Number Of Multidrug-resistant Tuberculosis Cases Research Articles

Clinical Epidemiology of Multidrug Resistant Tuberculosis in a Nodal Drug Resistant- TB Centre in Southern Odisha: A Cross-sectional Study

Introduction: Multidrug-Resistant Tuberculosis (MDR-TB) is a significant public health problem. The number of MDR-TB cases is very high in India and the management is inadequate due to resource constraints. The assessment of MDR-TB burden has to be reliable for programmatic management of MDR-TB under the Revised National Tuberculosis Control Program (RNTCP) of India. Aim: To find the clinico-demographic profile and pattern of MDR-TB among the tuberculosis patients reporting to a nodal tuberculosis centre in Southern Odisha, India. Materials and Methods: The patient record based cross-sectional study was carried out on a convenience sample of 125 sputum positive MDR-TB cases admitted to the Directly Observed Treatment Short-course (DOTS) plus centre of the Nodal Tuberculosis Centre at Berhampur, Odisha, India, during the period from April 2017 to March 2018. A predesigned case record form was used to collect data on the socio-demographic profile, addictions, co-morbidity, Human Immunodeficiency Virus (HIV) status, Bacille Calmette-Guerin (BCG) immunisation status, pattern of drug resistance, history of anti-TB treatment, presenting symptoms at admission, adverse drug reactions observed during the treatment for MDR-TB. The data was analysed using GraphPad Prism trial version 7.0. Descriptive statistics were used to present the final data. Results: Highest number of study participants (95, 76%) were within 18-45 years age group and 90 (72%) of the patients were males. Rural habitation (90, 72%), engagement in labour works (65, 52%), low socio-economic status (75, 60%) were the common socio-economic characteristics. Resistance to rifampicin was the commonest variety 101 (80.8%) and 80 (64%) were newly diagnosed cases of tuberculosis. The commonest presenting symptom was cough in 97 (77.6%) patients and gastrointestinal upset was the commonest adverse drug reaction encountered during therapy. Conclusion: The MDR-TB affects the population in their most productive age. Rifampicin resistant TB was the predominant variety observed in the study population. The MDR-TB can be successfully treated with maximally effective and complete drug regimes.

Current situation of tuberculosis and National Strategic Plan for Tuberculosis Control in Korea

Tuberculosis (TB) remains a serious public health problem in Korea. Korea has the highest incidence rate (59 per 100,000 population) and the second-highest TB mortality rate (four per 100,000 population) among Organisation for Economic Cooperation and Development member countries. However, some progress has been made in TB control over the past decade. The notification rate of new TB cases has been gradually decreasing since reaching its highest rate in 2011 (78.9 per 100,000 population). In 2019, the notification rate of new TB cases was 46.4 per 100,000 population, with a reduction of 9.9% from the 2018 rate. Additionally, the number of multidrug-resistant TB cases decreased from 618 in 2018 to 580 in 2019. This progress is thought the result of various TB control programs including a TB public–private mix model, insurance coverage for TB management, and a contact investigation program. Despite the progress made, new challenges have also emerged. The predominant challenges lie in the relatively increasing burden of TB in the vulnerable population (aging, socio-economically vulnerable, and foreign-born population), the implementation of latent TB infection management, and the high rate of multidrug-resistant TB. Since 2019, the Korean government has been implementing the “Midterm strategies to strengthen TB prevention and management” based on the 2nd National Strategic Plan for Tuberculosis Control (2018-2022). This program will be a turning point of TB control in Korea. The results produced in 2023 is expected to be favorable.

Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase.

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants () values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2.

