1060
HCV RNA. This HCV infection rate in spouses is higher than previous estimates,1-4 perhaps because we used both clOO and core antibodies and because our index patients had more advanced liver diseases. 51 spouses were available for liver function tests and the 8 who were seropositive for both clOO and core antibodies were also positive for HCV RNA and had abnormal transaminases. Most spouses who were positive for anti-core only were RNA negative and had normal liver-function tests. HCV RNA from 6 patient-spouse pairs was genotyped. HCV type II (the most abundant genotype in Japan) was identified in both patient and spouse in 4; type III wasidentified in both in 1; and in 1 couple both patient and spouse had mixed II/III (since double infection is rare this probably indicates transmission from one to the other). The genotype was thus identical within the pair, supporting intra-spouse transmission. We thank Dr
Lacy R. Overby for reading the text.
First Department of Internal Medicine, Yamanashi Medical College
YOSHIHIRO AKAHANE
Aikawa Internal Hospital
TATSUYA AIKAWA
Department of Internal Medicine, Iwaki Kyoritsu General Hospital
YOSHIKI SUGAI
Immunology Section, Kitasato Institute, Tokyo
FUMIO TSUDA
Immunology Division,
HIROAKI OKAMOTO
Jichi Medical School Institute of
Immunology,
Koraku 1-1-10,
SHUNJI MISHIRO
Bunkyo-ku, Tokyo 112, Japan 1. Esteban
JI, Lopez-Talavera JC, Genesca J, et al High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus. Ann Intern Med 1991; 115: 443-49. 2 Everhart JE, DiBisceglie AM, Murray LM, et al. Risk for non-A, non-B (type C) hepatitis through sexual or household contact with chronic carriers. Ann Intern Med 1990; 112: 544-45. 3. Wang J-T, Wang T-H, Sheu J-C, et al. Hepatitis C virus RNA in saliva of patients with posttransfusion hepatitis and low efficiency of transmission among spouses. J Med Virol 1992, 36: 28-31 4. Kiyosawa K, Sodeyama T, Tanaka E, et al. Intrafamilial transmission of hepatitis C
virus in Japan. J Med Virol 1991; 33: 114-16 Tajima K, Shimotohno K, Oki S. Natural horizontal transmission of HCV in microepidemic town in Japan. Lancet 1991; 337: 1410 6. Okamoto H, Munekata E, Tsuda F, et al. Enzyme-linked immunosorbent assay for antibodies against the capsid protein of hepatitis C virus with a synthetic oligopeptide. Jpn J Exp Med 1990; 60: 223-33. 7. Okamoto H, Tsuda F, Machida M, et al. Antibodies against synthetic oligopeptides deduced from the putative core gene for the diagnosis of hepatitis C virus infection. Hepatology 1992; 15: 180-86. 8 Okamoto H, Okada S, Sugiyama Y, et al. Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5’-noncoding region. Jpn J Exp Med 1990; 60: 215-22. 9. Okamoto H, Sugiyama Y, Okada S, et al. Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing 5.
