High Prevalence of Active and Latent Tuberculosis in Children and Adolescents in Tibetan Schools in India: The Zero TB Kids Initiative in Tibetan Refugee Children.

BACKGROUND: Tuberculosis (TB) prevalence is high among Tibetan refugees in India, with almost half of cases occurring in congregate facilities, including schools. A comprehensive program of TB case finding and treatment of TB infection (TBI) was undertaken in schools for Tibetan refugee children. METHODS: Schoolchildren and staff in Tibetan schools in Himachal Pradesh, India, were screened for TB with an algorithm using symptoms, chest radiography, molecular diagnostics, and tuberculin skin testing. Individuals with active TB were treated and those with TBI were offered isoniazid-rifampicin preventive therapy for 3 months. RESULTS: From April 2017 to March 2018, we screened 5391 schoolchildren (median age, 13 years) and 786 staff in 11 Tibetan schools. Forty-six TB cases, including 1 with multidrug resistance, were found in schoolchildren, for a prevalence of 853 per 100 000. Extensively drug-resistant TB was diagnosed in 1 staff member. The majority of cases (66%) were subclinical. TBI was detected in 930 of 5234 (18%) schoolchildren and 334 of 634 (53%) staff who completed testing. Children in boarding schools had a higher prevalence of TBI than children in day schools (915/5020 [18%] vs 15/371 [4%]; P < .01). Preventive therapy was provided to 799 of 888 (90%) schoolchildren and 101 of 332 (30%) staff with TBI; 857 (95%) people successfully completed therapy. CONCLUSIONS: TB prevalence is extremely high among Tibetan schoolchildren. Effective active case finding and a high uptake and completion of preventive therapy for children were achieved. With leadership and community mobilization, TB control is implementable on a population level.

Trend of microbiologically-confirmed tuberculosis in a low-incidence setting with high immigration rates.

BACKGROUND: The metropolitan area of Bologna, a city in Northern Italy (Emilia Romagna region), is considered a low incidence setting for TB, but has a high rate of foreign immigration (13.5% official resident immigrants relative to the whole population in 2011). The aim of this study was to describe the epidemiological trend of TB, focusing on differences between Italian and foreign-born cases. METHODS: We examined all bacteriologically confirmed TB cases identified in the Microbiology Unit of Bologna University Hospital from January 2008 and December 2011. We compared demographic, clinical and microbiological data for Italian vs. foreign-born TB cases. RESULTS: Out of 255 TB cases identified during the study period, 168 (65.9%) were represented by foreign-born cases. The proportion of immigrants with TB progressively increased over the study period (from 60.8% in 2008 to 67.5% in 2011). Although foreign-born cases were significantly younger than Italian cases (mean age 32.3±14.4 years vs 61.9±21.5 years), the mean age among the latter decreased from 71.2 in 2008 to 54.6 years in 2011 (p=0.036).Concerning TB localization, 65.9% (n=168) had pulmonary TB (P-TB) and 34.1% (n=87) extra-pulmonary TB (EP-TB). In this study, 35.6% of Italian-born P-TB cases were smear positive, versus 51.4% of foreign-born P-TB cases. The highest proportion of high-grade positive microscopy P-TB was among subjects between 25-34 years old (36.9%; p=0.004).Mono-resistance to isoniazid (mono-H) was found among 9.2% and 10.1% of Italian and foreign-born cases, respectively. Among Italian cases, resistance to H and any other first line drug (poly-H) and Multidrug resistant TB (MDR-TB) were 4.6% and 1.2%, respectively. In foreign-born cases poly-H (12.8%) and MDR-TB (6.9%) significantly increased over the time (p=0.003 and p=0.007, respectively). The proportion of MDR-TB was significantly higher among immigrants from Eastern Europe (10.9%) compared to Italian-born patients (p=0.043). All (n=9) MTB strains resistant to four or five first line drugs and Extensively drug resistant (XDR-TB) strains were from foreign-born cases. CONCLUSIONS: TB epidemiology in a low incidence setting is strongly influenced by immigration rates. Ethnicity, mean age, and incidence of MDR-TB among foreign-born cases reflect immigration trends in Northern Italy.

A surge of MDR and XDR tuberculosis in France among patients born in the Former Soviet Union.

