1359
avoid active intervention, which encouraged the of the villagers. It is reasonable to expect that the households in which children received no dose would also have availed themselves of advice from the health workers. Cravioto3 in a longitudinal survey, reported that infant mortality rate was lowest in families visited regularly. The rank correlation between the number ofhome visits and infant mortality was 0-67 which was significantly different from zero. Our analysis thus supports the hypothesis that the Hawthorne phenomenon (the act of studying an outcome changes the outcome) may have been responsible for the reduction in child mortality in the 2-dose groups receiving vitamin A or
instructed
to
cooperation
placebo. K. VIJAYARAGHAVAN G. RADHAIAH VINODINI REDDY
National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500 007, India
1. Vijayaraghavan K,
Radhaiah G, Prakasam BS, Sarma KVR, Reddy V. Effect of massive dose of vitamin A on morbidity and mortality in Indian children. Lancet 1990; 336: 1342-45. 2. Sommer A, West KP. Vitamin A and childhood mortality. Lancet 1991; 337: 925. 3. Cravioto J. Vitamin A supplementation and child mortality: examination of a claim. Nutr Found Ind Bull 1990; 11: 5-6.
Randomised trial of case finding and surveillance of elderly people at home SIR,-We are somewhat surprised by Professor Pathy and colleagues’ conclusions (Oct 10, p 890). First, 29 (8%) of the intervention group compared with 18 (5%) of the control group left the study to register elsewhere. Pathy et al seem not to have considered the bias that this might cause. Patients who select themselves out may do so to move to nursing home or hospice care and therefore they may have an increased mortality rate. Any excess mortality in the intervention group would greatly reduce the mortality difference. Moreover, the groups analysed are no longer those randomised and therefore may not be comparable on important demographic and health factors. We have completed a similar randomised controlled trial of the effect of social intervention on the mortality and morbidity of those aged 75 years and over.’ This study, with a 2-year follow-up, showed no statistically or clinically significant difference in mortality between the intervention and control groups, although social intervention did seem to improve self-perceived health (as Pathy et al also find). The difficulty of the mortality of subjects moving out of the practice area during the study was overcome by flagging the study population at the NHS Central Registry in Southport, which provided details for deaths of all subjects irrespective of where they had died. Second, Pathy et al offer no evidence that the reduced mortality in the intervention group was biologically plausible. For example, mortality rates for malignant disease are unlikely to be influenced by the screening questionnaire. These issues need to be addressed before suggesting to general practitioners that a postal screening questionnaire with elective follow-up will enhance the health of their elderly patients. Department of Epidemiology and Public Health, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK
MICHAEL CLARKE CAROL JAGGER
1. Clarke M, Clarke S, Jagger C. Social intervention and the elderly: controlled trial. Am J Epidemiol (in press).
*t* This letter has been shown whose reply follows.-ED. L.
to
Professor
Pathy
a
randomised
and Dr Bayer,
SIR,-Professor Clarke and Dr Jagger are surprised that our 3 study of health and functionally oriented intervention in elderly people was associated with a lower mortality, whereas their 2 Year study of "social intervention" was not. Ours is certainly not the first such randomised controlled trial to record improved s1,JrVÌval.1-3 Furthermore, the biological plausibility of targeted health and social intervention potentially favourably influencing morbidity, and consequently mortality, seems self-evident. Year
We, of course, agree that failure to include all subjects initially randomised in any final analysis can bias results. At the end of our study, we successfully traced 39 (24 intervention, 15 control) of the 47 patients who had left the practice. Of these, 21 of the intervention group and 13 of the control group were alive. At least 5 of the untraced patients had moved abroad and therefore could not be identified by the NHS Central Registry. If the missing patients with uncertain outcome are included in the mortality analysis, then between 70 (19%) and 75 (20%) of the intervention group died and between 88 (25%) and 91 (26%) of the control group. Our conclusion therefore remains that an effective case-finding programme in general practice can favourably influence patient outcome. Health Care Research Unit, St Woolos Hospital, Newport, Gwent NP9 4SZ, UK
