Approximately 100 million people are infected with Wuchereria bancrofti, a mosquito-transmitted nematode parasite that causes deforming lymphatic filariasis in the tropics. Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis (LF) and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated cycles of mass drug administration (MDA). Egypt was one of the first countries in the world to implement a national program for elimination of lymphatic filariasis (PELF) based on this strategy. Our current ICIDR has worked to document the impact of the Egyptian PELF on filariasis prevalence and transmission in sentinel villages, and we have conducted research on the value of different tools for monitoring progress in ELF programs. This new ICIDR proposal is a natural extension of that work. In addition to the current cohesive group of researchers with different scientific backgrounds (medical epidemiology, immunology, molecular biology, and entomology) at Washington University, Smith College, and the RTC at Ain Shams University (Cairo), the new project adds a strong research group at Erasmus MC (Rotterdam) with expertise in modeling LF transmission and assessing the impact of control measures. The new ICIDR program will begin approximately one year after the 5th and final round of MDA in the Egyptian PELF (completed in October, 2004). The program is comprised of two interrelated projects: Project 1 will use the best available diagnostic tools in extensive field studies to assess whether filariasis has been eliminated in Egypt; materials and data collected in the field will be used in Project 2. Project 2 is focused on development of new tools for monitoring PELFs (promoting the objectives of Project 1). We have assembled a strong package of Cores to support these Projects and strengthen research capacity at RTC. Our personnel, experience, and enthusiasm place us in an excellent position to conduct research that should directly benefit efforts to eliminate filariasis, not only in Egypt, but also in many other endemic countries around the world. ? ? PROJECT 1: Research for the Elimination of Lymphatic Filariasis (Weil, G.) ? ? PROJECT 1 DESCRIPTION (provided by applicant): Improved therapies and diagnostic methods have led to new thinking about lymphatic filariasis and the realization that it should be possible to interrupt transmission and eliminate this major public health problem by repeated, annual cycles of mass drug administration (MDA) with new single dose combination drug regimens. Egypt was one of the first countries to implement a national program for elimination of lymphatic filariasis (PELF) based on MDA (annual distribution of diethylcarbamazine and albendazole, initiated in September 2000). The Egyptian Ministry of Health and Population (MOHP) completed its 5th and final round of MDA in October, 2004. Our detailed studies of sentinel villages during the current ICIDR project showed that the initial years of the MDA program had a major impact on LF prevalence (microfilaremia and circulating antigenemia) and transmission parameters (using antibody prevalence rates in primary school children as a marker for exposure to the parasite and PCR detection of parasite DMA in mosquito pools to estimate mosquito infection rates). Indeed, it is likely that LF was eliminated by MDA in these villages. The new project is a natural extension (and major expansion) of that work. The new project takes advantage of the strong, multidisciplinary filariasis research team at RTC, Ain Shams University in Cairo. ICIDR personnel will work closely with the Egyptian Ministry of Health and Population to carry out this ambitious project with extensive field studies. This will be the first attempt to rigorously assess a national PELF on this scale and also the first to use a national ELF program as a research laboratory. We will explore strategies for managing late stages of a PELF, test elimination indicators, and test the hypothesis that filariasis has been eliminated in Egypt by 5 rounds of MDA. We will also assess the value of advanced diagnostic methods for detecting foci of continued transmission and for early detection of resurgent transmission following suspension of MDA. Lessons learned in Egypt will benefit PELFs around the world. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI065715-02
Application #
7113715
Study Section
Special Emphasis Panel (ZAI1-GSM-M (M1))
Program Officer
Rao, Malla R
Project Start
2005-09-01
Project End
2010-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
2
Fiscal Year
2006
Total Cost
$959,198
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Rao, Ramakrishna U; Nagodavithana, Kumara C; Samarasekera, Sandhya D et al. (2014) A comprehensive assessment of lymphatic filariasis inSri Lanka six years after cessation of mass drug administration. PLoS Negl Trop Dis 8:e3281
Abd Elaziz, Khaled M; El-Setouhy, Maged; Bradley, Mark H et al. (2013) Knowledge and practice related to compliance with mass drug administration during the Egyptian national filariasis elimination program. Am J Trop Med Hyg 89:260-4
Weil, Gary J; Curtis, Kurt C; Fischer, Peter U et al. (2011) A multicenter evaluation of a new antibody test kit for lymphatic filariasis employing recombinant Brugia malayi antigen Bm-14. Acta Trop 120 Suppl 1:S19-22
Laney, Sandra J; Ramzy, Reda M R; Helmy, Hanan H et al. (2010) Detection of Wuchereria bancrofti L3 larvae in mosquitoes: a reverse transcriptase PCR assay evaluating infection and infectivity. PLoS Negl Trop Dis 4:e602
Rao, Ramakrishna U; Huang, Yuefang; Bockarie, Moses J et al. (2009) A qPCR-based multiplex assay for the detection of Wuchereria bancrofti, Plasmodium falciparum and Plasmodium vivax DNA. Trans R Soc Trop Med Hyg 103:365-70
Weil, Gary J; Kastens, Will; Susapu, Melinda et al. (2008) The impact of repeated rounds of mass drug administration with diethylcarbamazine plus albendazole on bancroftian filariasis in Papua New Guinea. PLoS Negl Trop Dis 2:e344
Laney, Sandra J; Buttaro, Caitlin J; Visconti, Sabato et al. (2008) A reverse transcriptase-PCR assay for detecting filarial infective larvae in mosquitoes. PLoS Negl Trop Dis 2:e251
Weil, Gary J; Ramzy, Reda M R (2007) Diagnostic tools for filariasis elimination programs. Trends Parasitol 23:78-82
Fischer, Peter; Erickson, Sara M; Fischer, Kerstin et al. (2007) Persistence of Brugia malayi DNA in vector and non-vector mosquitoes: implications for xenomonitoring and transmission monitoring of lymphatic filariasis. Am J Trop Med Hyg 76:502-7
Farid, Hoda A; Morsy, Zakariya S; Helmy, Hanan et al. (2007) A critical appraisal of molecular xenomonitoring as a tool for assessing progress toward elimination of Lymphatic Filariasis. Am J Trop Med Hyg 77:593-600

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