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Journal of Clinical Microbiology, October 2001, p. 3815-3816, Vol. 39, No. 10
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.10.3815-3816.2001
LETTERS TO THE EDITOR
Tuberculosis Transmission in Botswana
 |
LETTER |
Lockman and colleagues recently described a study on
conventional and molecular epidemiology of tuberculosis in Botswana
(4) and found a rate of clustering cases of pulmonary
tuberculosis equal to 42%. The authors were surprised by the result,
since they expected a higher rate of clustering in a country such as Botswana, where the incidence of tuberculosis is extremely high (over
500 per 100,000). The authors discussed factors that might have biased
the estimation of the extent of recent transmission of tuberculosis and
indicated that high population mobility and a rather incomplete
epidemiological evaluation of the subjects enrolled likely accounted
for the level of transmission recorded.
In our opinion, a crucial issue was not taken into consideration to
explain the unexpected rate. In their paper (Materials and Methods),
the authors stated that only patients who had both acid-fast bacillus
(AFB)-positive and culture-positive sputum were recruited and
epidemiologically evaluated. This was probably due to obvious
organizational and logistic problems in such a setting, but sputum
smears are known to be AFB-positive only in 50 to 70% of
culture-positive pulmonary tuberculosis (2). This rate may
be affected by specific clinical and epidemiological conditions.
HIV-infected tuberculous subjects, for example, especially those who
are seriously immunosuppressed and develope cavitary lesions less
frequently (3), are prone to show a lesser degree of
AFB-positive sputum smears. These considerations and the high incidence
of human immunodeficiency virus-tuberculosis coinfection reported in
the study area (65% of the eligible patients) suggest that a sizeable
proportion of pulmonary tuberculosis was not included in the
epidemiological analysis of Lockman et al.
This may have led to their underestimating the clustering rate in two
different ways. First, a relevant portion of pulmonary tuberculosis due
to recent transmission might have not been evaluated in the clustering
analysis, because the secondary pulmonary cases generated in a cluster
would not necessarily have yielded an AFB-positive sputum smear.
Second, the infectiousness of smear-negative but culture-positive
tuberculosis was recently revalued by Behr et al. (1), who
showed that such cases were responsible for about 17% of tuberculosis
transmission in San Francisco, Calif., yet the potential sources of
transmission with smear-negative but culture-positive pulmonary
tuberculosis were not identified by Lockman and coworkers.
In conclusion, we think that fingerprinting limited to tuberculosis
cases where the sputum smear was AFB positive should be considered the
main confounding factor of the clustering analysis of this study.
| |
FOOTNOTES |
*
Phone and fax: 39 011 4393882 E-mail:
bonora67{at}yahoo.com
| |
REFERENCES |
| 1.
|
Behr, M. A.,
S. A. Warren,
H. Salomon,
P. C. Hopewell,
A. Ponce de Leon,
C. L. Daley, and P. M. Small.
1999.
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli.
Lancet
353:444-449[CrossRef][Medline].
|
| 2.
|
Garay, S. M.
1996.
Pulmonary tuberculosis, p. 373-412.
In
W. N. Rom, and S. M. Garay (ed.), Tuberculosis. Little, Brown and Company, New York, N.Y.
|
| 3.
|
Iseman, M. D.
2000.
Tuberculosis in relation to HIV and AIDS, p. 199-252.
In
M. D. Iseman (ed.), A clinician's guide to tuberculosis. Lippincott Williams and Wilkins, Philadelphia, Pa.
|
| 4.
|
Lockman, S.,
J. D. Sheppard,
C. R. Braden,
M. J. Mwasekaga,
C. L. Woodley,
T. A. Kenyon,
N. J. Binkin,
M. Steinmann,
F. Montsho,
M. Kesupile-Reed,
C. Hirschfeldt,
M. Notha,
T. Moeti, and J. W. Tappero.
2001.
Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.
