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

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 smear s negative for acid-fast bacilli are less infectious than those with positi ve smears, both theoretical and empirical evidence suggest that they can st ill transmit Mycobacterium tuberculosis. We aimed to estimate the risk of t ransmission from smear-negative individuals. Methods As part of an ongoing study of the molecular epidemiology of tuberc ulosis in San Francisco, patients with tuberculosis with mycobacterial isol ates with the same DNA fingerprint were assigned to clusters that were assu med to have involved recent transmission. Secondary cases with tuberculosis , whose mycobacterial isolates had the same DNA, were linked to their presu med source case to estimate transmission from smear-negative patients. Sens itivity analyses were done to assess potential bias due to misclassificatio n 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 7 1 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 attr ibuted to infection by smear-negative patients (17% [12-24]), The relative transmission rate of smear-negative compared with smear-positive patients w as calculated as 0.22 (95% CI 0.16-0.32). Sensitivity analyses and stratifi cation 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-positiv e tuberculosis appear responsible for about 17% of tuberculosis transmissio n.