Multidrug-resistant Tuberculosis Patients Research Articles

Identifying risk factors for recurrent multidrug resistant tuberculosis based on patient’s record data from 2016 to 2021: retrospective study

Globally, the prevalence of multidrug-resistant tuberculosis (MDR-TB) has been increasing recently. This is a major public health concern, as MDR-TB is more difficult to treat and has poorer outcomes compared to drug-sensitive tuberculosis. The main objective of the study was to identify risk factors for recurrent multidrug-resistant tuberculosis, at Alert Specialized Hospital, Addis Ababa, by using different parametric shared frailty models. From January 2016 to December 2021, a retrospective study was conducted on MDR-TB patients at Alert Specialized Hospital in Addis Ababa. The data for the study were collected from the medical records of MDR-TB patients at the hospital during this time period. Gamma and inverse-Gaussian shared frailty models were used to analyze the dataset, with the exponential, Weibull, and lognormal distributions included as baseline hazard functions. The data were analyzed using R statistical software. The median recurrence time of the patients was 12 months, and 149 (34.3%) had recurrences. The clustering effect was statistically significant for multiple drug-resistant tuberculosis patients’ recurrence. According to the Weibull-Inverse-Gaussian model, factors that reduced time to MDR-TB recurrence included lower weight (ɸ = 0.944), smoking (ɸ = 0.045), alcohol use (ɸ = 0.631), hemoptysis (ɸ = 0.041), pneumonia (ɸ = 0.564), previous anti-TB treatment (ɸ = 0.106), rural residence (ɸ = 0.163), and chronic diseases like diabetes (ɸ = 0.442) were associated with faster recurrence. While, higher education (ɸ = 3.525) and age (ɸ = 1.021) extended time to recurrence. For weight increment, smokers and alcohol users, clinical complications of hemoptysis and pneumonia, patients with pulmonary disease who had a history of previous anti-TB treatment, and being rural residents are prognostic factors. There was a significant clustering effect at the Alert Specialized Hospital in Addis Ababa, Ethiopia. The Weibull-Inverse Gaussian Shared Frailty Model was chosen as the best model for predicting the time to recurrence of MDR-TB.

Prevalence of depression among drug-resistant tuberculosis patients in South Asia: A systematic review and meta-analysis

Background: Drug-resistant tuberculosis (DR-TB) significantly increases the risk of depression, yet research on mental health in this population remains limited. Aim: This meta-analysis aimed to evaluate the prevalence of depression among multidrug-resistant TB (MDR-TB) patients, emphasizing the necessity for integrated mental health care. Methods: A systematic search across PubMed, Cochrane, EBSCOhost, and Google Scholar identified 536 articles, which were screened for eligibility after removing duplicates. Prevalence data were analyzed using R programming, with back-transformation applied to enhance accuracy. The methodological quality of the included studies was assessed with the JBI Critical Appraisal Checklist, and the study protocol is registered in PROSPERO (CRD42023449156). Results: Ultimately, twelve studies involving 3,258 participants were included in the analysis. The pooled prevalence of depression among MDR-TB patients was found to be 54% (95% CI: 42%-65%). Although substantial heterogeneity was noted (I² = 72%; P < 0.01), excluding one study (Walker et al.) due to high Cook’s distance revised the prevalence to 55% (95% CI: 43%-68%), with reduced heterogeneity (I² = 68%; P < 0.01). Subgroup analyses indicated minimal variability among studies using the Hamilton Depression Rating Scale (52%, 95% CI: 40%-64%) and substantial variability among those employing the Patient Health Questionnaire (54%, 95% CI: 30%-79%). Funnel plot analysis and Egger’s test revealed no significant publication bias (P = 0.2105). Conclusion: This study highlights a high prevalence of depression among MDR-TB patients, underscoring the urgent need for integrated mental health care strategies tailored for this vulnerable population. Further research is essential to refine these strategies effectively.

Whole-genome sequencing drug susceptibility testing is associated with positive MDR-TB treatment response.

