Multidrug-resistant Tuberculosis Control Research Articles

Multidrug resistant tuberculosis risk factors in Makassar, Indonesia

Multidrug resistant tuberculosis (MDR-TB) is a significant public health concern in Indonesia, resulting in substantial morbidity and mortality rates. This study aimed to quantify the impact of risk factors of MDR-TB. A case-control study was conducted at Makassar Community Lung Health Center (BBKPM) in Makassar City. A total of 132 respondents, 66 cases, and 66 controls have participated in the study. Data was analyzed using the Stata version 14 tool, odds ratio (OR), and multiple logistic regression. Multiple logistic regression analysis identified significant risk factors for the occurrence of MDR-TB include previous TB treatment (OR=8.46, 95% CI: 3.278-21.858), positive acid-fast bacilli (AFB) sputum (OR=6.40, 95% CI: 2.525-16.260), and adverse drug event (OR=3.45, 95% CI: 1.008-11.867). The probability of developing MDR-TB is 95.9% if there is previous TB treatment with cases of relapse/loss to follow-up/failed treatment, positive AFB sputum, and adverse drug event. The most dominant risk factor for the occurrence of MDR-TB is a previous TB treatment. We suggest that an efficient directly observed treatment shortcourse (DOTS) strategy, particularly in the management of adverse drug event, overseeing and supporting patients who have recovered from MDR-TB, involves the collaboration of MDR-TB healthcare professionals and patient supporters in the Yamali TB community, moving synergistically as an effort to MDR-TB control and prevention.

Modeling spread and control of multidrug-resistant tuberculosis in India

Modeling spread and control of multidrug-resistant tuberculosis in India

Identifying enablers and barriers to the control of multidrug-resistant tuberculosis in Abia State, Nigeria: A qualitative study

ObjectiveDrug-resistant tuberculosis (TB) is a significant public health threat in high-burden TB countries, including Nigeria, constraining the achievement of End TB targets. Nonetheless, Nigeria's health system factors shaping the care of patients with multidrug-resistant tuberculosis (MDR-TB) are understudied. The study assessed the enablers and barriers to implementing MDR-TB care and treatment in Abia State, Nigeria. MethodsThis is a qualitative interview study adopting a phenomenological approach. We interviewed twelve participants comprising health workers and TB policymakers with roles in MDR-TB patient management at the national (n = 2) and state (n = 10) levels in May 2022. We used maximum variation sampling to purposively select participants based on their roles, availability, and consent. The data were analysed thematically. ResultsThe factors enhancing care for patients with MDR-TB include using a certificate of readiness, community involvement, donor financing, availability of treatment centre, effective facility-community linkage, treatment support, multidisciplinary care team, training service providers, availability of oral drugs, expansion of diagnostic facilities, data tool availability, review meetings, and data-focused supervision. In contrast, the factors constraining MDR-TB management are poor implementation of infection control policy, donor dependence, delayed initiation of treatment, poorly motivated health workers, health worker stigma, shortage of personal protective equipment, and role conflict in data management. ConclusionThe findings highlight critical health systems strengths and weaknesses in MDR-TB control. MDR-TB care policies must build on the enablers and address the barriers to strengthen the care for patients with MDR-TB.

Cost-consequence analysis of ambulatory clinic- and home-based multidrug-resistant tuberculosis management models in Eswatini.

We compared the cost-consequence of a home-based multidrug-resistant tuberculosis (MDR-TB) model of care, based on task-shifting of directly observed therapy (DOT) and MDR-TB injection administration to lay health workers, to a routine clinic-based strategy within an established national TB programme in Eswatini. Data on costs and effects of the two ambulatory models of MDR-TB care was collected using documentary data and interviews in the Lubombo and Shiselweni regions of Eswatini. Health system, patient and caregiver costs were assessed in 2014 in US$ using standard methods. Cost-consequence was calculated as the cost per patient successfully treated. In the clinic-based and home-based models of care, respectively, a total of 96 and 106 MDR-TB patients were enrolled in 2014, with treatment success rates of 67.8% and 82.1%. Health system costs per patient treated were slightly lower in the home-based strategy (US$19 598) compared to the clinic-based model (US$20 007). The largest costs in both models were for inpatient care, administration of DOT and injectable treatment, and drugs. Costs incurred by patients and caregivers were considerably higher in the clinic-based model of care due to the higher direct travel costs to the nearest clinic to receive DOT and injections daily. In total, MDR patients in the clinic-based strategy incurred average costs of US$670 compared to US$275 for MDR-TB patients in the home-based model. MDR-TB patients in the home-based programme, where DOT and injections was provided in their homes, only incurred out-of-pocket travel expenses for monthly outpatient treatment monitoring visits averaging US$100. The cost per successfully treated patient was US$31 106 and US$24 157 in the clinic-based and home-based models of care, respectively. The analysis showed that, in addition to the health benefits, direct and indirect costs for patients and their caregivers were lower in the home-based care model. The home-based strategy used less resources and generated substantial health and economic benefits, particularly for patients and their caregivers, and decision makers can consider this approach as an alternative to expand and optimise MDR-TB control in resource-limited settings. Further research to understand the appropriate mix of treatment support components that are most important for optimal clinical and public health outcomes in the ambulatory home-based model of MDR-TB care is necessary.

