Proportion Of Multidrug-resistant Tuberculosis Cases Research Articles

Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the...

Morbidity surveillance and treatment of MDR-TB with the support of NGOs in Ukraine

ObjectiveDescribe the common work of Donetsk State Phthisiological Service and non-governmental organizations that has been conducted since 2014 in order to achieve the global goal for tuberculosis elimination.IntroductionThe global strategy for eliminating tuberculosis (TB) epidemic "End TB" has been implemented in the world since 2016. Its main goal is to reduce the 2015 TB incidence rate by 90% and 2015 TB mortality rate by 95% by 2035. In Ukraine, in 2016, the incidence rate of new cases of tuberculosis among the general population was 54.7 per 100 thousand of population (2015 - 55.9), the rate of decrease was 2.1 ± 0.1%. In Donetsk Oblast (that is under control of Ukrainian authorities), the incidence rate increased by 2.4% and was 56.4 per 100 thousand of population. The mortality rates were 19 ± 0.6% in the country and 29 ± 2.5% in Donetsk Oblast. However, according to the World Health Organization (WHO) estimates, we need to enhance the annual incidence rate reduction by 10% by 2025, and TB mortality rate should be reduced to 6.5% in order to achieve the strategy-targeted values.In Ukraine, as well as globally, there is a crisis of multidrug-resistant tuberculosis (MDR-TB). According to WHO estimates, Ukraine belongs to five European countries where 2/3 of MDR-TB cases were registered; the proportion of MDR-TB cases among newly diagnosed TB cases was 16%, and 48% of repeated cases. In Ukraine, this rate is equal to 24.3% and 58.2% in Donetsk Oblast, respectively.Such results in the Donetsk region may be related to the beginning of hostilities in eastern Ukraine in 2014, which lead to the active migration of population and breakdown of the supply of anti-TB drugs. According to monitoring data, 20% of with MDR-TB on the territory of the Donetsk region controlled by Ukraine were lost and did not seek medical assistance.MethodsThis work describes a retrospective cohort study of MDR-TB patients' treatment efficacy. The MDR-TB diagnosis was confirmed by the BSL3 laboratory by molecular genetic testing of sputum using Gene Expert and bacteriological methods to determine resistance to rifampicin and isoniazid.All MDR-TB patients were divided into 3 cohorts. The first cohort of 86 patients received outpatient treatment within the project “Outpatient Home Treatment Model Using Mobile Response Team" supported by the Foundation for Development of Ukraine in Kramatorsk, Donetsk Oblast, during one year (2014-2015). The response team consisting of a nurse, a driver and a doctor (if necessary) delivered drugs to patients with TB six times a week. The second cohort of 477 MDR-TB patients has received outpatient treatment via the Red Cross Society since 2015. A nurse visited patients every day and controlled drugs administration. In addition to the treatment, patients were given food kits twice a month. The third cohort of 391 MDR-TB patients received outpatient treatment in healthcare institutions without any support of non-governmental organizations. Before the beginning of the controlled treatment, psychologists worked with patients from risk groups.ResultsSurveillance data in Donetsk Oblast showed the increase of the MDR-TB morbidity rate from 15.0 to 20.1 per 100 thousand of population. According to the analysis results, MDR-TB is found in 31% of cases among all newly diagnosed TB cases.The successful treatment rate of all TB cases in Donetsk Oblast in 2015 was 61.9 ± 5.4%, which is lower than the average rate in Ukraine, which is 11.1 ± 1.0% (WHO indicator is 75%). The number of MDR-TB cases with "treatment failure" (treatment was completed, but bacterial secretion continued) - 9.3 ± 2.6% and "interrupted treatment" - 13.3 ± 2, 6% is very high in Donetsk Oblast.Results analysis of the controlled treatment showed that the treatment efficacy for MDR-TB patients in the first cohort was 75%. In the second cohort, 205 out of 477 patients completed their treatment. The treatment efficacy was 78.5%. In the third cohort 45.0% of patients were cured, which corresponds to general rates in this oblast. However, the treatment efficacy for MDR-TB patients, who received the support of non-governmental organizations, was 30,0-33.5% higher than among patients who did not receive such support (Table 1).ConclusionsThe cooperation of the State Phthisiatrician Service with non-governmental organizations concerning patients at the outpatient stage of treatment and development of treatment adherence increased the treatment efficacy for MDR-TB patients by almost 30%, which is important to control the spread of dangerous sources of tuberculosis agents in order to improve the epidemic situation.Cohort analysis of treatment results and clinical MDR-TB monitoring reflects the peculiarities of the epidemic situation and reveals errors in the work of the State Phthisiatrician Service in Donetsk Oblast. Nevertheless, the results show that common work of healthcare institutions, non-governmental organizations and volunteers can bring significant results in strengthening TB patients care.