<sec><title>BACKGROUND</title>Until recently, multidrug-resistant TB (MDR-TB) was treated with lengthy and toxic regimens. New three-drug anti-TB regimens raise the question of whether they are sufficiently active for MDR-TB in Central Asia, an MDR-TB hotspot region.</sec><sec><title>METHODS</title>In a cohort of rifampicin-resistant (RR) and MDR-TB patients in the Kyrgyz Republic, we investigated the impact of the number of drugs that were tested susceptible by whole-genome sequencing (WGS) and conventional drug susceptibility testing (DST) and used for treatment on the treatment response, defined as 'matches'. Logistic regressions were performed to assess the effect of having ≥ 4 susceptible drugs in a regimen at baseline and at Month 2 on the treatment response.</sec><sec><title>RESULTS</title>The study included 227 participants with RR/MDR-TB (30.8% female; median age 30.4 years). The age- and sex-adjusted analysis showed an association between a regimen with ≥ 4 WGS matches at baseline (adjusted odds ratio [aOR] 2.10, 95% CI 1.00-4.41). No association was found when using conventional DST to define matches.</sec><sec><title>CONCLUSION</title>Our study confirms that the inclusion of four efficacious anti-TB drugs in an MDR-TB regimen increases the chances of a positive treatment response. Susceptibility of at least four drugs in WGS-DST predicts a positive treatment response.</sec>.

Effect of Different Levofloxacin Doses on QTc Interval Prolongation in Multidrug-Resistant Tuberculosis Patients Treated with the 9-Month All-Oral Regimen

Introduction: The World Health Organization (WHO) has recommended the 9-month all-oral regimen for multidrug-resistant tuberculosis (MDR-TB) treatment. This regimen is expected to increase the treatment success rate. Bedaquiline, levofloxacin, and clofazimine are QT-prolonging drugs included in the 9-month all-oral regimen. Bedaquiline and clofazimine are given at the same dose for all patients, while levofloxacine dose is given in 750 mg and 1,000 mg based on the body weight. This study analyzed the correlation between different levofloxacin doses and certain factors on QTc interval prolongation. Methods: This observational retrospective study used the medical records of MDR-TB patients who underwent the 9-month all-oral regimen. Electrocardiography (ECG) for QTc interval measurement was recorded at the baseline before and 2 weeks after treatment. The measured variables included patient demographic data, body mass index (BMI), electrolyte levels, and comorbidities. Results: Thirty MDR-TB patients were included in this study. Gender, diabetes mellitus (DM), and levofloxacin dose did not correlate with QTc interval prolongation at 2 weeks after drug administration (p-values of 0.558, 0.197, and 0.134, respectively). Age, potassium level, magnesium level, calcium level, and baseline QTc interval also did not correlate with QTc interval prolongation at 2 weeks after drug administration (p-values of 0.433, 0.479, 0.705, 0.746, and 0.333, respectively). Multivariate analysis showed that the risk factor associated with QTc interval prolongation at 2 weeks after drug administration was a BMI of 0.013. Conclusion: Different levofloxacin doses did not correlate with QTc interval prolongation in MDR-TB patients treated with the 9-month all-oral regimen. The incidence of QTc interval prolongation was significantly associated with the lower BMI level.

Evaluation and application of population pharmacokinetic models for optimising linezolid treatment in non-adherence multidrug-resistant tuberculosis patients

BackgroundPopulation pharmacokinetic (popPK) models can optimise linezolid dosage regimens in patients with multidrug-resistant tuberculosis (MDR-TB); however, unknown cross-centre precision and poor adherence remain problematic. This study aimed to assess the predictive ability of published models and use the most suitable model to optimise dosage regimens and manage compliance. MethodsOne hundred fifty-eight linezolid plasma concentrations from 27 patients with MDR-TB were used to assess the predictive performance of published models. Prediction-based metrics and simulation-based visual predictive checks were conducted to evaluate predictive ability. Individualised remedial dosing regimens for various delayed scenarios were optimised using the most suitable model and Monte Carlo simulations. The influence of covariates, scheduled dosing intervals, and patient compliance were assessed. ResultsSeven popPK models were identified. Body weight and creatinine clearance were the most frequently identified covariates influencing linezolid clearance. The model with the best performance had a median prediction error (PE%) of -1.62 %, median absolute PE of 29.50 %, and percentages of PE within 20 % (F20, 36.97 %) and 30 % (F30, 51.26 %). Monte Carlo simulations indicated that a twice-daily 300 mg linezolid dose may be more efficient than 600 mg once daily. For the ‘typical’ patient treated with 300 mg twice daily, half the dosage should be taken after a delay of ≥ 3 h. ConclusionsMonte Carlo simulations based on popPK models can propose remedial regimens for delayed doses of linezolid in patients with MDR-TB. Model-based compliance management patterns are useful for balancing efficacy, adverse reactions, and resistance suppression.

