, Stanford, CA
- Durham University, Durham, UK
- Institute for Health Metrics and Evaluation, Seattle, WA
This program called "PRISM" is based in Uganda and represents the East African region for the International Centers of Excellence for Malaria Research network. Uganda is emblematic of the challenges faced by high burden countries, where routine surveillance systems are inadequate to assess trends in the burden of malaria or to monitor the impact of control interventions. Through PRISM researchers have implemented a comprehensive malaria surveillance program including enhanced health facility-based surveillance and detailed longitudinal studies with differing transmission intensities. Complementary laboratory-based studies include surveillance for markers of antimalarial drug and insecticide resistance and serologic measures of malaria exposure. These studies have greatly improved the understanding of the epidemiology of malaria in Uganda and of the impact of control interventions. This program will continue key components of the malaria surveillance work and expand the scope to address more fundamental questions about interactions between the parasite, mosquito vector, and human host. More intensive longitudinal evaluations will be conducted and cutting edge molecular studies will be added to better measure exposure to infective bites; more sensitively identify bloodstream infections; characterize parasite, vector, and human genetic factors that impact on malaria; and assess impacts of these factors on infectivity and transmission. The program will consist of three research projects linked together in an integrated manner to maximize scientific discovery.
- Resistance project: will use samples collected over time at multiple sites to characterize the evolution of phenotypic and genotypic markers of drug and insecticide resistance and assess the impacts of these markers on malaria transmission.
- Epidemiology project: will use longitudinal samples from cohorts to characterize factors that determine whether sporozoite inoculation results in the establishment of blood stage infection and characterize factors affecting the duration, density, and clinical consequences of blood stage infections.
- Transmission project: will use cohort samples to determine factors associated with gametocyte production and development, evaluate infectivity of the human host to mosquito vectors, and characterize the human infectious reservoir.
These highly interrelated projects will be conducted in settings with varied malaria epidemiology and differing population level control intervention to provide critical information needed to optimize strategies for the control and ultimate elimination of malaria in Uganda.
There has recently been a dramatic increase in the scale up of control interventions and reduction in the burden of malaria across Africa. However, progress has not been uniform, and in fact has been slowest in countries with the highest burden, such as Uganda. Uganda provides an ideal environment for this program as malaria covers a wide range of epidemiological settings in the country. This Center will conduct studies in health centers around Uganda, ranging from areas of relatively low transmission intensity to areas with some of the highest transmission intensities recorded in the world. Researchers hope to use the varied settings to evaluate intervention strategies and assess optimal control methods.
View Associated sites for the East Africa ICEMR in a larger map
Map description: Associated sites with the Uganda ICEMR: Districts of Amuru, Arua, Gulu, Oyam, Kole, Apec, Mubende, Kanungu, Kabale, Pader, Lamwo, Kitgum, Agago, Otuke, Alebtong, Nagongera, Dokolo, Amolatar, Tororo, and Jinja.
Select Publications from the 2010 Award
- Kigozi SP et al. Associations between urbanicity and malaria at local scales in Uganda. Malaria Journal. 2015, 14:374 DOI: 10.1186/s12936-015-0865-2
- Boyle MJ et al. Decline of FoxP3+ Regulatory CD4 T Cells in Peripheral Blood of Children Heavily Exposed to Malaria. PLoS Pathog. 2015;11(7):e1005041. PMID: 26182204; PMCID PMC4504515
- Helb D et al. Novel serologic biomarkers provide accurate estimates of recent P. falciparum exposure for individuals and communities. Proc Natl Acad Sci U S A. 2015;112(32):e4438-47. PMID: 26216993; PMCID PMC4538641
- Weetman D et al. Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae. Mol Ecol. 2015;24(11):2656-72. PMID: 25992620; PMCID PMC4437786
- Sullivan RT et al. FCRL5 Delineates Functionally Impaired Memory B Cells Associated with Plasmodium falciparum Exposure. PLoS Pathog. 2015;11(5):e1004894. PMID: 25993340; PMCID PMC4438005
- Tumwebaze P et al. Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from Ugandan children. Antimicrob Agents Chemother. 2015;59(6):3018-30. PMID:25753626; PMCID PMC4432194
- Yeka A et al. Factors associated with malaria parasitemia, anemia and serological responses in a spectrum of epidemiological settings in Uganda. PLoS One. 2015;10(3):e0118901. PMID 25768015; PMCID PMC4358889
- Boyle MJ et al. The effector phenotype of malaria-specific CD4 T cells is influenced by both age and transmission intensity in naturally exposed populations. J Infect Dis. 2015;212(3):416-25. PMID 25646355; PMCID PMC4539911
- Kamya MR et al. Malaria Transmission, Infection and Disease at Three Sites with Varied Transmission Intensity in Uganda: Implications for Malaria Control. Am J Trop Med Hyg. 2015;92(5):903-12. PMID 25778501; PMCID PMC4426576
- Wanzira H et al. Mind the gap: house structure and the risk of malaria in Uganda. PLoS One. 2015 ;10(1):e0117396. PMID 25635688; PMCID PMC4311957