High-risk screening and detection of multidrug-resistant tuberculosis in two prefectures of China: a drug susceptibility surveillance-based secondary data analysis

ABSTRACTBackground: In China, less than one-fifth of multidrug-resistant tuberculosis (MDR-TB) cases are detected. MDR-TB screening is conducted amongst the following five high-risk groups of TB patients: chronic cases, close contacts of MDR-TB patients, patients with treatment failure, relapsed and returned patients, and smear-positive patients at the end of the third month of initial treatment.Objective: To estimate the possibility of detecting MDR-TB cases if only the high-risk screening strategy is applied in China.Methods: A secondary analysis was applied to the surveillance-based longitudinal data of all sputum smear-positive TB patients in Prefecture E and Prefecture W of China from 2013 to 2015. The population attributable risk (PAR) was estimated using odds ratios for five risk factors/predictors and exposure proportions amongst all MDR-TB cases.Results: A total of 3513 TB patients (2807 from Prefecture E and 706 from Prefecture W) were included. Males accounted for 77.91% (2737/3513) of the patients. The average age was 52.5 ± 20.0 years old. Overall, 40.34% (71/176) of MDR-TB patients were from the five high-risk groups during the three-year study period. The detected proportion of MDR-TB cases using the high-risk screening strategy was significantly higher in Prefecture E than in Prefecture W. The PAR% for all five risk factors/predictors was 43.4% (95% CI: 24.6–61.7%), 49.9% (95% CI: 31.3–67.0%), and 30.3% (95% CI: 12.9–50.1%) in Prefecture E and 36.6% (95% CI: 10.4–64.5%), 13.3% (95% CI: −1.7–39.7%), and −82.5% (95% CI: −117.5–−11.2%) in Prefecture W in 2013, 2014, and 2015, respectively. The PAR% for the five specific risk factors/predictors ranged from 0.4% (95% CI: −0.2–4.8%) to 21.0% (95% CI: 13.1–30.0%) in these two prefectures.Conclusion: In general, a high-risk screening strategy would miss more than half of the MDR-TB patients because they do not belong to the five high-risk groups.

Has universal screening with Xpert® MTB/RIF increased the proportion of multidrug-resistant tuberculosis cases diagnosed in a routine operational setting?

SettingPrimary health services in Cape Town, South Africa where the introduction of Xpert® MTB/RIF (Xpert) enabled simultaneous screening for tuberculosis (TB) and drug susceptibility in all presumptive cases.Study aimTo compare the proportion of TB cases with drug susceptibility tests undertaken and multidrug-resistant tuberculosis (MDR-TB) diagnosed pre-treatment and during the course of 1st line treatment in the previous smear/culture and the newly introduced Xpert-based algorithms.MethodsTB cases identified in a previous stepped-wedge study of TB yield in five sub-districts over seven one-month time-points prior to, during and after the introduction of the Xpert-based algorithm were analysed. We used a combination of patient identifiers to identify all drug susceptibility tests undertaken from electronic laboratory records. Differences in the proportions of DST undertaken and MDR-TB cases diagnosed between algorithms were estimated using a binomial regression model.ResultsPre-treatment, the probability of having a DST undertaken (RR = 1.82)(p<0.001) and being diagnosed with MDR-TB (RR = 1.42)(p<0.001) was higher in the Xpert-based algorithm than in the smear/culture-based algorithm. For cases evaluated during the course of 1st-line TB treatment, there was no significant difference in the proportion with DST undertaken (RR = 1.02)(p = 0.848) or MDR-TB diagnosed (RR = 1.12)(p = 0.678) between algorithms.ConclusionUniversal screening for drug susceptibility in all presumptive TB cases in the Xpert-based algorithm resulted in a higher overall proportion of MDR-TB cases being diagnosed and is an important strategy in reducing transmission. The previous strategy of only screening new TB cases when 1st line treatment failed did not compensate for cases missed pre-treatment.

