- Email: [email protected]
RUBELLA REINFECTIONS
1452 of using cyanocobalamin as a prophylactic measure against the emergence of birth defects induced by diphenyl-
hydantoin. Department of Pharmacology, Temple University, Philadelphia 40, Pennsylvania, U.S.A.
DAVID E. MANN, JR. RONALD F. GAUTIERI.
EFFECTS OF INSTILLATION OF PARAFFINS IN TISSUES
SiR,—I should like to answer the views of Dr Campbell and Dr Henderson and Dr Penn (April 7, p. 776). In my experience, very large quantities of talc have often disappeared from the peritoneal cavity after paraffin-oil instillation. Reported side-effects are very rare. According to our experiments in dogs (8-10 kg.), when 30 ml. of cerebrospinal fluid was replaced by 30 ml. of paraffin oil no lesions were seen up to 40 days after injection, and the paraffin seemed to be totally absorbed. I have instilled into a dog’s peritoneal cavity 40 ml. of paraffin oil and 3 g. of talc. After 4 months, I found no oil, talc, or adhesions. Democritou Stret 18 (136), Athens, Greece.
L. KATSILABROS.
RUBELLA REINFECTIONS
SIR,-Dr Haukenes and his co-workers’ letter,! in which they state that failure to remove non-specific inhibitors adequately in rubella hsmagglutination-inhibition tests led to a misinterpretation in the diagnosis of a rubella infection, raises an important practical point in the assessof patients who have been exposed to rubella-like illnesses during pregnancy. Without undertaking timeconsuming and complex procedures, it is sometimes difficult to be certain whether inhibitors of haemagglutination, particularly if at a low level, are true antibodies or represent residual non-specific inhibitors which serum pretreatment failed to remove. Because of this, it is wise to obtain an additional serum sample some 21-25 days after first exposure in order to ensure that there has been no significant rise in antibody titre before finally declaring that patients who have low levels of antibody in sera collected soon after exposure were indeed immune. We also feel that second samples should be collected from patients who are exposed to household contacts, since the index case may be experiencing an apparent infection, whilst the patient herself may develop a rising titre whilst concurrently experiencing an infection that is subclinical or one in which the clinical features are minimal and unnoticed-e.g., mild lymphadenopathy, minimal arthralgia, ment
but no rash. Your editorialdiscusses two patients with clinical reinfection in whom virxmia had probably occurred but no rubella-specific IgM was detected. We feel that the case reported by Northrop and his colleagues 3 could well have been a primary infection, because evidence of reinfection was based on there being H.I. antibody but no detectable rubella-specific IgM in a serum sample obtained on the second day of the patient’s illness. However, in our experience, it is not at all unusual to obtain an antibody titre of this level at this stage of the disease. Failure to detect IgM could perhaps have been due to technical reasons, and we feel that in these circumstances more than 1. 2. 3.
Haukenes, G., Haram, K., Solberg, C. O. Lancet, June 9, 1973, p. 1313. ibid. May 5, 1973, p. 978. Northrop, R. L., Gardner, W. M., Geittmann, W. F. Obstet. Gynec., N.Y. 1972, 39, 524.
its detection should be used before one certain that no rubella-specific IgM is present. In addition, we have occasionally failed to detect rubella-specific IgM in a serum sample taken during the first week of illness, despite the presence of adequate levels of H.I. antibody, but have detected it in a sample obtained a few days later. Undoubtedly there will be further reports of cases of reinfection, but we feel that the presence of antibody rather than non-specific inhibitors in pre-illness sera and the presence or absence of virus-specific IgM should be confirmed, if possible by another laboratory, before such cases are firmly documented. As techniques for the detection of virus-specific IgM improve in reliability and sensitivity, it could well be that IgM may also be detected at low levels in both clinical and subclinical reinfections whether or not viraemia has taken place; its presence being merely indicative of an antigenic stimulus irrespective of the site from which this stimulus arises. one can
technique for be absolutely
St. Thomas’s Hospital, London SE1.
