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Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areasr

Published online by Cambridge University Press:  15 May 2009

W. J. Edmunds
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
G. F. Medley
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
D. J. Nokes
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
C. J. O'Callaghan
Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK
H. C. Whittle
MRC Laboratories, Fajara, PO Box 273, Banjul, The Gambia
A. J. Hall
London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK
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This paper uses meta-analysis of published data and a deterministic mathematical model of hepatitis B virus (HBV) transmission to describe the patterns of HBV infection in high endemicity areas. We describe the association between the prevalence of carriers and a simple measure of the rate of infection, the age at which half the population have been infected (A50), and assess the contribution of horizontal and perinatal transmission to this association. We found that the two main hyper-endemic areas of sub-Saharan Africa and east Asia have similar prevalences of carriers and values of A50, and that there is a negative nonlinear relationship between A50 and the prevalence of carriers in high endemicity areas (Spearman's Rank, P = 0·0086). We quantified the risk of perinatal transmission and the age-dependent rate of infection to allow a comparison between the main hyper-endemic areas. East Asia was found to have higher prevalences of HBeAg positive mothers and a greater risk of perinatal transmission from HBeAg positive mothers than sub-Saharan Africa, though the differences were not statistically significant. However, the two areas have similar magnitudes and age-dependent rates of horizontal transmission. Results of a simple compartmental model suggest that similar rates of horizontal transmission are sufficient to generate the similar patterns between A50 and the prevalences of carriers. Interrupting horizontal transmission by mass immunization is expected to have a significant, nonlinear impact on the rate of acquisition of new carriers.

Research Article
Copyright © Cambridge University Press 1996


1.Maynard, JE. Hepatitis B: global importance and need for control. Vaccine 1990; 8 (suppl): s18s20.CrossRefGoogle ScholarPubMed
2.Ghendon, Y. WHO strategy for the global elimination of new cases of hepatitis B. Vacine 1990; 8 (suppl): s129s133.CrossRefGoogle ScholarPubMed
3.Beasley, RP, Hwang, L-Y, Lin, C-C, Chien, C-SHepatocellular carcinoma and hepatitis B virus A prospective study of 22707 men in Taiwan. Lancet 1981; 2: 1129–33.CrossRefGoogle Scholar
4.Maynard, JE, Kane, MA, Hadler, SCGlobal controls of hepatitis B through vaccination: role of hepatitis B vaccine in the expanded programmes on immunization. Rev Infect Dis 1989; 11 (suppl 3): s574s578.Google Scholar
5.Andre, FE. Overview of a 5-year clinical experience with a yeast-derived hepatitis B vaccine. Vaccine 1980; 8 (suppl 3): s74s78.Google Scholar
6.Coursaget, P, Yvonnet, B, Chotard, J, et al. Seven-year study of hepatitis B vaccine efficacy in infants from an endemic area (Senegal). Lancet 1986; ii: 1143–5.Google Scholar
7.Coursaget, P., Yvonnet, B, Gilks, WR, et al. Scheduling of revaccination against hepatitis B virus. Lancet 1991; 337: 1180–3.CrossRefGoogle ScholarPubMed
8.Whittle, HC, Inskip, H, Hall, AJ, Mendy, M, Downes, R, Hoare, S. Vaccination against hepatitis B and protection against chronic viral carriage in The Gambia. Lancet 1991; 337: 747–50.Google Scholar