Transmission of multidrug-resistant tuberculosis in the UK: a cross-sectional molecular and epidemiological study of clustering and contact tracing

Between 2000 and 2012 the number of multidrug-resistant (MDR) tuberculosis cases in the UK increased from 28 per year to 81 per year. We investigated the proportion of MDR tuberculosis cases arising from transmission in the UK and associated risk factors. We identified patients with MDR tuberculosis notified in England, Wales, and Northern Ireland between Jan 1, 2004, and Dec 31, 2007, by linking national laboratory and surveillance data. Data for laboratory isolates, including drug sensitivities and 24-mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing were obtained routinely from the National Tuberculosis Reference laboratories as part of national tuberculosis surveillance. We investigated clusters of cases with indistinguishable MIRU-VNTR profiles to identify epidemiological links. We calculated transmission using the n-1 method and established associated risk factors by logistic regression. We also assessed the likelihood of transmission to additional secondary active tuberculosis cases, identified through conventional contact tracing. 204 patients were diagnosed with MDR tuberculosis in the study period; 189 (92·6%) had an MIRU-VNTR profile. We identified 12 clusters containing 40 individuals and 149 unique strains. The proportion of cases attributable to recent transmission, on the basis of molecular data, was 15% (40 cases clustered-12 clusters/189 with a strain type). The proportion of cases attributable to recent transmission (ie, transmission within the UK) after adjustment for epidemiological links was 8·5% (22 cases with epidemiological links-six clusters/189 cases with a strain type). Being UK born (odds ratio 4·81; 95% CI 2·03-11·36, p=0·0005) and illicit drug use (4·75; 1·19-18·96, p=0·026) were significantly associated with clustering. The most common transmission setting was the household but 21 of 22 of epidemiological links were missed by conventional contact tracing. 13 secondary active tuberculosis cases identified by conventional contact tracing were mostly contacts of patients with MDR tuberculosis from countries of high tuberculosis burden. 11 (85%) of 13 shared the same country of birth as the index case, of whom ten did not share a strain type or drug resistance pattern. Transmission of MDR tuberculosis in the UK is low and associated with being UK born or illicit drug use. MIRU-VNTR typing with cluster investigation was more successful at identifying transmission events than conventional contact tracing. Individuals with tuberculosis who have had contact with a known MDR tuberculosis source case from a country of high tuberculosis burden should have drug-sensitivity testing on isolates to ensure appropriate treatment is given. Public Health England.

Spoligotype-Based Comparative Population Structure Analysis of Multidrug-Resistant and Isoniazid-Monoresistant Mycobacterium tuberculosis Complex Clinical Isolates in Poland