Response to treatment and low serum vitamin D levels in North Indian patients with treatment-naive category I and multi-drug resistant pulmonary tuberculosis

Background Tuberculosis (TB) is a bacterial infection that usually affects the lungs, although it can also affect other parts of the body. Vitamin D deficiency and response to treatment have been demonstrated in patients with active TB in several studies, but not in MDR-TB patients, which is a new observation in the present study. Objective To study the time to initial sputum culture conversion and to associate baseline vitamin D levels and response to treatment in patients with PTB Cat I and MDR-TB. Methods A total of 897 North Indian participants were recruited and divided into three groups: treatment-naïve PTB Cat I, MDR-TB, and healthy controls. Serum biochemistry, including 25-hydroxyvitamin D and calcium, was measured in all participants with PTB, Cat I, and MDR-TB. Results PTB Cat I patients had high bacillary load grading at baseline compared to 2nd month followed by 6th month of treatment. More severe chest radiographic features, such as cavitation and the presence of bilateral disease at baseline. Mean sputum smear conversion times were 0.95 ± 0.7 months and culture conversion to negative occurred at a mean time of 0.8 ± 0.7 in PTB Cat I patients compared to MDR-TB patients on average sputum smear and time of 2.4 ± 3 months. Significantly lower mean serum 25-hyroxyvitamin D concentration was found in the 6th month than in the 2nd month and baseline in PTB Cat I. Conclusion Low serum vitamin D deficiency was observed in both groups during treatment and is one of the important factors responsible for susceptibility to TB in both groups; however, its significance is uncertain. Patients with continuous positive sputum for multidrug-resistant tuberculosis (MDR-TB) had a worse prognosis than those with sputum bacteriology conversion. Two months into a treatment regimen, sputum smear conversions may be a useful indicator of an MDR-TB patient’s prognosis.

Assessment of Quality of Life and Social Correlates among Drug Sensitive and Multidrug-resistant Tuberculosis Patients

Abstract Background: Tuberculosis (TB) has significant health, social, psychological, and economic impacts on patients. This study aimed to assess and compare quality of life (QOL) among multidrug-resistant (MDR) TB patients and drug-sensitive TB patients. Materials and Methods: A comparative study was conducted among 40 MDR-TB patients and 80 age- and gender-matched drug-sensitive TB patients in Chitradurga district, South India. Sociodemographic data were collected and QOL was assessed using the WHO BREF scale. Data were analyzed using SPSS v20. Results: The study population was predominantly male (65%) and aged 27–35 years. Education level and socioeconomic status differed significantly between MDR and sensitive TB groups (P &lt; 0.05). MDR-TB patients had significantly lower self-rated QOL and health satisfaction compared to sensitive TB patients (P &lt; 0.001). MDR-TB patients scored lower on all four QOL domains (physical, psychological, social relationships, and environmental), with the psychological domain most affected. The majority of both MDR and sensitive TB patients had “fair” QOL across domains. Conclusion: QOL was impaired in both MDR and sensitive TB patients, but more severely in MDR-TB. The psychological domain was most affected. Factors such as poor accessibility to health services, low socioeconomic status, and poor mental health may contribute to reduce QOL in TB patients.

A Mixed-Method Study of Medication-Related Burden Among Multi-Drug Resistant Tuberculosis Patients in West Java, Indonesia.