9.Pearce, N, Milne, AHepatitis B virus: the importance of age at infection. NZ Med J 1988; 101: 788–90.Google Scholar
10.McMahon, BJ, Alward, WLM, Hall, DB, et al. Acute hepatitis B virus infection: Relation of age to the clinical expression of disease and subsequent development of the carrier state. J Infect Dis 1985; 151: 599603.CrossRefGoogle Scholar
11.Coursaget, P, Yvonnet, B, Chotard, J, et al. Age- and sex-related study of hepatitis B virus chronic carrier state in infants from an endemic area (Senegal). J Med Virol 1987; 22: 15.CrossRefGoogle ScholarPubMed
12.Beasley, RP, Hwang, L-Y, Lin, C-C, et al. Hepatitis B immune globulin (HBIg) efficacy in the interuption of perinatal transmission of hepatitis B virus carrier state. Lancet 1981; ii: 388–93.Google Scholar
13.Stevens, CE, Beasley, RP, Tsui, J, Lee, W-CVertical transmission of hepatitis B antigen in Taiwan. New Engl J Med 1975; 292: 771–4.CrossRefGoogle ScholarPubMed
14.Stevens, CE, Neurath, RA, Beasley, RP, Szmuness, W. HBeAg and anti-HBe detection by radioimmunoassay: correlation with vertical transmission of hepatitis B virus in Taiwan. J Med Virol 1979; 3: 237–41.CrossRefGoogle ScholarPubMed
15.Iwarson, S.Hermodsson, SHepatitis associated antigen (HAA) in acute viral hepatitis. Scand J Infect Dis 1971; 3: 93101.Google Scholar
16.Tassopoulos, NC, Papaevangelou, GJ, Sjogren, MH, Roumeliotou-Karayannis, A, Germ, JL, Purcell, RHNatural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterol 1987;92: 1844–50.CrossRefGoogle ScholarPubMed
17.Nielsen, JO, Dietrichson, O, Elling, P, Christoffersen, P. Incidence and meaning of persistence of Australia antigen in patients with acute viral hepatitis: Development of chronic hepatitis. New Engl J Med 1971; 285: 1157–60.CrossRefGoogle ScholarPubMed
18.Edmunds, WJ, Medley, GF, Nokes, DJ, Hall, AJ, Whittle, HC. The influence of age on the development of the hepatitis B virus (HBV) carrier state. Proc Roy Soc (Lond) Series B 1993; 253: 197201.Google Scholar
19.Khashiwagi, S, Hayashi, J, Ikematsu, H, et al. Transmission of hepatitis B virus among siblings. Am J Epidemiol 1984; 120: 617–25.Google Scholar
20.Toukan, AU, Sharaiha, ZK, Abu-El-Rub, OA et al. The epidemiology of hepatitis B virus among family members in the Middle East. Am J Epidemiol 1990; 132:220–32.CrossRefGoogle ScholarPubMed
21.Overby, LR, Ling, C-M, Decker, RH, Mushahwar, IK, Chau, K. Serodiagnostic profiles of viral hepatitis. In: Szmuness, W, Alter, MJ, Maynard, JE, eds. Viralhepatitis. Philadelphia: Franklin Institute Press, 1982:169–82.Google Scholar
22.Prince, AM. An antigen detected in the blood during the incubation period of serum hepatitis. Proc Natl Acad Sci USA 1968; 60: 814–21.Google Scholar
23.Hadler, SC, Margolis, HS. Viral hepatitis. In: Evans, AS, ed. Viral infections of humans. Epidemiology and control, 3rd ed.New York: Plenum, 1991: 351–91.CrossRefGoogle Scholar
24.McMahon, BJ, Parkinson, AJ, Helminiak, C, et al. Response to hepatitis B vaccine of persons positive for antibody to hepatitis B core antigen. Gastroenterol 1992; 103: 590–4.Google Scholar
25.Deinhardt, F. Predictive value of markers of hepatitis virus infection. J infect Dis 1980; 141: 299305.CrossRefGoogle ScholarPubMed
26.Whittle, H, Inskip, H, Bradley, AK, et al. The pattern of childhood hepatitis B infection in two Gambian villages. J Infect Dis 1990; 161: 1112–5.Google Scholar
