- Email: [email protected]
Anti-HCV and transaminase testing of blood donors
187
rich diet stimulate some local immunity to H pylori? Might differences in dietary urease intake partly explain the variation in the prevalence of H pylori infection between diverse ethnic groups and, in particular, account for the low infection rate recorded in Australian aborigines?7.8 Department of Medical Microbiology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK
MARK J. FALLEN CHRISTOPHER L. CLAYTON
RP. Microbial ureases. significance, regulation and molecular characterisation. Microbiol Rev 1989, 53: 85-108 2. Clayton CL, Fallen MJ, Kleanthous H, Wren BW, Tabaqchali S. Nucleotide sequence of two genes from Helicobacter pylori encoding urease subunits. Nucleic Acids Res 1990, 18: 362. 3. Jones BD, Mobley HLT. Proteus mirabilis urease. nucleotide sequence determination and comparison with jackbean urease. J Bacteriol 1989; 171: 6414-22. 4. Morsdorf G, Kaltwasser H Cloning of the genes encoding urease from Proteus vulgaris and sequencing of the sturctural genes. FEMS Microbiol Lett 1990; 60: 67-74. 5. Blanchard A. Ureaplasma ureolyticum urease genes: use of a UGA tryptophan codon Mol Microbiol 1990, 4: 669-76. 6 Pimentel JL, Cook ME. Improved growth m the progeny of hens immunised with jackbean urease Poultry Sci 1988; 64: 434-39. 7. Dwyer B, Nanxiong S, Kaldor J, et al. Antibody response to Campylobacter pylori in an ethnic group lacking peptic ulceration Scand J Infect Dis 1988; 20: 63-68. 8 Dwyer B, Kaldor J, Tee W, et al. Antibody response to Campylobacter pylori in diverse ethnic groups. Scand J Infect Dis 1988; 20: 349-50.
1. Mobley HLT, Hansmger
Enalapril-induced antinuclear antibodies SIR,-Systemic lupus erythematosus (SLE) is drug induced in up 10% of all patients,l though most of the 50 or so implicated drugs induce the laboratory features only-ie, positive tests for a variety of antinuclear antibodies. Several of these drugs, such as captopril,z penicillamine, and propylthiouracil, contain sulfhydryl groups, and it has been suggested that this chemical structure has a role in the induction ofautoimmunity. Enalapril, which differs from captopril by the absence of sulfhydryl groups, was therefore not expected to be associated with adverse effects. Recently, while following up a group of elderly patients on enalapril, we were struck by the frequent occurrence of a positive fluorescent antinuclear antibody (FANA) test. Before the administration of enalapril, none of the 9 patients in our study group had any clinical or laboratory evidence of a connective tissue disorder. During a 6-week follow-up, 3 of the 9 patients developed a positive FANA test (titre > 160). The FANA had a speckled pattern in 1 patient and a homogeneous pattern in the to
other 2. This observation might be of clinical importance and deserves a prolonged follow-up in a larger group of patients, especially in view of the current belief that enalapril is less toxic than captopril. Our finding also suggests that autoimmunity induced by angiotensinconverting enzyme inhibitors is not dependent on the presence of
sulfhydryl groups. Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel
D. A. M. Y.
SCHWARTZ PINES AVERBUCH LEVO
Clinical and enologic considerations Rheum Dis Clin North Am 1988; 14: 187-202 2 Reidenberg MM, Case DB, Drayer DE, Reis S, Lorenzo B Development of antinuclear antibody in patients treated with high doses of captopril Arthr Rheum 1.
Solinger AM. Drug-related lupus
was normal. Do Van der Poel et al think that anti-HBc testing of blood donors should be continued as a surrogate marker for NANBH? The follow-up for donors was 45 months but only 8 months for the recipients so it is possible that 32% of the recipients who have lost their anti-HCV antibody, as happened with the donors, were not identified. If these "false positives" are taken into account the number of recipients who truly seroconverted for anti-HCV will be reduced from 18 to 12, and this will significantly alter the incidence of HCV infection after blood transfusion and may also change the sensitivity and specificity of anti-HCV and transaminase testing of blood donors in the prevention of NANBH.