Multidrug-resistant tuberculosis outbreak associated with poor treatment adherence and delayed treatment: Arua District, Uganda, 2013\u20132017

BackgroundIn August 2017, the Uganda Ministry of Health was notified of increased cases of multidrug-resistant tuberculosis (MDR-TB) in Arua District, Uganda during 2017. We investigated to identify the scope of the increase and risk factors for infection, evaluate health facilities’ capacity to manage MDR-TB, and recommend evidence-based control measures.MethodsWe defined an MDR-TB case-patient as a TB patient attending Arua Regional Referral Hospital (ARRH) during 2013–2017 with a sputum sample yielding Mycobacterium tuberculosis resistant to at least rifampicin and isoniazid, confirmed by an approved drug susceptibility test. We reviewed clinical records from ARRH and compared the number of MDR-TB cases during January–August 2017 with the same months in 2013–2016. To identify risk factors specific for MDR-TB among cases with secondary infection, we conducted a case-control study using persons with drug-susceptible TB matched by sub-county of residence as controls. We observed infection prevention and control practices in health facilities and community, and assessed health facilities’ capacity to manage TB.ResultsWe identified 33 patients with MDR-TB, of whom 30 were secondary TB infection cases. The number of cases during January–August 2017 was 10, compared with 3–4 cases in January–August from 2013 to 2016 (p = 0.02). Men were more affected than women (6.5 vs 1.6/100,000, p < 0.01), as were cases ≥18 years old compared to those < 18 years (8.7 vs 0.21/100,000, p < 0.01). In the case-control study, poor adherence to first-line anti-TB treatment (aOR = 9.2, 95% CI: 2.3–37) and initiating treatment > 15 months from symptom onset (aOR = 11, 95% CI: 1.5–87) were associated with MDR-TB. All ten facilities assessed reported stockouts of TB commodities. All 15 ambulatory MDR-TB patients we observed were not wearing masks given to them to minimize community infection. The MDR-TB ward at ARRH capacity was 4 patients but there were 11 patients.ConclusionThe number of cases during January–August in 2017 was significantly higher than during the same months in 2013–2016. Poor adherence to TB drugs and delayed treatment initiation were associated with MDR-TB infection. We recommended strengthening directly-observed treatment strategy, increasing access to treatment services, and increasing the number of beds in the MDR-TB ward at ARRH.

Tuberculosis remains a public health problem in Romania.

Tuberculosis (TB) remains a major public health problem in Romania, which has the highest TB incidence in the European Union. We undertook a retrospective study to describe changing trends in the main epidemiological indicators of TB in Romania from 1995 to 2016. Data were obtained from the Marius Nasta Institute of Pneumology, Bucharest, official data published by the National Center for Public Health Statistics and Informatics in Health Statistics Yearbooks, the European Health For All database and the World Health Organization 2017 global TB report. Overall TB notifications in Romania declined after 2002, from 142.2 to 74/100 000 in 2016. For new TB cases, the incidence declined after 2002, from 118.9 to 54.5/100 000 in 2016. After peaking in 2002, at 23.3/100 000, the notification rate of relapses declined to 11.8/100 000 in 2014, but almost doubled the following year. The number of multidrug-resistant TB cases decreased from 624 in 2009 to 530 in 2012, but then increased to 670 in 2015. The number of extensively drug-resistant TB cases tripled between 2012 and 2015, from 22 to 68 cases. Although the decline in TB nationwide after 2002 confirms the effectiveness of control measures, the current TB burden in Romania remains very high by European standards.

Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study

Global roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms. We screened records of 37 644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service-Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution. Ile491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa. A substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community. VLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS.

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.

Conducting high-quality tuberculosis clinical trials in China: opportunities and challenges.

Tuberculosis (TB) is an ancient disease that is a devastating threat to public health. As the country with the second highest number of TB cases and the highest number of multidrug-resistant TB cases in the world, China is now striving to be at the forefront of TB research and drug development. This article is based on the observations made by the authors during the recent partnership initiative between the National Institutes of Health and the Chinese TB community, as well as an extensive literature review. The article examines the advantages and challenges of conducting large-scale international multicenter TB clinical trials in China. China is becoming an excellent location for new TB drug trials, especially in collaboration with international organizations that bring considerable technical assistance, quality control, training, and oversight with these partnerships.