Prevalence of Multidrug-Resistant Tuberculosis (MDR-TB) in India: A Mini Systematic Review and Meta-Analysis (2016–2022)

ABSTRACT India carries the highest global burden of tuberculosis and multidrug-resistant tuberculosis (MDR-TB) (26%). There remains an uncertainty around the population-based estimates of MDR-TB in India. Applying a systematic review approach, we searched PubMed and Scopus to identify studies reporting the prevalence of MDR-TB among new and/or previously treated patients (cases) at any site in India and published during 2016–2022. Of 341 retrieved articles, we could select only 10 and excluded many as they were either unrelated or had limitations. From the meta-analysis of available studies, we found the pooled prevalence of MDR-TB among new cases as 3.9% (95% (CI 2.2–6.1) and as 13.4% (95% CI 8.8–18.7) among previously treated cases. Overall, it was 6.7% (95% CI 4.2–9.6). Albeit with a wider confidence intervals, the prevalence figures calculated from the present study are comparable to those reported by the National Anti-TB Drug Resistance Survey. Among selected studies, the majority were from North India and the recent data on prevalence are lacking for other Indian regions. This mini-review highlights the need for the Indian National TB Elimination Program to make provisions for regional periodic prevalence surveys for careful designing of MDR-TB control strategies.

The differences in drug resistance between drug-resistant tuberculosis patients with and without diabetes mellitus in northeast China: a retrospective study

BackgroundDiabetes mellitus (DM) and drug-resistant tuberculosis (DR-TB) are serious global public health problems. This study aimed to explore the differences in drug resistance between DR-TB patients with and without DM. Risk factors for developing multidrug-resistant tuberculosis (MDR-TB) were also investigated among DR-TB patients.MethodsThe patient’s basic demographic, clinical characteristics, and drug susceptibility testing (DST) data were collected from the Chinese Disease Control Information System. Descriptive statistics were used to estimate the frequency and proportion of included variables. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Chi-square tests for trends were used to determine changes and trends in MDR-TB and pre-extensively drug-resistantTB (pre-XDR-TB) patterns over time. Univariate and multivariate logistic regression analysis was used to explore the risk factors of MDR-TB.ResultsCompared with DR-TB patients with DM, DR-TB patients without DM had significantly higher rates of mono-resistant streptomycin (SM) and any resistance to kanamycin (KM), but significantly lower rates of any resistance to protionamide (PTO) and mono-resistance to levofloxacin (LFX), and pre-XDR-TB (P<0.05). The proportion of resistance to other anti-TB drugs was not statistically different between the DR-TB with and without DM. Among DR-TB patients without and with DM, the proportion of patients with MDR-TB and pre-XDR-TB patterns showed a significant downward trend from 2016 to 2021 (P<0.05). Among DR-TB patients without DM, male, previously treated DR-TB cases, and immigration were risk factors for MDR-TB (P<0.05). In DR-TB patients with DM, a negative sputum smear is a risk factor for MDR-TB (P<0.05).ConclusionThere was no statistical difference in resistance patterns between DR-TB with and without DM, except in arbitrary resistance to PTO and KM, mono-resistant SM and LFX, and pre-XDR-TB. Great progress has been made in the prevention and control of MDR-TB and pre-XDR-TB. However, DR-TB patients with and without DM differ in their risk factors for developing MDR-TB.

