AMERICAN JOURNAL OF EPIDEMIOLOGY Vol. 112, 4 Copyright 1980 by The Johns Hopkins University School of Hygiene and Public Health Printed in U.S-A. All rights reserved EPIDEMIOLOGIC CHARACTERISTICS OF HEPATITIS A VIRUS INFECTIONS IN GREECE 1 GEORGE J. PAPAEVANGELOU, 2 KYRIAKI P. GOURGOULI-FOTIOU AND HARALAMBOS G. VISSOULIS Papaevangelou, G. J. (National Centre for Viral Hepatitis, P.O. Box 3085, Athens, Greece), K. P. Gourgouli-Fotiou and H. G. Vissoulis. Epidemiologic characteristics of hepatitis A virus infections in Greece. Am J Epidemiol 112:482-486, 1980. The major epidemiologic characteristics of hepatitis A virus (HAV) infections in Greece were studied in a sample of Air Force recruits, 19-25 years old coming from every geographic region of Greece. Antibodies to HAV (anti- HAV) were detected by solid phase radioimmunoassay in of the recruits. Antibody frequency varied significantly in the various geographic regions of Greece and was inversely related to the size of the community. It was further shown that the prevalence of HAV infection was highly related to the recruit's social class and years of education as well as number of siblings and number of persons per room. These findings in accordance with previous reported data show that hepatitis A is hyperendemic and should be regarded as a childhood infection in Greece. Prevailing socioeconomic, hygienic living and housing conditions should be considered as the main epidemiologic determinants of HAV infections. antibodies; hepatitis A virus; infection; socioeconomic factors Viral hepatitis is considered a major says for the detection of hepatitis A virus public health problem. Extensive epide- (HAV) and its antibody (anti-hav) were miologic observations and experimental developed (3, 4). In previous studies we studies have defined the characteristics of have shown that in contrast to northwesttwo distinctive types of the disease (1). em European countries, HAV infection is However the discovery of hepatitis B sur- still hyperendemic in Greece (5, 6). In the face antigen (HBsAg) by Blumberg et al. present communication we report the re- (2) provided the specific laboratory assays suits of an investigation to define further for challenging some inferences based on the main epidemiologic characteristics of epidemiologic observations. Many of HAV infections in Greece, these epidemiologic characteristics were clarified when sensitive and specific as- MATERIALS AND METHODS Subjects. The sample consisted of men, 19 25 years old, recruited in the Received for publication September 24, 1979, and Air Force j 197g E geographic rein final form January 28, 1980.. j it i Abbreviations: HAV, hepatitis A virus; anti-hav, g lon was represented in the sample proantibody to hepatitis A virus. portionally to its size. Because no signifi- -From the Department of Epidemiology andimed- cant gex difference exists (5) and service ical Statistics, Athens School of Hygiene and Red.,,.,,-,.,,-. «. in Cross Hospital of Athens, Greece. th e Armed Forces is obligatory for 2 Reprint requests to Dr. Papaevangelou, National every man in Greece with recruitment Centre for Viral Hepatitis, P.O. Box 3085, Athens standards almost the Same for all This study was supported by a grant from the Ministry of Social Services of Greece. branches of the military, the sample studied should be considered as roughly 482
HEPATITIS A VIRUS INFECTIONS IN GREECE 483 representative of the 19-25-year-old population of Greece. Relevant epidemiologic information and a blood sample were collected on the day of recruitment. Recruits were classified in social classes according to their or their father's occupation (7). The number of years of education was used as another index of socioeconomic status. Information regarding family size, number of siblings and number of rooms per family was also collected from 570 of the recruits studied. Laboratory test. Anti-HAV was detected by solid phase radioimmunoassay using commercially available reagents ("HAVAB," Abbott Laboratories, North Chicago, IL). Statistical tests. Variation between frequency rates was tested by x 2 test. The x 2 test was also used for testing the significance of the trend in proportions (8). Geographic regions Greater Athens Rest of Central Greece and Euboea Pelopennesos Ionian Islands Epirus Thessaly Macedonia Thrace Aegean Islands