American Red Cross, St Louis, Missouri 63108, USA
RAM KAKAIYA MARIA D. GUDINO WILLIAM V. MILLER
This letter has been shown to Dr Van der Poel and colleagues, reply follows.-ED. L.
whose
SIR,-In earlier studies1,2 we showed that transfusion of donor blood with HCV antibodies is specifically associated with posttransfusion NANBH. Since about 25% of anti-HCV (ELISA) positive blood products were implicated in HCV seroconversion and/or NANBH-in recipients, we looked for co-factors, such as raised alanine aminotransferase (ALT), high ELISA optical density to cut-off ratio, and persistence of ELISA reactivity to discriminate infectious from non-infectious blood donors.’ The Ortho recombinant immunoblot assay (RIBA) makes use of the 5-1-1 antigen and the C100-3 antigen (this also being used in the ELISA). Although RIBA cannot, therefore, be regarded as an independent confirmatory assay, it is helpful in discriminating infectious from non-infectious donors.3 Dr Kakaiya and his colleagues ask about the 86% of ELISA seropositivity in recipients before they received transfusions.2 We have re-examined the ELISA positive sera by RIBA, in which sera reacting with both the 5-1-1 and the C100-3 antigen are positive, those reacting with just one are indeterminate, and sera that react with neither antigen are negative. Of the 33 recipients who were ELISA reactive before transfusion, 1 was RIBA positive, 4 were indeterminate, and 28 were negative. Of the recipients who were ELISA negative before transfusion 15/350 seroconverted for anti-HCV with ELISA.2 For all 15 seroconverting recipients the latest ELISA positive sample from the follow-up series was tested by RIBA: 4 were positive, 1 indeterminate, and 10 negative. The distribution of ELISA and RIBA results in recipients with and without post-transfusion-NANBH is shown in the table. 37/5150 (0-7%) blood product transfusions were anti-HCV ELISA positive? 6 were also positive by RIBA, 8 were indeterminate, and 23 were negative (table). Thus the prevalence of anti-HCV positivity in recipients before transfusion was only 1/383 (for ELISA+RIBA), which is not significantly different from the 6/5150 in blood products. We are asked if anti-HBc testing might provide additional prevention of post-transfusion NANBH. Of the 9 recipients with NANBH, 1/6 given anti-HCV ELISA positive blood and 1/3 who received anti-HCV ELISA negative blood only, were given an anti-HBc positive blood product. All anti-HCV positive products were anti-HBc negative,2 and 2/9 (22%) recipients with post-
1984, 27: 579-81.
Anti-HCV and transaminase testing of blood donors SIR,-In Dr Van der Poel and colleagues’ study (March 10, p 558) prevalence of antibody to hepatitis C virus (HCV) in the recipients even before they had had a blood transfusion was 8-8% (33 of 374), compared with 0-7% in the blood donors. Is there an explanation for this 13-fold difference? Since none of the 37 HCV seropositive donors was anti-HBc positive, do the data show if an anti-HBc positive donor can be identified for those 5 recipients who had non-A, non-B hepatitis (NANBH) despite receiving anti-HCV negative blood or blood for which the alanine transferase activity the
ANTI-HCV ELISA AND RIBA RESULTS IN RECIPIENTS WITH OR WITHOUT POST-TRANSFUSION NANBH
188
transfusion NANBH received one or more anti-HBc positive blood products, as compared with 67/374 (18%) of recipients without NANBH.’ These observations do not suggest that, in the Netherlands, donor testing for anti-HBc would help to prevent post-transfusion NANBH. Could elimination of false-positive ELISA results in seroconverters affect the sensitivity and specificity of anti-HCV and transaminase testing? The sensitivity and specificity that we calculated (67% and 93%, respectively, for anti-HCV and 78% and 64% for ALT) were based on clinical disease prevented and are thus independent of non-specific anti-HCV reactivity in recipients. We conclude that testing by RIBA adds to the specificity of anti-HCV testing but at some loss of sensitivity. RIBA is not a true confirmatory test; nonetheless a positive RIBA result is a very specific co-factor for infectivity of anti-HCV ELISA positive blood. The incorporation of additional HCV antigens might add to the value of the RIBA test system. C. L. VAN DER POEL Red Cross Blood Bank Amsterdam, H. W. REESINK 1066 CX Amsterdam, Netherlands
Central Laboratory of the Red Cross Blood Transfusion Service, Amsterdam
P. N. LELIE P. EXEL-OEHLERS I. WINKEL W. SCHAASBERG
Chiron
A. POLITO
Corporation, Emeryville, California, USA
The high positivity of the US plasma pools might be due to false positives but we know of no difference between the treatment of American and European plasma pools that would account for the difference seen. Another possibility is that the Ortho/Chiron test detects antibodies induced by American strains of HCV more effectively than it does antibodies induced by European strains. The third possibility is that the US pools contain a very high proportion of strongly positive donations. When a positive pool and a positive UK donation were titrated in parallel, antibody was undetectable in both at dilutions of 1 in 10. It is therefore not surprising that the UK pools were found to be negative. Our findings imply that the prevalence of positive donations in the American pools is very high, possibly approaching 100%. This may reflect the fact that in the US plasma for blood products often comes from paid donors. Examination of pools for HCV RNA is planned.
