- Email: [email protected]
RUBELLA SCREENING
534
TABLE
RUBELLA SCREENING
1-HBSAg AND HBeAg IN SEVEN INSTITUTIONS FOR MENTALLYY HANDICAPPED
SIR,-We would like to comment on Dr Champsaur’s letter (Jan. 22, p. 182). We do not have the resources to screen routinely for
antibody by both radial haemolysis (RH) and haemagglutination inhibition (HI), nor would we wish to do so. We believe the prime consideration is to avoid false positive results since these may engender a false sense of security in both clinician and patient. We agree with Champsaur that false positive results do not occur in the RH test if done correctly, but they are a problem with the HI test, particularly at low titres, because of non-specific rubella
inhibitors. We have not seen HI titres of 256 attributable to residual
non-specific inhibitors except in a small, defined group of patients *HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative. f% of total patients. TABLE
II-HBSAg AND HBeAg IN MENTALLY HANDICAPPED INPATIENTS BY DIAGNOSIS AND BY SEX
*HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative. - 1% of total patients.
hospital environment, whereas anti-HBe positive carriers do not.5 Patients with Down’s syndrome were 16 times more likely to be "infectious" carriers (HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative) than those without Down’s syndrome. Males were six times more likely to be "infectious carriers" than were
females. All but 1 of the female carriers without Down’s
syndrome were anti-HBe positive, and she was negative for both HBeAg and anti-HBe. In hospital A, with the highest carrier rate, 60% of male Down’s syndrome patients were carriers and of these, two-thirds were "infectious". To decide whether to recommend hepatitis B vaccine to staff in institutions for the mentally handicapped, a possible course might be to screen all male Down’s syndrome patients for HBsAg. If no carriers are found, or only anti-HBe positive carriers are found, vaccination of patients or staff might not be recommended. If "infectious" carriers are found, vaccine could be offered to all staff with close patient contact and to all newly admitted patients. Alternatively, if hepatitis screening facilities are available, it might be wise to screen in addition all female Down’s syndrome patients and all aggressive male patients. In our view, vaccine might then be offered to staff and newly admitted patients in contact with "infectious" carriers. It would probably not be necessary to screen female patients without Down’s syndrome. At a later stage, when vaccine becomes more easily available, all staff with patient contact and all susceptible patients in those hospitals with "infectious" carriers might be offered vaccine. Public Health Laboratory, Kingsdown, Bristol BS2 8EL
Stoke Park
Stapleton, Hortham
S. K. R. CLARKE E. O. CAUL
where their occurrence may lead to an incorrect diagnosis of congenital rubella. Three infants, aged 4-8 months, had HI titres of 200-400 IU but were RH negative, rubella-specific IgG negative by sucrose density gradient and immunofluorescence (Dr J. Cradock-Watson, Manchester), and did not have rubella-specific IgM detectable by M-antibody capture radioimmunoassay (MACRIA). Indeed, one of the mothers was rubella antibody negative by RH. All three infants had persistent, severe jaundice, and their HI titres were probably due to residual non-specific inhibitors. The frequency with which such a problem occurs in routine screening sera probably depends on the quality of the serum (i.e., whether it is microbially contaminated) and on the technique used for the HI test. When we compared 1000 antenatal sera by HI and RHwe saw a single serum with an HI titre of >12 IU that was RH negative, so such discordance is very rare in our hands. This would also suggest that Champsaur’s "blocking factor" is rarely significant in sera with reasonable levels (> 12 IU) of rubella antibody. How often does he find this factor? The example he gives (his own serum) would appear to be due to rubella-specific IgM, with sequential changes in appearance of the zone being due to changes in the relative concentrations of rubella-specific IgM and IgG. In our laboratory the RH technique we use2has a sensitivity of 5 IU (3 IU when sensitised methods are used). Theoretically, false negative RH results could occur with sera having higher titres than this, perhaps due to high levels of IgM rheumatoid factor when low levels of rubella antibody are present, but they appeared to be infrequent. A false negative screening result may lead to avoidable anxiety and to needless administration of rubella vaccine. This was what happened for many years when we used HI for screening and had to take non-specific inhibitors into consideration; however, although not desirable, this situation is not unacceptable. However, we agree that more sensitive techniques, when available, should be used to investigate patients who have been repeatedly immunised without an apparent rubella antibody response. Champsaur asks if routine rubella-specific IgM screening is indicated. Even where the resources are available, currently the answer is, we believe, No. We have experience of three assay systems for rubella-specific IgM which might be able to cope with the numbers of sera requiring testing-namely, MACRIA and two ELISA systems (Abbott’s ’Rubazyme-M’; ’Rubenz-M’, from Northumbria Biologicals Ltd, UK). The problem would be the occasional equivocal or low positive result in the absence of supporting evidence of recent primary rubella. If further testing and inquiry were unproductive and the low positive or equivocal result persisted, what should we advise? We would be interested in further opinions on rubella-specific IgM screening since Dr Urquhart and Dr Carson (Nov. 27, p. 1226) have indicated that cases of recent rubella found by screening antenatal clinic sera could usually also have been detected by clinical questioning and appropriate investigations, with full details being supplied to the laboratory. .
