ArticlesTransmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli
Introduction
Microscopic examination of sputum smears for acid-fast bacilli is used widely throughout the world as a diagnostic test in people who are suspected of having pulmonary tuberculosis.1 The finding of acid-fast bacilli in sputum establishes a presumptive diagnosis of tuberculosis and indicates that the patient is capable of transmitting the infection. Conversely, when making decisions regarding isolation and public-health management, the absence of acid-fast bacilli from sputum smears has been used as an indication that such a patient is relatively less infectious.2, 3, 4 It has even been inferred by some advisory panels that only acid-fast bacilli smear-positive patients with tuberculosis are infectious.5, 6
However, both theoretical considerations and empirical observations indicate that transmission does occur from smear-negative patients. The threshold for detecting bacilli on light microscopy is about 5000–10000 bacilli/mL, while the infecting dose of Mycobacterium tuberculosis is estimated to be fewer than ten organisms.7, 8, 9 In addition, epidemiological studies have shown that people exposed to patients who are smear-negative and culture-positive have a higher prevalence of disease and infection than does the general population in the same community.10, 11, 12, 13
In developed countries, the practical implications of assessing the degree of infectiousness of a patient with tuberculosis relate to the need to isolate the patient and the breadth of evaluation of the patient's contacts. Resources should not be allocated to isolation and investigation if there is little chance that transmission can occur. The implications are perhaps greater in low-income countries, where the acid-fast smear is the only diagnostic test used. In these countries, smear-negative patients are generally not diagnosed, and consequently frequently not treated.
To study the infective potential of patients who are smear-negative, we have analysed data from an ongoing study of the molecular epidemiology of tuberculosis in San Francisco.14 For cases sharing identical DNA fingerprints, we have linked secondary cases to their presumed source case to quantify transmission from patients who are smear-negative culture-positive.
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Patients
The study population included all patients newly reported as having culture-positive tuberculosis in San Francisco between Jan 1, 1991, and Dec 31, 1996. Data were collected as part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, which has been approved by the human subjects research committees of the University of California San Francisco, the San Francisco Department of Public Health, and Stanford University.
Patients were excluded if they met predefined
Results
Between 1991 and 1996 there were 1855 cases of tuberculosis reported in San Francisco, 1599 of whom were confirmed by positive culture. Of these, 25 were subsequently reclassified as laboratory crosscontamination. For the remaining 1574, cultures were received for fingerprinting and an adequate fingerprint was available for 1359 (86%) cases. On bivariate analysis, the absence of a DNA fingerprint was significantly associated with older age, foreign birth, Asian origin, and HIV-1 negativity, all
Discussion
Our results suggest that transmission of M tuberculosis from patients who have smear-negative pulmonary tuberculosis contributes significantly to the incidence of the disease in San Francisco. This observation can be quantified in three different ways. In at least 17% of the episodes in which M tuberculosis was presumed transmitted between individuals, the source patient was smear-negative. About 27% of cases that resulted from recently transmitted infection were acquired in a chain of
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