National Institute for Biological Standards and Control, South Mimms EN6 3QG, UK
1. Editorial.
Antibody to hepatitis C virus in plasma pools SIR,—Transfusion centres in several countries have introduced screening of blood donations for antibody to hepatitis C virus (HCV) and have reported significant reductions in transmission of non-A, non-B hepatitis.l The value of the test in ensuring the safety of medicinal products derived from blood remains to be established, however. We report here the results of tests with the Ortho Diagnostics anti-HCV ELISA on plasma pools from which such
products are prepared. 87 plasma pools ranging in size from 500 to 25 000 donations were examined. 46 were from American manufacturers, 37 from manufacturers in the UK, 2 from Swedish sources, and 2 from Austria (these being known to include plasma from American donors). 538 individual plasma samples from donors attending transfusion centres in the UK were also tested. 41 of the American pools and the 2 "Austrian" pools were strongly positive, giving similar, high readings to a known positive single donor serum from the Netherlands which constitutes a standard hepatitis B antiserum and with an optical density (OD) of 2.70. None of the pools from the UK or Sweden was positive. A US factor VIII preparation was also tested and was negative but the pool from which it was prepared was almost certainly positive:
Hepatitis C virus upstanding. Lancet 1990; 335:
1431-32.
Safety of monoclonal antibody purified factor VIII
H. HOUGHTON
1. Van der Poel CL, Reesink HW, Lelie PN, et al. Anti-hepatitis C antibodies and non-A, non-B post-transfusion hepatitis m the Netherlands. Lancet 1989; ii: 297-98. 2. Van der Poel CL, Reesink HW, Lelie PN, et al. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990; 335: 558-60. 3. Ebeling F, Naukkarinen R, Leikola J. Recombinant immunoblot assay for hepatitis C antibody as predictor of infectivity. Lancet 1990; 335: 982-83. 4. Reesink HW, Leentvaar-Kuypers A, Van der Poel CL, et al. Non-A, non-B posttransfusion hepatitis in open heart surgery patients m the Netherlands: preliminary results of a prospective study. In Zuckerman AJ, ed. Viral hepatitis and liver disease. New York: Alan R Liss, 1988: 558-60.
