- Email: [email protected]
Leprosy and BCG in southern Vietnam
1536
products at all.8 Prophylactic use may prevent uncontrollable bleeding after open heart surgery, which arises in a few patients. Its routine prophylactic use during cardiac surgery can be recommended. 66 Harley Street, London W1 N 1AE, UK
BEN BIDSTRUP
1. Tice DA, Worth MH, Clauss RH, Reed GH. The inhibition of Trasylol of fibrinolytic activity associated with cardiovascular operations. Surg Gynec Obstet 1964; 119: 71-74. 2. van Oeveren W, Janssen N, Bidstrup B, et al. Effects of aprotinin on haemostatic mechanisms in cardiopulmonary bypass. Ann Thorac Surg 1987; 44: 640-45. 3. Popov-Cenic S, Murday H, Kirchhoff P, Hack G, Fenyes J. Anlage und zusammenfassendes Ergebnis einer klinischen Doppelblindstudie bei aortokoronaren Bypass Operationen. In: Dudziak AR, Kirckhoff PG, Reuter HD, Schumann F, eds. Proteolyse und Proteinaseninhibition in der Herz- und Gefa&bgr;chirurgie. Stuttgart: Schattauer Verlag, 1985: 171-86. 4. Hannekum A, Reuter HD, Dalichau H, Horpáscy G, Selbeherr J. Anlage und zusammenfassendes Ergebnis einer klinischen Doppelblindstudie bei Operationen am offenen Herzen. Einflu&bgr; von Aprotinin auf Thrombozytenzahl und -funktion. In: Dudziak AR, Kirckhoff PG, Reuter HD, Schumann F, eds. Proteolyse und Proteinaseninhibition in der Here- und Gefa&bgr;chirurgie. Stuttgart: Schattauer Verlag, 1985: 221-33. 5. Russell G, Peterson S, Harper S, Fox M. Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom Br Med J 1988; 297: 1390-91. 6. Salzman E, Weinstein M, Weintraub R, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. N Engl J Med 1986; 314: 1402-06. 7. Hackmann T, Gascoyne RD, Naiman SC, et al. A trial of desmopressin (1-desamino8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery. N Engl J Med 1989; 312: 1437-43. 8. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction on blood loss and blood use after cardiopulmonary bypass using high dose aprotinin (Trasylol). J Thorac Cardiovasc Surg 1989; 97: 364-72.
patients younger than 20 were retained because BCG vaccination (with Pasteur Institute freeze-dried vaccine) has been common since 1970. The diagnosis was checked by a leprosy specialist and skin biopsy was done in doubtful cases. The 50 cases were classified either lepromatous (including borderline and polar as lepromatous4) or non-lepromatous. 50 controls were matched by age within 2 years, sex, and socioeconomic status. The presence of a BCG scar was taken to indicate a positive exposure. 50% of cases and 66% of controls had a BCG scar (not significant). However, lepromatous patients had a proportion of BCG scars very close to that of their controls (21/34 vs 23/34), whereas non-lepromatous patients had a BCG scar less often than their controls (4/16 vs 10/16; p=0’03). For non-lepromatous leprosy, BCG efficacy, computed as 1 minus the estimated relative risk/ was 80% but the 95% confidence interval was wide
(13-96%). BCG seems to be protective against non-lepromatous leprosy in southern Vietnam, as observed in other areas. The efficacy (80%) is close to that reported in the Uganda study;’ however, more patients are needed for a reliable estimate. BCG had no protective efficacy against lepromatous leprosy, which is consistent with the immunological status of the two subtypes of leprosy patients considered; BCG is not expected to be effective in lepromatous patients, who have defective antimycobacterial cellular immunity. These conclusions have important implications for the control of leprosy in countries with a high proportion of lepromatous cases and indicate that the distinction between lepromatous and nonlepromatous is important in the evaluation of the protective role of BCG. We thank Dr J.
Ice
hockey lung and NO2 poisoning
SIR,-Nitrogen dioxide is known to be responsible for silofillers’ (with some deaths) and, as your May 19 editorial suggests, ice-hockey lung. Some solutes react with NOz fast enough to greatly assist the absorption of the gas from air into water.’ At physiological pH, ascorbic acid is most effective (unpublished). The gas is well absorbed by the lung, but it seems possible that a 1 g oral dose of ascorbic acid would temporarily protect against the subsequent toxic effects, by competing with the sensitive sites for freshly absorbed gas. Any protection thus afforded would depend on raising the ascorbic acid blood concentration from the normal low disease
value to
an
effective level.
