Abstract
BackgroundMultiple drug-resistance in new tuberculosis (TB) cases accounts for the majority of all multiple drug-resistant TB (MDR-TB) worldwide. Effective control requires determining which new TB patients should be tested for MDR disease, yet the effectiveness of global screening recommendations of high-risk groups is unknown.MethodsSixty MDR-TB cases with no history of previous TB treatment, 80 drug-sensitive TB and 80 community-based controls were recruited in Lima, Peru between August and December, 2008 to investigate whether recommended screening practices identify individuals presenting with MDR-TB. Odd ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression to study the association of potential risk factors with case/control variables.ResultsMDR-TB cases did not differ from drug-sensitive TB and community controls in rates of human immunodeficiency virus infection, reported hospital or prison visits in the 3 years prior to diagnosis. MDR-TB cases were more likely than drug-sensitive TB controls to have had a recent MDR-TB household contact (OR 4.66, (95% CI 1.56–13.87)); however, only 15 cases (28.3%) reported this exposure. In multivariate modeling, recent TB household contact, but not contact with an MDR-TB case, remained predictive of MDR-TB, OR 7.47, (95% CI 1.91–29.3). Living with a partner rather than parents was associated with a lower risk of MDR-TB, OR 0.15, (95% CI 0.04–0.51).ConclusionTargeted drug susceptibility testing (DST) linked to reported MDR-TB contact or other high-risk exposures does not identify the majority of new TB cases with MDR disease in Lima where it is endemic. All new TB cases should be screened with DST to identify MDR patients. These findings are likely applicable to other regions with endemic MDR-TB.
Highlights
[1] In 2008 there were an estimated 440,000 incident MDRTB cases globally; among those tested, 5.4% of multiple drug-resistant TB (MDR-TB) patients had extensively drug-resistant (XDR)-TB. [2,3] Inappropriate or inadequate TB treatment programs are assumed to be responsible for generating MDR disease, and TB patients with a history of previous treatment are as much as 10 times more likely to have MDR disease than those without previous TB therapy. [4,5] Despite the welldocumented association between previous TB treatment and MDR disease, transmission of MDR-TB, instead of inadequate or inappropriate therapy, is responsible for the majority of cases worldwide. [6]
[10] Understanding MDR-TB transmission is crucial to global TB control efforts, yet little is known about MDR-TB risk factors in new TB cases with either no history or,1 month history of previous TB therapy. [11,12]
Selected groups such as social, nosocomial or household contacts of MDR-TB patients have been shown to be at highrisk for acquiring MDR disease, [13,14,15,16] and global TB control plans call for targeted screening of selected new TB patients for MDR-TB prevention
Summary
Multiple drug-resistant tuberculosis (MDR-TB) is growing worldwide, and threatens to undermine global tuberculosis (TB) control efforts. [1] In 2008 there were an estimated 440,000 incident MDRTB cases globally; among those tested, 5.4% of MDR-TB patients had extensively drug-resistant (XDR)-TB. [2,3] Inappropriate or inadequate TB treatment programs are assumed to be responsible for generating MDR disease, and TB patients with a history of previous treatment are as much as 10 times more likely to have MDR disease than those without previous TB therapy. [4,5] Despite the welldocumented association between previous TB treatment and MDR disease, transmission of MDR-TB, instead of inadequate or inappropriate therapy, is responsible for the majority of cases worldwide. [6]Even excellent national TB control programs (NTP) based on the Directly-Observed Therapy, Short-course (DOTS) strategy may experience substantial increases in MDR-TB, [6] and observational and modeling studies suggest that DOTS treatment expansion may preferentially select for drug-resistant TB transmission in endemic locations. [7,8,9] TB incidence has declined substantially in Peru since the introduction of its NTP in 1990; MDR-TB cases grew 27-fold from 1997 to 2005. [10] Understanding MDR-TB transmission is crucial to global TB control efforts, yet little is known about MDR-TB risk factors in new TB cases with either no history or ,1 month history of previous TB therapy. [11,12]Selected groups such as social, nosocomial or household contacts of MDR-TB patients have been shown to be at highrisk for acquiring MDR disease, [13,14,15,16] and global TB control plans call for targeted screening of selected new TB patients for MDR-TB prevention. [17] the percentage of new TB patients with MDR disease likely to be identified by targeted screening is unknown. Even excellent national TB control programs (NTP) based on the Directly-Observed Therapy, Short-course (DOTS) strategy may experience substantial increases in MDR-TB, [6] and observational and modeling studies suggest that DOTS treatment expansion may preferentially select for drug-resistant TB transmission in endemic locations. If global MDR-TB control efforts are to succeed, it is imperative to understand if recommended screening strategies will identify most individuals at risk for MDR disease in TB-endemic locations. Effective control requires determining which new TB patients should be tested for MDR disease, yet the effectiveness of global screening recommendations of high-risk groups is unknown
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