martes, 13 de octubre de 2009

SURVEILLANCE, EPIDEMIOLOGY, AND OUTBREAK INVESTIGATIONS BRANCH UPDATE


TB Notes Newsletter
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No. 3, 2009
SURVEILLANCE, EPIDEMIOLOGY, AND OUTBREAK INVESTIGATIONS BRANCH UPDATE
2009 American Thoracic Society International Conference

A real-time outbreak detection system, alternative treatment regimens, and immunogenetic risk factors for TB infection were the focus of the joint Tuberculosis Epidemiologic Studies Consortium (TBESC)/Tuberculosis Trials Consortium (TBTC) session at the 2009 American Thoracic Society International Conference in San Diego. The purpose of the joint session, held on May 20, 2009, was to present data on recent studies performed by the consortia, as well as plans for current and future studies.

Patrick Moonan, DrPH, discussed TBESC Task Order 26, “Improving the utilization and integration of TB genotyping into routine TB program practice: analyzing the impact through program interventions.” The ultimate purpose of Task Order 26 is to develop an algorithm for real-time detection of potential TB outbreaks, therefore promoting the use of genotyping as routine practice for TB programs. The goal, Dr. Moonan said, is to develop a system that is highly sensitive and dynamic, and has good positive predictive value. One of the challenges in creating a real-time algorithm will be to find the best way to group TB cases to detect possible transmission. This study aims to better understand the variables needed to prioritize clusters and maximize public health response.

Stefan Goldberg, MD, presented findings from TBTC Studies 27 and 28, “Controversies in TB treatment: evolving data on moxifloxacin.” These studies evaluated the substitution of moxifloxacin for ethambutol and INH, respectively, in the intensive phase of the TB treatment regimen. Study researchers found a suggestion that moxifloxacin was better than ethambutol at 4 weeks in culture conversion, but there was no statistically significant difference between the two regimens at 8 weeks. These findings contrasted, in part, with two other recently published non-TBTC Phase II studies, in Brazil and South Africa, which found advantages to using moxifloxacin during the intensive phase, although microbiological and statistical methods were different between the TBTC and non-TBTC studies. Dr. Goldberg pointed out that Phase III treatment shortening trials are under way and concluded that moxifloxacin would be a safe and efficacious second-line treatment agent.

Tim Sterling, MD, presented data from TBESC Task Order 2, titled “Immunogenetic factors associated with TB.” He reported that higher levels of interferon-gamma (IFN-γ) in the first 30 days after exposure to a TB case, and particularly 16–30 days after exposure, were correlated with tuberculin skin test (TST) conversion. Conversely, elevated levels of interleukin-10 more than 60 days following TB exposure may correlate with protection from infection. These findings were important because they may assist us in determining high-risk contacts for LTBI as well as the best time to perform the TST or an interferon gamma release assay (IGRA) following exposure.

Payam Nahid, MD, MPH, discussed “Validation of biomarkers in CDC/TBTC studies.” Biomarkers have a variety of applications in TB, including predicting adverse reactions to medications and performing early assessments of therapy effectiveness. Dr. Nahid delineated the differences between prognostic markers and surrogate biomarkers, the latter being used as a substitute endpoint in clinical trials. In regard to biomarkers of treatment response, factors such as time to culture detection, monthly culture status, immune activation markers, and IGRAs all hold promise but need to be validated as putative surrogate markers in the context of clinical trials with bacteriologically confirmed relapse as an endpoint. TBTC studies provide an ideal platform on which to evaluate promising biomarkers and should be designed with this objective in mind.

Despite its being held on the final day of the ATS conference, the TBESC/TBTC session was very well attended. The talks generated interesting and informative questions and discussion from the audience. These presentations were demonstrations of the productivity of both consortias and the important work being done towards accelerating the development of new tools for TB elimination in the United States.
—Reported by Suzanne Beavers, MD
Div of TB Elimination

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