Department of Medical Microbiology, King’s College Hospital Medical School,
P. MORGAN-CAPNER
London SE5 8RX
J.
Bristol
Hospital, Almondsbury, Bristol
J. JANCAR J. B. GORDON-RUSSELL D. H. FOX
1
Morgan-Capner P, Pullen HJM, Pattison JR, Bidwell DE, Bartlett A, Voller A A comparison of three tests for rubella antibody screening.J Clin Pathol 1979, 32: 542-45. JB, Mortimer PP, Mortimer PR, Morgan-Capner P, Shafi MS, White GBB Rubella antibody measured by radial haemolysis. Characteristics and performance ofa simple screening method for use in diagnostic laboratories J Hyg (Camb) 1980; 84: 213-22
2. Kurtz 5 Follett
HODGSON
Hospital,
EAC, MacFarlane TW. Infectivity in hepatitis B surface antigen (Australia antigen) positive patients. Br Dent J 1981; 150: 92-94
TABLE
RUBELLA SCREENING
1-HBSAg AND HBeAg IN SEVEN INSTITUTIONS FOR MENTALLYY HANDICAPPED
SIR,-We would like to comment on Dr Champsaur’s letter (Jan. 22, p. 182). We do not have the resources to screen routinely for
antibody by both radial haemolysis (RH) and haemagglutination inhibition (HI), nor would we wish to do so. We believe the prime consideration is to avoid false positive results since these may engender a false sense of security in both clinician and patient. We agree with Champsaur that false positive results do not occur in the RH test if done correctly, but they are a problem with the HI test, particularly at low titres, because of non-specific rubella
inhibitors. We have not seen HI titres of 256 attributable to residual
non-specific inhibitors except in a small, defined group of patients *HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative. f% of total patients. TABLE
II-HBSAg AND HBeAg IN MENTALLY HANDICAPPED INPATIENTS BY DIAGNOSIS AND BY SEX
*HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative. - 1% of total patients.
