Double infection with a resistant and a multidrug-resistant strain of Mycobacterium tuberculosis.

An immunocompetent patient was dually infected with a resistant and a multidrug-resistant strain of Mycobacterium tuberculosis (TB). The multidrug-resistant strain, which belongs to the W- strain/Beijing family, was first isolated after 3 months of therapy. Inappropriate treatment led to further drug resistance and unsuccessful therapy. Thus, additional infections with resistant M. tuberculosis strains should be considered when tuberculosis therapy fails

High genetic diversity among Mycobacterium tuberculosis complex strains from Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Among tuberculosis (TB) high incidence regions, Sub-Saharan Africa is particularly affected with approx. 1.6 million new cases every year. Besides this dramatic situation, data on the diversity of <it>Mycobacterium tuberculosis </it>complex (MTBC) strains causing this epidemic in this area are only sparsely available. Here we analyzed the population structure of strains from Sierra Leone with a special focus on the prevalence of <it>M. africanum</it>.</p> <p>Results</p> <p>A total of 97 strains isolated from smear positive cases registered for re-treatment in the Western Area and Kenema districts in years 2003/2004 were investigated by susceptibility testing (first line drugs) and molecular typing (IS<it>6110 </it>fingerprinting, spoligotyping, and MIRU-VNTR typing).</p> <p>Among the strains analyzed, 32 were resistant to isoniazid, and 11 were multidrug resistant (at least resistant to isoniazid and rifampin). The population diversity was high with two previously described <it>M. africanum </it>lineages (West African-1, n = 6; West African-2, n = 17) and seven <it>M. tuberculosis </it>lineages (Haarlem, n = 14; LAM, n = 15; EAI, n = 4; Beijing, n = 4; S-type, n = 4, X-type, n = 1; Cameroon, n = 4). Furthermore, two new <it>M. tuberculosis </it>genotypes Sierra Leone-1 (n = 7) and -2 (n = 10) were found. Strain classification according to a 7 bp deletion in pks1/15 revealed that the majority of <it>M. tuberculosis </it>strains belonged to the Euro American lineage (66 out of 74).</p> <p>Conclusion</p> <p>Resistance rates in Sierra Leone have reached an alarming level. The population structure of MTBC strains shows an intriguing diversity raising the question of possible consequences for TB epidemic and for the introduction of new diagnostic tests or treatment strategies in West Africa.</p

Mycobacterium avium subsp. paratuberculosis Infection in a Patient with HIV, Germany

Mycobacterium avium subsp. paratuberculosis (MAP), the causative agent of Johne disease in ruminants, has been incriminated as the cause of Crohn disease in humans. We report the first case of human infection with MAP in a patient with HIV; infection was confirmed by obtaining isolates from several different specimen types

Integration of molecular typing results into tuberculosis surveillance in Germany-A pilot study.

An integrated molecular surveillance for tuberculosis (TB) improves the understanding of ongoing TB transmission by combining molecular typing and epidemiological data. However, the implementation of an integrated molecular surveillance for TB is complex and requires thoughtful consideration of feasibility, demand, public health benefits and legal issues. We aimed to pilot the integration of molecular typing results between 2008 and 2010 in the German Federal State of Baden-Württemberg (population 10.88 Million) as preparation for a nationwide implementation. Culture positive TB cases were typed by IS6110 DNA fingerprinting and results were integrated into routine notification data. Demographic and clinical characteristics of cases and clusters were described and new epidemiological links detected after integrating typing data were calculated. Furthermore, a cross-sectional survey was performed among local public health offices to evaluate their perception and experiences. Overall, typing results were available for 83% of notified culture positive TB cases, out of which 25% were clustered. Age <15 years (OR = 4.96, 95% CI: 1.69-14.55) and being born in Germany (OR = 2.01, 95% CI: 1.44-2.80) were associated with clustering. At cluster level, molecular typing information allowed the identification of previously unknown epidemiological links in 11% of the clusters. In 59% of the clusters it was not possible to identify any epidemiological link. Clusters extending over different counties were less likely to have epidemiological links identified among their cases (OR = 11.53, 95% CI: 3.48-98.23). The majority of local public health offices found molecular typing useful for their work. Our study illustrates the feasibility of integrating typing data into the German TB notification system and depicts its added public health value as complementary strategy in TB surveillance, especially to uncover transmission events among geographically separated TB patients. It also emphasizes that special efforts are required to strengthen the communication between local public health offices in different counties to enhance TB control

Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

Mycobacterium bovis Isolates with M. tuberculosis Specific Characteristics

Our study is the first report of exceptional Mycobacterium bovis strains that have some characteristics of M. tuberculosis. The strains were isolated from 8 patients living in Kazakhstan. While molecular markers were typical for M. bovis, growth characteristics and biochemical test results were intermediate between M. bovis and M. tuberculosis

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis.

SETTING: Civilian population of the Republic of Azerbaijan. OBJECTIVES: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. DESIGN: National cross-sectional survey conducted in 2012-2013. RESULTS: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6-39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1-4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1-7.4). CONCLUSION: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance

Worldwide Emergence of Extensively Drug-resistant Tuberculosis

Mycobacterium tuberculosis strains are becoming resistant to not only the most powerful first-line drugs but also many second-line drugs