The spoligotyping-based population structure of multidrug-resistant (MDR) Mycobacterium tuberculosis strains isolated in Poland (n = 46), representing all culture-positive MDR tuberculosis (MDR-TB) cases, was compared to that of isoniazid (INH)-monoresistant strains (n = 71) isolated in 2004. The latter data set from a previous study (E. Augustynowicz-Kopeć, T. Jagielski, and Z. Zwolska, J. Clin. Microbiol. 2008, 46:4041-4044) represented 87% of all INH-monoresistant strains. The clustering rates and genotypic-diversity indexes for the 2 subpopulations were not significantly different (P = 0.05). The results were entered in the SITVIT2 database to assign specific shared type designations, corresponding genotypic lineages, and geographical distributions and compared to available data from neighboring countries (Germany, n = 704; Czech Republic, n = 530; Sweden, n = 379; Kaliningrad, Russia, n = 90) and strains from previous studies in Poland (n = 317). MDR strains resulted in 27 patterns (20 unique strains within the study and 7 clusters containing 2 to 6 isolates per cluster with a clustering rate of 56.5%) and belonged to the following genotypic lineages: ill-defined T family (28.3%), Haarlem (17.4%), Latin American and Mediterranean (LAM) (13%), Beijing (8.7%), S family (4.35%), and the X clade (2.17%). Comparison of the genetic structure of the MDR strains with that of INH-monoresistant strains showed that a total of 9 patterns were shared by both groups; these represented 1/3 of the MDR strains and 2/3 of the INH-monoresistant strains. Interestingly, 76.1% of the MDR isolates and 71.8% of the INH-resistant isolates yielded spoligotypes that were previously reported from Poland. The observation that nearly half of the spoligotypes identified among both MDR (48.1%) and INH-monoresistant (43.3%) M. tuberculosis isolates were present in Poland's neighboring countries suggested that a significant proportion of MDR and INH-resistant TB cases in Poland were caused by strains actively circulating in Poland or its neighbors. Our results corroborate the leading role of the T and Haarlem genotypes in the epidemiology of drug-resistant TB in Poland. Nevertheless, the LAM and Beijing family strains that infected, correspondingly, 13% and 9% of patients with MDR-TB were absent among the strains from patients with INH-monoresistant TB, suggesting that a proportion of MDR-TB cases in Poland are due to ongoing transmission of MDR clones exhibiting specific genotypes. Study of the population genetic relationships between MDR and INH-monoresistant strains by drawing minimum spanning trees showed that ill-defined T1 sublineage strains (1/3 of all INH-monoresistant strains), represented by its prototype, SIT53, constituted the central node of the tree, followed by strains belonging to the well-defined H3, H1, and S subgroups. However, the MDR group, in addition, contained LAM (n = 6) and Beijing (n = 4) lineage isolates. With the exception of the 4 Beijing lineage strains in the latter group and a single orphan isolate in the INH-monoresistant group, none of the remaining 112/117 isolates belonged to principal genetic group 1 (PGG1) in our study. Given the high rate of clustering and the near absence of immigrants in the study, the persistence of MDR-TB in Poland seems to result from active transmission of MDR strains within the autochthonous population, the bulk of it caused by evolutionarily recent tubercle bacilli.

Paradigm shift to address drug resistant tuberculosis in people living with HIV needed, and needed now

