There is a well-recognized need for improved diagnostic methods for human filariasis. Clinical examination and microfilaria detection are insensitive, and serologic tests based on measurement of antifilarial antibodies have shown poor specificity. Our laboratory has been involved in studies of circulating filarial antigens (primarily in canine dirofilariasis) for the past two years. We developed a monoclonal antibody-based ELISA to detect circulating Dirofilaria immitis antigens and evaluated it with an extensive panel of well-characterized dog sera. Antigen detection was more sensitive and specific than microfilarial tests or antibody assays, and it provided an estimate of infection intensity not previously available for any filarial infection. Two D. immitis antigens were identified in infected dog sera by rocket-line electrophoresis. These antigens have been partially purified, and they appear to be acidic proteoglycans associated with the uterus and eggs in adult female worms. We now plan to perform similiar studies of circulating parasite antigens in human filariasis. Preliminary studies have indicated that parasite antigens are detectable by counterimmunoelectrophoresis in the serum and urine of patients infected with W. bancrofti. We will develop sensitive monoclonal antibody-based assays for circulating antigens of W. bancrofti and Brugia malayi with techniques used in our D. immitis study. We will also identify and characterize circulating filarial antigens and study their immunogenicity in the human host. Filarial antigen assays will be systematically evaluated as clinical and epidemiological tools in collaboration with the Indian National Intitute of Communicable Diseases which has extensive ongoing studies of filariasis epidemiology in Kerala (endemic for W. bancrofti and B. malayi). This evaluation will include studies of the distribution of infection intensities in populations, the age at acquisition of infection, the possible influence of the infection status of the mother on susceptibility to infection in offspring, and the use of parasite antigen detection to monitor filariasis treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
5R22AI022488-02
Application #
3444824
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110
Weil, G J; Steel, C; Liftis, F et al. (2000) A rapid-format antibody card test for diagnosis of onchocerciasis. J Infect Dis 182:1796-9
Zhang, S; Li, B W; Weil, G J (2000) Paper chromatography hybridization: a rapid method for detection of Onchocerca volvulus DNA amplified by PCR. Am J Trop Med Hyg 63:85-9
Vincent, J A; Lustigman, S; Zhang, S et al. (2000) A comparison of newer tests for the diagnosis of onchocerciasis. Ann Trop Med Parasitol 94:253-8
Zhang, S; Li, B; Weil, G J (1999) Human antibody responses to Brugia malayi antigens in brugian filariasis. Int J Parasitol 29:429-36
Faris, R; Hussain, O; El Setouhy, M et al. (1998) Bancroftian filariasis in Egypt: visualization of adult worms and subclinical lymphatic pathology by scrotal ultrasound. Am J Trop Med Hyg 59:864-7
Chandrashekar, R; Curtis, K C; Lu, W et al. (1998) Molecular cloning of an enzymatically active thioredoxin peroxidase from Onchocerca volvulus. Mol Biochem Parasitol 93:309-12
Chandrashekar, R; Ogunrinade, A F; Weil, G J (1996) Use of recombinant Onchocerca volvulus antigens for diagnosis and surveillance of human onchocerciasis. Trop Med Int Health 1:575-80
Weil, G J; Ramzy, R M; Chandrashekar, R et al. (1996) Parasite antigenemia without microfilaremia in bancroftian filariasis. Am J Trop Med Hyg 55:333-7
Eberhard, M L; Dickerson, J W; Tsang, V C et al. (1995) Onchocerca volvulus: parasitologic and serologic responses in experimentally infected chimpanzees and mangabey monkeys. Exp Parasitol 80:454-62
Chandrashekar, R; Curtis, K C; Weil, G J (1995) Molecular characterization of a parasite antigen in sera from onchocerciasis patients that is immunologically cross-reactive with human keratin. J Infect Dis 171:1586-92

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