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Hepatitis C virus antibody in Swaziland
Acta Tropica, 51(1992)159-161
159
© 1992 Elsevier Science Publishers B.V. All rights reserved 0001-706X/92/$05.00 ACTROP 00210
Short Communication
Hepatitis C virus antibody in Swaziland A n t o n i o A c e t i a, G l o r i a T a l i a n i a, R o b e r t a B r u n i a, Giovanni Di Mauro b and Domenico Celestino a alnstitute of the Clinic of Tropical and Infectious Diseases, La Sapienza University, Rome, and bNational Health Service, Rome, Italy
(Received 3 October 1991; revisedversion received 17 January 1992; accepted 20 January 1992) Key words: Hepatitis C virus; Swaziland; False positivity
Advances in knowledge about the epidemiology of non-A non-B hepatitis have been stymied by the lack of a sensitive and specific assay for this infection. Very few data exist on relative rates of infection in various population groups or in geographic areas. Recently, a complementary DNA clone derived from a blood-borne non-A non-B hepatitis virus genome that has been named hepatitis C virus (HCV) has been isolated, and a specific recombinant based immunoassay to determine antibodies against HCV is now available (Kuo et al., 1989). By using this test, in Europe and in the United States the prevalence of HCV antibody positivity is generally reported to be less than 1.5o in blood donors (Janot et al., 1989; Kuehnl et al., 1989; Sirchia et al., 1989; Stevens et al., 1990), while there are no significant data from African populations. Preliminary studies, in addition, have raised doubts about the test's reliability in seropidemiological analysis in populations living in developing countries (Aceti et al., 1990; Wong et al., 1990). On the basis of the clinical importance of HCV infection and our still-evolving understanding of its epidemiology, we investigated the presence of antibodies to HCV in healthy people in Swaziland, an area hyperendemic for chronic liver disease, hepatocellular carcinoma, and hepatitis B virus (HBV) infection (Peers et al., 1987). Sera were obtained from 194 consecutive persons (96 females and 98 males), aged 16-50 years (mean 30.3 years), followed at the Center for Family Planning of the Mbabane Hospital (topographic region: Highveld; administrative region: Hhohho). None had a history of parenteral exposure to blood or blood products, a clinical or pathologic picture compatible with viral hepatitis, and no other apparent cause of liver disease. To assess the prevalence of HCV antibody, we used an enzyme-linked immunosorbent assay (Ortho HCV ELISA Test System 2nd Generation) for screening purposes, and a recombinant immuno blot assay (Chiron RIBA HCV Test System 2nd Generation) for confirmation. Correspondence address: A. Aceti, Istituto di Clinica delle Malattie Tropicali e Infettive, Policlinico Umberto I, 00161 Roma, Italy.
160
To establish HBV exposure, tests for serum hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBsAg) were performed by enzyme immune analysis with commercial kits (Abbott Laboratories). Out of 194 serum samples examined, 19 (9.8%) were above the threshold limit of positivity for anti-HCV antibody in two repeated sets of ELISA analysis. As reported in Table 1, of these sera 10 showed an optical density value under 1.000 (low), 6 between 1.000 and 2.000 (intermediate), and 3 over 2.000 (high). Of the 19 ELISAreactive sera, 3 (15.8%) were confirmed by RIBA to be anti-HCV positive. All specimens with RIBA-confirmed seropositivity had a high ELISA value (Table 1). Thus, the true prevalence of HCV antibody in healthy people from Swaziland seems to be 1.5%. A high HBV exposure was present in subjects studied. Indeed, 26 (13.5%) tested positive for HBsAg and 106 (54.9%) for anti-HBsAg. The data reported suggest that the frequency of antibodies to HCV in normal donors from Swaziland is low despite the high prevalence of HBV infection. In subSaharan Africa, routes of HBV transmission that do not involve overt percutaneous transfer are the rule and hepatitis C virus does not seem to be as easily transmitted as HBV through this pattern of spread. This may be regarded as a consequence of the low titers of HCV in the blood and presumably in other body fluids, which result in infrequent transmission by non-percutaneous transfer. Our data also show that ELISA-anti-HCV false positivity can occur among healthy subjects living in this part of Africa. However, the likelihood of a truepositive result increases proportionally with the ELISA optical density; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true-positive reaction. Previous studies have shown the occurrence of anti-HCV false positivity in sera from patients with Plasmodium falciparum infection (Aceti et al., 1990) and with helminthiases (Aceti and Taliani, 1990). As in Swaziland malaria, amoebiasis, and intestinal and urinary schistosomiasis are endemic, this may be the case. Thus, in the absence of supplementary assays to discriminate between true and false positivity, HCV reactivity should be interpreted with great caution.
