Since the late 1980s, a series of Plasmodium falciparum malaria epidemics have occurred in the highlands of African countries. The current pattern of malaria in the highlands exhibits the characteristics of an expanded geographic area, increased frequency, and increased fatality rates. What has caused the more frequent and more widespread malaria epidemics since the late 1980s in African highlands? Can we forecast when and where an epidemic will occur so that appropriate actions can be taken in advance to reduce morbidity and mortality? How can we maximize the efficacy and cost-effectiveness of vector control to reduce malaria transmission and incidence in the highlands? These questions are not only of scientific interest, but they are also of paramount importance for malaria control. The long-term objectives of this research are to determine the mechanisms of malaria epidemics in African highlands, and to develop efficient vector control methods for epidemic malaria control. In the previous period of support, we made significant progress elucidating the effects of land use and land cover on malaria transmission in African highlands. We proposed the climate- landscape hypothesis as a leading mechanism for the emergence of epidemic malaria in African highlands. This competing renewal application will test the climate-landscape hypothesis using epidemiological, entomological, and molecular population genetics data in western Kenya highlands. The project will use community-based longitudinal cohort studies as a central platform for the following three inter-related specific aims. First, we will develop models for malaria dynamics and epidemics forecasting in the highlands and determine the accuracy and sensitivity of the models using prospective climate and malaria incidence data. Second, we will determine the effects of landscape factors on the spread of malaria infections and identify transmission hotspots for targeted malaria vector control. Third, we will assess the impact of mosquito vector control targeted at transmission hotspots on rates of malaria transmission, infection incidence, and clinical malaria occurrence. This project will achieve the following goals: a) reveal critical parameters needed for the development of malaria early warning systems in African highlands, b) significantly enhance our understanding of the relationships between climate, landscape, and the transmission dynamics of malaria, and c) facilitate the development of cost-effective malaria vector control methods. We anticipate that our results will have broad applicability to malaria prevention and control in Africa.

Public Health Relevance

In Africa highlands, malaria transmission is unstable, and epidemic malaria poses a serious public health problem. It was estimated that epidemic malaria kills about 110,000 people each year and 110 million people are at risk. Understanding the mechanisms leading to malaria epidemics in the highlands will facilitate the development of malaria early warning system so that timely preparedness and preventative measures can be implemented. We hypothesize that mosquito vector control by targeting the malaria transmission hotspots is a cost-effective approach for malaria control in the highlands. This application will combine epidemiological, molecular population genetic and modeling approaches with an interventional analysis to determine the mechanisms causing malaria epidemics and to develop cost-effective vector control methods in western Kenya highlands. Unique to this application is that we will collaborate with scientists at the National Center for Atmospheric Research to incorporate seasonal climate forecasting into our model, thus we can test the sensitivity and reliability of our model in a real-time manner. We will then determine the effects of targeted vector control on both mosquito larvae and adults in transmission hotspots on malaria incidences. This project will reveal critical parameters needed for the development of malaria early warning system, and will develop novel and cost-effective vector control methods for reducing malaria incidence and preventing malaria epidemics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050243-11
Application #
8213731
Study Section
Clinical Research and Field Studies of Infectious Diseases Study Section (CRFS)
Program Officer
Costero, Adriana
Project Start
2001-09-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
11
Fiscal Year
2012
Total Cost
$542,527
Indirect Cost
$118,563
Name
University of California Irvine
Department
None
Type
Schools of Public Health
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Kweka, Eliningaya J; Kamau, Luna; Munga, Stephen et al. (2013) A first report of Anopheles funestus sibling species in western Kenya highlands. Acta Trop 128:158-61
Vardo-Zalik, Anne M; Zhou, Guofa; Zhong, Daibin et al. (2013) Alterations in Plasmodium falciparum genetic structure two years after increased malaria control efforts in western Kenya. Am J Trop Med Hyg 88:29-36
Zhong, Daibin; Chang, Xuelian; Zhou, Guofa et al. (2013) Relationship between knockdown resistance, metabolic detoxification and organismal resistance to pyrethroids in Anopheles sinensis. PLoS One 8:e55475
Wang, Mei-Hui; Marinotti, Osvaldo; Zhong, Daibin et al. (2013) Gene expression-based biomarkers for Anopheles gambiae age grading. PLoS One 8:e69439
Kweka, Eliningaya J; Zhou, Goufa; Beilhe, Leila B et al. (2012) Effects of co-habitation between Anopheles gambiae s.s. and Culex quinquefasciatus aquatic stages on life history traits. Parasit Vectors 5:33
Afrane, Yaw A; Githeko, Andrew K; Yan, Guiyun (2012) The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands. Ann N Y Acad Sci 1249:204-10
Githeko, A K; Ototo, E N; Guiyun, Yan (2012) Progress towards understanding the ecology and epidemiology of malaria in the western Kenya highlands: opportunities and challenges for control under climate change risk. Acta Trop 121:19-25
Zhong, Daibin; Bonizzoni, Mariangela; Zhou, Guofa et al. (2011) Genetic diversity of Plasmodium vivax malaria in China and Myanmar. Infect Genet Evol 11:1419-25
Wang, Ying; Gilbreath 3rd, Thomas M; Kukutla, Phanidhar et al. (2011) Dynamic gut microbiome across life history of the malaria mosquito Anopheles gambiae in Kenya. PLoS One 6:e24767
Yakob, Laith; Dunning, Rebecca; Yan, Guiyun (2011) Indoor residual spray and insecticide-treated bednets for malaria control: theoretical synergisms and antagonisms. J R Soc Interface 8:799-806

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