A marked increase in the number of multidrug-resistant (MDR) tuberculosis (TB) cases entirely related to patients born in the Former Soviet Union was observed in France in the last two years. Very few cases were clustered, suggesting it is a consequence of recent immigration of patients already infected in their country of origin. This major increase challenges the existing structures for management of MDR and extensively drug-resistant TB (XDR-TB).

Multidrug-resistant and extensively drug-resistant tuberculosis in multi-ethnic region, Xinjiang Uygur Autonomous Region, China.

BACKGROUND: The multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has emerged as a global threat. Xinjiang is a multi-ethnic region and suffered second highest incidence of TB in China. However, epidemiological information on MDR and XDR TB is scarcely investigated. METHODOLOGY/PRINCIPAL FINDINGS: A prospective study was conducted to analyze the prevalence of MDR and XDR TB and the differences of drug resistance TB between Chinese Han and other nationalities population at Chest Hospital of Xinjiang Uygur Autonomous Region, China. We performed in vitro drug susceptibility testing of Mycobacterium tuberculosis to first- and second-line anti-tuberculosis drugs for all 1893 culture confirmed positive TB cases that were diagnosed between June 2009 and June 2011. Totally 1117 (59.0%, 95% CI, 56.8%-61.2%) clinical isolates were resistant to ≥1 first-line drugs; the prevalence of MDR TB was 13.2% (95% CI, 11.7%-14.7%), of which, 77 (30.8%; 95% CI, 25.0%-36.6%) and 31 (12.8%; 95% CI, 8.6%-17.0%) isolates were pre-XDR and XDR TB respectively. Among the MDR/XDR TB, Chinese Han patients were significantly less likely to be younger with an odds ratio 0.42 for age 20-29 years and 0.52 for age 40-49 years; P(trend) = 0.004), and Chinese Han patients has a lower prevalence of XDR TB (9.6%) than all the other nationality (14.9%). CONCLUSIONS/SIGNIFICANCE: The burden of drug resistance TB cases is sizeable, which highlights an urgent need to reinforce the control, detection and treatment strategies for drug resistance TB. However, the difference of MDR and XDR TB between Chinese Han and other nationalities was not observed.

[Outcome and treatment among patients with multidrug-resistant tuberculosis]. / Evolución y tratamiento de pacientes con tuberculosis multirresistente.

BACKGROUND AND OBJECTIVE: Although progress has been made to reduce the global incidence of tuberculosis, the emergence of multidrug-resistant tuberculosis during the past decade threatens to limit these results. The aim of this study is to evaluate the geographic distribution, clinical and microbiological characteristics and outcomes of multidrug-resistant tuberculosis patients in Spain. PATIENTS AND METHODS: Retrospective study between January 1998 and December 2010 of patients attended in Cantoblanco-La Paz Hospital Isolation Internal Medicine Unit. RESULTS: Forty-seven patients were studied, with a mean age of 36 years. There were 33 male. Sixty-four per cent were immigrants and the mean residence time in Spain was 12 months. Twenty-six patients (55.3%) were new cases. Patients were resistant to a median of 5 drugs (interquartile range [IQR] 3-7) and 3 patients had extensively drug-resistant tuberculosis. Cultures became negative after a median of 68.5 days (IQR 49.5-91.8). The median length of hospitalization was 2.75 months (IQR 1.3-4.6). They were treated during a median of 22.4 months (IQR 15.3-24.3). The overall success rate was 93%. A directly observed treatment was carried out in 79% of patients. Sixty-eight per cent patients presented side effects. In 75% of the cases the effects were mild and moderate with no need to replace the drug. Fourteen patients were followed up for a median of 40.5 months (IQR 7.4-55) and no clinical or bacteriological manifestation of disease was detected. CONCLUSIONS: Most patients with multidrug-resistant tuberculosis can be cured with the use of appropriate and intensive regimens, management of side effects and implementation of strategies to improve adherence to treatment.

Second-line drug resistance in multidrug-resistant tuberculosis cases of various origins in the Netherlands.