Acknowledgements This work was supported in part by a grant from MURST, project 'Cirrosi ed epatiti virali'. TABLE 1 Results of H C V RIBA assay on ELISA reactive sera according to optical density values Optical density value
No. sera
RIBA-positive (No.)
Below 1.000 1.000-2.000 Above 2.000 Total
10 6 3 19
0 0 3 3 (15.8%)
161
References Aceti, A. and Taliani, G. (1990) Hepatitis C virus antibodies in parasitic infections. Ann. Intern. Med. 113, 560. Aceti, A., Taliani, G., De Bac, C. and Sebastiani, A. (1990) Anti-HCV false positivity in malaria. Lancet 336, 1442-1443, Janot, C., Courouc6, A.M. and Maniez, M. (1989) Antibodies to hepatitis C virus in French blood donors. Lancet ii, 796-797. Kuehnl, P., Seidl, S., Stangel, W., Beyer, J., Sibrowski, W. and Flik, J. (1989) Antibody to hepatitis C virus in German blood donors. Lancet ii, 324. Kuo, G., Choo, Q.-L., Alter, H.J., Gitnick, G.L., Redeker, A.G., Purcell, R.H., Miyamura, T., Dienstag, J.L., Alter, M.J., Stevens, C.E., Tegtmeier, G.E., Bonino, M., Colombo, M., Lee, W.S., Berger, K., Shuster, J.R., Overby, L.R., Bradley, D.W. and Houghton, M. (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244, 362-364. Peers, F., Bosch, X., Kaldor, J., Linsell, A. and Pluijmen, M. (1987) Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Int. J. Cancer 39, 545-553. Sirchia, G., Bellobuono, A., Giovannetti, A. and Marconi, M. (1989) Antibodies to hepatitis C virus in Italian blood donors. Lancet ii, 797. Stevens, C.E., Taylor, P.E., Pindyck, J., Cho, Q.-L., Bradley, D.W., Kuo, G. and Houghton, M. (1990). Epidemiology of hepatitis C virus. A preliminary study in volunteer blood donors. J. Am. Med. Assoc. 263, 49-53. Wong, D.C., Diwan, A.R., Rosen, L., Gerin, J.L., Johnson, R.G., Polito, A. and Purcell, R.H. (1990) Non-specificity of anti-HCV test for seroepidemiological analysis. Lancet 336, 750-751.
159
© 1992 Elsevier Science Publishers B.V. All rights reserved 0001-706X/92/$05.00 ACTROP 00210
Short Communication
Hepatitis C virus antibody in Swaziland A n t o n i o A c e t i a, G l o r i a T a l i a n i a, R o b e r t a B r u n i a, Giovanni Di Mauro b and Domenico Celestino a alnstitute of the Clinic of Tropical and Infectious Diseases, La Sapienza University, Rome, and bNational Health Service, Rome, Italy
(Received 3 October 1991; revisedversion received 17 January 1992; accepted 20 January 1992) Key words: Hepatitis C virus; Swaziland; False positivity
Advances in knowledge about the epidemiology of non-A non-B hepatitis have been stymied by the lack of a sensitive and specific assay for this infection. Very few data exist on relative rates of infection in various population groups or in geographic areas. Recently, a complementary DNA clone derived from a blood-borne non-A non-B hepatitis virus genome that has been named hepatitis C virus (HCV) has been isolated, and a specific recombinant based immunoassay to determine antibodies against HCV is now available (Kuo et al., 1989). By using this test, in Europe and in the United States the prevalence of HCV antibody positivity is generally reported to be less than 1.5o in blood donors (Janot et al., 1989; Kuehnl et al., 1989; Sirchia et al., 1989; Stevens et al., 1990), while there are no significant data from African populations. Preliminary studies, in addition, have raised doubts about the test's reliability in seropidemiological analysis in populations living in developing countries (Aceti et al., 1990; Wong et al., 1990). On the basis of the clinical importance of HCV infection and our still-evolving understanding of its epidemiology, we investigated the presence of antibodies to HCV in healthy people in Swaziland, an area hyperendemic for chronic liver disease, hepatocellular carcinoma, and hepatitis B virus (HBV) infection (Peers et al., 1987). Sera were obtained from 194 consecutive persons (96 females and 98 males), aged 16-50 years (mean 30.3 years), followed at the Center for Family Planning of the Mbabane Hospital (topographic region: Highveld; administrative region: Hhohho). None had a history of parenteral exposure to blood or blood products, a clinical or pathologic picture compatible with viral hepatitis, and no other apparent cause of liver disease. To assess the prevalence of HCV antibody, we used an enzyme-linked immunosorbent assay (Ortho HCV ELISA Test System 2nd Generation) for screening purposes, and a recombinant immuno blot assay (Chiron RIBA HCV Test System 2nd Generation) for confirmation. Correspondence address: A. Aceti, Istituto di Clinica delle Malattie Tropicali e Infettive, Policlinico Umberto I, 00161 Roma, Italy.