People living with HIV have a higher risk of multi-drug resistant (MDR) (Wells et al. 2007; Dubrovina et al. 2008; WHO 2008b) and extensively drug resistant (XDR) tuberculosis (Gandhi et al. 2006) with increased mortality, and greatly reduced survival time. Only 6% (less than 30,000) of the half million estimated incident MDR cases were diagnosed and notified globally by the end of 2007. Fifty-four countries had reported at least one case of XDRTB (WHO 2009a,b). Data on the HIV prevalence among these notified cases and the extent of the problem in children are not available. In the latest global antituberculosis drug resistance survey of WHO, only seven countries, none of which have a generalized HIV epidemic, reported tuberculosis (TB) drug resistance stratified by HIV status (WHO 2008a). However, people living with HIV are particularly vulnerable to the impact of drug resistant TB due to the difficulties and delays in the diagnosis (Wells et al. 2007), complications of concomitant treatment with TB and antiretroviral therapy (ART) (Havlir et al. 2008) and poor TB infection control measures in many HIV care settings (Gandhi et al. 2006; Kawai et al. 2006). Diagnosis of drug resistant TB requires sophisticated infrastructure and expertise, which at the moment is scarcely available in most resource constrained and HIV prevalent settings. The emergence of XDR TB, and its fatal association with HIV, has exposed the failures of implementing the measures recommended in the Stop TB Strategy of WHO (Raviglione & Smith 2007). It is encouraging to note that a global momentum is building towards accelerated nationwide implementation of collaborative TB/HIV activities(WHO 2004) and the scalingup of the management of MDR-TB(WHO 2008b), critical components of the Stop TB Strategy (WHO 2009a). In this editorial, we argue that not enough attention has yet been given to the interface between MDR and XDR with HIV and a framework of priority actions is needed to address the problem and consolidate synergy between TB and HIV stakeholders at all levels. The first step is to understand the extent of the problem systematically and promptly. Although current global surveillance activities identified countries in the former Soviet Union and regions of China as having a high proportion of MDR TB cases, and nearly half of the estimated MDR cases reside in China and India (WHO 2008a) the extent of the MDR problem in people living with HIV, including children, has not been properly documented. Furthermore, the situation in subSaharan Africa is largely unknown (Ben Amor et al. 2008; Zager & McNerney 2008) due mainly to lack of laboratory infrastructure. However, the XDR-TB outbreaks affecting primarily people living with HIV in KwaZulu Natal (Gandhi et al. 2006) and other provinces of South Africa (O’Donnell et al. 2009) give cause for serious concern. New HIV infections are on the rise in those countries with higher proportions of MDR TB cases including China, the Russian Federation and Ukraine (UNAIDS 2008). Data on the risk of MDR TB among HIV positive TB patients is available from just two places in the former Soviet Union, Donetsk, Ukraine, and Latvia which showed TB patients living with HIV are almost nearly twice as likely to have MDR-TB as patients without HIV (Dubrovina et al. 2008; WHO 2008a). Therefore, an urgent and systematic review of the extent and magnitude of the convergence of the HIV and drug resistant TB epidemics is needed, particularly in Africa and Eastern Europe. High quality anti-TB drug resistance surveys are needed which include HIV testing as an essential component, and synergistic opportunities between the expansion of global HIV Tropical Medicine and International Health doi:10.1111/j.1365-3156.2009.02266.x

Multidrug Resistance Among Persons With Tuberculosis in California, 1994-2003

Between 1994 and 2003, tuberculosis (TB) cases in California declined 33% (4834 to 3224). However, in 2003 California reported the largest number of cases in the nation, and over the past decade the proportion of cases with multidrug-resistant tuberculosis (MDR-TB) has not decreased. To describe the magnitude, trends, geographic distribution, clinical characteristics, risk factors, and outcomes of MDR-TB cases reported to the California registry of Reports of Verified Cases of TB. DESIGN, SETTING, AND CASES: Analysis of 38,291 TB cases reported from all 61 local health jurisdictions in California during 1994-2003. Multidrug-resistant TB was defined as resistance to at least isoniazid and rifampin. Results of univariate and multivariable analyses of MDR-TB magnitude, trends, geographic distribution, clinical characteristics, associated factors, and outcomes. Of 38,291 reported TB cases, 28,712 (75%) were tested for resistance to at least isoniazid and rifampin; of these, 407 MDR-TB cases (1.4%) were reported from 38 of 61 California health jurisdictions (62%); the proportion of MDR-TB cases did not significantly change over the study period (P = .87). Cases of MDR-TB were twice as likely to have cavitary lesions compared with non-MDR-TB cases (P<.001) and were 7 times more likely to have reported previous treatment for TB (P<.001). Of MDR-TB cases with outcomes, 231 (67%) completed therapy, and those with MDR-TB were significantly less likely to complete therapy than those without MDR-TB (P<.001). Multivariate analysis identified previous TB diagnosis, positive acid-fast bacilli sputum smear results, Asian/Pacific Islander ethnicity, time in the United States less than 5 years at the time of diagnosis, and outcomes of "died" and "moved" as factors associated with MDR-TB. Multidrug-resistant TB, an airborne disease with limited, costly treatment options, persists in 1% to 2% of all cases despite California's control efforts. Local and global TB control efforts are needed to prevent the further development and spread of MDR-TB.