Multidrug-resistant tuberculosis presents a challenging obstacle in global TB control. It necessitates complex and long-term therapy, which can potentially lead to medication-related burdens that may ultimately reduce therapy adherence and quality of life. This study aimed to gain a deep understanding of the medication-related burdens experienced by multidrug-resistant tuberculosis patients. The study was conducted using a convergent mixed-method approach involving MDR-TB patients and their caregivers. Qualitative data were collected through semi-structured in-depth interviews, while quantitative data were gathered using the validated Living with Medicine Questionnaire 3. In the quantitative part, associations between patients' characteristics and burden levels were analysed using bivariate and multivariate analyses. Seventy-four participants were involved in the study, with 71 of them completing the questionnaire and 36 participating in interviews. The qualitative results revealed the subjectivity of medication-related burden perception, which could not be fully captured by the quantitative method. Four themes of medication-related burdens emerged: personal beliefs, regimen burdens, socioeconomic burdens, and healthcare burdens. The quantitative results provided a generalized representation of the population. Age and side effects were found to be significantly associated with higher burden levels, with those aged 18-30having an odds ratio (OR) of 7.303 (95% CI: 1.045-51.034), and those aged 31-40having an OR of 6.53 (95% CI: 1.077-39.607). Additionally, experiencing side effects had a substantial impact, with an OR of 46.602 (95% CI: 2.825-768.894). Both sets of results are valuable for designing patient-centered care. MDR-TB therapy imposes a significant burden, particularly regarding the characteristics of regimen. By understanding this burden, healthcare professionals can help improve the quality of life for these patients.

Treatment outcomes of standardized injectable shorter regimen for multi-drugs resistant tuberculosis in Ethiopia: a retrospective cohort study

BackgroundThe injectable shorter multi-drug resistant tuberculosis (MDR-TB) regimen, has been reported to be less costly and more effective in the treatment of MDR-TB compared to the longer regimen. Ethiopia introduced the injectable shorter regimen (SR) in April 2018 following official recommendation by the World Health Organization (WHO) in 2016. While the WHO recommendation was based on evidence coming from extensive programmatic studies in some Asian and African countries, there is paucity of information on patient outcomes in the Ethiopian context. Thus, we aimed to assess the treatment outcomes and identify factors associated with the outcomes of MDR-TB patients on injectable SR.MethodsA multi-center facility-based retrospective cohort study was conducted in Ethiopia on 245 MDR-TB patients who were treated between April 2018 and March 2020. Data were collected from patients’ medical records and analyzed using SPSS version 25. Descriptive statistics was used to summarize the results while inferential analysis was employed to investigate predictors of treatment outcomes and survival status.ResultsA total of 245 patients were included in the study, with 129 (52.7%) of them being female. Median age of the patients was 27 (IQR: 21–33). The overall treatment success rate was 87.8%, with 156 (63.7%) cured and 59 (24.1%) patients who completed treatment. The unfavorable outcomes accounted for 12.2%, with 16 (6.5%) treatment failure, 8 (3.3%) death and 6 (2.4%) lost to follow up. Majority of the unfavorable outcomes occurred during the early phase of therapy, with median time to event of 1.8 months (95% CI: 0.99—2.69). The use of khat (a green leafy shrub abused for its stimulant like effect) and being diagnosed with MDR-TB than rifampicin resistant only, were identified as independent factors associated with unfavorable outcomes.ConclusionThe injectable SR for MDR-TB was found to have positive treatment outcomes in the context of programmatic management in Ethiopia.

Understanding the role of video direct observed therapy for patients on an oral short-course regimen for multi-drug resistant tuberculosis: findings from a qualitative study in Eswatini

BackgroundImproving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini.MethodsBetween April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo.ResultsFour themes emerged that reflected participants’ experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones.ConclusionsvDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences.

Predictors of mortality among multidrug-resistant tuberculosis patients after decentralization of services in Tanzania from 2017 to 2019: retrospective cohort study