SETTING: The Netherlands. OBJECTIVE: To investigate the frequency of resistance to second-line drugs among multidrug-resistant tuberculosis (MDR-TB) cases and its correlation with patients' geographic origin. DESIGN: Retrospective laboratory database study of multidrug-resistant Mycobacterium tuberculosis complex strains isolated in the Netherlands between January 1993 and October 2007. RESULTS: We found 153 patients with MDR-TB, of whom 18 (12%) were native Dutch. Complete second-line drug susceptibility testing was performed for 131 MDR-TB patients. Resistance to second-line drugs was noted in primary samples of 28 (21%) MDR-TB patients. Resistance to a single second-line drug was most frequent (24/28 [86%]; 9 to prothionamide [PTH], 6 to para-aminosalicylic acid, 4 to amikacin [AMK], 4 to ciprofloxacin and 1 to cycloserine). Four MDR-TB patients had strains resistant to multiple second-line drugs; two were extensively drug-resistant M. bovis. In MDR-TB patients of European and Central Asian origin, resistance to second-line drugs was most frequent and involved the widest range of drugs. PTH resistance was frequent among African and American MDR-TB patients, while AMK resistance was frequent among South-East Asians. CONCLUSION: Resistance to second-line drugs is infrequent among MDR-TB patients in the Netherlands. Most second-line drug resistance is recorded among immigrants, with substantial differences in second-line drug resistance in MDR-TB patients originating from different geographical areas.

Extensively drug-resistant tuberculosis in california, 1993-2006.

BACKGROUND: Extensively drug-resistant (XDR) tuberculosis (TB) is a global public health emergency. We investigated the characteristics and extent of XDR TB in California to inform public health interventions. METHODS: XDR TB was defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone, and 1 of 3 injectable second-line drugs (amikacin, kanamycin, or capreomycin). Pre-XDR TB was defined as TB with resistance to isoniazid and rifampin and either a fluoroquinolone or second-line injectable agent but not both. We analyzed TB case reports submitted to the state TB registry for the period 1993-2006. Local health departments and the state TB laboratory were queried to ensure complete drug susceptibility reporting. RESULTS: Among 424 multidrug-resistant (MDR) TB cases with complete drug susceptibility reporting, 18 (4.2%) were extensively drug resistant, and 77 (18%) were pre-extensively drug resistant. The proportion of pre-XDR TB cases increased over time, from 7% in 1993 to 32% in 2005 (P = .02)). Among XDR TB cases, 83% of cases involved foreign-born patients, and 43% were diagnosed in patients within 6 months after arrival in the United States. Mexico was the most common country of origin. Five cases (29%) of XDR TB were acquired during therapy in California. All patients with XDR TB had pulmonary disease, and most had prolonged infectious periods; the median time for conversion of sputum culture results was 195 days. Among 17 patients with known outcomes, 7 (41.2%) completed therapy, 5 (29.4%) moved, and 5 (29.4%) died. One patient continues to receive treatment. CONCLUSIONS: XDR TB and pre-XDR TB cases comprise a substantial fraction of MDR TB cases in California, indicating the need for interventions that improve surveillance, directly observed therapy, and rapid drug susceptibility testing and reporting.

Extensively drug resistant tuberculosis in a high income country: a report of four unrelated cases.

BACKGROUND: Multi drug resistance of Mycobacterium tuberculosis (M. tuberculosis) remains a major threat to public health, reinforced by recent reports about the clinical course of patients infected with extensively drug resistant (XDR) strains in South Africa. There is little information about the clinical course of XDR tuberculosis patients in industrialised countries. METHODS: We evaluated all isolates of M. tuberculosis, in which drug susceptibility testing was performed at our institution since 1997, for multi and extensive drug resistance. Clinical courses of patients infected by strains fulfilling the recently revised criteria for XDR tuberculosis were analysed. RESULTS: Four XDR M. tuberculosis isolates were identified. All patients had immigrated to Germany from Russia, Georgia, and former Yugoslavia and none were infected by the human immunodeficiency virus. All patients where treated for tuberculosis for 5.5 to 15 years and for XDR tuberculosis for 1.9 to 2.5 years. They received inhospital treatment in Germany for 11 months, 4.5 years and twice for 6 years. Non-compliance was an important factor in all four patients, three patients had to be treated in Germanys only locked facility for tuberculosis treatment. One patient with XDR tuberculosis died, one patient had still open pulmonary tuberculosis at last contact and 2 patients were cured. CONCLUSION: Cases of XDR tuberculosis have been treated in our region for several years. Even in a high income setting, XDR tuberculosis has a tremendous impact on quality of live, outcome and the total cost. All reasonable efforts to prevent the spread of XDR tuberculosis must be made and maintained.