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Drug resistance among acid-fast bacilli
CORRESPONDENCE
Drug resistance among acid-fast bacilli Sir—M A Behr and colleagues’ (Feb 6, p 444) 1 study shows that smearnegative cases are indeed less infectious, but contribute substantially to disease transmission. Pulmonary tuberculosis patients with acid-fast bacilli detected by direct sputum smear examination only were included in the WHO union against tuberculosis and lung disease global project on antituberculosis drug resistance surveillance.2 To establish whether this surveillance strategy yields biased results, we investigate the frequency of drug resistance among acid-fast bacilli smear-positive and smear-negative patients in Huauchinango Mexico, located in the eastern region of the Sierra Madre of Mexico with 391 000 inhabitants in an area of 3000 km2. More than two-thirds of the population uses the health-care services provided by the Ministry of Health. All patients with productive cough attending these health-care units were studied with direct smear examination and culture in Lowenstein-Jensen media and in radiometric broth (Bactec 12B, Becton Dickinson, Cockesville, MD, USA). Mycobacterium tuberculosis isolates underwent radiometric drug susceptibility testing. 2 test was used to analyse differences. Between June, 1995, and May, 1998, we studied 1374 patients. Tuberculosis was diagnosed in 269 (20%) patients and in 242 cases M tuberculosis was recovered. Drug susceptibility test results were available for 230 patients, 189 (82%) of which were susceptible across the entire range. Clinical data were available for 165 (72%) patients. 117 (71%) patients had never received anti-tuberculosis treatment from which 73 (62%) had a positive acid-fast bacilli smear. The frequency of primary resistance to isoniazid was 12% and to rifampicin 4%, and multidrug resistance (resistant at least to isoniazid and rifampicin) was 2·5%. The proportion of primary resistant isolates Patients without previous history of anti-tuberculosis treatment Smear Smear positive (n=73) negative (n=44) Resistant Isoniazid Streptomycin Rifampicin Ethambutol Polyresistance Multidrug resistance
8 (11%) 5 (7%) 1 (1%) 2 (3%) 1 (1%) 2 (3%) 0
9 (20%) 9 (20%)* 4 (9%) 3 (7%) 0 7 (16%)† 3 (7%)
*p=0·05. †p=0·02.
Primary drug resistance in pulmonary tuberculosis patients with positive and negative smear examination
THE LANCET • Vol 353 • May 15, 1999
was higher among patients with a negative acid-fast bacilli smear (table). By contrast, most of the isolates that showed secondary resistance were obtained from acid-fast bacilli smearpositive patients, independently of the antimicrobial susceptibility profile of their isolates. Smear-negative pulmonary tubercul osis patients have been thought to be less contagious and therefore without the same public health impact as smear-positive cases.3,4 In this region, limiting drug resistance surveillance to acid-fast bacilli smear-positive cases significantly underestimates the rate of primary multidrug resistance. In combination with the results of Behr and colleagues, our findings suggest that smear-negative patients can be an important factor for the dissemination of resistant M tuberculosis. This study was supported by the Consejo Nacional de Ciencias y Tecnologia (CONACYT), grant number: 4987-M9406.
M Kato-Maeda, *J Sifuentes-Osornio, M Bobadilla-del-Valle, G M Ruiz-Palacios, A Ponce-de-León Instituto Nacional de Nutrición, Mexico City, 14000, Mexico 1
Behr MA, Warren SA, Salomon H, et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet 1999; 353: 444–49. 2 WHO/IUATLD global project on antituberculosis drug resistance surveillance. Anti-tuberculosis drug resistance in the world. Geneva: WHO global tuberculosis programme, (WHO/GTB/97.229). 1997; 60–90. 3 van Zwanenberg D. The influence of the number of bacilli on the development of tuberculosis disease in children. Am Rev Respir Dis 1960; 82: 31–44. 4 Shaw JB, Wynn-Williams N. Infectivity of pulmonary tuberculosis in relation to sputum status. Am Rev Tuberc 1954; 69: 724–32.