27.Tabor, E, Bayley, AC, Cairns, J, Pelleu, , Gerety, RJ. Horizontal transmission of hepatitis B virus among children and adults in five rural villages in Zambia. J Med Virol 1985; 15: 113–20.CrossRefGoogle ScholarPubMed
28.Bowry, TR. Seroepidemiology of hepatitis B in an urban population of Nairobi, Kenya. J Infect Dis 1983; 148:1122.CrossRefGoogle Scholar
29.Hyams, KC, Al-Arabi, MA, Al-Tagani, AA, Messiter, JF, Al-Gaali, AA, George, JFEpidemiology of hepatitis B in the Gezira Region of Sudan. Am J Trop Med Hyg 1989; 40: 200–6.Google Scholar
30.Feret, E, Larouze, B, Diop, B, Sow, M, London, WT, Blumberg, BS. Epidemiology of hepatitis B infection in the rural community of Tip, Senegal. Am J Epidemiol 1987; 125: 140–9.CrossRefGoogle ScholarPubMed
31.Prozesky, OW, Szmuness, W, Stevens, CE, et al. Baseline epidemiological studies for a hepatitis B vaccine trial in Kangwane. S Afr Med J 1983; 64: 891–3.Google ScholarPubMed
32.Chung, D-C, Ko, Y-C, Chen, C-J, et al. Seroepidemiological studies on hepatitis B and D viruses infection among five ethnic groups in Southern Taiwan. J Med Virol 1988; 26: 411–8.Google Scholar
33.Lingao, AL, Domingo, EO, West, S, et al. Seroepidemiology of hepatitis B in the Philippines. Am J Epidemiol 1986; 123: 473–80.CrossRefGoogle ScholarPubMed
34.Hu, M, Schenzle, D, Deinhardt, F, Scheid, R. Prevalence of markers of hepatitis A and B in the Shanghai Area. J. Infect Dis 1983; 147: 360.CrossRefGoogle Scholar
35.Mazzur, S, Bastiaans, MJS, Nath, N. Hepatitis B virus (HBV) infection among children and adults in the Soloman Islands. Am J Epidemiol 1981; 113: 510–9.Google Scholar
36.Boutin, J-P, Flye Sainte Marie, F, Cartel, J-L, Cardines, R, Girard, M, Roux, J. Prevalence of hepatitis B virus infection in the Austral archipelago, French Polynesia: identification of transmission patterns for the formulation of immunization strategies. Trans R Soc Trop Med Hyg 1990; 84: 283–7.CrossRefGoogle ScholarPubMed
37.Torres, JR, Mondolfi, A. Protracted outbreak of severe delta hepatitis: Experience in an isolated Amerindian population of the Upper Orinoco Basin. Rev Infect Dis 1991; 13: 52–5.Google Scholar
38.Swenson, PD. Hepatitis viruses. In: Balows, A, Hausler, WJ Jr, Herrmann, KL, Isenberg, HD, Shadomy, HJ, eds. Manual of clinical microbiology, 5th ed.Washington D.C.: American Society for Microbiology, 1991: 959–83.Google Scholar
39.Schweitzer, IL. Vertical transmission of the hepatitis B surface antigen. Am J Med Sci 1975; 270: 287–91.CrossRefGoogle ScholarPubMed
40.Sokal, RR, Rohlf, FJBiometry. San Francisco: W. H. Freeman and Company, 1969.Google Scholar
41.Anderson, RM, May, RM. Infectious diseases of humans. Oxford: Oxford University Press, 1991.Google Scholar
42.Anderson, RM, May, RM. Vaccination against rubella and measles: quantitative investigations of different policies. J Hyg 1983; 90: 259325.CrossRefGoogle ScholarPubMed
43.Grenfell, BT, Anderson, RMThe estimation of age-related rates of infection from case notifications and serological data. J Hyg 1985; 95: 419–36.Google Scholar
44.Margolis, HSPrevention of chronic liver disease through immunization: Hepatitis B and beyond. J Infect Dis 1993; 168: 914.CrossRefGoogle ScholarPubMed
45.Gebreselassie, L. Prevalance of specific markers of viral hepatitis A and B among an Ethiopian population. Bull WHO 1983; 61: 991–6.Google Scholar
46.Milne, A, Allwood, GK, Moyes, CD, Pearce, NE, Lucas, CR. Prevalence of hepatitis B infections in a multiracial New Zealand community. NZ Med J 1985; 98: 529–32.Google Scholar