P. MINOR P. PIPKIN R. THORPE D. THOMAS
SiR,—The evidence in Dr Bemtorp and colleagues’ letter (June 23, 1531) suggesting that non-A, non-B hepatitis (NANBH) was
p
associated in one haemophilia patient with the administration of ’Monoclate’ is incomplete and disregards published data on the safety of monoclonal antibody purification. Of the three lots of monoclate that the boy received, two could be readily eliminated as a causal agent because a second hepatitisnegative boy did not acquire NANBH when he received the same two lots. The third suspect lot was traced, in an attempt to identify another "virgin" or at least hepatitis-negative patient, but none could be found. An aetiological association could not therefore be either confirmed or ruled out. There is little question that the child did have NANBH, but hepatitis C may be acquired in several ways.’1 Armour’s decision to change to a pasteurised version of monoclate antedated this report by over a year and was in response to worldwide marketing requirements. In a longitudinal multicentre study of twenty lots of monoclate among 39 virgin patients with haemophilia, none met the accepted criteria for NANBH.2 Furthermore, none of 33 for whom samples were available had seroconverted to anti-HCV positivity after at least 6 months (unpublished). Armour Pharmaceutical Company, Blue Bell, Pennsylvania 19422, USA
MICHAEL B. RODELL GARRETT E. BERGMAN
MJ, Gerety RJ, et al. Sporadic non-A, non-B hepatitis. frequency and epidemiology in an urban US population. J Infect Dis 1982; 145: 886-93. 2. Lusher JM, Salzman PM, et al. Viral safety and inhibitor development associated with factor VIII:C ultra-purified from plasma in hemophiliacs previously unexposed to factor VIII:C concentrates. Hematol 1990; 27 (suppl 2): 1-8. 1. Alter
Exophiala dermatitidis infection
in
cystic
fibrosis
2 of 538 donations from UK
sources were positive, a frequency of 0.4% consistent with previously reported figures. The readings for the 2 positive donations (OD 0-69 and 0-83) were far lower than those from the US plasma pools.
SIR,-Exophiala dermatitidis (Wangiella dermatitidis) is a rare isolated agent of phaeohyphomycosis, causing infections ranging from the subcutaneous to severe systemic manifestations.’ This "black yeast" is normally encountered in tropical or subtropical areas.1,2 We isolated this fungus incidentally from the sputum of a 5-year-old girl with cystic fibrosis (CF). This finding was confirmed by repeated isolations during the ensuing 8 months. Because this girl had round mottling in the parahilar region, atypical of CF and not responding to antimicrobial chemotherapy, we decided to try amphotericin B (up to 0-5 mg/kg per day) and 5-fluorocytosine (150 mg/kg per day) over 6 weeks. The patient
rich diet stimulate some local immunity to H pylori? Might differences in dietary urease intake partly explain the variation in the prevalence of H pylori infection between diverse ethnic groups and, in particular, account for the low infection rate recorded in Australian aborigines?7.8 Department of Medical Microbiology, St Bartholomew’s Hospital Medical College, London EC1A 7BE, UK
MARK J. FALLEN CHRISTOPHER L. CLAYTON
RP. Microbial ureases. significance, regulation and molecular characterisation. Microbiol Rev 1989, 53: 85-108 2. Clayton CL, Fallen MJ, Kleanthous H, Wren BW, Tabaqchali S. Nucleotide sequence of two genes from Helicobacter pylori encoding urease subunits. Nucleic Acids Res 1990, 18: 362. 3. Jones BD, Mobley HLT. Proteus mirabilis urease. nucleotide sequence determination and comparison with jackbean urease. J Bacteriol 1989; 171: 6414-22. 4. Morsdorf G, Kaltwasser H Cloning of the genes encoding urease from Proteus vulgaris and sequencing of the sturctural genes. FEMS Microbiol Lett 1990; 60: 67-74. 5. Blanchard A. Ureaplasma ureolyticum urease genes: use of a UGA tryptophan codon Mol Microbiol 1990, 4: 669-76. 6 Pimentel JL, Cook ME. Improved growth m the progeny of hens immunised with jackbean urease Poultry Sci 1988; 64: 434-39. 7. Dwyer B, Nanxiong S, Kaldor J, et al. Antibody response to Campylobacter pylori in an ethnic group lacking peptic ulceration Scand J Infect Dis 1988; 20: 63-68. 8 Dwyer B, Kaldor J, Tee W, et al. Antibody response to Campylobacter pylori in diverse ethnic groups. Scand J Infect Dis 1988; 20: 349-50.