M. S.
Department of Geriatric Medicine, University of Wales College of Medicine, Cardiff Royal Infirmary, Cardiff
ANTONY BAYER
JOHN PATHY
1. Vetter N, Jones DA, Victor CR. Effects of health visitors working with elderly patients in general practice: a randomised controlled trial. BMJ 1984; 288: 369-72. 2. Hendnksen C, Lund E, Stromgard E. Consequences of assessment and intervention among elderly people: three year randomised controlled trial. BMJ 1984; 289: 1522-24. 3. Rubenstein LZ, Josephson KR, Wieland GD, et al. Effectiveness of a geriatric evaluation unit: a randomised controlled trial. N Engl J Med 1984; 310: 1664-70.
Congenital complete heart block in children of mothers with primary Sjögren’s syndrome SIR,-We report high relative risk for congenital complete heart
(CCHB) in children of mothers with primary Sjogren’s syndrome (Copenhagen criteria).1 In 1983 in Denmark, 71 affected mothers, and in 1991 in Sweden, 97 affected mothers received a questionnaire about their obstetric history. All the Danish and 91 of block
the 97 Swedish mothers answered. The two groups were similar in number of pregnancies, legal and spontaneous abortions, and still and liveborn children (table). The number of pregnancies and frequencies of abortions and stillbirths were similar to the general populations. The incidence in the general population of CCHB is 1 per 20 000.34 of the Swedish children had CCHB (relative risk 506) as did 3 Danish children (500). For the mothers and the newborn infants for whom we had serum samples, all had Sjogren’s syndrome antibodies B in high titre. All these samples had antinuclear and Sjogren’s syndrome antibodies, while DNA antibodies were normal. No family had more than 1 child with CCHB: 3 of the children had no siblings, and 2 had 1 and 1 had 2 healthy siblings. 2 of the patients in the Swedish group and 1 in the Danish group did not have any symptoms of primary Sjogren’s syndrome at delivery (or at any time before). They were positive for antinuclear antigens, and objective investigations after delivery showed keratoconjunctivitis sicca and xerostomia. The strength of our investigation was that, for classification of patients with primary Sjogren’s syndrome, only objective tests were used. The 3 patients with no symptoms at delivery would probably not have been diagnosed as Sjogren’s patients if other classification criteria had been used.4 In neither of the populations did we find an DETAILS OF PREGNANCIES IN PATIENTS WITH PRIMARY SJOGREN’S SYNDROME
1360
increased frequency of infertility, abortion, or premature deliveries, contrasts with observations in patients with systemic lupus erythematosus.s It is important that a young woman with a chronic inflammatory connective tissue disease is correctly diagnosed to avoid unneccesary speculation and anxiety about high risk of spontaneous abortions, premature deliveries, and increased fetal
which
ACCUPROBE TESTING ON MYCOBACTERIAL ISOLATES FROM AIDS PATIENTS
mortality. The increased frequency for CCHB in children means that 1 of about 40 deliveries from patients with primary Sj6gren’s syndrome will result in a baby with CCHB. Our policy is to have a paediatric cardiologist in the delivery room in case cardiac pacing is necessary. CCHB should not prevent planning for a vaginal delivery. Only 1 of the infants needed a pacemaker, and the children usually develop well with no signs of cardiac insufficiency, although with a low
pulse. CCHB especially occurs in patients with various connective tissue diseases and is correlated with presence of Sjogren’s syndrome A and B antibodies in the mothers 6 The pathophysiological explanation for CCHB is not known. However, the mothers always seem to be positive for A and B antibodies. We thank our patients and colleagues at the Sjögren Center Malmo for assistance with this project and Jan-Åke Nilsson for statistical help. The study was supported by grants from the Sjögren Syndrome Center of Research, and the Börje Dahlin and the Alf Österlund foundation.