hospital environment, whereas anti-HBe positive carriers do not.5 Patients with Down’s syndrome were 16 times more likely to be "infectious" carriers (HBeAg positive/anti-HBe negative or HBeAg negative/anti-HBe negative) than those without Down’s syndrome. Males were six times more likely to be "infectious carriers" than were
females. All but 1 of the female carriers without Down’s
syndrome were anti-HBe positive, and she was negative for both HBeAg and anti-HBe. In hospital A, with the highest carrier rate, 60% of male Down’s syndrome patients were carriers and of these, two-thirds were "infectious". To decide whether to recommend hepatitis B vaccine to staff in institutions for the mentally handicapped, a possible course might be to screen all male Down’s syndrome patients for HBsAg. If no carriers are found, or only anti-HBe positive carriers are found, vaccination of patients or staff might not be recommended. If "infectious" carriers are found, vaccine could be offered to all staff with close patient contact and to all newly admitted patients. Alternatively, if hepatitis screening facilities are available, it might be wise to screen in addition all female Down’s syndrome patients and all aggressive male patients. In our view, vaccine might then be offered to staff and newly admitted patients in contact with "infectious" carriers. It would probably not be necessary to screen female patients without Down’s syndrome. At a later stage, when vaccine becomes more easily available, all staff with patient contact and all susceptible patients in those hospitals with "infectious" carriers might be offered vaccine. Public Health Laboratory, Kingsdown, Bristol BS2 8EL
Stoke Park
Stapleton, Hortham
S. K. R. CLARKE E. O. CAUL
where their occurrence may lead to an incorrect diagnosis of congenital rubella. Three infants, aged 4-8 months, had HI titres of 200-400 IU but were RH negative, rubella-specific IgG negative by sucrose density gradient and immunofluorescence (Dr J. Cradock-Watson, Manchester), and did not have rubella-specific IgM detectable by M-antibody capture radioimmunoassay (MACRIA). Indeed, one of the mothers was rubella antibody negative by RH. All three infants had persistent, severe jaundice, and their HI titres were probably due to residual non-specific inhibitors. The frequency with which such a problem occurs in routine screening sera probably depends on the quality of the serum (i.e., whether it is microbially contaminated) and on the technique used for the HI test. When we compared 1000 antenatal sera by HI and RHwe saw a single serum with an HI titre of >12 IU that was RH negative, so such discordance is very rare in our hands. This would also suggest that Champsaur’s "blocking factor" is rarely significant in sera with reasonable levels (> 12 IU) of rubella antibody. How often does he find this factor? The example he gives (his own serum) would appear to be due to rubella-specific IgM, with sequential changes in appearance of the zone being due to changes in the relative concentrations of rubella-specific IgM and IgG. In our laboratory the RH technique we use2has a sensitivity of 5 IU (3 IU when sensitised methods are used). Theoretically, false negative RH results could occur with sera having higher titres than this, perhaps due to high levels of IgM rheumatoid factor when low levels of rubella antibody are present, but they appeared to be infrequent. A false negative screening result may lead to avoidable anxiety and to needless administration of rubella vaccine. This was what happened for many years when we used HI for screening and had to take non-specific inhibitors into consideration; however, although not desirable, this situation is not unacceptable. However, we agree that more sensitive techniques, when available, should be used to investigate patients who have been repeatedly immunised without an apparent rubella antibody response. Champsaur asks if routine rubella-specific IgM screening is indicated. Even where the resources are available, currently the answer is, we believe, No. We have experience of three assay systems for rubella-specific IgM which might be able to cope with the numbers of sera requiring testing-namely, MACRIA and two ELISA systems (Abbott’s ’Rubazyme-M’; ’Rubenz-M’, from Northumbria Biologicals Ltd, UK). The problem would be the occasional equivocal or low positive result in the absence of supporting evidence of recent primary rubella. If further testing and inquiry were unproductive and the low positive or equivocal result persisted, what should we advise? We would be interested in further opinions on rubella-specific IgM screening since Dr Urquhart and Dr Carson (Nov. 27, p. 1226) have indicated that cases of recent rubella found by screening antenatal clinic sera could usually also have been detected by clinical questioning and appropriate investigations, with full details being supplied to the laboratory. .
Department of Medical Microbiology, King’s College Hospital Medical School,
P. MORGAN-CAPNER
London SE5 8RX
J.
Bristol
Hospital, Almondsbury, Bristol
J. JANCAR J. B. GORDON-RUSSELL D. H. FOX
1
Morgan-Capner P, Pullen HJM, Pattison JR, Bidwell DE, Bartlett A, Voller A A comparison of three tests for rubella antibody screening.J Clin Pathol 1979, 32: 542-45. JB, Mortimer PP, Mortimer PR, Morgan-Capner P, Shafi MS, White GBB Rubella antibody measured by radial haemolysis. Characteristics and performance ofa simple screening method for use in diagnostic laboratories J Hyg (Camb) 1980; 84: 213-22
2. Kurtz 5 Follett
HODGSON
Hospital,
EAC, MacFarlane TW. Infectivity in hepatitis B surface antigen (Australia antigen) positive patients. Br Dent J 1981; 150: 92-94