1. Mobley HLT, Hansmger
Enalapril-induced antinuclear antibodies SIR,-Systemic lupus erythematosus (SLE) is drug induced in up 10% of all patients,l though most of the 50 or so implicated drugs induce the laboratory features only-ie, positive tests for a variety of antinuclear antibodies. Several of these drugs, such as captopril,z penicillamine, and propylthiouracil, contain sulfhydryl groups, and it has been suggested that this chemical structure has a role in the induction ofautoimmunity. Enalapril, which differs from captopril by the absence of sulfhydryl groups, was therefore not expected to be associated with adverse effects. Recently, while following up a group of elderly patients on enalapril, we were struck by the frequent occurrence of a positive fluorescent antinuclear antibody (FANA) test. Before the administration of enalapril, none of the 9 patients in our study group had any clinical or laboratory evidence of a connective tissue disorder. During a 6-week follow-up, 3 of the 9 patients developed a positive FANA test (titre > 160). The FANA had a speckled pattern in 1 patient and a homogeneous pattern in the to
other 2. This observation might be of clinical importance and deserves a prolonged follow-up in a larger group of patients, especially in view of the current belief that enalapril is less toxic than captopril. Our finding also suggests that autoimmunity induced by angiotensinconverting enzyme inhibitors is not dependent on the presence of
sulfhydryl groups. Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel
D. A. M. Y.
SCHWARTZ PINES AVERBUCH LEVO
Clinical and enologic considerations Rheum Dis Clin North Am 1988; 14: 187-202 2 Reidenberg MM, Case DB, Drayer DE, Reis S, Lorenzo B Development of antinuclear antibody in patients treated with high doses of captopril Arthr Rheum 1.
Solinger AM. Drug-related lupus
was normal. Do Van der Poel et al think that anti-HBc testing of blood donors should be continued as a surrogate marker for NANBH? The follow-up for donors was 45 months but only 8 months for the recipients so it is possible that 32% of the recipients who have lost their anti-HCV antibody, as happened with the donors, were not identified. If these "false positives" are taken into account the number of recipients who truly seroconverted for anti-HCV will be reduced from 18 to 12, and this will significantly alter the incidence of HCV infection after blood transfusion and may also change the sensitivity and specificity of anti-HCV and transaminase testing of blood donors in the prevention of NANBH.
American Red Cross, St Louis, Missouri 63108, USA
RAM KAKAIYA MARIA D. GUDINO WILLIAM V. MILLER
This letter has been shown to Dr Van der Poel and colleagues, reply follows.-ED. L.
whose
SIR,-In earlier studies1,2 we showed that transfusion of donor blood with HCV antibodies is specifically associated with posttransfusion NANBH. Since about 25% of anti-HCV (ELISA) positive blood products were implicated in HCV seroconversion and/or NANBH-in recipients, we looked for co-factors, such as raised alanine aminotransferase (ALT), high ELISA optical density to cut-off ratio, and persistence of ELISA reactivity to discriminate infectious from non-infectious blood donors.’ The Ortho recombinant immunoblot assay (RIBA) makes use of the 5-1-1 antigen and the C100-3 antigen (this also being used in the ELISA). Although RIBA cannot, therefore, be regarded as an independent confirmatory assay, it is helpful in discriminating infectious from non-infectious donors.3 Dr Kakaiya and his colleagues ask about the 86% of ELISA seropositivity in recipients before they received transfusions.2 We have re-examined the ELISA positive sera by RIBA, in which sera reacting with both the 5-1-1 and the C100-3 antigen are positive, those reacting with just one are indeterminate, and sera that react with neither antigen are negative. Of the 33 recipients who were ELISA reactive before transfusion, 1 was RIBA positive, 4 were indeterminate, and 28 were negative. Of the recipients who were ELISA negative before transfusion 15/350 seroconverted for anti-HCV with ELISA.2 For all 15 seroconverting recipients the latest ELISA positive sample from the follow-up series was tested by RIBA: 4 were positive, 1 indeterminate, and 10 negative. The distribution of ELISA and RIBA results in recipients with and without post-transfusion-NANBH is shown in the table. 37/5150 (0-7%) blood product transfusions were anti-HCV ELISA positive? 6 were also positive by RIBA, 8 were indeterminate, and 23 were negative (table). Thus the prevalence of anti-HCV positivity in recipients before transfusion was only 1/383 (for ELISA+RIBA), which is not significantly different from the 6/5150 in blood products. We are asked if anti-HBc testing might provide additional prevention of post-transfusion NANBH. Of the 9 recipients with NANBH, 1/6 given anti-HCV ELISA positive blood and 1/3 who received anti-HCV ELISA negative blood only, were given an anti-HBc positive blood product. All anti-HCV positive products were anti-HBc negative,2 and 2/9 (22%) recipients with post-
1984, 27: 579-81.
