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Infection and Immunity, December 2003, p. 7236-7237, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.7236-7237.2003

LETTER TO THE EDITOR

Are Cultures Needed To Enroll Tuberculosis Patients?


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LETTER
 
I found the study by Cardoso et al. (1) to be interesting, but I think that the selection criteria for enrolled tuberculosis patients are flawed. The authors enrolled some patients based only on their smear-positive status, their histories of respiratory symptoms for at least 4 weeks, and suggestive lesions on the chest X rays. Research performed in Liverpool showed that as many as 32% of positive acid-fast bacillus (AFB) smears yielded environmental mycobacteria (EM) in cultures (3). The positive predictive value of AFB for Mycobacterium tuberculosis in respiratory specimens from human immunodeficiency virus (HIV)-negative Brazilian patients is unclear, because the prevalence of EM in this group remains unknown (2). Since the EM are indistinguishable from M. tuberculosis in an AFB smear, the culture results are required in order to enroll these patients in a statistical study about tuberculosis.


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REFERENCES
 
    1
  1. Cardoso, F. L. L., P. R. Z. Antas, A. S. Milagres, A. Geluk, K. L. M. C. Franken, E. B. Oliveira, H. C. Teixeira, S. A. Nogueira, E. N. Sarno, P. Klatser, T. H. M. Ottenhoff, and E. P. Sampaio. 2002. T-cell responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 in Brazilian tuberculosis patients. Infect. Immun. 70:6707-6714.[Abstract/Free Full Text]
    2. 2
  2. Conde, M. B., C. M. Figueira, R. Moraes, L. S. Fonseca, K. Deriemer, and A. L. Kritski. 1999. Predictive value of the acid fast smear for detection of Mycobacterium tuberculosis in respiratory specimens in a reference center of HIV/AIDS in Rio de Janeiro, Brazil. Mem. Inst. Oswaldo Cruz 94:787-790.[Medline]
    3. 3
  3. Corless, J. A., P. A. Stockton, and P. D. Davies. 2000. Mycobacterial culture results of smear-positive patients with suspected pulmonary tuberculosis in Liverpool. Eur. Respir. J. 16:976-979.[Abstract]
Mihai-Sergiu Jalba1*
Division of Research, Emergency Department, Brooklyn Hospital, Brooklyn, New York,1

* Corresponding author. Phone: 347-881-0770 Fax: 212-656-1669 E-mail: msj{at}about.com.


Authors' Reply


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LETTER 
 
The correspondence of Dr. Jalba has raised an interesting issue related to our recent study (1), that is, the predictive value of AFB for M. tuberculosis in respiratory specimens. Dr. Jalba mentioned one study that showed that 32% of positive AFB smears yielded environmental mycobacteria in cultures (3).

Nevertheless, nontuberculous mycobacteria (NTM) tend to be less virulent for humans than M. tuberculosis. Before the advent of AIDS, disease caused by NTM generally comprised self-limited infections involving the cervical lymph nodes of young children or was restricted to the skin. Pulmonary disease was found predominantly in males in the sixth decade of life. Most of these patients had a preexisting lung disease, such as pneumoconiosis. The major pulmonary NTM were Mycobacterium kansasii, Mycobacterium avium, and Mycobacterium intracellulare. M. kansasii infection was frequently associated with urban areas, whereas M. avium and M. intracellulare infection was typically associated with rural areas (5). In the absence of evidence of person-to-person transmission, it was proposed that humans with lung disease were infected from environmental sources via aerosol.

The emergence of AIDS epidemics greatly changed the significance of NTM. In Europe and the United States, the prevalence of development of NTM-related disease in patients with AIDS ranges from 25 to 50%, with M. avium being the most frequent cause of opportunistic disease (4, 5).

