Probability of negative mycobacterium tuberculosis complex cultures based on time to detection of positive cultures: a multicenter evaluation of commercial-broth-based culture systems.

We conducted a multicenter study to determine whether Mycobacterium tuberculosis complex (MTBC) cultures in automated broth-based systems could reliably be considered negative sooner than 6 weeks. Laboratory sites used Bactec MGIT or BacT/Alert and tracked results of time to detection of all mycobacteria (TTD-all, n = 1547) and of MTBC (TTD-MTBC, n = 466) over 6-month periods from primarily (93%) respiratory specimens. Cumulative percentages by day detected and median TTD of initial and follow-up specimens were analyzed. The median TTD-MTBC for MGIT (n = 6 sites) was 14 days. For laboratories using standard processing procedures, 100% of MTBC were detected from initial and follow-up specimens in 28 and 35 days, respectively, and no yield of MTBC on solid or MGIT liquid media was observed after 5 weeks. The median TTD-MTBC for BacT/Alert (n = 3 sites) was 18 days, with 95% and 100% detected within 37 and 42 days, respectively. Analysis of TTD of positive MTBC cultures in broth can predict the probability of culture negativity at defined time points. Receipt of interim negative reports earlier than 6 weeks could assist clinicians in considering alternative diagnoses and could alter the timing and prioritization of public health interventions. Laboratories should analyze their own TTD data to inform protocol decisions. Laboratories using MGIT could issue reports of no growth of MTBC on initial specimens as early as 4 weeks and for patients undergoing treatment as early as 5 weeks postinoculation.

Estimating the true prevalence of Mycobacterium bovis in free-ranging elk in Michigan.

Although relatively small, Michigan's elk (Cervus elaphus nelsoni) herd is highly valued by both hunters and the general public. Elk and red deer (Cervus elaphus elaphus) are highly susceptible to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), and outbreaks have been documented worldwide. The Michigan elk range lies entirely within counties where TB is known to be enzootic in white-tailed deer (Odocoileus virginianus). Consequently, a project was undertaken to estimate the true prevalence of TB in Michigan's free-ranging elk herd. All elk harvested by licensed hunters during 2002-2004, and all nonharvest elk mortalities examined by the Michigan Department of Natural Resources Wildlife Disease Laboratory from November 2002-May 2005, were screened for gross lesions of TB with samples of cranial lymph nodes and palatine tonsils collected for histopathology and mycobacterial culture. In all, 334 elk were included in the study. Twenty-three elk with gross lesions were considered TB suspects; all were culture-negative for M. bovis. However, M. bovis was cultured from two elk without gross lesions. The sensitivity, specificity, and negative predictive value of the current TB surveillance protocol were 0%, 100%, and 99.4%, respectively, while the apparent prevalence and true prevalence calculated directly from the sample were 0% and 0.6%, respectively. The positive predictive value and the estimated true prevalence of the population were undefined. The poor sensitivity of current surveillance was likely an artifact of its application to a relatively small sample, in order to detect a disease present at very low prevalence. The low prevalence of TB in Michigan elk, and the early stage of pathogenesis of the few infected animals, does not suggest elk are maintenance hosts at the present time.

Estimating the true prevalence of Mycobacterium bovis in hunter-harvested white-tailed deer in Michigan.

Apparent prevalence, although useful as a consistent index, may underestimate the true prevalence of disease. In Michigan, the ability to estimate the true prevalence of bovine tuberculosis (TB; caused by Mycobacterium bovis) in free-ranging white-tailed deer (Odocoileus virginianus) will become increasingly important to accurately assess progress towards eradication. Our objectives were threefold: to estimate the true prevalence of M. bovis in free-ranging deer in Michigan, to evaluate the effectiveness of existing TB surveillance methods, and to indirectly assess whether TB epidemiologic data from captive cervid herds can be meaningfully extrapolated to free-ranging populations. The study population consisted of all free-ranging deer submitted for TB testing in 2001 from six townships in northeastern Lower Michigan. Tissue samples of tonsil and cranial lymph nodes were collected bilaterally from all deer eligible for the study that did not have gross lesions suggestive of TB (n = 701). Samples were subjected to histopathologic, acid-fast (AF) staining, mycobacterial culture, and polymerase chain reaction (PCR) testing. Seven deer cultured positive for M. bovis that would not have been detected by current surveillance, yielding apparent and true prevalence estimates (95% confidence limits) of 2.7% (1.6, 3.8) and 3.6% (2.3, 4.9), respectively. The sensitivity, specificity, and positive and negative predictive values of the current surveillance protocol were 75, 100, 100, and 99%, respectively. Histologic lesions were present only in tonsils, and ranged from simple necrosis to caseation, suppuration, and granuloma formation. Acid-fast staining and PCR detected M. bovis in only one of the seven culture-positive deer. Our study provides the first estimate of the true prevalence of M. bovis in Michigan's free-ranging deer population and suggests modest underestimation of that prevalence by current surveillance. This study also suggests that caution is warranted when extrapolating epidemiologic data on TB in captive cervids to free-ranging populations and confirms the pivotal role of the tonsil in early infections.