12 Lenthay Court, Sherborne, Dorset DT9 6BQ, UK
1. Nash T. Absorption of A3023.
nitrogen
T. NASH dioxide
by
aqueous
solutions. J
Chem Soc 1970;
Leprosy and BCG in southern Vietnam SIR,-Dr Fine and Dr Rodrigues (April 28, p 1016) discuss the protective role of BCG vaccines in mycobacterial diseases. The efficacy of BCG against tuberculosis is difficult to assess because the variation in vaccine efficacy seen in different trials seems to be dependent more on geography than on vaccine strain.l However, in leprosy, five prospective studies have provided consistent results, showing a protective effect of BCG in Uganda, Burma, New Guinea, and south India, and in Malawi.2 Vaccine efficacy varied from 20% to 80%. In these trials non-lepromatous forms constituted the large majority of incident cases. Case-control methods have been widely used to evaluate the efficacy of BCG in tuberculosis3 and seem to be a cheap and useful tool for the assessment of vaccination programmes in developing countries. In leprosy, only one case-control study has been done,2providing results consistent with the prospective trials. In Vietnam the prevalence of leprosy is about 15 per 1000, 30-70% of cases (depending on the region) being lepromatous, the most infectious form. We have done a case-control study of the protective efficacy of BCG in southern Vietnam. Cases were taken at random from a file of leprosy cases being followed up at the Dermatology Hospital, Ho Chi Minh City. Only
Feingold and Dr E. Bois for helpful discussion.
Genetic
Epidemiology Research Unit (INSERM U155) and Department of Biomathematics, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France, Dermatology Hospital, Ho Chi Minh City, Vietnam; Microbiology and Antibacterial Immunology Unit (INSERM U65), Montpellier, Institute of Dermatology, Hanoi, Department of Bacteriology, Hôpital de la Pitié-Salpêtrière, and Department of Microbiology, Hôpital Hôtel-Dieu, Paris
L. ABEL V. V. CUA J. OBERTI V. D. LAP L. K. DUE J. GROSSET P. H. LAGRANGE
1. Fine PEM. BCG vaccination against tuberculosis and leprosy. Br Med Bull 1988; 44: 691-703. 2. Fine PEM, Ponnighaus JM, Maine N, Clarkson JA, Bliss L. Protective efficicacy of BCG against leprosy in northern Malawi. Lancet 1986; ii: 499-502. 3. Comstock GW. Vaccine evaluation by case-control or prospective studies. Am J
Epidemiol 1990; 131: 205-07. Ridley DS, Jopling WH. Classification of leprosy according to immunity: a five group 1966; 34: 255-73. J system. Int Lepr 5. Smith PG. Retrospective assessment of the effectiveness of BCG vaccination against tuberculosis using the case-control method. Tubercle 1982; 62: 22-35. 4.
