Journal of Medical Virology 84:587–595 (2012) Multiple Intra-Familial Transmission Patterns of Hepatitis B Virus Genotype D in North-Eastern Egypt Mostafa Ragheb, 1 Abeer Elkady, 2 Yasuhito Tanaka, 2 * Shuko Murakami, 2 Fadia M. Attia, 3 Adel A. Hassan, 1 Mohamed F. Hassan, 1 Mahmoud M. Shedid, 1 Hassan B. Abdel Reheem, 1 Anis Khan, 2 and Masashi Mizokami 4 1 Department of Endemic and Infectious Disease, Suez Canal University, Ismailia, Egypt 2 Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya, Japan 3 Department of Clinical Pathology Faculty of Medicine, Suez Canal University, Ismailia, Egypt 4 Research Centre for Hepatitis and Immunology, International Medical Centre of Japan Konodai Hospital, Tokyo, Japan The transmission rate of intra-familial hepatitis B virus (HBV) and mode of transmission were investigated in north eastern Egypt. HBV infec- tion was investigated serologically and con- firmed by molecular evolutionary analysis in family members (N ¼ 230) of 55 chronic hepati- tis B carriers (index cases). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prevalence was 12.2% and 23% among family members, respectively. HBsAg carriers were prevalent in the age groups; <10 (16.2%) and 21–30 years (23.3%). The preva- lence of HBsAg was significantly higher in the family members of females (19.2%) than males (8.6%) index cases (P ¼ 0.031). HBsAg and anti- HBc seropositive rates were higher significantly in the offspring of females (23%, 29.8%) than those of the males index cases (4.3%, 9.8%) (P ¼ 0.001, 0.003), as well as higher in the off- spring of an infected mother (26.5, 31.8%) than those of an infected father (4.7%, 10.5%) (P ¼ 0.0006, 0.009). No significant difference was found in HBsAg seropositive rates between vaccinated (10.6%) and unvaccinated family members (14.8%). Phylogenetic analysis of the preS2 and S regions of HBV genome showed that the HBV isolates were of subgenotype D1 in nine index cases and 14 family members. HBV familial transmission was confirmed in five of six families with three transmission pat- terns; maternal, paternal, and sexual. It is con- cluded that multiple intra-familial transmission routes of HBV genotype D were determined; in- cluding maternal, paternal and horizontal. Uni- versal HBV vaccination should be modified by including the first dose at birth with (HBIG) administration to the newborn of mothers infected with HBV. J. Med. Virol. 84:587– 595, 2012. ß 2012 Wiley Periodicals, Inc. KEY WORDS: HBV genotype D; intra-familial transmission; vaccine INTRODUCTION Chronic hepatitis B virus (HBV) infection is a major health problem worldwide and is affecting approxi- mately 350 million individuals [Lee, 1997]. Infection with HBV may lead to chronic state of hepatitis in 5–10% of patients who acquired the infection in the adult life and in 80–90% of patients who acquired the infection in the infancy [Chen, 1993]. Infection with HBV can lead to a progressive liver disease including liver cirrhosis and hepatocellular carcinoma (HCC) with approximately 1 million HBV-associated deaths from HCC every year [Seeger and Mason, 2000; Kao and Chen, 2002]. Based on the proportion of the population who are seropositive for hepatitis B surface antigen (HBsAg), Grant sponsor: The Grant for National Center For Global Health and Medicine; Grant number: 22A-9; Grant sponsor: Grant-in-Aid for Japan Society for the Promotion of Science (JSPS) Fellows; Grant number: 21.09355. Mostafa Ragheb and Abeer Elkady contributed equally to this study. *Correspondence to: Yasuhito Tanaka, MD, PhD, Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho, Nagoya 467- 8601, Japan. E-mail: ytanaka@med.nagoya-cu.ac.jp Accepted 19 December 2011 DOI 10.1002/jmv.23234 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2012 WILEY PERIODICALS, INC.