Conde et al. analyzed the medical records of patients with positive cultures in a general hospital. Among 313 respiratory specimens, 295 cultures (94.2%) were positive for M. tuberculosis and 18 (5.8%) were positive for NTM (27% were positive for M. avium), yet 66% of the NTM cultures were from HIV-positive patients. Accordingly, in HIV-negative individuals, only 6 among 173 (3.5%) had cultures positive for NTM (2). In the study by Corless et al. (3), NTM cultures were detected for 37 (32%) out of 116 patients, while M. tuberculosis was cultured in 57 (49%) of these cases. Although this is curious data, the study is retrospective and there is no information on patients' clinical manifestations or the occurrence of preexisting lung diseases, and it is not reported whether patients were tested for HIV infection. Furthermore, isolation of NTM in culture can represent specimen contamination or respiratory tract colonization and not necessarily infection. It has been found that the M. avium complex can colonize the bronchial and intestinal mucosal surfaces of healthy individuals (6).

We agree that it would be ideal to confirm M. tuberculosis infection by culture. However, in our study, all 10 patients with pleural effusion had granulomatous pleuritis, a hallmark for pleural tuberculosis (TB), and in four cases there was culture identification of M. tuberculosis. We cannot assure that all 50 patients with pulmonary TB were infected with M. tuberculosis. Even so, in a country like Brazil (where TB is highly endemic), there are many reasons that make it likely: all patients were HIV negative, none had preexisting lung disease or other comorbidity factors that could predispose to an opportunistic infection, and although M. kansasii and M. marinum can respond to the standard antituberculous drugs, the M. avium complex is usually resistant to rifampin, isoniazid, and pyrazinamide. Finally, all 60 TB patients were clinically cured in response to standard anti-TB therapy.


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REFERENCES 
 
    1
  1. Cardoso, F. L. L., P. R. Z. Antas, A. S. Milagres, A. Geluk, K. L. M. C. Franken, E. B. Oliveira, H. C. Teixeira, S. A. Nogueira, E. N. Sarno, P. Klatser, T. H. M. Ottenhoff, and E. P. Sampaio. 2002. T-cell responses to the Mycobacterium tuberculosis-specific antigen ESAT-6 in Brazilian tuberculosis patients. Infect. Immun. 70:6707-6714.
    2. 2
  2. Conde, M. B., C. M. Figueira, R. Moraes, L. S. Fonseca, K. Deriemer, and A. L. Kritski. 1999. Predictive value of the acid fast smear for detection of Mycobacterium tuberculosis in respiratory specimens in a reference center of HIV/AIDS in Rio de Janeiro, Brazil. Mem. Inst. Oswaldo Cruz 94:787-790.
    3. 3
  3. Corless, J. A., P. A. Stockton, and P. D. Davies. 2000. Mycobacterial culture results of smear-positive patients with suspected pulmonary tuberculosis in Liverpool. Eur. Respir. J. 16:976-979.
    4. 4
  4. Falkinham, J. O., III. 1996. Epidemiology of infection by nontuberculous mycobacteria. Clin. Microbiol. Rev. 9:177-215.[Medline]
    5. 5
  5. Grange, J. M. 1996. The biology of the genus Mycobacterium. J. Appl. Bacteriol. 81:1S-9S.
    6. 6
  6. Hoffner, S. E. 1994. Pulmonary infections caused by less frequently encountered slow-growing environmental mycobacteria. Eur. J. Clin. Microbiol. Infect. Dis. 13:937-941.[CrossRef][Medline]
Fernando L. L. Cardoso1
Euzenir N. Sarno1
Elizabeth P. Sampaio1*
Alexandre S. Milagres2
Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Avenue Brasil 4365, Manguinhos, 21045-900 Rio de Janeiro, Brazil,1
Department of Lung Diseases, Hospital Raphael de Paula Souza, Rio de Janeiro, Brazil,2

* Corresponding author. esampaio@gene.dbbm.fiocruz.brPhone: 55 21 598-4287 Fax: 55 (021) 270-9997 E-mail: esampaio{at}gene.dbbm.fiocruz.br.

Infection and Immunity, December 2003, p. 7236-7237, Vol. 71, No. 12
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.12.7236-7237.2003





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