A meta-analysis of risk factors for multidrug-resistant tuberculosis in China

Objective: To explore the main risk factors of multidrug-resistant tuberculosis (MDR-TB) in China and to provide evidence-based evidence for MDR-TB preventon and control. Methods: All relevant literatures were searched in thedatabases, such as Pubmed, Web of Science and CNKI, Wanfang, VIP and SinoMed from 2000 to 2021. Quality evaluation and data extraction were carried out, and then a meta-analysis was performed using Stata 16.0 software. Results: A total of 59 literatures (36 cross-sectional and 23 case-control) including 75 793 participants were included in this study, and meta-analysis results showed age (OR=1.27, 95%CI: 1.05-1.54), education level (OR=1.29, 95%CI: 1.02-1.65), positive sputum smear (OR=2.56, 95%CI: 1.09-6.04), pulmonary cavity (OR=1.99, 95%CI: 1.57-2.52), course of disease (OR=4.25, 95%CI: 1.95-9.30), history of tuberculosis treatment (OR=6.42,95%CI:5.40-7.63), treatment interruption (OR=2.81, 95%CI: 1.50-5.29), irregular medication (OR=5.02, 95%CI: 2.95-8.54), adverse drug reactions (OR=4.27, 95%CI: 2.22-8.19), combined chronic obstructive pulmonary disease (COPD) (OR=2.21, 95%CI: 1.45-3.37), tuberculosis exposure history (OR=1.99, 95%CI: 1.36-2.91), smoking history (OR=1.35, 95%CI: 1.09-1.66) and floating population (OR=1.60, 95%CI: 1.04-2.44) were associated with the occurrence of MDR-TB. Conclusions: The high risk groups were farmer, low education level, pulmonary cavity, long course of disease, history of tuberculosis treatment, treatment interruption, irregular medication, adverse drug reaction, co-COPD, contact history of tuberculosis, smoking history, rural residence, and floating population. We should pay attention to high-risk groups, strengthen management and take effective measures such as early screening, knowledge education on tuberculosis, standardized and personalized treatment and whole-course supervision.

Genotypic Distribution and the Epidemiology of Multidrug Resistant Tuberculosis in Upper Northern Thailand.

The epidemiology and genotypes of multidrug-resistant tuberculosis (MDR-TB), a global public health threat, remain limited. The genotypic distribution and factors associated with MDR-TB in upper northern Thailand between 2015 and 2019 were investigated. The DNA sequencing of rpoB, katG, and inhA promoter of 51 multidrug-resistant Mycobacterium tuberculosis isolates revealed nine patterns of the rpoB gene mutation distributed in seven provinces. The S531L mutation was the most common mutation in all provinces. The rpoB mutation in Chiang Rai, Chiang Mai, and Lampang was highly diverse compared to other areas. Here, the mutation profiles that have yet to be reported in northern Thailand (H526P, Q513P, and H526C) were detected in Chiang Rai province. The S315T katG mutation was the most common genotype associated with INH resistance, especially in Chiang Mai and Lampang. Further analysis of data from 110 TB patients (42 MDR-TB and 68 drug-susceptible TB) revealed that &lt;60 years of age was a significant factor associated with MDR-TB (OR = 0.316, 95% CI 0.128-0.784, p = 0.011) and ≥60 years of age was a significant factor associated with the S315T katG-mutation (OR = 8.867, 95% CI 0.981-80.177, p = 0.047). This study highlighted the necessity for continuous surveillance and risk factor monitoring for effective control of MDR-TB.

Knowledge of multidrug-resistant tuberculosis amongst Durban University of Technology students in KwaZulu-Natal, South Africa: the need for integrating public health education.

Kwazulu-Natal is the epicenter of South Africa's Multidrug-resistant Tuberculosis (MDR-TB) burden which represents a growing threat to public health. Knowledge and awareness of MDR-TB are crucial for effective management and University students are an important vehicle for knowledge transfer of public health education. This study aimed to evaluate the knowledge of MDR TB and risk factors for transmission, prevention, treatment and control of MDR-TB among Durban University of Technology (DUT) students. This quantitative cross-sectional study was conducted among 150 randomly sampled undergraduate students from 3 faculties and data was collected using a validated questionnaire. While a majority of participants (70.67%) had previous knowledge on TB, only 30.67% knew of MDR-TB. Only 23.49% of students reported knowledge of preventative measures associated with MDR TB. Women had a lower probability of having knowledge of MDR-TB compared to men (OR=0.45; CI:0.22,0.95; p<0.05) and students from the Accounting and Informatics faculty were less likely to believe that MDR-TB was a life-threatening illness (OR=0.24; CI:0.05,1.44; p<0.05) and showed limited knowledge of MDR-TB transmission. This study showed that students lacked knowledge of MDR-TB with respect to risk factors, treatment and prevention, which necessitates intervention strategies at a tertiary level to educate and inform students about MDR-TB.