Virol 1992, 73: 673-79. infectious sources. Gen J
HIV false
positivity after hepatitis
B
vaccination SIR,-Next month the World Health Assembly will consider a recommendation that hepatitis B (HB) vaccination be included in the routine vaccination schedule for infants in all countries by 1997.’ The American Academy of Pediatrics has made a similar recommendation.2HB vaccination is now compulsory in Italy and some 35 countries already have a national policy on HB immunisation. This drive for universal immunisation is highly commendable in view of the human and social costs of viral hepatitis but it may unwittingly increase the number of false positives in the screening of blood for HIV antibodies. This prediction is based on a recent observation. A blood donor had consistently tested ELISA negative for anti-HIV since 1985. In 1989, after the second injection of an HB surface antigen recombinant vaccine (Recombivax-HB; Merck, Sharp and Dohme) he tested HIV-false positive, being ELISA positive but negative by western blot and indirect immunofluorescence assay. In the summer of 1990 he still tested false positive. At this time, to show that the false positivity was vaccine dependent, he was given a booster injection with another
recombinant vaccine (Engerix-B; SmithKline Biologicals) that is interchangeable with Recombivax-HB.’ Serum was monitored over 3 weeks by AUSRIA (Abbott Laboratories) for anti-HBs and by Vironostika ELISA (Organon Teknika) for anti-HIV. Both titres rose in parallel (p = 0 003). The "HIV titre" was low, as expected for cross-reactive antibodies, but it was more than 3SD above the negative controls. Neither titre was boosted by an influenza/pneumococcus vaccine given in August, 1991, indicating that the HIV false positivity was HB vaccine specific. This positivity could not be due to DR antibodies,4since he was not exposed to allogeneic blood as a patient nor is he an intravenous drug user. Moreover, he was tested by an ELISA that was free of contaminating MHC class II antigens. This apparent crossreactivity may have gone unnoticed hitherto because false-positive individuals form a small percentage of the immunised population and are not adversely affected by the false positivity. Moreover, in the past false-positive results were not recorded and the individuals were not routinely notified. Since HBV is much more prevalent than HIV, HBV-positive individuals with HIV crossreacting antibodies could outnumber true HIV positives. In current ELI SA screenings for HIV, false positives are much more frequent than true positives in the general population. Higher HIV false-positive rates would be expected in subpopulations at risk; notably, very high false-positive rates for HIV, not associated with DR antibodies, have been reported in subpopulations with endemic HBV or HBV exposure.5-7 Even if the frequency of HIV false positives in HBV-vaccinated individuals is no greater than that in the general population (0-5%8), the doubling of their number could greatly increase the cost of screening since confirmatory tests are more expensive than ELISA. Much greater would be the human cost-that is, the psychological impact associated with the notification of HIV false positivity. Despite these potential drawbacks to universal HBV vaccination, the WHO goal of eradicating HBV hepatitis must outweigh the extra costs of HIV screening. Departments of Microbiology, Pathology, and Pediatrics, Loma Linda University, Loma Linda, California 92350, USA
DEAN A. LEE WILLIAM C. EBY GIUSEPPE A. MOLINARO
1 Anon Hepatitis B in WHO’s EPI. Lancet 1992; 339: 610. 2. American Academy of Pediatrics, Committee on Infectious Diseases. Univesal hepatitis B immunization, policy statement. AAP News 1992; 8(2): 13-22. 3. SmithKline Beckman Corp. Engerix-B hepatitis B vaccine (recombinant) fact sheet, 1989. 4 Kuhnl P, Seidl S, Holzberger G HLA DR4 antibodies cause positive HTLV-III antibody ELISA results. Lancet 1985; i: 1222. 5. Smith DM, Dewhurst S, Shepherd S, Volsky DJ, Goldsmith JC. False-positive enzyme-linked immunosorbent assay reactions for antibody to human immunodeficiency virus in a population of midwestem patients with congenital bleeding disorders. Transfusion 1987; 27: 112. 6. Ujhelyi E, Fust G, Illei E. Different types of false positive anti-HIV reactions in patients on haemodialysis. Immunol Lett 1989; 22: 35-40. 7. Ujhelyi E, Gal G, Mako J, et al. False positive results of HIV virus tests in patients undergoing chronic hemodialysis. Orv Hetil 1989; 130: 67-70. 8. Menitove JE, Richards WA, Bauer P. False-positive anti-HIV tests and blood donation. Lancet 1987; ii. 1213.
HIV among south London heroin 1991
users
in
SIR,—To what extent do drug injecting and sexual behaviour determine HIV risk among heroin users? Injecting drug users are now the fastest-growing group in which HIV is spreading in Europe.1 They are exposed to infection by two routes-injections and sexual activity. Early reports2 mistakenly predicted an imminent epidemic amongst heroin addicts in London. Studies done in cities with established HIV epidemics3,4have examined only injecting heroin users, thus making separate consideration of sexual and injecting risks of HIV transmission difficult. We have interviewed 407 heroin users in south London, and have obtained saliva samples for anonymous HIV testing from 219 for whom we have linked, anonymous data on drug taking and sociodemographic characteristics. 129 (59%) were regular injectors, another 35 (16%) had at some time injected, and 55 (25%) had never injected (most taking their heroin by "chasing the dragon"-ie, heating heroin in a piece of tinfoil and inhaling the vapours5) . Duration of heroin use ranged from less than 1 year to 37 years: 70% had started drug misuse after 1980.
