Journal of Medical Virology 80:1181–1188 (2008) Outbreaks of Hepatitis A in England and Wales Associated With Two Co-Circulating Hepatitis A Virus Strains Siew-Lin Ngui, 1 * Julia Granerod, 2 Linda A. Jewes, 3 Natasha S. Crowcroft, 2 and Chong-Gee Teo 1 on behalf of The 2002 Hepatitis A Outbreaks Investigation Network 1 Virus Reference Department, Health Protection Agency, London, United Kingdom 2 Immunisation Department Centre for Infections, Health Protection Agency, London, United Kingdom 3 Microbiology Department, Doncaster Royal Infirmary, Doncaster, United Kingdom During 2002, an upsurge in frequency of hepatitis A outbreaks among injecting drug users was observed in England and Wales. As lack of risk factor information and the high mobility of the cases made linkage of outbreaks difficult, the relationship of nucleotide sequences in the VP1/2PA junction of the hepatitis A virus (HAV) genome amplified from serum of case-patients was investigated. A total of 204 HAV RNA positive sera obtained from a network of 23 laboratories were studied. Comparison of the sequences identified two principal strains: ES1 (n ¼ 95) belonging to type IB, and ES2 (n ¼ 72) to type IIIA. Of the remaining samples, 15 were type IA, 11 were type IB and 11 were type IIIA. ES1 predominated in Doncaster and other towns in Trent and northern England, and ES2 in the Midlands and southern England; the difference in geographical distribution between these two strains was significant (P < 0.0001). In com- parison to the sporadic cases, cases infected by either ES1 or ES2 tended to be younger, injecting drug users, people in contact with injecting drug users, or those with a history of incarceration in prisons or homelessness (P < 0.0001). Cases infected by ES1 tended to be younger than those by ES2 (P < 0.0001). The association of the outbreaks to two geographically restricted strains implicates two principal transmission pathways associated with injecting behavior. Identifying these routes may be conducive to preventing further outbreaks. J. Med. Virol. 80:1181–1188, 2008. ß 2008 Wiley-Liss, Inc. KEY WORDS: molecular epidemiology; HAV; injecting drug use INTRODUCTION Hepatitis A virus (HAV) is a common cause of acute hepatitis worldwide. Seven different genotypes have been identified based on sequence variation in the VP1/2PA junction of the viral genome [Robertson et al., 1992]. Four genotypes (I–VII) circulate in humans and three (IV–VI) in Old World monkeys. Genotypes I and III have been subdivided into IA and IB, and into IIIA and IIIB, respectively. Globally, genotype I is dominant (comprising >80% of strains), followed by genotype III. Genotypes II and VII are represented by single strains. The four human genotypes are of a single serotype [Lemon and Binn, 1983], and current vaccine preparations, although generated against subtype IB, are protective against all. In hyper- endemic areas, the genotypes tend to be geographically restricted. In non-hyper-endemic regions, however, the circulating genotypes can differ due to importation from hyper-endemic regions. Transmission of HAV is primarily fecal–oral and the virus spreads easily from person to person. Trans- mission is common in crowded situations where poor sanitation prevails, that is, in childcare centers [de Paula et al., 2003], and following the ingestion of contaminated food [Massoudi et al., 1999; Sanchez et al., 2002; Wheeler et al., 2005]. Transmission also occurs among active homosexual men [Stene-Johansen et al., 2002], after parenteral administration of con- taminated blood clotting factors [Chudy et al., 1999], and among injecting drug users [Grinde et al., 1997; Stene-Johansen et al., 1998]. Although parenteral transmission is not the principal route of spread, its risk is greatest following contact with blood of an individual who is incubating HAV and about to enter the icteric phase of infection [Normann et al., 2004]. The authors have no commercial or other association that might pose a conflict of interest. *Correspondence to: Dr. Siew-Lin Ngui, Virus Reference Department, Centre for Infections, Health Protection Agency, 61 Colindale Avenue, London, UK. E-mail: siewlin.ngui@hpa.org.uk Accepted 11 March 2008 DOI 10.1002/jmv.21207 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2008 WILEY-LISS, INC.