Identification and attribute analysis of key stakeholders who influence multidrug-resistant tuberculosis prevention and control in China

BackgroundThere could be various stakeholders who influencing multidrug-resistant tuberculosis (MDR-TB) policy development and implementation, yet their attributes and roles remain unclear in practice. This study aimed to identify key stakeholders in the process of policy-making for MDR-TB control and prevention and to analyse the attributes and relationships of the stakeholders, providing evidence for further policy research on MDR-TB control.MethodsThis study was conducted from October 2018 to March 2019 and applied the stakeholder analysis guidelines and domestic stakeholder analysis. An initial candidate stakeholder list was developed by policy scanning. Ten experts were invited to identify these candidate stakeholders. The major attribute of these stakeholders were analysed using the Michell scoring method. Based on these results, the intertwined relationships among groups of stakeholders were analysed and mapped through a systematic scan of the policy and literature on MDR-TB control, as well as information obtained from the interviews.ResultsA list of 21 types of candidate stakeholders was developed after a literature review and policy scanning, of which 11 received 100% approval. After expert evaluation and identification (the total expert authority was 0.80), 19 categories of stakeholders were approved and included in the stakeholder analysis. We categorized all of the stakeholders into three groups: (i) definitive stakeholders who are mainly involved in administrative departments and the Provincial Center for Disease Control and Prevention (CDC); (ii) expectant stakeholders who are mainly involved with MDR-TB patients, clinical departments of TB hospitals at different levels, community health care facilities, prefectural CDC and charity organizations; and (iii) latent stakeholders who mainly involved family members and neighbours of MDR-TB patients and TB related products manufacturers. Government departments and higher-level CDCs have strong decision-making power in developing MDR-TB control policies whereas the recommendations from service providers and the concerns of patients should be considered.ConclusionsThe MDR-TB prevention system was a multistakeholder cooperation system that was mainly led by government stakeholders. Enhancing communications with front-line service providers and patients on their unmet needs and evidence-based suggestions would highly benefit policy-making of MDR-TB prevention and control.Graphical abstract

Prevalence of Multidrug-Resistant Tuberculosis in Dalian, China: A Retrospective Study.

PurposeMultidrug-resistant tuberculosis (MDR-TB) is the cause of serious health and economic burdens worldwide. The present study aimed to explore the initial and acquired drug-resistance rates among TB patients from 2012 to 2019 in Dalian, China. The effectiveness of MDR-TB prevention and control strategies were then evaluated.Patients and MethodsDrug susceptibility testing (DST) was performed for 6429 diagnosed, culture-positive, Mycobacterium tuberculosis (MTB) strains, including 4661 new cases and 1768 previously treated cases. Descriptive statistics were employed to calculate the frequencies and percentages of TB strains, and the average annual growth rates (AAGRs) for each strain were calculated. The Chi-square test was applied to examine the significance of linear drug-resistance trends over time during the study period.ResultsOver the eight-year study period, the percentages of both initial (from 9.01% to 4.82%) and acquired (from 40.85% to 9.09%) MDR-TB cases decreased significantly, AAGRs of 8.55% and 19.32%, respectively. Among new and previously treated TB patients, significant downtrends were observed for the rates of both initial and acquired MDR-TB among young and middle-aged individuals (P < 0.05). Additionally, among both new and previously treated TB patients, the percentages of individuals with drug resistance against isoniazid (INH), rifampicin (RFP), ofloxacin (OFX), and amikacin (AMK) decreased significantly (P < 0.05) from 2012 to 2019 in Dalian, China.ConclusionThe initial and acquired multidrug resistance rates exhibited significantly decreasing trends from 2012 to 2019, suggesting that MDR-TB prevalence has been controlled effectively in Dalian, China. The MDR-TB epidemic was reversed in the short term by establishing feasible strategies for detection, diagnosis, treatment, and infection control.

New short-course regimen in multidrug-resistant tuberculosis control- A need of the hour

New short-course regimen in multidrug-resistant tuberculosis control- A need of the hour

Adverse treatment outcomes in multidrug resistant tuberculosis go beyond the microbe-drug interaction: Results of a multiple correspondence analysis.