Department of Gynaecology and Obstetrics, Lund University Hospital; and Division of Rheumatology, Department of Internal Medicine, Malmö General Hospital, Lund University, S-21401 Malmo Sweden
TOVE MANTHORPE ROLF MANTHORPE
Manthorpe R, Oxholm P, Prause JU, Schiødt M. The Copenhagen criteria for Sjogren’s syndrome. Scand J Rheumatol 1986; 61 (suppl): 19-21. 2. Manthorpe T, Manthorpe R. The outcome of pregnancies of patients with primary Sjögren’s syndrome. Prog Rheumatol 1984; ii: 141-44. 3. Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. In: Engle MA, ed. Pediatric cardiology, 1972; 4: 85-101. 4. Manthorpe R, Andersen V, Jensen OA, Oxholm P, Prause J, Schiødt M. Editorial comments to the four sets of criteria for Sjögren’s syndrome. Scand J Rheumatol 1.
1986; 61: 31-35. G, Rodriguez-Alvarez E. Systemic lupus erythematosus. In- Zurier RB, ed. Pregnancy in patients with rheumatic diseases. Rheum Dis Clin North Am 1989; 15:
5. Mintz
225-74. 6. Petri M, Watson R, Hochberg MC. Anti-Ro antibodies and neonatal lupus. In: Zurier RB, ed. Pregnancy in patients with rheumatic diseases. Rheum Dis Clin North Am 1989; 15: 335-60.
Rapid misdiagnosis by Mycobacterium avium-intracellulare masquerading as tuberculosis in PCR/DNA probe tests
MAIC-X
=
M avium-intracellulare
complex, subtype X.
However, these isolates failed to give characteristic products with other MTBC specific primers, notably IS6110.6 We conclude that rapid identification of mycobacterial isolates should not be attempted with PCR primers to MBP64 because false-positive results can be obtained with occasional MAIC strains. We recommend that MAIC AccuProbe-positive results can be confidently reported as consistent with MAIC but because of our observations we have discontinued reporting results with the MTBC AccuProbe system. We thank Mr M. D. Yates, Regional Tuberculosis Centre, Dulwich Public Health Laboratory for provision of some of the isolates and for confirming the identity of all isolates by conventional methods.
Department of Medical Microbiology, Westminster Hospital, London SW1P 2AR, UK
T. J. BULL D. C. SHANSON
TJ, Shanson DC. Evaluation of a commercial chemiluminescent gene probe system ’AccuProbe’ for the rapid differentiation of mycobacteria, including ’MAIC-X’, isolated from blood and other sites, from patients with AIDS. J Hosp Infect 1992; 21: 143-49. 2. Evans DE, Nakasone AS, Sutherland PA, et al. Identification of Mycobacterium tuberculosis and Mycobacterium avium-M intracellulare directly from primary BACTEC cultures by using acridinium-ester-labelled probes. J Clin Microbiol 1. Bull
1992; 30: 2427-31. 3. Lebrun L, Espinasse F, Poveda JD, et al. Evaluation of nonradioactive DNA probes for identification of mycobacteria. J Clin Microbiol 1992; 30: 2476-78. 4. Hampson SJ, Portaels F, Thompson J, et al. DNA probes demonstrate a single highly conserved strain of Mycobacterium avium infecting AIDS patients. Lancet 1989; i: 65-68. 5. Shankar P, Manjunath N, Mohan K, et al. Rapid diagnosis of tuberculosis meningitis by polymerase chain reaction. Lancet 1991; 337: 5-7. 6. Brisson-Noel A, Aznar C, Chureau C, et al. Diagnosis of tuberculosis by DNA amplification in clinical practice. Lancet 1991; 338: 364-66.