47.Sobeslavsky, O. Prevalence of markers of hepatitis B virus infection in various countries: a WHO collaborative study. Bull WHO 1980; 58: 621–8.Google ScholarPubMed
48.Beasley, RP, Trepo, C, Stevens, CE, Szmuness, W. The e antigen and vertical transmission of hepatitis B surface antigen. Am J Epidemiol 1977; 105: 94–8.CrossRefGoogle Scholar
49.Beasley, RP, Hwang, L-Y, Lee, GC-Y, et al. Prevention of perinatally transmitted hepatitis B virus infections with hepatitis B immune globulin and hepatitis B vaccine. Lancet 1983; ii: 1099–102.Google Scholar
50.Bortolotti, F, Cadrobbi, P, Crivellaro, C, Bertaggia, A, Alberti, A, Realdi, G. Chronic hepatitis type B in childhood: longitudinal study of 35 cases. Gut 1981; 22: 499504.CrossRefGoogle ScholarPubMed
51.Alward, WLM, McMahon, BJ, Hall, DB, Heyward, WL, Francis, DP, Bender, TR. The long term serological course of asymptomatic B virus carriers and the development of primary hepatocellular carcinoma. J Infect Dis 1985; 151: 604–9.Google Scholar
52.McMahon, BJ, Alberts, SR, Wainwright, RB, Bulkow, L, Lanier, AP. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers. Arch Intern Med 1990; 150:1051–4.Google Scholar
53.Bortolotti, F, Cadrobbi, P, Crivellaro, C, et al. Long-term outcome of chronic type B hepatitis in patients who acquire hepatitis B virus infection in childhood. Gastroenterol 1990; 99: 805–10.Google Scholar
54.Tong, MJ, Thursby, MW, Lin, J-H, Weissman, JY, McPeak, CM. Studies on the maternal-infant transmission of the hepatitis B virus and HBV infection within families. Prog Med Virol 1981; 27 137–47.Google ScholarPubMed
55.Schweitzer, IL, Mosley, JW, Ashcavai, M, Edwards, VM, Overby, LB. Factors influencing neonatal infection by hepatitis B virus. Gastroenterol 1973; 65: 277–83.CrossRefGoogle ScholarPubMed
56.Shiraki, K, Yoshihara, N, Kawana, T, Yasui, H, Sakurai, M. Hepatitis B Surface Antigen and Chronic Hepatitis in Infants born to Asymptomatic Carrier Mothers. Am J Dis Child 1977; 131: 644647.Google ScholarPubMed
57.Okada, K, Yamada, T, Miyakawa, Y, Mayumi, M. Hepatitis B Surface Antigen in the Serum of Infants After Delivery from Asymptomatic Carrier Mothers. J Pediatric 1975; 87: 360363.CrossRefGoogle ScholarPubMed
58.Greenfield, C, Osidiana, V, Karayiannis, P, Galpin, S, Musoke, R, Jowett, TP, et al. Perinatal Transmission of Hepatitis B Virus Transmission in Kenya: Its Relation to the Level of Serum HBV-DNA and Anti-HBe in the Mother. J Med Virol 1986; 19: 135142.Google Scholar
59.Lau, Y-L, Chow, C-B, Leung, T-H. Changing epidemiology of measles in Hong Kong from 1961 to 1990 – Impact of measles vaccination program. J Infec Dis 1991; 165: 11111115.Google Scholar
60.Marinier, E, Barrois, V, Larouze, B, London, WT, Cofer, A, Diakhate, L, et al. Lack of Perinatal Transmission of Hepatitis B Virus Infection in Senegal, West Africa. J Pediatric 1985; 106: 843849.Google Scholar
61.Barin, F, Perrin, J, Chotard, J, Denis, F, N'Doye, R, Mar, ID, et al. Cross-sectional and longitudinal epidemiology of hepatitis B in Senegal. Prog Med Virol 1981; 27: 148162.Google Scholar
62.Tsega, E, Tsega, M, Mengesha, B, Nordenfelt, E, Hansson, B-G, Lindberg, J. Transmission of Hepatitis B virus Infection in Ethiopia with Emphasis on the Importance of Vertical Transmission. Int J Epidemiol 1988; 17: 874879.Google Scholar
63.Botha, JF, Ritchie, MJJ, Dushieko, GM, Mouton, HWK, Kew, MC. Hepatitis B Virus Carrier State in Black Children in Ovamboland: Role of Perinatal and Horizontal Infection. Lancet 1984; 1: 12101212.Google Scholar
64.Haukenes, G, Shao, JF, Mbena, E, Rustad, S. Hepatitis B markers in the population of Dar es Salaam, Tanzania. J Infect 1987; 15: 183–8.Google Scholar