The best of respiratory infections from the 2015 European Respiratory Society International Congress.

The breadth and quality of scientific presentations on clinical and translational research into respiratory infections at the 2015 European Respiratory Society (ERS) International Congress in Amsterdam, the Netherlands, establishes this area as one of the leadings fields in pulmonology. The host–pathogen relationship in chronic obstructive pulmonary disease, and the impact of comorbidities and chronic treatment on clinical outcomes in patients with pneumonia were studied. Various communications were dedicated to bronchiectasis and, in particular, to different prognostic and clinical aspects of this disease, including chronic infection with Pseudomonas and inhaled antibiotic therapy. Recent data from the World Health Organization showed that Europe has the highest number of multidrug-resistant tuberculosis cases and the poorest countries have the least access to suitable treatments. Latent tuberculosis and different screening programmes were also discussed with particular attention to risk factors such as HIV infection and diabetes. Several biomarkers were proposed to distinguish between active tuberculosis and latent infection. Major treatment trials were discussed (REMOX, RIFQUIN and STREAM). The possibility of once-weekly treatment in the continuation phase (RIAQUIN) was especially exciting. The continuing rise of Mycobacterium abscessus as a significant pathogen was noted. This article reviews some of the best contributions from the Respiratory Infections Assembly to the 2015 ERS International Congress.

Does Alcohol consumption during multidrug-resistant tuberculosis treatment affect outcome?. A population-based study in Kerala, India.

India reports the largest number of multidrug-resistant tuberculosis cases in the world; yet, no longitudinal study has assessed factors related to treatment outcomes under programmatic conditions in the public sector. To describe demographic, clinical, and risk characteristics associated with treatment outcomes for all patients with multidrug-resistant tuberculosis registered in the Revised National Tuberculosis Control Programme, Kerala State, India from January 1, 2009 to June 30, 2010. Cox regression methods were used to calculate adjusted hazard ratios with 95% confidence intervals (CIs) to assess factors associated with an unsuccessful treatment outcome. Of 179 patients with multidrug-resistant tuberculosis registered, 112 (63%) had successful treatment outcomes (77 bacteriologically cured, 35 treatment completed) and 67 (37%) had unsuccessful treatment outcomes (30 died, 26 defaulted, 9 failed treatment, 1 stopped treatment because of drug-related adverse events, and 1 developed extensively drug-resistant tuberculosis). The hazard for unsuccessful outcome was significantly higher among patients who consumed alcohol during treatment (adjusted hazard ratio, 4.3; 95% CI, 1.1-17.6) than those who did not. Persons who consumed alcohol during treatment, on average, missed 18 more intensive-phase doses (95% CI, 13-22) than those who did not. Although many patients had diabetes (33%), were ever smokers (39%), or had low body mass index (47%), these factors were not associated with outcome. Overall treatment success was greater than global and national averages; however, outcomes among patients consuming alcohol remained poor. Integration of care for multidrug-resistant tuberculosis and alcoholism should be considered to improve treatment adherence and outcomes.

Surgical treatment to increase the success rate of multidrug-resistant tuberculosis