Introduction: Multidrug-resistant tuberculosis treatment is effective in 50% of patients due to several factors including antibiotic susceptibility of the microorganism, adverse treatment reactions, social factors, and associated comorbidities.Objectives: In this study, we describe the demographics, clinical characteristics, and factors associated with treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients in Medellín, Colombia.Materials and methods: We conducted a retrospective analysis using data from patients diagnosed with MDR-TB attending Hospital La María in Medellín, Colombia, for treatment between 2010 and 2015. Patients were categorized as having successful (cured) or poor (failure, lost to follow-up, and death) treatment outcomes. Associations between demographic, clinical factors, laboratory results, treatment outcomes, and follow-up information were evaluated by univariate, multivariate, and multiple correspondence analyses. Results: Of the 128 patients with MDR-TB, 77 (60%) had successful outcomes. Of those with poor outcomes, 26 were lost to follow-up, 15 died, and 10 were treatment failures. Irregular treatment, the presence of comorbidities, and positive cultures after more than two months of treatment were associated with poor outcomes compared to successful ones (p<0.05 for all). The multiple correspondence analyses grouped patients who were lost to follow-up, had HIV, and drug addiction, as well as patients with treatment failure, irregular treatment, and chronic obstructive pulmonary disease.Conclusion: The recognition of factors affecting treatment is essential and was associated with treatment outcomes in this series of patients. Early identification of these factors should increase the rates of treatment success and contribute to MDR-TB control.

Gridlock from diagnosis to treatment of multidrug resistant tuberculosis (MDR-TB) in Tanzania: patients\u2019 perspectives from a focus group discussion

BackgroundMolecular diagnostics have revolutionized the diagnosis of multidrug resistant tuberculosis (MDR-TB). Yet in Tanzania we found delay in diagnosis with more than 70% of MDR-TB patients having a history of several previous treatment courses for TB signaling prior opportunities for diagnosis. We aimed to explore patients’ viewpoints and experiences with personal and socio-behavioral obstacles from MDR-TB diagnosis to treatment in an attempt to understand these prior findings.MethodsThe study was conducted in December 2016 with MDR-TB patients admitted at Kibong’oto Infectious Diseases Hospital. A qualitative approach deploying focus group discussions (FGDs) was used to gather information. Groups were sex aggregated to allow free interaction and to gauge gender specific issues in the social and behavioral contexts. The FGDs explored pathways and factors in the service delivery that may have contributed in the delay in accessing MDR-TB diagnostics and/or treatment. Collected data were coded, categorized and thematically interpreted.ResultsForty MDR-TB patients participated in six FGDs. Challenges and barriers contributing to the delay in accessing MDR-TB diagnosis to treatment were as follows: 1) Participants had a different understanding of MDR-TB that led to seeking services outside the conventional health system; 2) Socio-economic adversity made health-seeking behavior difficult and often unproductive; 3) In the health system, challenges included inadequacy of MDR-TB diagnostic centers, lack of knowledge on behalf of health care providers to consider MDR-TB and order appropriate diagnostics; 4) The specimen referral system for early diagnosis of MDR-TB was inefficient. Non-adherence of TB patients to first-line anti-TB drugs prior to MDR-TB diagnosis, given the multitude of barriers discussed, was coupled with both intentional and unintentional non-adherence of health care providers to international standards of TB care.ConclusionPatient-centered strategies bridging communities and the health system are urgently required for optimum MDR-TB control in Tanzania.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012\u20132017) retrospective study

BackgroundIn Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.MethodsFor 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.ResultsThe geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.ConclusionsAn expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Analysis on drug sensitivity spectrum of 167 multidrug-resistant Mycobacterium tuberculosis in China