65.Wong, VCW, Lee, AKY, Ip, MMH. Transmission of hepatitis B antigen from symptom free carrier mothers to the fetus and the infant. Br J Obstet Gynecol 1980; 87: 958–65.Google Scholar
66.Wong, VCW, Ip, HMH, Reesink, HW, et al. Prevention of the HBsAg carrier state in newborn infants of mothers who are chronic carriers of HBsAg and HBeAg by administration of hepatitis-B vaccine and hepatitis-B immunoglobulin. Lancet 1984; 8: 921–6.Google Scholar
67.Okada, K, Yamada, T, Miyakawa, Y, Mayumi, M. Hepatitis B surface antigen in the serum of infants after delivery from asymptomatic carrier mothers. J Pediatric 1975; 87: 360–3.CrossRefGoogle ScholarPubMed
68.Pongpipat, D, Suvatte, V, Assateerawatts, A. Vertical transmission of the hepatitis B surface antigen in Thailand. Southeast Asian J Trop Med Pub Hlth 1980; 11: 582–7.Google Scholar
69.Nayak, NC, Panda, SK, Zuckerman, AJ, Bhan, MK, Guha, DK. Dynamics and impact of perinatal transmission of hepatitis B virus in North India. J Med Virol 1987; 21: 137–45.CrossRefGoogle ScholarPubMed
70.Biswas, SC, Gupta, I, Ganguly, NK, Chawla, Y, Dilawari, JBPrevalence of hepatitis B surface antigen in pregnant mothers and its perinatal transmission. Trans R Soc Trop Med Hyg 1989; 83: 698700.CrossRefGoogle ScholarPubMed
71.Hyams, KC, Osman, NM, Khaled, EM, et al. Maternal- infant transmission of hepatitis B in Egypt. J Med Virol 1988; 24: 191–7.Google Scholar
72.Reniers, J, Vrancks, R, Ngantung, W, Sugita, E, Meheus, A. Prevalence and determinants of hepatitis B virus markers in pregnant women in West Java, Indonesia. J Trop Med Hyg 1987; 90: 249–53.Google ScholarPubMed
73.Al-Nakib, B, El-Mekki, A, Al-Kandari, S, Nordenfelt, E, Al-Nakib, W. Hepatitis B virus perinatal transmission among arab women. Ann Trop Ped 1986; 6: 239–41.CrossRefGoogle ScholarPubMed
74.Goudeau, A, Yvonnet, B, Lesage, G, et al. Lack of antiHBc IgM in neonates with HBsAg carrier mothers argues against transplacental transmission of hepatitis B virus infection. Lancet 1983; 2: 1103–4.Google Scholar
75.Chen, D-S, Sung, J-L, Lai, M-Y, et al. Inadequacy of immunoglobulin M hepatitis B core antibody in detecting acute hepatitis B virus infection in infants of HBsAg carrier mothers. J Med Virol 1985; 16: 309–14.Google Scholar
76.Shiraki, K, Yoshihara, N, Sakurai, M, Eto, T, Kawana, T. Acute hepatitis B in infants born to carrier mothers with the antibody to hepatitis B e antigen. J Pediatric 1980; 97: 768–72.Google Scholar
77.Hwang, L-Y, Roggendorf, M, Beasley, RP, Deinhardt, F. Perinatal transmission of hepatitis B virus: role of maternal HBeAg and anti-HBc IgM. J Med Virol 1985; 15: 265–9.Google Scholar
78.Lee, AKY, Ip, HMH, Wong, VCW. Mechanisms of maternal-fetal transmission of hepatitis B virus. J Infect Dis 1978; 138: 668–71.CrossRefGoogle ScholarPubMed
79.Panda, SK, Gupta, A, Datta, R, Nayak, NC. Transplacental transmission of hepatitis B virus. Lancet 1986; ii: 919–20.Google Scholar
80.Panda, SK, Bhan, MK, Guha, DK, et al. Significance of maternal and infant serum antibodies to hepatitis B core antigen in hepatitis B virus infection in infancy. J Med Virol 1988; 24: 343–9.Google Scholar
81.Derso, A, Boxall, EH, Tarlow, MJ, Flewett, TH. Transmission of HBsAg from mother to infant four ethnic groups. BMJ 1978; 1: 949–52.CrossRefGoogle ScholarPubMed
82.De Virgiliis, S, Frau, F, Sanna, G, et al. Perinatal hepatitis B virus detection by hepatitis B virus-DNA analysis. Arch Dis Child 1985; 60: 5660.Google Scholar