HCV RNA. This HCV infection rate in spouses is higher than previous estimates,1-4 perhaps because we used both clOO and core antibodies and because our index patients had more advanced liver diseases. 51 spouses were available for liver function tests and the 8 who were seropositive for both clOO and core antibodies were also positive for HCV RNA and had abnormal transaminases. Most spouses who were positive for anti-core only were RNA negative and had normal liver-function tests. HCV RNA from 6 patient-spouse pairs was genotyped. HCV type II (the most abundant genotype in Japan) was identified in both patient and spouse in 4; type III wasidentified in both in 1; and in 1 couple both patient and spouse had mixed II/III (since double infection is rare this probably indicates transmission from one to the other). The genotype was thus identical within the pair, supporting intra-spouse transmission. We thank Dr
Lacy R. Overby for reading the text.
First Department of Internal Medicine, Yamanashi Medical College
YOSHIHIRO AKAHANE
Aikawa Internal Hospital
TATSUYA AIKAWA
Department of Internal Medicine, Iwaki Kyoritsu General Hospital
YOSHIKI SUGAI
Immunology Section, Kitasato Institute, Tokyo
FUMIO TSUDA
Immunology Division,
HIROAKI OKAMOTO
Jichi Medical School Institute of
Immunology,
Koraku 1-1-10,
SHUNJI MISHIRO
Bunkyo-ku, Tokyo 112, Japan 1. Esteban
JI, Lopez-Talavera JC, Genesca J, et al High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus. Ann Intern Med 1991; 115: 443-49. 2 Everhart JE, DiBisceglie AM, Murray LM, et al. Risk for non-A, non-B (type C) hepatitis through sexual or household contact with chronic carriers. Ann Intern Med 1990; 112: 544-45. 3. Wang J-T, Wang T-H, Sheu J-C, et al. Hepatitis C virus RNA in saliva of patients with posttransfusion hepatitis and low efficiency of transmission among spouses. J Med Virol 1992, 36: 28-31 4. Kiyosawa K, Sodeyama T, Tanaka E, et al. Intrafamilial transmission of hepatitis C
virus in Japan. J Med Virol 1991; 33: 114-16 Tajima K, Shimotohno K, Oki S. Natural horizontal transmission of HCV in microepidemic town in Japan. Lancet 1991; 337: 1410 6. Okamoto H, Munekata E, Tsuda F, et al. Enzyme-linked immunosorbent assay for antibodies against the capsid protein of hepatitis C virus with a synthetic oligopeptide. Jpn J Exp Med 1990; 60: 223-33. 7. Okamoto H, Tsuda F, Machida M, et al. Antibodies against synthetic oligopeptides deduced from the putative core gene for the diagnosis of hepatitis C virus infection. Hepatology 1992; 15: 180-86. 8 Okamoto H, Okada S, Sugiyama Y, et al. Detection of hepatitis C virus RNA by a two-stage polymerase chain reaction with two pairs of primers deduced from the 5’-noncoding region. Jpn J Exp Med 1990; 60: 215-22. 9. Okamoto H, Sugiyama Y, Okada S, et al. Typing hepatitis C virus by polymerase chain reaction with type-specific primers: application to clinical surveys and tracing 5.