Crete TABLE 1 Frequency () of anti-hav by geographic region examined 220 99 113 19 38 71 201 33 29 54 RESULTS Anti-HAV was detected in (83.3 per cent) of the recruits studied. Table 1 shows that the prevalence of anti-hav varies (69-95 per cent) significantly (xi = 47.9, p < 0.01) in the geographic regions of Greece. The lowest frequency was found in the Greater Athens area (69 per cent). Similarly, table 2 shows that there is a statistically significant (p < 0.01) inverse relationship between the size of the community and the frequency of anti-hav. The prevalence of HAV infections is highly related to the prevailing socioeconomic conditions. A significant (p < 0.01) trend in the frequency of anti- HAV according to social class (table 3) or years of education (table 4) was found. The trend is more significant when the father's rather than the recruit's occupation is used as the criterion of socioeconomic status, indicating that the conditions prevailing during childhood are more important for the spread of the infection. Living and housing conditions are very important in the spread of infections. Thus, the frequency of anti-hav increases from 79.0 per cent when there is no sibling to 94.8 per cent in families with more than four siblings (table 5). Similarly, the frequency increases significantly (p < 0.01) with the number of persons per room (table 6), indicating that overcrowding facilitates the person to person transmission of HAV. DISCUSSION The results of the present investigation reveal a high and widespread prevalence of anti-hav, presumably largely induced by subclinical infections, which confirm Anti-HAV 152 93 98 15 36 67 173 27 24 50 positive 69.0 93.9 86.7 78.9 94.7 94.3 86.0 81.8 82.7 92.5
484 PAPAEVANGELOU, GOURGOULI-FOTIOU AND V1SSOULIS that hepatitis A is hyperendemic in Greece (5). Our results stress the importance of the prevailing socioeconomic, hygienic and housing conditions in the spread of HAV infection. Hygienic and housing conditions are relatively satisfactory in urban areas and especially in the larger cities. In contrast, adequate water distribution and sewage disposal are lacking in many villages and hygiene and housing are substandard. This accounts for waterborne epidemics that do occur occasionally (9), although most infections TABLE 2 Frequency () of anti-hav by size of community Size of community examined < 10,000 10,000-99.999 5=100,000 363 218 296 330 190 215 90.9 87.2 72.6 are transmitted from person to person by close contact (10). Socioeconomic and hygienic conditions prevailing during early childhood rather than later in life should be considered as the major determinants of HAV infection. This has been indicated by the larger social class difference in the frequency of anti-hav shown when classification is based on the father's rather than the recruit's occupation. The data on anti-hav prevalence in Greece should be considered as typical of what we expect in person to person transmission of an hyperendemic infection, and characterize hepatitis A as a childhood infection in Greece. These findings are in accordance with our previous investigations showing that HAV accounts for the great majority (78 per cent) of the sporadic acute viral hepatitis cases in children (11), but only for a very small fraction (11 per cent) of such cases among adults (12). TABLE 3 Frequency () of anti-hav by social class according to the occupation of the recruit or his father class I* II III IV + V Occupation of the recruit examined 227 206 203 241 * I, highest social class. 176 174 175 210 77.5 84.5 86.2 87.1 Occupation examined 53 199 107 518 of the father Anti-HAV 34 151 88 462 positive 64.2 75.9 82.2 89.2 TABLE 4 TABLE 5 Frequency () of anti-hav by number of siblings Years of study >12 9-12 <9 of school education examined 478 317 82 Anti-HAv positive 386 276 73 80.8 87.1 89.0 : of siblings 0 2 3 4+ examined 48 282 145 56 39 570 38 240 123 52 37 490 79.0 85 1 84.8 92.8 94.8 85.9