BackgroundMultidrug-resistant tuberculosis (MDR-TB) presents persistent global health challenges, characterized by low treatment success rates among patients enrolled for treatment. The World Health Organization recommends decentralization to improve outcomes. This study aims to assess predictors of mortality among MDR-TB patients after decentralization of services in Tanzania. This was a retrospective cohort study involving all MDR-TB patients enrolled in treatment in all 31 regions in Tanzania from 2017 to 2019. The overall mortality rate among MDR-TB patients was calculated using the incidence rate. Additionally, independent factors of MDR-TB mortality were determined using multivariable cox proportional hazards models.ResultsThe study followed 985 patients for a total of 12,929 months. During this time, it found that approximately 12 out of every 1000 patients died each month. Specifically, the death rates were about 18 out of 1000 patients at 6 months, 8 out of 1000 at 12 months, and 7 out of 1000 at 24 months. Patients who had both MDR-TB and HIV, as well as those who were malnourished, had a lower chance of surviving at 6, 12, and 24 months. Malnourished patients had almost three times the risk of dying [adjusted hazard ratio (aHR) 2.96, with a 95% confidence interval (CI) of 2.10–4.19], while those with HIV had nearly double the risk [aHR 1.91, with a 95% CI of 1.37–2.65].ConclusionIn summary, our study on MDR-TB patient outcomes in Tanzania between 2017 and 2019 reveals a pattern of high mortality rates within the first 6 months of treatment. Furthermore, malnutrition and HIV co-infection were found to be significant predictors of mortality. To decrease mortality, it is crucial to closely monitor patients during the initial 6 months of treatment, especially those who are malnourished or co-infected with HIV, and ensure they receive appropriate and timely care. Additionally, further investigation is needed to find out what may be contributing to possible rise in mortality rate.

Factors associated with tuberculosis drug resistance among presumptive multidrug resistance tuberculosis patients identified in a DRTB surveillance study in western Kenya

Multidrug-resistant tuberculosis (MDR-TB) is caused by M. tuberculosis (Mtb) with resistance to the first-line anti-TB medicines isoniazid (INH) and rifampicin (RIF). In Western Kenya, there is reported low prevalence of drug resistant strains among HIV tuberculosis patients, creating a need to determine factors associated with drug resistance patterns among presumptive MDR-TB patients. To determine factors associated with drug resistance patterns among presumptive MDR-TB patients in western Kenya. Three hundred and ninety (390) sputum sample isolates from among presumptive multidrug TB patients, were analyzed for TB drug resistance as per Ministry of Health (MoH) TB program diagnostic algorithm. Frequency and percentages were used to summarize categorical data while median and interquartile range (IQR) were used for continuous data. Multivariable logistic regression was carried out to identify factors associated with TB drug resistance. Out of 390 participants enrolled, 302/390 (77.4 %) were males, with a median age of 34 years. The HIV-infected were 118/390 (30.3 %). Samples included 322 (82.6 %) from presumptive patients, while 68/390 (17.4 %) were either lost to follow-up patients, failures to first-line treatment or newly diagnosed cases. A total of 64/390 (16.4 %) of the isolates had at least some form of drug resistance. Out of 390, 14/390 (3.6 %) had MDR, 12 (3.1 %) were RIF mono-resistance, 34 (8.7 %) had INH, while 4 (1 %) had ethambutol resistance. The category of previously treated patients (those who received or are currently on TB treatment) had a 70 % reduced likelihood of resistance (aOR: 0.30; 95 % CI: 0.13–0.70). In contrast, older age was associated with an increased likelihood of resistance to INH and RIF, with an adjusted odds ratio of 1.04 per year (95 % CI: 1.00–1.08). Prompt MDR-TB diagnosis is essential for appropriate patient care, management, and disease prevention and control. We recommend active surveillance on drug resistant TB in these regions to detect drug resistance patterns for rapid disease management.

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.

Delayed Presentation of Intradural Extramedullary Tuberculoma of Spine in an Immunocompetent MDR-TB Patient

Abstract Intradural spinal tuberculoma is a rare entity, constituting &lt;5% of CNS tuberculoma, whereas intradural extramedullary tuberculoma of spinal cord (IETSC) is even less frequently encountered. Here, we report a case of IETSC at two noncontiguous levels in spinal cord presenting with compressive myelopathy in a patient on multidrug-resistant tuberculosis (MDR-TB) treatment. Surgical decompression and appropriate ATT regimen resulted in gradual return to near-normal neurological function with no functional disability. To our knowledge, this is the first case report of IETSC developing in an immunocompetent patient on MDR regimen for drug resistant sputum-positive pulmonary tuberculosis.