J. E. BANATVALA J. M. BEST.
ANTIBODIES TO ADENOVIRUS IN PATIENTS WITH INFECTIOUS HEPATITIS
SIR,-There have been a number of reports on changes in the incidence and titre of antibodies to microbial antigens in liver disease. 1-5 In general, it appears that antibodies to intestinal bacteria (Escherichia coli 2,3 and Salmonella Spp.4,5) are increased in incidence, in titre, or in both, in patients with chronic hepatitis. Similar increases have been reported for antibodies to measles and rubella viruses.1 I have tested 50 pairs of sera from patients with Australiaantigen-negative acute infectious hepatitis and 50 control sera for antibody neutralising adenovirus type 5. The paired hepatitis sera were taken during the acute phase of the illness and three months later. They were received from general practitioners and Public Health Laboratory Service laboratories throughout the country in response to a request published in the Communicable Disease Report, through the courtesy of Sir James Howie. The control sera, obtained originally for tissue-typing from the healthy relatives of patients with kidney disease, were a gift from Dr S. John Starkie of St. Mary’s Hospital Medical School, London. All the 50 pairs of hepatitis sera contained antibody neutralising adenovirus type 5, compared with only 57% of the 50 control sera. In 7 of the hepatitis sera there was a twofold or greater, and in 5 a fourfold or greater, rise in titre; and in 2 there was a twofold or greater, and in 3 a fourfold or greater, drop in titre. The geometric mean titres were 1/84 for the acute phase sera, 1/81 for the convalescent sera, and 1/14 for the control sera. The mean titres of the acute phase and control sera, omitting the negative results, were 1/103 and 1/93, respectively, and did not differ significantly by Student’s t test. The mean titres of the acute and convalescent phase sera were not significantly different. There has been much discussion 1-5 of the significance of increased titres of antibody to viruses and bacteria in diseases of the liver. My findings are compatible with a current hypothesis 1,5 that during liver disease antibodies D. R., Kurtz, J. B., MacCallum, F. O., Wright, R. Lancet, 1972, i, 665. 2. Bjorneboe, M., Prytz, H., Orskov, F. ibid. p. 58. 1.
Triger,
3. 4.
Triger, D. R., Alp, M. H., Wright, R. ibid. p. 60. Protell, R. L., Soloway, R. D., Martin, W. J., Schoenfield, L. J., Summerskill, W. H. J. ibid. 1971, ii, 330. Bjorneboe, M. ibid. p. 484.
5.
hydantoin. Department of Pharmacology, Temple University, Philadelphia 40, Pennsylvania, U.S.A.
DAVID E. MANN, JR. RONALD F. GAUTIERI.
EFFECTS OF INSTILLATION OF PARAFFINS IN TISSUES
SiR,—I should like to answer the views of Dr Campbell and Dr Henderson and Dr Penn (April 7, p. 776). In my experience, very large quantities of talc have often disappeared from the peritoneal cavity after paraffin-oil instillation. Reported side-effects are very rare. According to our experiments in dogs (8-10 kg.), when 30 ml. of cerebrospinal fluid was replaced by 30 ml. of paraffin oil no lesions were seen up to 40 days after injection, and the paraffin seemed to be totally absorbed. I have instilled into a dog’s peritoneal cavity 40 ml. of paraffin oil and 3 g. of talc. After 4 months, I found no oil, talc, or adhesions. Democritou Stret 18 (136), Athens, Greece.
L. KATSILABROS.
RUBELLA REINFECTIONS
SIR,-Dr Haukenes and his co-workers’ letter,! in which they state that failure to remove non-specific inhibitors adequately in rubella hsmagglutination-inhibition tests led to a misinterpretation in the diagnosis of a rubella infection, raises an important practical point in the assessof patients who have been exposed to rubella-like illnesses during pregnancy. Without undertaking timeconsuming and complex procedures, it is sometimes difficult to be certain whether inhibitors of haemagglutination, particularly if at a low level, are true antibodies or represent residual non-specific inhibitors which serum pretreatment failed to remove. Because of this, it is wise to obtain an additional serum sample some 21-25 days after first exposure in order to ensure that there has been no significant rise in antibody titre before finally declaring that patients who have low levels of antibody in sera collected soon after exposure were indeed immune. We also feel that second samples should be collected from patients who are exposed to household contacts, since the index case may be experiencing an apparent infection, whilst the patient herself may develop a rising titre whilst concurrently experiencing an infection that is subclinical or one in which the clinical features are minimal and unnoticed-e.g., mild lymphadenopathy, minimal arthralgia, ment
but no rash. Your editorialdiscusses two patients with clinical reinfection in whom virxmia had probably occurred but no rubella-specific IgM was detected. We feel that the case reported by Northrop and his colleagues 3 could well have been a primary infection, because evidence of reinfection was based on there being H.I. antibody but no detectable rubella-specific IgM in a serum sample obtained on the second day of the patient’s illness. However, in our experience, it is not at all unusual to obtain an antibody titre of this level at this stage of the disease. Failure to detect IgM could perhaps have been due to technical reasons, and we feel that in these circumstances more than 1. 2. 3.
