A major focus of my current work is lymphatic filariasis (LF), an infection now targeted for global elimination. I’m interested in both the pathogenesis of LF and in understanding how to optimize LF elimination strategies.
Filariasis affects an estimated 120 million people, causing lymphatic dysfunction in virtually all those infected; however, lymphedema and elephantiasis occur in only a subset of affected persons, primarily women. Lymphangiectasia, or dilatation of the lymphatic vessel, is associated with the presence of filarial worms and is considered to be pathognomonic for LF. We are interested in understanding how the presence of the worm leads to the development of lymphangiectasia and why risk of chronic disease is not uniform across all persons living in endemic areas. We are analyzing the direct and indirect effects of excretory-secretory (ES) products released by living parasites on the function of lymphatic endothelial cells. In addition, since persons with filarial lymphedema typically have higher levels of antifilarial responsiveness than persons with active infection, we are trying to determine whether or not these responses play a role in the pathogenesis of filarial disease.
LF elimination programs are based on the strategy of annual mass treatment of persons living in areas with active transmission. LF elimination programs have been started in more than 50 countries and more than 500 million people are targeted for treatment each year. From the programmatic standpoint, we are interested in understanding what can be done to improve the impact of interventions to eliminate LF. From the perspective of LF-endemic countries, it is also very important to understand when mass treatment can be safely stopped, without fear of recrudescence. Consequently, we are working to evaluate serologic and entomologic tools to monitor transmission of filariasis to better define program endpoints.
Finally, programs focused on specific neglected tropical diseases (NTDs), including LF, trachoma and onchocerciasis, have achieved tremendous success as disease-specific programs by reducing the prevalence and intensity of infection through mass treatment. Drugs used for these programs provide benefits beyond the targeted infections. Ivermectin, for example, through its effect on scabies, reduces secondary skin infections and the combination of ivermectin and albendazole dramatically decreases the intensity of intestinal helminth infections, including Strongyloides. We are developing a project designed to measure the public health benefits of integrated NTD programs and to correlate disease-specific indicators with more general health outcomes. A major objective of this work is to develop new approaches to carry out surveillance for NTDs in endemic settings.
Immunoparasitology; immunoregulation; lymphatic filariasis; crytosporidiosis
Liang, J.L., King, J., Ichimori, K., Handzel, T., Pa’au, M., and Lammie, P.J. (2008). Impact of five annual rounds of mass treatment with diethylcarbamazine and albendazole on Wuchereria bancrofti infection in American Samoa. Am. J. Trop. Med. Hyg. 78:924-928.
Won, K.Y., Beau de Rochars, M., Kyelem, D., Streit, T.G., and Lammie, P.J. (2009). Assessing the impact of a missed MDA in Haiti. PLoS NTDhttp://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0000443
Chambers, E.W., McClintock, S.K., Avery, M.F., King, J.D., Bradley, M.H., Schmaedick, M.A, Lammie, P.J., and Burkot, T.R. (2009). Xenomonitoring ofWuchereria bancrofti and Dirofilaria immitis infections in mosquitoes from American Samoa: trapping considerations and a comparison of polymerase chain reaction (PCR) assays with dissection. Am. J. Trop. Med. Hyg. 80:774-781.
Weinkopff, T., Atwood, J., Punkosdy, G., Weatherly, B., Orlando, R., and Lammie, P. (2009). Identification of Antigenic Brugia Adult Worm Proteins by Peptide Mass Fingerprinting. J. Parasitol. 95:1429-1435.
Boyd, A., Won, K.Y., McClintock, S.K., Donovan, C.V., Laney, S.J., Williams, S.A., Pilotte, N., Streit, T., Beau de Rochars, M., and Lammie. P.J. (2010). Factors associated with continuing transmission of lymphatic filariasis in Leogane, Haiti. PLoS NTD http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000640
Krolewiecki, A.J., Ramanathan, R., Fink, V., McAuliffe, I., Won, K., Cajal, S.P., Juarez, M., Di Paolo, A., Tapia, L., Acosta, N., Lee, R., Lammie, P., Abraham, D., Nutman, T.B. (2010). Improved diagnosis of Strongyloides stercoralis using recombinant antigen-based serologies in a community-wide study in northern Argentina. Clin. Vac. Immunol. 17:1624-1630.