BCG vaccination and nutrition SiR,—Dr Fine and Dr Rodrigues (April 28, p 1016) discuss the efficacy and impact conundrums surrounding the use of BCG in mycobacterial diseases. These issues are of growing importance because of the resurgence of tuberculosis in conjunction with HIV infection and the implications for a vaccine against HIV, where stimulation of cellular immunity is critical. Little attention is given, however, to the connection between nutrition and immunity in the evaluation of BCG efficacy. The impact of malnutrition on T helper cells and on complement levels is well understood, yet none of the major clinical trials of BCG have adequately controlled for the nutritional levels of the recipients. Both the "take" of vaccinations and the duration of protective immunity may be affected. Chandra’ showed a response continuum of tuberculin conversion, when tested 3-4 months after BCG vaccination. In healthy infants there is an 85% conversion rate; in those with slight malnutrition (greater than 70% of standard) 70% convert; with moderate malnutrition (61-70% of standard) 55% convert; and with severe malnutrition (less than 60%), only 23% convert. In a study of Cree Indians in Canada,
products at all.8 Prophylactic use may prevent uncontrollable bleeding after open heart surgery, which arises in a few patients. Its routine prophylactic use during cardiac surgery can be recommended. 66 Harley Street, London W1 N 1AE, UK
BEN BIDSTRUP
1. Tice DA, Worth MH, Clauss RH, Reed GH. The inhibition of Trasylol of fibrinolytic activity associated with cardiovascular operations. Surg Gynec Obstet 1964; 119: 71-74. 2. van Oeveren W, Janssen N, Bidstrup B, et al. Effects of aprotinin on haemostatic mechanisms in cardiopulmonary bypass. Ann Thorac Surg 1987; 44: 640-45. 3. Popov-Cenic S, Murday H, Kirchhoff P, Hack G, Fenyes J. Anlage und zusammenfassendes Ergebnis einer klinischen Doppelblindstudie bei aortokoronaren Bypass Operationen. In: Dudziak AR, Kirckhoff PG, Reuter HD, Schumann F, eds. Proteolyse und Proteinaseninhibition in der Herz- und Gefa&bgr;chirurgie. Stuttgart: Schattauer Verlag, 1985: 171-86. 4. Hannekum A, Reuter HD, Dalichau H, Horpáscy G, Selbeherr J. Anlage und zusammenfassendes Ergebnis einer klinischen Doppelblindstudie bei Operationen am offenen Herzen. Einflu&bgr; von Aprotinin auf Thrombozytenzahl und -funktion. In: Dudziak AR, Kirckhoff PG, Reuter HD, Schumann F, eds. Proteolyse und Proteinaseninhibition in der Here- und Gefa&bgr;chirurgie. Stuttgart: Schattauer Verlag, 1985: 221-33. 5. Russell G, Peterson S, Harper S, Fox M. Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom Br Med J 1988; 297: 1390-91. 6. Salzman E, Weinstein M, Weintraub R, et al. Treatment with desmopressin acetate to reduce blood loss after cardiac surgery. N Engl J Med 1986; 314: 1402-06. 7. Hackmann T, Gascoyne RD, Naiman SC, et al. A trial of desmopressin (1-desamino8-D-arginine vasopressin) to reduce blood loss in uncomplicated cardiac surgery. N Engl J Med 1989; 312: 1437-43. 8. Bidstrup BP, Royston D, Sapsford RN, Taylor KM. Reduction on blood loss and blood use after cardiopulmonary bypass using high dose aprotinin (Trasylol). J Thorac Cardiovasc Surg 1989; 97: 364-72.
patients younger than 20 were retained because BCG vaccination (with Pasteur Institute freeze-dried vaccine) has been common since 1970. The diagnosis was checked by a leprosy specialist and skin biopsy was done in doubtful cases. The 50 cases were classified either lepromatous (including borderline and polar as lepromatous4) or non-lepromatous. 50 controls were matched by age within 2 years, sex, and socioeconomic status. The presence of a BCG scar was taken to indicate a positive exposure. 50% of cases and 66% of controls had a BCG scar (not significant). However, lepromatous patients had a proportion of BCG scars very close to that of their controls (21/34 vs 23/34), whereas non-lepromatous patients had a BCG scar less often than their controls (4/16 vs 10/16; p=0’03). For non-lepromatous leprosy, BCG efficacy, computed as 1 minus the estimated relative risk/ was 80% but the 95% confidence interval was wide
(13-96%). BCG seems to be protective against non-lepromatous leprosy in southern Vietnam, as observed in other areas. The efficacy (80%) is close to that reported in the Uganda study;’ however, more patients are needed for a reliable estimate. BCG had no protective efficacy against lepromatous leprosy, which is consistent with the immunological status of the two subtypes of leprosy patients considered; BCG is not expected to be effective in lepromatous patients, who have defective antimycobacterial cellular immunity. These conclusions have important implications for the control of leprosy in countries with a high proportion of lepromatous cases and indicate that the distinction between lepromatous and nonlepromatous is important in the evaluation of the protective role of BCG. We thank Dr J.