Anti-HCV and transaminase testing of blood donors SIR,-In Dr Van der Poel and colleagues’ study (March 10, p 558) prevalence of antibody to hepatitis C virus (HCV) in the recipients even before they had had a blood transfusion was 8-8% (33 of 374), compared with 0-7% in the blood donors. Is there an explanation for this 13-fold difference? Since none of the 37 HCV seropositive donors was anti-HBc positive, do the data show if an anti-HBc positive donor can be identified for those 5 recipients who had non-A, non-B hepatitis (NANBH) despite receiving anti-HCV negative blood or blood for which the alanine transferase activity the
ANTI-HCV ELISA AND RIBA RESULTS IN RECIPIENTS WITH OR WITHOUT POST-TRANSFUSION NANBH
188
transfusion NANBH received one or more anti-HBc positive blood products, as compared with 67/374 (18%) of recipients without NANBH.’ These observations do not suggest that, in the Netherlands, donor testing for anti-HBc would help to prevent post-transfusion NANBH. Could elimination of false-positive ELISA results in seroconverters affect the sensitivity and specificity of anti-HCV and transaminase testing? The sensitivity and specificity that we calculated (67% and 93%, respectively, for anti-HCV and 78% and 64% for ALT) were based on clinical disease prevented and are thus independent of non-specific anti-HCV reactivity in recipients. We conclude that testing by RIBA adds to the specificity of anti-HCV testing but at some loss of sensitivity. RIBA is not a true confirmatory test; nonetheless a positive RIBA result is a very specific co-factor for infectivity of anti-HCV ELISA positive blood. The incorporation of additional HCV antigens might add to the value of the RIBA test system. C. L. VAN DER POEL Red Cross Blood Bank Amsterdam, H. W. REESINK 1066 CX Amsterdam, Netherlands
Central Laboratory of the Red Cross Blood Transfusion Service, Amsterdam
P. N. LELIE P. EXEL-OEHLERS I. WINKEL W. SCHAASBERG
Chiron
A. POLITO
Corporation, Emeryville, California, USA
The high positivity of the US plasma pools might be due to false positives but we know of no difference between the treatment of American and European plasma pools that would account for the difference seen. Another possibility is that the Ortho/Chiron test detects antibodies induced by American strains of HCV more effectively than it does antibodies induced by European strains. The third possibility is that the US pools contain a very high proportion of strongly positive donations. When a positive pool and a positive UK donation were titrated in parallel, antibody was undetectable in both at dilutions of 1 in 10. It is therefore not surprising that the UK pools were found to be negative. Our findings imply that the prevalence of positive donations in the American pools is very high, possibly approaching 100%. This may reflect the fact that in the US plasma for blood products often comes from paid donors. Examination of pools for HCV RNA is planned.
National Institute for Biological Standards and Control, South Mimms EN6 3QG, UK
1. Editorial.
Antibody to hepatitis C virus in plasma pools SIR,—Transfusion centres in several countries have introduced screening of blood donations for antibody to hepatitis C virus (HCV) and have reported significant reductions in transmission of non-A, non-B hepatitis.l The value of the test in ensuring the safety of medicinal products derived from blood remains to be established, however. We report here the results of tests with the Ortho Diagnostics anti-HCV ELISA on plasma pools from which such
products are prepared. 87 plasma pools ranging in size from 500 to 25 000 donations were examined. 46 were from American manufacturers, 37 from manufacturers in the UK, 2 from Swedish sources, and 2 from Austria (these being known to include plasma from American donors). 538 individual plasma samples from donors attending transfusion centres in the UK were also tested. 41 of the American pools and the 2 "Austrian" pools were strongly positive, giving similar, high readings to a known positive single donor serum from the Netherlands which constitutes a standard hepatitis B antiserum and with an optical density (OD) of 2.70. None of the pools from the UK or Sweden was positive. A US factor VIII preparation was also tested and was negative but the pool from which it was prepared was almost certainly positive:
Hepatitis C virus upstanding. Lancet 1990; 335:
1431-32.
