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PROBLEM:
Tuberculosis (TB), which is caused by infection with Mycobacterium tuberculosis (MTB), remains a major global health threat, with over nine million new cases and close to two million deaths annually. Detection of active TB cases in endemic countries still relies on sputum smear microscopy, which only has an average sensitivity of 65% and which is highly dependent on the individual examiner. The more sensitive culture methodology on the other hand takes weeks, thus further delaying initiation of treatment and potential spread of pathogens. Better diagnostics are therefore urgently needed. Since a high percentage of patients are co‐infected with HIV, diagnostics should be suitable for immunocompromised individuals. Furthermore, a specific molecular marker which reflects clearance of bacteria from lungs would be helpful to monitor treatment response in pre‐clinical and clinical trials.
RESULTS:
Using ESI/MS analysis of small amounts of human sputum (200 µl), we could demonstrate that mycobacteria‐derived MAs serve as a reliable and direct marker for detection of acute TB. We used this tool in a well‐controlled retrospective case–control study of patients with pulmonary TB with varying disease burdens from South Korea, Vietnam, Uganda and South Africa (n = 110). Infected patients (70, 19 of whom were HIV+) could be separated from controls (40, 20 of whom were HIV+) with a sensitivity and specificity of 94 and 93%, respectively. In an animal model of TB infection, our methodology was further able to distinguish active TB cases from cured ones.
IMPACT:
MAs are an attractive diagnostic marker for TB infection because they are bacteria derived, contain information about bacterial species and are chemically inert. Our results demonstrate for the first time the feasibility and clinical relevance of direct detection of mycobacterial lipids as biomarkers for TB infection as well as infections caused by NTM. The developed methodology is robust, due to the stability of the analysed molecules and the independence of host factors, and also fast, giving reliable results within a day. Further we could show that MAs can serve as a reliable marker of infection in drug efficacy studies, featuring fast clearance from animal lungs after successful drug treatment.
INTRODUCTION
The number of mycobacterial infections has increased dramatically over the past two decades due to, among other factors, the HIV/AIDS epidemic (Harries...