Haukenes, G., Haram, K., Solberg, C. O. Lancet, June 9, 1973, p. 1313. ibid. May 5, 1973, p. 978. Northrop, R. L., Gardner, W. M., Geittmann, W. F. Obstet. Gynec., N.Y. 1972, 39, 524.
its detection should be used before one certain that no rubella-specific IgM is present. In addition, we have occasionally failed to detect rubella-specific IgM in a serum sample taken during the first week of illness, despite the presence of adequate levels of H.I. antibody, but have detected it in a sample obtained a few days later. Undoubtedly there will be further reports of cases of reinfection, but we feel that the presence of antibody rather than non-specific inhibitors in pre-illness sera and the presence or absence of virus-specific IgM should be confirmed, if possible by another laboratory, before such cases are firmly documented. As techniques for the detection of virus-specific IgM improve in reliability and sensitivity, it could well be that IgM may also be detected at low levels in both clinical and subclinical reinfections whether or not viraemia has taken place; its presence being merely indicative of an antigenic stimulus irrespective of the site from which this stimulus arises. one can
technique for be absolutely
St. Thomas’s Hospital, London SE1.
J. E. BANATVALA J. M. BEST.
ANTIBODIES TO ADENOVIRUS IN PATIENTS WITH INFECTIOUS HEPATITIS
SIR,-There have been a number of reports on changes in the incidence and titre of antibodies to microbial antigens in liver disease. 1-5 In general, it appears that antibodies to intestinal bacteria (Escherichia coli 2,3 and Salmonella Spp.4,5) are increased in incidence, in titre, or in both, in patients with chronic hepatitis. Similar increases have been reported for antibodies to measles and rubella viruses.1 I have tested 50 pairs of sera from patients with Australiaantigen-negative acute infectious hepatitis and 50 control sera for antibody neutralising adenovirus type 5. The paired hepatitis sera were taken during the acute phase of the illness and three months later. They were received from general practitioners and Public Health Laboratory Service laboratories throughout the country in response to a request published in the Communicable Disease Report, through the courtesy of Sir James Howie. The control sera, obtained originally for tissue-typing from the healthy relatives of patients with kidney disease, were a gift from Dr S. John Starkie of St. Mary’s Hospital Medical School, London. All the 50 pairs of hepatitis sera contained antibody neutralising adenovirus type 5, compared with only 57% of the 50 control sera. In 7 of the hepatitis sera there was a twofold or greater, and in 5 a fourfold or greater, rise in titre; and in 2 there was a twofold or greater, and in 3 a fourfold or greater, drop in titre. The geometric mean titres were 1/84 for the acute phase sera, 1/81 for the convalescent sera, and 1/14 for the control sera. The mean titres of the acute phase and control sera, omitting the negative results, were 1/103 and 1/93, respectively, and did not differ significantly by Student’s t test. The mean titres of the acute and convalescent phase sera were not significantly different. There has been much discussion 1-5 of the significance of increased titres of antibody to viruses and bacteria in diseases of the liver. My findings are compatible with a current hypothesis 1,5 that during liver disease antibodies D. R., Kurtz, J. B., MacCallum, F. O., Wright, R. Lancet, 1972, i, 665. 2. Bjorneboe, M., Prytz, H., Orskov, F. ibid. p. 58. 1.
Triger,
3. 4.
Triger, D. R., Alp, M. H., Wright, R. ibid. p. 60. Protell, R. L., Soloway, R. D., Martin, W. J., Schoenfield, L. J., Summerskill, W. H. J. ibid. 1971, ii, 330. Bjorneboe, M. ibid. p. 484.
5.