S alt, diet, and health Sir—John Swales in his review of our book 1 declares an interest in that we state that in 1986 he disputed the relationship between salt intake and blood pressure at a press conference and he implies that to have done so is unremarkable. But he does not reveal that the press conference was funded and organised by the Salt Manufacturers’ Association in conjunction with Kingsway, a public relations company.2 They also set up a so-called Salt Data Centre that claimed to give impartial and independent advice on the relation between salt and blood pressure. The press conference was held in January, 1986, in London. Swales was the sole
speaker: his solicited, unopposed, and commercially popular view received widespread media publicity. 2 One of the major aims of the Salt Manufacturers’ Association is to protect the sale of salt, particularly that added to processed food, which accounts for about 40% by value of all salt sales, and to try and increase salt sales. The subsequent campaign developed by the Kingsway Rowland Company was so successful that it was used as an example on how to influence public opinion in the marketing for their company. Swales’ continued opinion that there is no consensus about the effects on blood pressure of a moderate permanent reduction in salt intake to around 100 mmol per day is based on a meta-analysis of extremely short periods of salt restriction, which resulted in a mean 24 h sodium excretion of 41 mmol/L for a median duration of 8 days in 2581 n o r m o t e n s i v e s . 3 He regards this analysis as “the most rigorous systematic review of intervention trials” and concludes “that salt restriction in healthy people produces no worthwhile lowering of the blood pressure”. We agree that it may be the best review of what a few days of salt restriction can do to blood pressure. However, there was a highly significant mean fall in systolic pressure of 1·5 mm Hg which, if prolonged and on a population basis, would nevertheless have a major effect on reducing cardiovascular disease. But these short-term studies are utterly irrelevant to a discussion of the merits of a sustained, moderate reduction in salt intake on blood pressure that one wonders why they were introduced. There are huge commercial reasons for protecting the high salt content of processed food.2 It is not surprising, therefore, that some food and softdrink companies and the salt industry have fought a careful and largely covert campaign akin to the tobacco manufacturers suggesting there is a lack of consensus about the need to reduce our unnecessarily high salt consumption. Nevertheless, consensus that salt intake should be reduced in the whole population does now exist. For instance, in the UK, a Government-appointed expert committee on diet and cardiovascular disease reviewed all the evidence and unequivocally recommended a reduction in salt intake for the whole UK population from 9 to 6 g per day.4 Meetings at the British Heart Foundation in December, 1997, the National Heart Lung and Blood
1709
Drug resistance among acid-fast bacilli Sir—M A Behr and colleagues’ (Feb 6, p 444) 1 study shows that smearnegative cases are indeed less infectious, but contribute substantially to disease transmission. Pulmonary tuberculosis patients with acid-fast bacilli detected by direct sputum smear examination only were included in the WHO union against tuberculosis and lung disease global project on antituberculosis drug resistance surveillance.2 To establish whether this surveillance strategy yields biased results, we investigate the frequency of drug resistance among acid-fast bacilli smear-positive and smear-negative patients in Huauchinango Mexico, located in the eastern region of the Sierra Madre of Mexico with 391 000 inhabitants in an area of 3000 km2. More than two-thirds of the population uses the health-care services provided by the Ministry of Health. All patients with productive cough attending these health-care units were studied with direct smear examination and culture in Lowenstein-Jensen media and in radiometric broth (Bactec 12B, Becton Dickinson, Cockesville, MD, USA). Mycobacterium tuberculosis isolates underwent radiometric drug susceptibility testing. 2 test was used to analyse differences. Between June, 1995, and May, 1998, we studied 1374 patients. Tuberculosis was diagnosed in 269 (20%) patients and in 242 cases M tuberculosis was recovered. Drug susceptibility test results were available for 230 patients, 189 (82%) of which were susceptible across the entire range. Clinical data were available for 165 (72%) patients. 117 (71%) patients had never received anti-tuberculosis treatment from which 73 (62%) had a positive acid-fast bacilli smear. The frequency of primary resistance to isoniazid was 12% and to rifampicin 4%, and multidrug resistance (resistant at least to isoniazid and rifampicin) was 2·5%. The proportion of primary resistant isolates Patients without previous history of anti-tuberculosis treatment Smear Smear positive (n=73) negative (n=44) Resistant Isoniazid Streptomycin Rifampicin Ethambutol Polyresistance Multidrug resistance
8 (11%) 5 (7%) 1 (1%) 2 (3%) 1 (1%) 2 (3%) 0
9 (20%) 9 (20%)* 4 (9%) 3 (7%) 0 7 (16%)† 3 (7%)
*p=0·05. †p=0·02.
