Hepatitis viruses. Clinical samples from patients with acute or chronic non-A, B, C, D, E hepatitis in the United States are being studied for biological, serological or molecular evidence of transmissible agents. Patients with fulminant non-A to E hepatitis remain a diagnostic enigma and may be infected with one or more previously unrecognized viruses. We are attempting to discover the etiology of this disease. Evidence for the existence of an additional water-borne hepatitis virus has come from our seroepidemiologic studies in India, Egypt and Saudi Arabia. We are attempting to transmit an agent from clinical specimens of such patients. Hepatitis E virus may be emerging as a greater public health problem than previously thought. We are studying its epidemiology in developing and industrialized countries worldwide. Serologic evidence of infection of swine with hepatitis E virus (HEV) was obtained. A new and unique HEV strain was recovered from infected swine and characterized. It was shown to have a worldwide distribution. Seroepidemiological studies of swine handlers and matched blood donors have shown an excess of antibody to HEV in swine handlers, suggesting that the virus may be zoonotically spread. Similar serologic evidence for infection of wild rats with HEV has also been obtained and the infecting agent is being sought. To date we have successfully transmitted the agent from rats trapped in Los Angeles to laboratory rats of the same species (Rattus norvegicus). However, transmission has been difficult, suggesting that the virus replicates at low titer. We have prepared a relatively high-titered pool of the virus in SCID rats. Studies to determine if rat HEV is linked to human infection are in progress. Modern techniques of molecular biology have been used to discover new viruses in recent years. These are now being applied to prospectively collected sera from patients with transfusion-associated hepatitis in a search for new hepatitis viruses that may cause up to 15% of such hepatitis in the US. In an attempt to increase the sensitivity of specific virus discovery technologies (i.e., those capable of amplifying unique sequences without regard to the sequence), we have introduced modifications to existing techniques that have improved the sensitivity of the assay. Using the new technology, we have discovered two previously unrecognized bovine parvoviruses that contaminate most lots of bovine serum. This finding has implications for the safety of biologicals that are prepared with bovine serum. Kawasaki Disease is a life-threatening illness of young children. It has the epidemiologic characteristics of an infectious disease. The HVS and MHS are attempting to transmit a putative agent from acute phase clinical samples of children with Kawasaki Disease to nonhuman primates. Preliminary results have been promising.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000311-24
Application #
7192828
Study Section
(LID)
Project Start
Project End
Budget Start
Budget End
Support Year
24
Fiscal Year
2005
Total Cost
Indirect Cost
Name
Niaid Extramural Activities
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Christensen, Peer B; Engle, Ronald E; Hjort, Charlotte et al. (2008) Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin Infect Dis 47:1026-31
Purcell, R H; Emerson, S U (2008) Hepatitis E: an emerging awareness of an old disease. J Hepatol 48:494-503
Yu, Claro; Zimmerman, Carl; Stone, Roger et al. (2007) Using improved technology for filter paper-based blood collection to survey wild Sika deer for antibodies to hepatitis E virus. J Virol Methods 142:143-50
Easterbrook, J D; Kaplan, J B; Vanasco, N B et al. (2007) A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland, USA. Epidemiol Infect 135:1192-9
Meky, Fatma A; Stoszek, Sonia K; Abdel-Hamid, Mohamed et al. (2006) Active surveillance for acute viral hepatitis in rural villages in the Nile Delta. Clin Infect Dis 42:628-33
Stoszek, Sonia K; Abdel-Hamid, Mohamed; Saleh, Doa'a A et al. (2006) High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans R Soc Trop Med Hyg 100:95-101
Stoszek, Sonia K; Engle, Ronald E; Abdel-Hamid, Mohamed et al. (2006) Hepatitis E antibody seroconversion without disease in highly endemic rural Egyptian communities. Trans R Soc Trop Med Hyg 100:89-94
Graff, Judith; Nguyen, Hanh; Yu, Claro et al. (2005) The open reading frame 3 gene of hepatitis E virus contains a cis-reactive element and encodes a protein required for infection of macaques. J Virol 79:6680-9
Graff, Judith; Nguyen, Hanh; Kasorndorkbua, Chaiyan et al. (2005) In vitro and in vivo mutational analysis of the 3'-terminal regions of hepatitis e virus genomes and replicons. J Virol 79:1017-26
Emerson, Suzanne U; Arankalle, Vidya A; Purcell, Robert H (2005) Thermal stability of hepatitis E virus. J Infect Dis 192:930-3

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