Mycobacterium tuberculosis infects more than one-third of the world's population and causes an estimated 2-3 million deaths annually. The medical treatment of multidrug-resistant tuberculosis (MDR-TB) can cure 50-75% of cases. The median prevalence of new MDR-TB cases is 1.1%, while that of previously treated cases is 7%. We carried out a retrospective study on 45 patients with MDR-TB who underwent surgical resection at the Leon Daniello Hospital (Regional Surgery Department) between January 1995 and December 2005. The number of MDR-TB cases has continued to increase despite the implementation of MDR-TB treatment strategies. Drug susceptibility tests showed that all our patients were resistant to at least isoniazid (hydrazide) and rifampicin. Therefore, individual drug regimens including at least five antibiotics were prescribed. Surgery under general anaesthesia (double-lumen endotracheal intubation) was performed by a team of thoracic surgeons. The patients had received anti-tuberculosis (TB) treatment for at least 1 month preoperatively as well as postoperatively. We collected and analysed patients' demographic data, clinical characteristics, place of origin, radiological findings, smear and culture status before surgery, TB localization, primary or secondary drug resistance, surgical procedures, complications, bacteriological smear and culture status after surgical treatment. The indications for surgery include medical treatment failure in 39 patients, persistent cavitary lesions with possible relapses in 3 patients and massive haemoptysis in 3 patients. Lobectomy was carried out in 30 cases, segmentectomy in four cases and cavernoplasty (speleoplasty) in 11 cases. Four weeks postoperatively, there were 83% smear-negative and 17% smear-positive patients. Only minor complications were registered: three patients had wound infections, two had minor haemorrhages and one presented a minor pneumothorax. Operative mortality was zero. The absolute indications for the surgical treatment of MDR-TB include failure of medical therapy (due to persistent cavitary disease and lung or lobar destruction) and massive haemoptysis. Proper patient selection and the timing of operations are crucial to avoid relapses and to provide a definitive cure. Good cooperation between chest physicians and thoracic surgeons as well as patients' adherence to pre- and post-chemotherapy can increase the success rate of MDR-TB treatment.

Molecular Characterization of Multidrug-Resistant Mycobacterium tuberculosis Isolated in Nepal

Despite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing this trend. To develop such tools, information about the frequency and distribution of mutations that are associated with phenotypic drug resistance in Mycobacterium tuberculosis is required. In the present study, we investigated the prevalence of mutations in rpoB and katG genes and the inhA promoter region in 158 M. tuberculosis isolates (109 phenotypically MDR and 49 non-MDR isolates collected in Nepal) by DNA sequencing. Mutations affecting the 81-bp rifampin (RIF) resistance-determining region (RRDR) of rpoB were identified in 106 of 109 (97.3%) RIF-resistant isolates. Codons 531, 526, and 516 were the most commonly affected, at percentages of 58.7, 15.6, and 15.6%, respectively. Of 113 isoniazid (INH)-resistant isolates, 99 (87.6%) had mutations in the katG gene, with Ser315Thr being the most prevalent (81.4%) substitution. Mutations in the inhA promoter region were detected in 14 (12.4%) INH-resistant isolates. The results from this study provide an overview of the current situation of RIF and INH resistance in M. tuberculosis in Nepal and can serve as a basis for developing or improving rapid molecular tests to monitor drug-resistant strains in this country.

Molecular tools for rapid identification and novel effective therapy against MDRTB/XDRTB infections

Tuberculosis (TB) is mainly an intracellular infection of the lung alveolar macrophages, and any anti-TB agent must therefore be active at the macrophage. Among the available therapies, isoniazid and rifampicin are the most effective drugs against susceptible Mycobacterium tuberculosis, but they are ineffective against multidrug-resistant TB (MDRTB) strains. Rates of MDRTB in Portugal are the highest in Western Europe, demanding effective measures for their control. Our application of molecular techniques for the early identification of MDRTB assisted in the reduction of these rates. Further examination revealed that a large number of MDRTB cases were extensively-drug resistant (XDRTB), providing evidence for the urgent need of new and effective anti-MDRTB/XDRTB therapeutic strategies. This review describes in detail: the characteristics of the main M. tuberculosis strains circulating in Portugal; the creation of a Task Force for TB control, based on molecular tools that allow 1-day identification of an MDRTB patient; the usefulness of evaluating the ex vivo activity of anti-tubercular agents against the M. tuberculosis isolated from the patient’s sputum; and the mode of action by which phenothiazines have been shown to promote the killing of intracellular MDRTB/XDRTB by nonkilling macrophages.