Africa, Western; Developing Countries; Ghana; Hookworm Infections; Malaria; Microbiology; Pediatrics; Public Health; Tropical Medicine; Global Health; Infectious Disease Medicine
Public Health Interests
Our research encompasses laboratory and field based studies of parasitic diseases that affect children in developing countries. This work focuses on bloodfeeding hookworms, intestinal nematodes that infect nearly one billion people worldwide, and malaria, a major killer of children in the tropics. Using molecular, immunological, and biochemical techniques, we study pathogenesis in order to develop new drugs, vaccines and diagnostics for use in resource limited settings. Collaborative field based research is focused on identifying risk factors for parasitic infections, characterizing the impact of polyparasitism on child health, and monitoring the effectiveness of current control strategies.
Specialized Terms: Molecular parasitology; Hookworm pathogenesis and vaccine development; International child health
Extensive Research Description
We conduct laboratory and field based investigations aimed at characterizing the epidemiology and molecular pathogenesis of parasitic diseases, specifically hookworm and malaria. We also study the pathogenesis of parasite coinfection and the role of host nutritional status in mediating susceptibility to disease. Our group utilizes molecular methods to identify parasite virulence factors, as well as define the genetic basis of treatment failure in endemic areas. Using laboratory models, we are developing novel drugs, vaccines, and diagnostics for parasitic diseases, with a goal of implementing new technologies for disease control in resource limited settings.
Our field-based research is focused on the epidemiology of hookworm and malaria in West Africa. In collaboration with the Noguchi Memorial Institute for Medical Research at the University of Ghana, we have defined the prevalence and intensity of hookworm/malaria in endemic communities, identified host factors that mediate susceptibility to infection, and also demonstrated high rates of deworming treatment failure. This work suggests the potential emergence of anthelminthic resistance, threatening the effectiveness of mass deworming campaigns in Africa. The long-range goal of our work is to improve the health of poor people around the world through laboratory and field based research on endemic infectious diseases.
In 2007 we launched the Yale Partnerships for Global Health, an initiative aimed at building human research capacity through education and training. Through this innovative program, students and post-doctoral fellows from Ghana, Brazil, Saudi Arabia, China, Singapore, and Australia have been hosted at Yale for mentored research training in clinical and translational research. The long range goal of the Yale Partnerships is to build a global network of scientists committed to improving health through collaborative research.
- Humphries D, Simms BT, Davey D, Otchere J, Quagraine J, Terryah S, Newton S, Berg A, Harrison LM, Boakye D, Wilson MD, Cappello M. Hookworm infection among school age children in Kintampo North Municipality, Ghana: Nutritional risk factors and response to albendazole treatment Am J Trop Med Hyg 2013;89:540-8.
- Davey D, Manickam N, Harrison LM, Simms B, Bungiro, RD, Vermeire JJ, Cappello M. Frequency and intensity of exposure mediate resistance to experimental infection with the hookworm, Ancylostoma ceylanicum. Exp Parasitol 2013;133:243-249
- Kotze AC, Dobson RJ, Humphries D, Wilson M, Cappello M. Analysis of two human hookworm drug efficacy trials in Ghana highlights the impact of low pre-treatment egg counts on the faecal egg count reduction test. Int J Parasitol: DDR 2014;4:64-70
- Nguyen J, Pool CD, Wong CYB, Treger RS, Williams D, Cappello M, Leah WA, Simeonov A, Vermeire J, Modis Y. Peroxiredoxin-1 from the human hookworm Ancylostoma ceylanicum forms a stable oxidized decamer and is inhibited by the covalent inhibitor conoidin A. Chem Biol 2013;20:1-11
- Treger, RS, Otchere J, Keil M, Quagraine J, Rai G, Mott B, Humphries DL, Wilson M, Cappello M, Vermeire JJ. In vitro screening of compounds against laboratory and field isolates of human hookworm reveals quantitative differences in anthelminthic susceptibility. Am J Trop Med Hyg 2014;90:71-4
- Humphries D, Nguyen S, Boakye D, Wilson M, Cappello M. The promise and perils of mass drug administration to control intestinal helminth infections. Curr Opin Infect Dis 2012;25:584-9
- Humphries D, Mosites M, Otchere J, Twum A, Woo L, Benham-Pyle B, Jones-Sanpei H, Harrison LM, Bungiro RD, Bosompem K, Wilson M, Cappello M. Epidemiology of hookworm infection in Kintampo North Municipality, Ghana: patterns of malaria coinfection, anemia, and albendazole treatment failure. Am J Trop Med Hyg. 2011 May;84(5):792-800. doi: 10.4269/ajtmh.2011.11-0003.
- Bungiro RD, Cappello M. 21st century progress toward the global control of human hookworm infection. Clin Infect Dis Rep 2011;13:1-8
- Kucera K, Harrison LM, Cappello M, Modis Y. Excretory-Secretory Protein 2 from the human hookworm Ancylostoma ceylanicum adopts a netrin-like fold and defines a novel family of nematode proteins. J Molec Biol 2011;408:9-17
- Sorensen W, Cappello M, Bell D, DiFedele LM, Brown MA. Poly-helminth infection in east Guatemalan school children. J Global Infect Dis 2011;3:25-31
- Dondji B, Sun T, Bungiro Jr. RD, Vermeire J, Harrison LM, Bifulco C, et al. CD4+ T cells mediate mucosal and systemic immune responses to experimental hookworm infection. Parasite Immunol. 2010;32:406-13.
- Bungiro RD, Sun T, Harrison LM, Shoemaker CB, Cappello M. Mucosal antibody responses in experimental hookworm infection Parasite Immunol 2008;30:2293-303
- Dondji B, Bungiro RD, Harrison LM, Bifulco C, Vermeire J, McMahon-Pratt D, Cappello M. A role for nitric oxide in hookworm associated immune suppression Infect Immun 2008;76:2560-7
- Cho Y, Jones BF, Vermeire JJ, Leng L, DiFedele L, Harrison LM, Xiong H, Kwong YK, Chen Y, Bucala R, Lolis E, Cappello M (Aug 2007) Structural and functional characterization of a secreted hookworm Macrophage Migration Inhibitory Factor (MIF) that interacts with the human MIF receptor CD74., The Journal of biological chemistry, 282(32)23447-56
- Cappello, M., et al. (2006). A purified Bacillus thuringiensis crystal protein with therapeutic activity against the hookworm parasite Ancylostoma ceylanicum. Proc. Natl. Acad. Sci. (USA) 103:15154-15159.
- Held, M.R., Bungiro, R.D., Harrison, L.M., Hamza, I., and Cappello, M. (2006). Dietary iron content mediates hookworm pathogenesis in vivo. Infect. Immun. 74:289-295.