Grantee Research Project Results
2001 Progress Report: Infectivity and Virulence of Cryptosporidium Genotype H Oocysts in Healthy Adult Volunteers
EPA Grant Number: R828035Title: Infectivity and Virulence of Cryptosporidium Genotype H Oocysts in Healthy Adult Volunteers
Investigators: Chappell, Cynthia L. , Okhuysen, Pablo C.
Current Investigators: Chappell, Cynthia L. , Okhuysen, Pablo C. , Widmer, Giovanni , Tzipori, Saul
Institution: The University of Texas Health Science Center at San Antonio
EPA Project Officer: Hahn, Intaek
Project Period: March 1, 2000 through March 1, 2003 (Extended to February 28, 2005)
Project Period Covered by this Report: March 1, 2001 through March 1, 2002
Project Amount: $503,884
RFA: Drinking Water (1999) RFA Text | Recipients Lists
Research Category: Drinking Water , Water
Objective:
The overall goal of this research project is to generate dose response curves in healthy volunteers using genotype 1 oocysts and to compare several outcome parameters to previous genotype 2 results. The specific objectives are to: (1) establish the infectious dose (ID50), clinical outcomes, and intensity of infection for two Cryptosporidium genotype 1 isolates in seronegative individuals; (2) investigate the antibody and cellular responses in volunteers to genotype 1 isolates; and (3) examine isolates for genetic differences and determine the stability of DNA markers prior to and after passage in humans and gnotobiotic (GNB) pigs.
Progress Summary:
This project is proceeding based on the original objectives and specific aims. Technical difficulties with the microbiological purity have been solved, and the volunteer challenges have proceeded. A total of 15 healthy adult volunteers have been challenged with a single dose of oocysts (range 10-100 oocysts). To date, preliminary data suggest that the ID50 for the C. parvum genotype 1 isolate, TU502, will be low; perhaps 30 oocysts or fewer.
Serum samples from each volunteer were collected prior to challenge and at days 5, 10, 30, and 45 post-challenge. Sera were aliquoted and stored for batch assay after all of the volunteer challenges were completed for TU502. Batch testing will be performed to minimize any variation in antigen preparation.
A genotype 1 isolate (TU502) has been multiply passaged and shown by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis of the Cryptosporidium oocyst wall protein (COWP) marker to be genetically stable. In addition, stool samples were collected from volunteers following challenge and examined by enzyme immuno assays (EIA) and immuno fluorescence assay (IFA) using Cryptosporidium specific antibody preparations. Positive stool samples were prepared for shipment for genetic polymorphism studies.
Future Activities:
Dose response curves for TU502 and a second genotype 1 isolate will be completed. In addition, serological and lymphocyte proliferation tests will be done.
Journal Articles on this Report : 6 Displayed | Download in RIS Format
| Other project views: | All 19 publications | 10 publications in selected types | All 10 journal articles |
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Alcantara CS, Yang C-H, Steiner TS, Barrett LJ, Lima AAM, Chappell CL, Okhuysen PC, White Jr AC, Guerrant RL. Interleukin-8, tumor necrosis factor-alpha, and lactoferrin in immunocompetent hosts with experimental and Brazilian children with acquired cryptosporidiosis. American Journal of Tropical Medicine and Hygiene 2003;68(3):325-328. |
R828035 (2001) R829180 (2002) |
Exit Exit |
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Messner MJ, Chappell CL, Okhuysen PC. Risk assessment for Cryptosporidium: a hierarchical Bayesian analysis of human dose response data. Water Research 2001;35(16):3934-3940. |
R828035 (2001) R829180 (2002) |
Exit Exit |
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Okhuysen PC, Chappell CL. Cryptosporidium virulence determinants – are we there yet? International Journal for Parasitology 2002;32(5):517-525. |
R828035 (2001) R829180 (2002) R829180 (Final) |
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Okhuysen PC, Rich SM, Chappell CL, Grimes KA, Widmer G, Feng X, Tzipori S. Infectivity of a Cryptosporidium parvum isolate of cervine origin for healthy adults and interferon-gamma knockout mice. Journal of Infectious Diseases 2002;185(9):1320-1325. |
R828035 (2001) R829180 (2002) |
Exit Exit |
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Padda RS, Tsai A, Chappell CL, Okhuysen PC. Molecular cloning and analysis of the Cryptosporidium parvum aminopeptidase N gene. International Journal for Parasitology 2002;32(2):187-197. |
R828035 (2001) R829180 (2002) |
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Teunis PFM, Chappell CL, Okhuysen PC. Cryptosporidium dose-response studies: variation between hosts. Risk Analysis 2002;22(3):475-485. |
R828035 (2001) R829180 (2002) |
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Supplemental Keywords:
mucosal immunity, coccidia, water quality, human subjects, animal subjects., RFA, Health, Scientific Discipline, Water, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, POLLUTANTS/TOXICS, Health Risk Assessment, Risk Assessments, Environmental Chemistry, Analytical Chemistry, Exposure, Microorganisms, Drinking Water, Genetics, Risk Assessment, immune system response, dietary exposure, Safe Drinking Water, treatment, water quality, water quality parameters, infectious disease, genotoxic biomarkers, human exposure, virulence characteristics, monitoring, genetic susceptibility, drinking water system, drinking water contaminants, drinking water treatment, infectivity, water treatment, cellular responses, coccidia, serologically positive humnas, microbial exposure, cryptosporidium parvum oocysts, gnotobiotic pigs, cryptosporidium, human health risk, exposure and effectsProgress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.