Objective: To investigate the drugs-sensitivity spectrum of multidrug-resistant tuberculosis (MDR-TB) in China and provide a scientific evidence for the drug selection in clinical therapy and the control of MDR-TB. Methods: A total of 167 strains of MDR-TB were included in this study. Every strain was genotyped by lysX gene sequencing and their sensitivity to 13 different anti-TB drugs was tested by using MicroDST(TM) and BACTEC(TM) MGIT 960(TM) liquid-culturing method. The association between drug resistance and genotypes as well as cross drug resistance was also analyzed. The results were analyzed by means of the comparison of enumeration data between two groups with χ(2) test. Results: The overall resistance rate of 167 MDR-TB strains to 11 anti-TB drugs, except isoniazide and rifampicin, was 95.81%, the rates of pre-extensive drug-resistance (pre-XDR) and extensive drug-resistance were 31.14%(52/167) and 6.59% (11/167), respectively. The streptomycin resistance rate of Beijing genotypes was significantly higher than that of the non-Beijing genotypes ( χ(2)=30.682, P<0.05), while the pre-XDR proportion in Beijing genotypes was lower than that in non-Beijing genotypes (χ(2)=5.332, P<0.05). The resistance rates of Ofloxacin and Pyrazinamide in the modern Beijing genotype were significantly higher than those in classical ones (χ(2)=4.105 and χ(2)=3.912, P<0.05). In addition, the cross-resistance rate to rifampicin and rifabutin was 86.23%. A significant difference in drug-resistance rate to rifabutin was seen among groups with different levels of rifampicin resistance (χ(2)=45.912, P<0.05). There was positive correlation not only between ofloxac resistance and moxifloxac resistance, but also between amikacin resistance and kanamycin resistance, with the coefficient of 0.87 and 0.91, respectively. Conclusions: In this study, we observed that there were high incidences of the resistance to 11 anti-TB drugs in 167 clinical MDR-TB strains and the cross resistance phenomena between drugs of the same type were quite serious. The majority of MDR-TB strains belonged to Beijing genotype, which was highly associated with streptomycin resistance.

The novel potential biomarkers for multidrug-resistance tuberculosis using UPLC-Q-TOF-MS.

The lack of rapid and efficient diagnostics impedes largely the epidemic control of multidrug-resistant tuberculosis, and might misguide the therapeutic strategies as well. This study aimed to identify novel multidrug-resistant tuberculosis biomarkers to improve the early intervention, symptomatic treatment and control of the prevalence of multidrug-resistant tuberculosis. The serum small molecule metabolites in healthy controls, patients with drug-susceptible tuberculosis, and patients with multidrug-resistant tuberculosis were screened using ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The differentially abundant metabolites were filtered out through multidimensional statistical analysis and bioinformatics analysis. Compared with drug-susceptible tuberculosis patients and healthy controls, the levels of 13 metabolites in multidrug-resistant tuberculosis patients altered. Among them, the most significant changes were found in N1-Methyl-2-pyridone-5-carboxamide (N1M2P5C), 1-Myristoyl-sn-glycerol-3-phosphocholine (MG3P), Caprylic acid (CA), and D-Xylulose (DX). And a multidrug-resistant tuberculosis/drug-susceptible tuberculosis differential diagnostic model was built based on these four metabolites, achieved the accuracy, sensitivity, and specificity of 0.928, 86.7%, and 86.7%, respectively. The enrichment analysis of metabolic pathways showed that the phospholipid remodeling of cell membranes was active in multidrug-resistant tuberculosis patients. In addition, in patients with tuberculosis, the metabolites of dipalmitoyl phosphatidylcholine (DPPC), a major component of pulmonary surfactant, were down-regulated. N1M2P5C, MG3P, CA, and DX may have the potential to serve as novel multidrug-resistant tuberculosis biomarkers. This research provides a preliminary experimental basis to further investigate potential multidrug-resistant tuberculosis biomarkers. Impact statement The MDR-TB incidence remains high, making the effective control of TB epidemic yet challenging. Rapid and accurate diagnosis is vitally important for improving the therapeutic efficacy and controlling the prevalence of drug resistance TB. Metabolomics has dramatic potential to distinguish MDR-TB and DS-TB. N1M2P5C, MG3P, CA, and DX that we identified in this study might have potential as novel MDR-TB biomarkers. The phospholipid remodeling of cell membranes was highly active in MDR-TB. The DPPC metabolites in TB were significantly down-regulated. This work aimed to investigate potential MDR-TB biomarkers to enhance the clinical diagnostic efficacy. The metabolic pathway distinctly altered in MDR-TB might provide novel targets to develop new anti-TB drugs.