SIR,-We report the potential for misdiagnosis of tuberculosis with
a "specific" commercial chemiluminescent gene probe (AccuProbe, GenProbe), and a "specific" polymerase chain reaction (PCR) protocol. In the 5 instances we describe, the correct identification of Mycobacterium avium-intracellulare complex (MAIC) infection was only obtained by conventional culture and biochemical testing and would have been reported as M tuberculosis complex (MTBC) if AccuProbe and PCR were used alone. The MTBC AccuProbe test has been reported as 100% specific.1-3 Until recently preliminary reports of AccuProbe results were issued with smear-positive BACTEC 13A blood culture broths and acid-fast isolates from Loewenstein-Jensen medium, to facilitate rapid identification.’ In a retrospective analysis of 139 MAIC isolates from 139 AIDS patients, mainly from Westminster Hospital, 5 were MTBC AccuProbe positive, MAIC AccuProbe negative (table). Further investigation of these isolates confirmed that they were pure cultures with biochemical and culture
characteristics of MAIC rather than MTBC. These 5 strains were resistant to at least three first-line antituberculous drugs (rifampicin, isoniazid, and pyrazinamide). These isolates form a group distinct from commonly isolated MAIC types when investigated with DNA probes to distinguish restriction fragment
length polymorphisms.4 The results of PCR tests on the 5 isolates also indicated that they MTBC, with primers "specific" for MTBC to Mop64.5
were
Immunotherapy for drug-resistant tuberculosis SIR,-Multiple drug-resistant tuberculosis is increasing patients infected with these organisms are never cured, although chemotherapy may contribute to prolongation of life. In the past, the infrequency of cases with primary drug resistance (ie, initial infection with a drug-resistant strain) promoted the idea of reduced virulence. By contrast, recent reports from the US suggest that they may be no less virulent than drug-sensitive strains, but much more dangerous. To combat the problem that is aggravated in Mashad by the flood of Afghan refugees, among whom drug-resistant tuberculosis is common, we have been using immunotherapy with Mycobacterium vaccaé as an adjunct to chemotherapy for such patients. Although we had hoped that a single intradermal injection of the killed suspension would be sufficient, this was only true for a few cases and we have explored up to four multiple doses. We studied 41 volunteer inpatients at the Tahleghani Pulmonary Diseases Hospital with advanced and usually bilateral tuberculosis, mainly cavitating and resistant to treatment with isoniazid, streptomycin, rifampicin, and ethambutol. All had been treated with chemotherapy for 1-12 years before receiving immunotherapy. Initially, each patient received an intradermal worldwide. Most
avoid active intervention, which encouraged the of the villagers. It is reasonable to expect that the households in which children received no dose would also have availed themselves of advice from the health workers. Cravioto3 in a longitudinal survey, reported that infant mortality rate was lowest in families visited regularly. The rank correlation between the number ofhome visits and infant mortality was 0-67 which was significantly different from zero. Our analysis thus supports the hypothesis that the Hawthorne phenomenon (the act of studying an outcome changes the outcome) may have been responsible for the reduction in child mortality in the 2-dose groups receiving vitamin A or
instructed
to
cooperation
placebo. K. VIJAYARAGHAVAN G. RADHAIAH VINODINI REDDY
National Institute of Nutrition, Indian Council of Medical Research, Hyderabad 500 007, India
1. Vijayaraghavan K,
Radhaiah G, Prakasam BS, Sarma KVR, Reddy V. Effect of massive dose of vitamin A on morbidity and mortality in Indian children. Lancet 1990; 336: 1342-45. 2. Sommer A, West KP. Vitamin A and childhood mortality. Lancet 1991; 337: 925. 3. Cravioto J. Vitamin A supplementation and child mortality: examination of a claim. Nutr Found Ind Bull 1990; 11: 5-6.
Randomised trial of case finding and surveillance of elderly people at home SIR,-We are somewhat surprised by Professor Pathy and colleagues’ conclusions (Oct 10, p 890). First, 29 (8%) of the intervention group compared with 18 (5%) of the control group left the study to register elsewhere. Pathy et al seem not to have considered the bias that this might cause. Patients who select themselves out may do so to move to nursing home or hospice care and therefore they may have an increased mortality rate. Any excess mortality in the intervention group would greatly reduce the mortality difference. Moreover, the groups analysed are no longer those randomised and therefore may not be comparable on important demographic and health factors. We have completed a similar randomised controlled trial of the effect of social intervention on the mortality and morbidity of those aged 75 years and over.’ This study, with a 2-year follow-up, showed no statistically or clinically significant difference in mortality between the intervention and control groups, although social intervention did seem to improve self-perceived health (as Pathy et al also find). The difficulty of the mortality of subjects moving out of the practice area during the study was overcome by flagging the study population at the NHS Central Registry in Southport, which provided details for deaths of all subjects irrespective of where they had died. Second, Pathy et al offer no evidence that the reduced mortality in the intervention group was biologically plausible. For example, mortality rates for malignant disease are unlikely to be influenced by the screening questionnaire. These issues need to be addressed before suggesting to general practitioners that a postal screening questionnaire with elective follow-up will enhance the health of their elderly patients. Department of Epidemiology and Public Health, University of Leicester, Leicester Royal Infirmary, Leicester LE2 7LX, UK