Virol 1992, 73: 673-79. infectious sources. Gen J
HIV false
positivity after hepatitis
B
vaccination SIR,-Next month the World Health Assembly will consider a recommendation that hepatitis B (HB) vaccination be included in the routine vaccination schedule for infants in all countries by 1997.’ The American Academy of Pediatrics has made a similar recommendation.2HB vaccination is now compulsory in Italy and some 35 countries already have a national policy on HB immunisation. This drive for universal immunisation is highly commendable in view of the human and social costs of viral hepatitis but it may unwittingly increase the number of false positives in the screening of blood for HIV antibodies. This prediction is based on a recent observation. A blood donor had consistently tested ELISA negative for anti-HIV since 1985. In 1989, after the second injection of an HB surface antigen recombinant vaccine (Recombivax-HB; Merck, Sharp and Dohme) he tested HIV-false positive, being ELISA positive but negative by western blot and indirect immunofluorescence assay. In the summer of 1990 he still tested false positive. At this time, to show that the false positivity was vaccine dependent, he was given a booster injection with another
recombinant vaccine (Engerix-B; SmithKline Biologicals) that is interchangeable with Recombivax-HB.’ Serum was monitored over 3 weeks by AUSRIA (Abbott Laboratories) for anti-HBs and by Vironostika ELISA (Organon Teknika) for anti-HIV. Both titres rose in parallel (p = 0 003). The "HIV titre" was low, as expected for cross-reactive antibodies, but it was more than 3SD above the negative controls. Neither titre was boosted by an influenza/pneumococcus vaccine given in August, 1991, indicating that the HIV false positivity was HB vaccine specific. This positivity could not be due to DR antibodies,4since he was not exposed to allogeneic blood as a patient nor is he an intravenous drug user. Moreover, he was tested by an ELISA that was free of contaminating MHC class II antigens. This apparent crossreactivity may have gone unnoticed hitherto because false-positive individuals form a small percentage of the immunised population and are not adversely affected by the false positivity. Moreover, in the past false-positive results were not recorded and the individuals were not routinely notified. Since HBV is much more prevalent than HIV, HBV-positive individuals with HIV crossreacting antibodies could outnumber true HIV positives. In current ELI SA screenings for HIV, false positives are much more frequent than true positives in the general population. Higher HIV false-positive rates would be expected in subpopulations at risk; notably, very high false-positive rates for HIV, not associated with DR antibodies, have been reported in subpopulations with endemic HBV or HBV exposure.5-7 Even if the frequency of HIV false positives in HBV-vaccinated individuals is no greater than that in the general population (0-5%8), the doubling of their number could greatly increase the cost of screening since confirmatory tests are more expensive than ELISA. Much greater would be the human cost-that is, the psychological impact associated with the notification of HIV false positivity. Despite these potential drawbacks to universal HBV vaccination, the WHO goal of eradicating HBV hepatitis must outweigh the extra costs of HIV screening. Departments of Microbiology, Pathology, and Pediatrics, Loma Linda University, Loma Linda, California 92350, USA
DEAN A. LEE WILLIAM C. EBY GIUSEPPE A. MOLINARO
1 Anon Hepatitis B in WHO’s EPI. Lancet 1992; 339: 610. 2. American Academy of Pediatrics, Committee on Infectious Diseases. Univesal hepatitis B immunization, policy statement. AAP News 1992; 8(2): 13-22. 3. SmithKline Beckman Corp. Engerix-B hepatitis B vaccine (recombinant) fact sheet, 1989. 4 Kuhnl P, Seidl S, Holzberger G HLA DR4 antibodies cause positive HTLV-III antibody ELISA results. Lancet 1985; i: 1222. 5. Smith DM, Dewhurst S, Shepherd S, Volsky DJ, Goldsmith JC. False-positive enzyme-linked immunosorbent assay reactions for antibody to human immunodeficiency virus in a population of midwestem patients with congenital bleeding disorders. Transfusion 1987; 27: 112. 6. Ujhelyi E, Fust G, Illei E. Different types of false positive anti-HIV reactions in patients on haemodialysis. Immunol Lett 1989; 22: 35-40. 7. Ujhelyi E, Gal G, Mako J, et al. False positive results of HIV virus tests in patients undergoing chronic hemodialysis. Orv Hetil 1989; 130: 67-70. 8. Menitove JE, Richards WA, Bauer P. False-positive anti-HIV tests and blood donation. Lancet 1987; ii. 1213.
HIV among south London heroin 1991
users
in
SIR,—To what extent do drug injecting and sexual behaviour determine HIV risk among heroin users? Injecting drug users are now the fastest-growing group in which HIV is spreading in Europe.1 They are exposed to infection by two routes-injections and sexual activity. Early reports2 mistakenly predicted an imminent epidemic amongst heroin addicts in London. Studies done in cities with established HIV epidemics3,4have examined only injecting heroin users, thus making separate consideration of sexual and injecting risks of HIV transmission difficult. We have interviewed 407 heroin users in south London, and have obtained saliva samples for anonymous HIV testing from 219 for whom we have linked, anonymous data on drug taking and sociodemographic characteristics. 129 (59%) were regular injectors, another 35 (16%) had at some time injected, and 55 (25%) had never injected (most taking their heroin by "chasing the dragon"-ie, heating heroin in a piece of tinfoil and inhaling the vapours5) . Duration of heroin use ranged from less than 1 year to 37 years: 70% had started drug misuse after 1980.