Ice
hockey lung and NO2 poisoning
SIR,-Nitrogen dioxide is known to be responsible for silofillers’ (with some deaths) and, as your May 19 editorial suggests, ice-hockey lung. Some solutes react with NOz fast enough to greatly assist the absorption of the gas from air into water.’ At physiological pH, ascorbic acid is most effective (unpublished). The gas is well absorbed by the lung, but it seems possible that a 1 g oral dose of ascorbic acid would temporarily protect against the subsequent toxic effects, by competing with the sensitive sites for freshly absorbed gas. Any protection thus afforded would depend on raising the ascorbic acid blood concentration from the normal low disease
value to
an
effective level.
12 Lenthay Court, Sherborne, Dorset DT9 6BQ, UK
1. Nash T. Absorption of A3023.
nitrogen
T. NASH dioxide
by
aqueous
solutions. J
Chem Soc 1970;
Leprosy and BCG in southern Vietnam SIR,-Dr Fine and Dr Rodrigues (April 28, p 1016) discuss the protective role of BCG vaccines in mycobacterial diseases. The efficacy of BCG against tuberculosis is difficult to assess because the variation in vaccine efficacy seen in different trials seems to be dependent more on geography than on vaccine strain.l However, in leprosy, five prospective studies have provided consistent results, showing a protective effect of BCG in Uganda, Burma, New Guinea, and south India, and in Malawi.2 Vaccine efficacy varied from 20% to 80%. In these trials non-lepromatous forms constituted the large majority of incident cases. Case-control methods have been widely used to evaluate the efficacy of BCG in tuberculosis3 and seem to be a cheap and useful tool for the assessment of vaccination programmes in developing countries. In leprosy, only one case-control study has been done,2providing results consistent with the prospective trials. In Vietnam the prevalence of leprosy is about 15 per 1000, 30-70% of cases (depending on the region) being lepromatous, the most infectious form. We have done a case-control study of the protective efficacy of BCG in southern Vietnam. Cases were taken at random from a file of leprosy cases being followed up at the Dermatology Hospital, Ho Chi Minh City. Only
Feingold and Dr E. Bois for helpful discussion.
Genetic
Epidemiology Research Unit (INSERM U155) and Department of Biomathematics, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France, Dermatology Hospital, Ho Chi Minh City, Vietnam; Microbiology and Antibacterial Immunology Unit (INSERM U65), Montpellier, Institute of Dermatology, Hanoi, Department of Bacteriology, Hôpital de la Pitié-Salpêtrière, and Department of Microbiology, Hôpital Hôtel-Dieu, Paris
L. ABEL V. V. CUA J. OBERTI V. D. LAP L. K. DUE J. GROSSET P. H. LAGRANGE
1. Fine PEM. BCG vaccination against tuberculosis and leprosy. Br Med Bull 1988; 44: 691-703. 2. Fine PEM, Ponnighaus JM, Maine N, Clarkson JA, Bliss L. Protective efficicacy of BCG against leprosy in northern Malawi. Lancet 1986; ii: 499-502. 3. Comstock GW. Vaccine evaluation by case-control or prospective studies. Am J
Epidemiol 1990; 131: 205-07. Ridley DS, Jopling WH. Classification of leprosy according to immunity: a five group 1966; 34: 255-73. J system. Int Lepr 5. Smith PG. Retrospective assessment of the effectiveness of BCG vaccination against tuberculosis using the case-control method. Tubercle 1982; 62: 22-35. 4.
BCG vaccination and nutrition SiR,—Dr Fine and Dr Rodrigues (April 28, p 1016) discuss the efficacy and impact conundrums surrounding the use of BCG in mycobacterial diseases. These issues are of growing importance because of the resurgence of tuberculosis in conjunction with HIV infection and the implications for a vaccine against HIV, where stimulation of cellular immunity is critical. Little attention is given, however, to the connection between nutrition and immunity in the evaluation of BCG efficacy. The impact of malnutrition on T helper cells and on complement levels is well understood, yet none of the major clinical trials of BCG have adequately controlled for the nutritional levels of the recipients. Both the "take" of vaccinations and the duration of protective immunity may be affected. Chandra’ showed a response continuum of tuberculin conversion, when tested 3-4 months after BCG vaccination. In healthy infants there is an 85% conversion rate; in those with slight malnutrition (greater than 70% of standard) 70% convert; with moderate malnutrition (61-70% of standard) 55% convert; and with severe malnutrition (less than 60%), only 23% convert. In a study of Cree Indians in Canada,