MICHAEL CLARKE CAROL JAGGER
1. Clarke M, Clarke S, Jagger C. Social intervention and the elderly: controlled trial. Am J Epidemiol (in press).
*t* This letter has been shown whose reply follows.-ED. L.
to
Professor
Pathy
a
randomised
and Dr Bayer,
SIR,-Professor Clarke and Dr Jagger are surprised that our 3 study of health and functionally oriented intervention in elderly people was associated with a lower mortality, whereas their 2 Year study of "social intervention" was not. Ours is certainly not the first such randomised controlled trial to record improved s1,JrVÌval.1-3 Furthermore, the biological plausibility of targeted health and social intervention potentially favourably influencing morbidity, and consequently mortality, seems self-evident. Year
We, of course, agree that failure to include all subjects initially randomised in any final analysis can bias results. At the end of our study, we successfully traced 39 (24 intervention, 15 control) of the 47 patients who had left the practice. Of these, 21 of the intervention group and 13 of the control group were alive. At least 5 of the untraced patients had moved abroad and therefore could not be identified by the NHS Central Registry. If the missing patients with uncertain outcome are included in the mortality analysis, then between 70 (19%) and 75 (20%) of the intervention group died and between 88 (25%) and 91 (26%) of the control group. Our conclusion therefore remains that an effective case-finding programme in general practice can favourably influence patient outcome. Health Care Research Unit, St Woolos Hospital, Newport, Gwent NP9 4SZ, UK
M. S.
Department of Geriatric Medicine, University of Wales College of Medicine, Cardiff Royal Infirmary, Cardiff
ANTONY BAYER
JOHN PATHY
1. Vetter N, Jones DA, Victor CR. Effects of health visitors working with elderly patients in general practice: a randomised controlled trial. BMJ 1984; 288: 369-72. 2. Hendnksen C, Lund E, Stromgard E. Consequences of assessment and intervention among elderly people: three year randomised controlled trial. BMJ 1984; 289: 1522-24. 3. Rubenstein LZ, Josephson KR, Wieland GD, et al. Effectiveness of a geriatric evaluation unit: a randomised controlled trial. N Engl J Med 1984; 310: 1664-70.
Congenital complete heart block in children of mothers with primary Sjögren’s syndrome SIR,-We report high relative risk for congenital complete heart
(CCHB) in children of mothers with primary Sjogren’s syndrome (Copenhagen criteria).1 In 1983 in Denmark, 71 affected mothers, and in 1991 in Sweden, 97 affected mothers received a questionnaire about their obstetric history. All the Danish and 91 of block
the 97 Swedish mothers answered. The two groups were similar in number of pregnancies, legal and spontaneous abortions, and still and liveborn children (table). The number of pregnancies and frequencies of abortions and stillbirths were similar to the general populations. The incidence in the general population of CCHB is 1 per 20 000.34 of the Swedish children had CCHB (relative risk 506) as did 3 Danish children (500). For the mothers and the newborn infants for whom we had serum samples, all had Sjogren’s syndrome antibodies B in high titre. All these samples had antinuclear and Sjogren’s syndrome antibodies, while DNA antibodies were normal. No family had more than 1 child with CCHB: 3 of the children had no siblings, and 2 had 1 and 1 had 2 healthy siblings. 2 of the patients in the Swedish group and 1 in the Danish group did not have any symptoms of primary Sjogren’s syndrome at delivery (or at any time before). They were positive for antinuclear antigens, and objective investigations after delivery showed keratoconjunctivitis sicca and xerostomia. The strength of our investigation was that, for classification of patients with primary Sjogren’s syndrome, only objective tests were used. The 3 patients with no symptoms at delivery would probably not have been diagnosed as Sjogren’s patients if other classification criteria had been used.4 In neither of the populations did we find an DETAILS OF PREGNANCIES IN PATIENTS WITH PRIMARY SJOGREN’S SYNDROME