J. Clin. Microbiol.
39:1042-1047[Abstract/Free Full Text].
|
| | | | |
S. Bonora*
M. Boffito
S. Audagnotto
G. Di
Perri
Department of Infectious Diseases
University of Turin
10149 Turin, Italy
|
| |
AUTHORS' REPLY |
We thank Bonora et al. for their letter to the editor regarding our
article, "Molecular and Conventional Epidemiology of
Mycobacterium tuberculosis in Botswana: a Population-Based
Prospective Study of 301 Pulmonary Tuberculosis Patients"
(2).
The authors of the letter suggest a potential source of bias that may
have led to underestimation of the true rate of M. tuberculosis restriction fragment length polymorphism (RFLP)
clustering in our study population: that only patients with both acid
fast bacillus (AFB)-positive and culture-positive tuberculosis (TB)
were enrolled, and that a sizeable proportion of persons with
culture-positive, AFB smear-negative TB may have been omitted from the
study. We agree that it is important to consider how this aspect of our study design may have biased our results.
Indeed, our study was conducted in a country in which initial TB
diagnosis depends on sputum microscopy and in which M. tuberculosis culture is not routinely performed. Although
inclusion of patients with AFB smear-negative, culture-positive TB in
our study would have been optimal, it was not feasible in this setting.
Despite this limitation, however, we believe that the exclusion of
persons with smear-negative, culture-positive TB had limited impact on
our estimation of clustering. In this and other studies conducted in
Botswana, sputum is centrifuged prior to performing smears, which
results in a AFB smear-positive yield higher than that observed in many
developing-country settings where only direct smears are used. Although
human immunodeficiency virus prevalence is high in Botswana, a separate
study that was conducted in Botswana during the same time period as
this study and that utilized the same TB laboratory found that only 23 (22%) of 103 persons with M. tuberculosis culture-positive
TB had negative AFB smears. In that study, 86% of the patients were
HIV-positive, and AFB smear status did not differ by HIV status (S. Lockman, N. Hone, T. A. Kenyon, M. Mwasekaga, M. Villauthapillia,
E. Zell, A. Kirby, W. L. Thacker, D. Talkington, I. N. S. Moura, N. J. Binkin, T. Creek, J. W. Tappero, and the
Botswana Respiratory Diseases Working Group, unpublished data). In
models of clustering that examine the effects of increasing the
percentage of TB patients sampled, the proportion of clustered results
plateaus at about 60 to 70% (1). It is unlikely that more
than a quarter of our study population would have had culture-positive,
smear-negative TB, and therefore the impact of omitting these patients
from our study should be relatively small.
| |
FOOTNOTES |
*
Phone: (617) 432-2334
Fax: (617) 739-8348
E-mail: slockman{at}hsph.harvard.edu
| |
REFERENCES |
| 1.
|
Glynn, J. R.,
E. Vynnycky, and P. E. M. Fine.
1999.
Influence of sampling on estimates of clustering and recent transmission of Mycobacterium tuberculosis derived from DNA fingerprinting techniques.
Am. J. Epidemiol.
149:366-371[Abstract/Free Full Text].
|
| 2.
|
Lockman, S.,
J. D. Sheppard,
C. R. Braden,
M. J. Mwasekaga,
C. L. Woodley,
T. A. Kenyon,
N. J. Binkin,
M. Steinman,
F. Montsho,
M. Kesupile-Reed,
C. Hirschfeldt,
M. Notha,
T. Moeti, and J. W. Tappero.
2001.
Molecular and conventional epidemiology of Mycobacterium tuberculosis in Botswana: a population-based prospective study of 301 pulmonary tuberculosis patients.
J. Clin. Microbiol.
39:1042-1047.
|
| | | | |
S. Lockman*
C. R. Braden
J.
W. Tappero
N. J. Binkin
Division of Tuberculosis Elimination
National Centers for HIV/AIDS
STD and TB Prevention
Centers for Disease Control and Prevention
Atlanta, Georgia
|
Journal of Clinical Microbiology, October 2001, p. 3815-3816, Vol. 39, No. 10
0095-1137/01/$04.00+0 DOI: 10.1128/JCM.39.10.3815-3816.2001