Safety of monoclonal antibody purified factor VIII
H. HOUGHTON
1. Van der Poel CL, Reesink HW, Lelie PN, et al. Anti-hepatitis C antibodies and non-A, non-B post-transfusion hepatitis m the Netherlands. Lancet 1989; ii: 297-98. 2. Van der Poel CL, Reesink HW, Lelie PN, et al. Infectivity of blood seropositive for hepatitis C virus antibodies. Lancet 1990; 335: 558-60. 3. Ebeling F, Naukkarinen R, Leikola J. Recombinant immunoblot assay for hepatitis C antibody as predictor of infectivity. Lancet 1990; 335: 982-83. 4. Reesink HW, Leentvaar-Kuypers A, Van der Poel CL, et al. Non-A, non-B posttransfusion hepatitis in open heart surgery patients m the Netherlands: preliminary results of a prospective study. In Zuckerman AJ, ed. Viral hepatitis and liver disease. New York: Alan R Liss, 1988: 558-60.
P. MINOR P. PIPKIN R. THORPE D. THOMAS
SiR,—The evidence in Dr Bemtorp and colleagues’ letter (June 23, 1531) suggesting that non-A, non-B hepatitis (NANBH) was
p
associated in one haemophilia patient with the administration of ’Monoclate’ is incomplete and disregards published data on the safety of monoclonal antibody purification. Of the three lots of monoclate that the boy received, two could be readily eliminated as a causal agent because a second hepatitisnegative boy did not acquire NANBH when he received the same two lots. The third suspect lot was traced, in an attempt to identify another "virgin" or at least hepatitis-negative patient, but none could be found. An aetiological association could not therefore be either confirmed or ruled out. There is little question that the child did have NANBH, but hepatitis C may be acquired in several ways.’1 Armour’s decision to change to a pasteurised version of monoclate antedated this report by over a year and was in response to worldwide marketing requirements. In a longitudinal multicentre study of twenty lots of monoclate among 39 virgin patients with haemophilia, none met the accepted criteria for NANBH.2 Furthermore, none of 33 for whom samples were available had seroconverted to anti-HCV positivity after at least 6 months (unpublished). Armour Pharmaceutical Company, Blue Bell, Pennsylvania 19422, USA
MICHAEL B. RODELL GARRETT E. BERGMAN
MJ, Gerety RJ, et al. Sporadic non-A, non-B hepatitis. frequency and epidemiology in an urban US population. J Infect Dis 1982; 145: 886-93. 2. Lusher JM, Salzman PM, et al. Viral safety and inhibitor development associated with factor VIII:C ultra-purified from plasma in hemophiliacs previously unexposed to factor VIII:C concentrates. Hematol 1990; 27 (suppl 2): 1-8. 1. Alter
Exophiala dermatitidis infection
in
cystic
fibrosis
2 of 538 donations from UK
sources were positive, a frequency of 0.4% consistent with previously reported figures. The readings for the 2 positive donations (OD 0-69 and 0-83) were far lower than those from the US plasma pools.
SIR,-Exophiala dermatitidis (Wangiella dermatitidis) is a rare isolated agent of phaeohyphomycosis, causing infections ranging from the subcutaneous to severe systemic manifestations.’ This "black yeast" is normally encountered in tropical or subtropical areas.1,2 We isolated this fungus incidentally from the sputum of a 5-year-old girl with cystic fibrosis (CF). This finding was confirmed by repeated isolations during the ensuing 8 months. Because this girl had round mottling in the parahilar region, atypical of CF and not responding to antimicrobial chemotherapy, we decided to try amphotericin B (up to 0-5 mg/kg per day) and 5-fluorocytosine (150 mg/kg per day) over 6 weeks. The patient