1360
increased frequency of infertility, abortion, or premature deliveries, contrasts with observations in patients with systemic lupus erythematosus.s It is important that a young woman with a chronic inflammatory connective tissue disease is correctly diagnosed to avoid unneccesary speculation and anxiety about high risk of spontaneous abortions, premature deliveries, and increased fetal
which
ACCUPROBE TESTING ON MYCOBACTERIAL ISOLATES FROM AIDS PATIENTS
mortality. The increased frequency for CCHB in children means that 1 of about 40 deliveries from patients with primary Sj6gren’s syndrome will result in a baby with CCHB. Our policy is to have a paediatric cardiologist in the delivery room in case cardiac pacing is necessary. CCHB should not prevent planning for a vaginal delivery. Only 1 of the infants needed a pacemaker, and the children usually develop well with no signs of cardiac insufficiency, although with a low
pulse. CCHB especially occurs in patients with various connective tissue diseases and is correlated with presence of Sjogren’s syndrome A and B antibodies in the mothers 6 The pathophysiological explanation for CCHB is not known. However, the mothers always seem to be positive for A and B antibodies. We thank our patients and colleagues at the Sjögren Center Malmo for assistance with this project and Jan-Åke Nilsson for statistical help. The study was supported by grants from the Sjögren Syndrome Center of Research, and the Börje Dahlin and the Alf Österlund foundation.
Department of Gynaecology and Obstetrics, Lund University Hospital; and Division of Rheumatology, Department of Internal Medicine, Malmö General Hospital, Lund University, S-21401 Malmo Sweden
TOVE MANTHORPE ROLF MANTHORPE
Manthorpe R, Oxholm P, Prause JU, Schiødt M. The Copenhagen criteria for Sjogren’s syndrome. Scand J Rheumatol 1986; 61 (suppl): 19-21. 2. Manthorpe T, Manthorpe R. The outcome of pregnancies of patients with primary Sjögren’s syndrome. Prog Rheumatol 1984; ii: 141-44. 3. Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. In: Engle MA, ed. Pediatric cardiology, 1972; 4: 85-101. 4. Manthorpe R, Andersen V, Jensen OA, Oxholm P, Prause J, Schiødt M. Editorial comments to the four sets of criteria for Sjögren’s syndrome. Scand J Rheumatol 1.
1986; 61: 31-35. G, Rodriguez-Alvarez E. Systemic lupus erythematosus. In- Zurier RB, ed. Pregnancy in patients with rheumatic diseases. Rheum Dis Clin North Am 1989; 15:
5. Mintz
225-74. 6. Petri M, Watson R, Hochberg MC. Anti-Ro antibodies and neonatal lupus. In: Zurier RB, ed. Pregnancy in patients with rheumatic diseases. Rheum Dis Clin North Am 1989; 15: 335-60.
Rapid misdiagnosis by Mycobacterium avium-intracellulare masquerading as tuberculosis in PCR/DNA probe tests
MAIC-X
=
M avium-intracellulare
complex, subtype X.
However, these isolates failed to give characteristic products with other MTBC specific primers, notably IS6110.6 We conclude that rapid identification of mycobacterial isolates should not be attempted with PCR primers to MBP64 because false-positive results can be obtained with occasional MAIC strains. We recommend that MAIC AccuProbe-positive results can be confidently reported as consistent with MAIC but because of our observations we have discontinued reporting results with the MTBC AccuProbe system. We thank Mr M. D. Yates, Regional Tuberculosis Centre, Dulwich Public Health Laboratory for provision of some of the isolates and for confirming the identity of all isolates by conventional methods.