Challenge of the Rising Multidrug-Resistant Tuberculosis in China: A Predictive Study Using Markov Modeling

Background: Multidrug-resistant tuberculosis (MDR-TB) is emerging in China. We used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050, and assess the effects of alternative control measures. Methods Eight states of TB transmission were set up in the Markov model using a hypothetical cohort of 100,000 people. Prevalence of MDR-TB and bacteriological confirmed drug-susceptible TB (DS-TB+) were simulated. MDR-TB was stratified into being treated with the recommended regimen or not. Findings: Under the current China’s TB control conditions, by 2050, prevalence of DS-TB+ could be estimated to decrease to 39 per 100,000 people, a 37·1% reduction from 2019 , whereas MDR-TB would increase by three times to 58/100,000. Furthermore, by the year of 2050, 86·2% of the MDR-TB cases would be left untreated. If the detection rate of MDR-TB could reach 50% or 70% at 5% per year, the decline of MDR-TB prevalence would be 25·9% and 36·2% respectively. If treatment coverage was improved to 70% or 100% by 5% yearly , MDR-TB prevalence in 2050 would gain a reduction of 13·8% and 24·1%, respectively. If both detection rate and treatment coverage could reach 70%, the prevalence of MDR-TB would be reduced to 28/100, 000, a 51·7% reduction by 2050. Interpretation: MDR-TB, especially untreated MDR-TB, would rise rapidly under current MDR-TB control strategies in China. Interventions on promoting effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics. Funding Statement: The Sweden-China (VR-NSFC) joint project (PI, Biao Xu, 81361138019 and Sven Hoffner, 540-2013-8797). Declaration of Interests: The authors stated: None declared. Ethics Approval Statement: Not required.

English

Tuberculosis is one of the major public health problems in Kano. With the occurrence of multi-drug resistant tuberculosis, little is known about the views of health care workers on this disease. The aim of this study was to investigate the knowledge, attitudes, and practices of healthcare professionals about prevention and control of Multi-Drug Resistant Tuberculosis (MDR-TB) at Infectious Diseases Hospital (IDH), Kano, Nigeria.&nbsp; A cross-sectional study was conducted at Infectious Diseases Hospital (IDH), Kano, Nigeria from November, 2018 to December, 2018. Data was collected using a pretested structured questionnaire. The data obtained were analyzed using SPSS software package (SPSS 16.0). Descriptive analysis was performed to obtain the frequency distribution of the variables. The results of this study indicate that, overall, less than half (68%) of respondents had good level of knowledge of MDR-TB; but the overwhelming majority of them held negative attitude towards patients with MDR-TB. In conclusion, less than half of respondents had good level of knowledge about MDR-TB, but 28.7% of them held negative attitude towards patients suffering from MDR-TB. Although the level of knowledge of MDR-TB was found not to have influenced the attitude of respondents towards patients suffering from MDR-TB; and that their attitude did not influence practices, good level of knowledge was positively associated with safer practices such as using protective masks, educating patients on MDR-TB, and referring to the MDR-TB guidelines manual. An educational remedial intervention and in-service training on the MDR-TB is recommended for all professionals especially primary health care workers. Key words: Multi drug- resistant, extensively drug-resistant, tuberculosis, health care workers &nbsp

Resistance Sniffer: An online tool for prediction of drug resistance patterns of Mycobacterium tuberculosis isolates using next generation sequencing data

The effective control of multidrug resistant tuberculosis (MDR-TB) relies upon the timely diagnosis and correct treatment of all tuberculosis cases. Whole genome sequencing (WGS) has great potential as a method for the rapid diagnosis of drug resistant Mycobacterium tuberculosis (Mtb) isolates. This method overcomes most of the problems that are associated with current phenotypic drug susceptibility testing. However, the application of WGS in the clinical setting has been deterred by data complexities and skill requirements for implementing the technologies as well as clinical interpretation of the next generation sequencing (NGS) data. The proposed diagnostic application was drawn upon recent discoveries of patterns of Mtb clade-specific genetic polymorphisms associated with antibiotic resistance. A catalogue of genetic determinants of resistance to thirteen anti-TB drugs for each phylogenetic clade was created. A computational algorithm for the identification of states of diagnostic polymorphisms was implemented as an online software tool, Resistance Sniffer (http://resistance-sniffer.bi.up.ac.za/), and as a stand-alone software tool to predict drug resistance in Mtb isolates using complete or partial genome datasets in different file formats including raw Illumina fastq read files. The program was validated on sequenced Mtb isolates with data on antibiotic resistance trials available from GMTV database and from the TB Platform of South African Medical Research Council (SAMRC), Pretoria. The program proved to be suitable for probabilistic prediction of drug resistance profiles of individual strains and large sequence data sets.