Primary drug resistance in pulmonary tuberculosis patients with positive and negative smear examination
THE LANCET • Vol 353 • May 15, 1999
was higher among patients with a negative acid-fast bacilli smear (table). By contrast, most of the isolates that showed secondary resistance were obtained from acid-fast bacilli smearpositive patients, independently of the antimicrobial susceptibility profile of their isolates. Smear-negative pulmonary tubercul osis patients have been thought to be less contagious and therefore without the same public health impact as smear-positive cases.3,4 In this region, limiting drug resistance surveillance to acid-fast bacilli smear-positive cases significantly underestimates the rate of primary multidrug resistance. In combination with the results of Behr and colleagues, our findings suggest that smear-negative patients can be an important factor for the dissemination of resistant M tuberculosis. This study was supported by the Consejo Nacional de Ciencias y Tecnologia (CONACYT), grant number: 4987-M9406.
M Kato-Maeda, *J Sifuentes-Osornio, M Bobadilla-del-Valle, G M Ruiz-Palacios, A Ponce-de-León Instituto Nacional de Nutrición, Mexico City, 14000, Mexico 1
Behr MA, Warren SA, Salomon H, et al. Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli. Lancet 1999; 353: 444–49. 2 WHO/IUATLD global project on antituberculosis drug resistance surveillance. Anti-tuberculosis drug resistance in the world. Geneva: WHO global tuberculosis programme, (WHO/GTB/97.229). 1997; 60–90. 3 van Zwanenberg D. The influence of the number of bacilli on the development of tuberculosis disease in children. Am Rev Respir Dis 1960; 82: 31–44. 4 Shaw JB, Wynn-Williams N. Infectivity of pulmonary tuberculosis in relation to sputum status. Am Rev Tuberc 1954; 69: 724–32.
S alt, diet, and health Sir—John Swales in his review of our book 1 declares an interest in that we state that in 1986 he disputed the relationship between salt intake and blood pressure at a press conference and he implies that to have done so is unremarkable. But he does not reveal that the press conference was funded and organised by the Salt Manufacturers’ Association in conjunction with Kingsway, a public relations company.2 They also set up a so-called Salt Data Centre that claimed to give impartial and independent advice on the relation between salt and blood pressure. The press conference was held in January, 1986, in London. Swales was the sole
speaker: his solicited, unopposed, and commercially popular view received widespread media publicity. 2 One of the major aims of the Salt Manufacturers’ Association is to protect the sale of salt, particularly that added to processed food, which accounts for about 40% by value of all salt sales, and to try and increase salt sales. The subsequent campaign developed by the Kingsway Rowland Company was so successful that it was used as an example on how to influence public opinion in the marketing for their company. Swales’ continued opinion that there is no consensus about the effects on blood pressure of a moderate permanent reduction in salt intake to around 100 mmol per day is based on a meta-analysis of extremely short periods of salt restriction, which resulted in a mean 24 h sodium excretion of 41 mmol/L for a median duration of 8 days in 2581 n o r m o t e n s i v e s . 3 He regards this analysis as “the most rigorous systematic review of intervention trials” and concludes “that salt restriction in healthy people produces no worthwhile lowering of the blood pressure”. We agree that it may be the best review of what a few days of salt restriction can do to blood pressure. However, there was a highly significant mean fall in systolic pressure of 1·5 mm Hg which, if prolonged and on a population basis, would nevertheless have a major effect on reducing cardiovascular disease. But these short-term studies are utterly irrelevant to a discussion of the merits of a sustained, moderate reduction in salt intake on blood pressure that one wonders why they were introduced. There are huge commercial reasons for protecting the high salt content of processed food.2 It is not surprising, therefore, that some food and softdrink companies and the salt industry have fought a careful and largely covert campaign akin to the tobacco manufacturers suggesting there is a lack of consensus about the need to reduce our unnecessarily high salt consumption. Nevertheless, consensus that salt intake should be reduced in the whole population does now exist. For instance, in the UK, a Government-appointed expert committee on diet and cardiovascular disease reviewed all the evidence and unequivocally recommended a reduction in salt intake for the whole UK population from 9 to 6 g per day.4 Meetings at the British Heart Foundation in December, 1997, the National Heart Lung and Blood
1709