Elsevier

The Lancet

Volume 353, Issue 9151, 6 February 1999, Pages 444-449
The Lancet

Articles
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli

https://doi.org/10.1016/S0140-6736(98)03406-0Get rights and content

Summary

Background

The microscopic examination of sputum for acid-fast bacilli, is a simple and rapid test that is used to provide a presumptive diagnosis of infectious tuberculosis. While patients with tuberculosis with sputum smears negative for acid-fast bacilli are less infectious than those with positive smears, both theoretical and empirical evidence suggest that they can still transmit Mycobacterium tuberculosis. We aimed to estimate the risk of transmission from smear-negative individuals.

Methods

As part of an ongoing study of the molecular epidemiology of tuberculosis in San Francisco, patients with tuberculosis with mycobacterial isolates with the same DNA fingerprint were assigned to clusters that were assumed to have involved recent transmission. Secondary cases with tuberculosis, whose mycobacterial isolates had the same DNA, were linked to their presumed source case to estimate transmission from smear-negative patients. Sensitivity analyses were done to assess potential bias due to misclassification of source cases, unidentified source cases, and HIV-1 co-infection.

Findings

1574 patients with culture-positive tuberculosis were reported and DNA fingerprints were available for 1359 (86%) of these patients. Of the 71 clusters of patients infected with strains that had matching fingerprints, 28 (39% [95% CI 28–52]) had a smear-negative putative source. There were 183 secondary cases in these 71 clusters, of whom a minimum of 32 were attributed to infection by smear-negative patients (17% [12–24]). The relative transmission rate of smear-negative compared with smear-positive patients was calculated as 0·22 (95% CI 0·16–0·32). Sensitivity analyses and stratification for HIV-1 status had no impact on these estimates.

Interpretation

In San Francisco, the acid-fast-bacilli smear identifies the most infectious patients, but patients with smear-negative culture-positive tuberculosis appear responsible for about 17% of tuberculosis transmission.

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.

Section snippets

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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