160
To establish HBV exposure, tests for serum hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBsAg) were performed by enzyme immune analysis with commercial kits (Abbott Laboratories). Out of 194 serum samples examined, 19 (9.8%) were above the threshold limit of positivity for anti-HCV antibody in two repeated sets of ELISA analysis. As reported in Table 1, of these sera 10 showed an optical density value under 1.000 (low), 6 between 1.000 and 2.000 (intermediate), and 3 over 2.000 (high). Of the 19 ELISAreactive sera, 3 (15.8%) were confirmed by RIBA to be anti-HCV positive. All specimens with RIBA-confirmed seropositivity had a high ELISA value (Table 1). Thus, the true prevalence of HCV antibody in healthy people from Swaziland seems to be 1.5%. A high HBV exposure was present in subjects studied. Indeed, 26 (13.5%) tested positive for HBsAg and 106 (54.9%) for anti-HBsAg. The data reported suggest that the frequency of antibodies to HCV in normal donors from Swaziland is low despite the high prevalence of HBV infection. In subSaharan Africa, routes of HBV transmission that do not involve overt percutaneous transfer are the rule and hepatitis C virus does not seem to be as easily transmitted as HBV through this pattern of spread. This may be regarded as a consequence of the low titers of HCV in the blood and presumably in other body fluids, which result in infrequent transmission by non-percutaneous transfer. Our data also show that ELISA-anti-HCV false positivity can occur among healthy subjects living in this part of Africa. However, the likelihood of a truepositive result increases proportionally with the ELISA optical density; thus, in most cases a low ELISA value probably represents a false-positive reaction, while a high ELISA value probably represents a true-positive reaction. Previous studies have shown the occurrence of anti-HCV false positivity in sera from patients with Plasmodium falciparum infection (Aceti et al., 1990) and with helminthiases (Aceti and Taliani, 1990). As in Swaziland malaria, amoebiasis, and intestinal and urinary schistosomiasis are endemic, this may be the case. Thus, in the absence of supplementary assays to discriminate between true and false positivity, HCV reactivity should be interpreted with great caution.
Acknowledgements This work was supported in part by a grant from MURST, project 'Cirrosi ed epatiti virali'. TABLE 1 Results of H C V RIBA assay on ELISA reactive sera according to optical density values Optical density value
No. sera
RIBA-positive (No.)
Below 1.000 1.000-2.000 Above 2.000 Total
10 6 3 19
0 0 3 3 (15.8%)
161
References Aceti, A. and Taliani, G. (1990) Hepatitis C virus antibodies in parasitic infections. Ann. Intern. Med. 113, 560. Aceti, A., Taliani, G., De Bac, C. and Sebastiani, A. (1990) Anti-HCV false positivity in malaria. Lancet 336, 1442-1443, Janot, C., Courouc6, A.M. and Maniez, M. (1989) Antibodies to hepatitis C virus in French blood donors. Lancet ii, 796-797. Kuehnl, P., Seidl, S., Stangel, W., Beyer, J., Sibrowski, W. and Flik, J. (1989) Antibody to hepatitis C virus in German blood donors. Lancet ii, 324. Kuo, G., Choo, Q.-L., Alter, H.J., Gitnick, G.L., Redeker, A.G., Purcell, R.H., Miyamura, T., Dienstag, J.L., Alter, M.J., Stevens, C.E., Tegtmeier, G.E., Bonino, M., Colombo, M., Lee, W.S., Berger, K., Shuster, J.R., Overby, L.R., Bradley, D.W. and Houghton, M. (1989) An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. Science 244, 362-364. Peers, F., Bosch, X., Kaldor, J., Linsell, A. and Pluijmen, M. (1987) Aflatoxin exposure, hepatitis B virus infection and liver cancer in Swaziland. Int. J. Cancer 39, 545-553. Sirchia, G., Bellobuono, A., Giovannetti, A. and Marconi, M. (1989) Antibodies to hepatitis C virus in Italian blood donors. Lancet ii, 797. Stevens, C.E., Taylor, P.E., Pindyck, J., Cho, Q.-L., Bradley, D.W., Kuo, G. and Houghton, M. (1990). Epidemiology of hepatitis C virus. A preliminary study in volunteer blood donors. J. Am. Med. Assoc. 263, 49-53. Wong, D.C., Diwan, A.R., Rosen, L., Gerin, J.L., Johnson, R.G., Polito, A. and Purcell, R.H. (1990) Non-specificity of anti-HCV test for seroepidemiological analysis. Lancet 336, 750-751.