Department of Medical Microbiology, Westminster Hospital, London SW1P 2AR, UK
T. J. BULL D. C. SHANSON
TJ, Shanson DC. Evaluation of a commercial chemiluminescent gene probe system ’AccuProbe’ for the rapid differentiation of mycobacteria, including ’MAIC-X’, isolated from blood and other sites, from patients with AIDS. J Hosp Infect 1992; 21: 143-49. 2. Evans DE, Nakasone AS, Sutherland PA, et al. Identification of Mycobacterium tuberculosis and Mycobacterium avium-M intracellulare directly from primary BACTEC cultures by using acridinium-ester-labelled probes. J Clin Microbiol 1. Bull
1992; 30: 2427-31. 3. Lebrun L, Espinasse F, Poveda JD, et al. Evaluation of nonradioactive DNA probes for identification of mycobacteria. J Clin Microbiol 1992; 30: 2476-78. 4. Hampson SJ, Portaels F, Thompson J, et al. DNA probes demonstrate a single highly conserved strain of Mycobacterium avium infecting AIDS patients. Lancet 1989; i: 65-68. 5. Shankar P, Manjunath N, Mohan K, et al. Rapid diagnosis of tuberculosis meningitis by polymerase chain reaction. Lancet 1991; 337: 5-7. 6. Brisson-Noel A, Aznar C, Chureau C, et al. Diagnosis of tuberculosis by DNA amplification in clinical practice. Lancet 1991; 338: 364-66.
SIR,-We report the potential for misdiagnosis of tuberculosis with
a "specific" commercial chemiluminescent gene probe (AccuProbe, GenProbe), and a "specific" polymerase chain reaction (PCR) protocol. In the 5 instances we describe, the correct identification of Mycobacterium avium-intracellulare complex (MAIC) infection was only obtained by conventional culture and biochemical testing and would have been reported as M tuberculosis complex (MTBC) if AccuProbe and PCR were used alone. The MTBC AccuProbe test has been reported as 100% specific.1-3 Until recently preliminary reports of AccuProbe results were issued with smear-positive BACTEC 13A blood culture broths and acid-fast isolates from Loewenstein-Jensen medium, to facilitate rapid identification.’ In a retrospective analysis of 139 MAIC isolates from 139 AIDS patients, mainly from Westminster Hospital, 5 were MTBC AccuProbe positive, MAIC AccuProbe negative (table). Further investigation of these isolates confirmed that they were pure cultures with biochemical and culture
characteristics of MAIC rather than MTBC. These 5 strains were resistant to at least three first-line antituberculous drugs (rifampicin, isoniazid, and pyrazinamide). These isolates form a group distinct from commonly isolated MAIC types when investigated with DNA probes to distinguish restriction fragment
length polymorphisms.4 The results of PCR tests on the 5 isolates also indicated that they MTBC, with primers "specific" for MTBC to Mop64.5
were
Immunotherapy for drug-resistant tuberculosis SIR,-Multiple drug-resistant tuberculosis is increasing patients infected with these organisms are never cured, although chemotherapy may contribute to prolongation of life. In the past, the infrequency of cases with primary drug resistance (ie, initial infection with a drug-resistant strain) promoted the idea of reduced virulence. By contrast, recent reports from the US suggest that they may be no less virulent than drug-sensitive strains, but much more dangerous. To combat the problem that is aggravated in Mashad by the flood of Afghan refugees, among whom drug-resistant tuberculosis is common, we have been using immunotherapy with Mycobacterium vaccaé as an adjunct to chemotherapy for such patients. Although we had hoped that a single intradermal injection of the killed suspension would be sufficient, this was only true for a few cases and we have explored up to four multiple doses. We studied 41 volunteer inpatients at the Tahleghani Pulmonary Diseases Hospital with advanced and usually bilateral tuberculosis, mainly cavitating and resistant to treatment with isoniazid, streptomycin, rifampicin, and ethambutol. All had been treated with chemotherapy for 1-12 years before receiving immunotherapy. Initially, each patient received an intradermal worldwide. Most