TABLE 6 Frequency () of anti-hav by number of persons per room of persons per room 1 2 3 4+ 349 183 23 15 570 HEPATITIS A VIRUS INFECTIONS IN GREECE 485 293 162 21 14 490 83.9 88.5 91.3 93.3 85.9 The situation is not similar in the more developed countries. The frequency of anti-hav among comparable population groups is substantially lower in Sweden (3 per cent), Germany (30 per cent), USA (35-40 per cent), Australia (!"" 45 per cent) and other more developed countries (6, 13-16). Similarly, the relative proportion of acute hepatitis A among adults is more common in Germany (17 per cent), USA (20-25 per cent), Australia (43 per cent) and other developed countries (17-19). The decrease of HAV infections and the increase of the proportion of cases among young adults should be attributed to recent improvements in hygiene and sanitation in the more developed countries. Thus, in Australia (19) the morbidity of non-b hepatitis has declined during the last decade and its proportion among young adults has increased considerably (33 per cent in 1969, 61 per cent in 1977). In USA a steady downward trend in type A hepatitis cases has been established since 1971 (20). A like trend has been reported for Denmark and other countries. Mathematical analysis of anti- HAV prevalence data has shown that a slight decline in the incidence of HAV infection has recently started in urban in contrast to rural areas of Greece (6). Such a decline is expected to cause an increase in the relative proportion of cases among adults and a higher attack rate in common vehicle epidemics as has been already reported in USA (21). REFERENCES 1. Krugman S, Giles JP, Hammond J: Infectious hepatitis: Evidence for two distinctive clinical, epidemiological, and immunological types of infection. JAMA 200:365-373, 1967 2. Blumberg BS, Gerstley BJS, Hungerford DA, et al: A serum antigen (Australia antigen) in Down's syndrome, leukemia, and hepatitis. Ann Intern Med 66:924-931, 1967 3. Feinstone SM, Kapikian AZ, Purcell RH: Hepatitis A: Detection by immune electron microscopy of a virus-like antigen associated with acute illness. Science 182:1026-1028, 1973 4. Purcell RH, Wong DC, Moritsugu Y, et al: A microtiter solid-phase radioimmunoassay for hepatitis A antigen and antibody. J Immunol 116:349-356, 1976 5. Papaevangelou G, Frosner G: Seroepidemiological studies of hepatitis A virus infection in Greece. Iatriki 34:226-229, 1978 6. Frosner G, Papaevangelou G, Butler R, et al: Antibody against hepatitis A in seven European countries. I. Comparison of prevalence data in different age groups. Am J Epidemiol 110:63-69, 1979 7. General Register Office: Classification of occupations. Her Majesty's Stationery Office, London, 1950 8. Armitage P: Statistical methods in medical research. Oxford, Blackwell Scientific Publication, 1971, p 363 9. Kanellakis A, Violaki M, Papadakis J: Investigation of the infectious hepatitis epidemic in Seres, Greece. Arch Hyg 16:334-343, 1966 10. Papaevangelou G, Mosley JW, Kyriakidou A, et al: Viral hepatitis: Lack of transmission in an Athenian school. Int J Epidemiol 7: 341-345, 1978 11. Papaevangelou G: Epidemiological aspects of hepatitis A virus infection. International Symposium on Viral Hepatitis Munchen, FRG, April 1979, p 8 12. Papaevangelou G, Decker R, Contoyannis P, et al: Differential serodiagnosis of sporadic acute viral hepatitis. Proc Soc Exp Biol Med 161:322-325, 1979 13. Szmuness W, Dienstag JL, Purcell RH, et al: Distribution of antibody to hepatitis A antigen in urban adult populations. N Engl J Med 295:755-759, 1976 14. Maynard JE, Bradley DW, Hornbeck CL, et al: Preliminary serologic studies of antibody to hepatitis A virus in populations in the United States. J Infect Dis 134:528-530, 1976 15. Dienstag JL, Szmuness W, Stevens CE, et al: Hepatitis A virus infection: new insights from seroepidemiologic studies. J Infect Dis 137:328-340, 1978 16. Lehmann NI, Gust ID: The prevalence of antibody to hepatitis A virus in two populations in Victoria. Med J Aust 2:731-732, 1977
486 PAPAEVANGELOU, GOURGOULI-FOTIOU AND VISSOULIS 17. Mtiller R, Willers H, Frosner G, et al: The seroepidemiological pattern of acute viral hepatitis in the Hannover region. Infection 6:65-70, 1978 18. Dienstag J, Alaama A, Mosley J, et al: Etiology of sporadic hepatitis B surface antigen-negative hepatitis. Ann Intern Med 87:1-6, 1977 19. Gust ID, Lehmann NI, Lucas CR: Relationship between prevalence of antibody to hepatitis A antigen and age: a cohort effect? J Infect Dis 138:425-426, 1978 20. Center for Disease Control: Hepatitis Surveillance Report No 42, 1978 21. Mosley JW: Epidemiology of hepatitis A virus infection. In Vyas GN, Cohen SN, Schmid R: Viral Hepatitis. Philadelphia, Franklin Institute Press, 1978