Correlation between Gene polymorphism levels of serum matrix metalloproteinases with cavitary features and pulmonary fibrosis of the Patient tuberculosis multi-drug resistance using high-resolution computerized tomography of the Thorax

Matrix metalloproteinases (MMPs) are proteins that play a role in the inflammatory and remodeling processes caused by infections, including pulmonary tuberculosis (TB), especially multidrug resistance. This study aims to investigate the relationship between variations in MMP-1 and MMP-9 blood levels, cavity features such as number, diameter, and wall thickness, and the location of fibrosis in multidrug-resistant (MDR) and drug-sensitive (DS) tuberculosis patients. This study used a comparative cross-sectional study design. The subjects, who were outpatients at Abdoel Moelok Hospital, Lampung, Indonesia, had passed the ethical test. We divided the subjects into two groups: 34 in the MDR-TB group and 36 in the DS-TB group. An ELISA test determined the levels of MMP-1 and MMP-9, while the PCR-sequencing method determined the genotypes of MMP-1 and MMP-9. Additionally, we measured cavities and fibrosis using thoracic high-resolution computerized tomography (HRCT) imaging. In MDR-TB patients, there was a significant difference in the number of cavities larger than 6.6 mm in diameter, as well as cavity thickness, compared to DS-TB patients. The distribution of fibrosis in lung segments was also significantly different in MDR-TB compared to DS-TB. Although MMP-9 levels in the MDR-TB group were higher than in the DS-TB group, there was no statistically significant difference. Based on HRCT measurements, this study found a link between MDR-TB and DS-TB in terms of the number of cavities, the diameter of the cavities, the thickness of the cavity walls, and the location of fibrosis in the affected lung segments. There was no link between the MMP-1 (−1607G) and MMP-9 (C1562T) genotypes and the levels of MMP-1 and MMP-9 in the blood. The MMP-1 genotype in the two study groups was very different and was linked to twice as many cases of MDR-TB. In addition, there was a substantial difference in cavity wall thickness between the G/G MMP-1 1607 genotype and the T/T MMP-9 genotype in the two study groups.

Coarse particulate air pollution and mortality in a multidrug-resistant tuberculosis cohort

RationaleThe association between ambient coarse particulate matter (PM2.5–10) and mortality in multi-drug resistant tuberculosis (MDR-TB) patients has not yet been studied. The modifying effects of temperature and humidity on this association are completely unknown. ObjectivesTo evaluate the effects of long-term PM2.5–10 exposures, and their modifications by temperature and humidity on mortality among MDR-TB patients. MethodsA Chinese cohort of 3469 MDR-TB patients was followed up from diagnosis until death, loss to follow-up, or the study's end, averaging 2567 days per patient. PM2.5–10 concentrations were derived from the difference between PM10 and PM2.5. Cox proportional hazard models estimated hazard ratios (HRs) per 3.74 μg/m3 (interquartile range, IQR) exposure to PM2.5–10 and all-cause mortality for the full cohort and individuals at distinct long-term and short-term temperature and humidity levels, adjusting for other air pollutants and potential covariates. Exposure-response relationships were quantified using smoothed splines. ResultsHazard ratios of 1.733 (95% CI, 1.407, 2.135) and 1.427 (1.114, 1.827) were observed for mortality in association with PM2.5–10 exposures for the full cohort under both long-term and short-term exposures to temperature and humidity. Modifying effects by temperature and humidity were heterogenous across sexes, age, treatment history, and surrounding environment measured by greenness and nighttime light levels. Nonlinear exposure-response curves suggestes a cumulative risk of PM2.5–10-related mortality starting from a low exposure concentration around 15 μg/m3. ConclusionLong-term exposure to PM2.5–10 poses significant harm among MDR-TB patients, with effects modified by temperature and humidity. Immediate surveillance of PM2.5–10 is crucial to mitigate the progression of MDR-TB severity, particularly due to co-exposures to air pollution and adverse weather conditions.

Factors associated with unfavorable treatment outcomes among multidrug-resistant tuberculosis patients, Sierra Leone: a cross-sectional secondary data analysis

BackgroundGlobally, multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The tuberculosis rate in Sierra Leone is 298 per 100,000 people, and Sierra Leone is considered a country with a high burden of tuberculosis. In Sierra Leone, there are few studies on the outcomes of MDR-TB treatment, especially those exacerbated by COVID-19. We identified factors associated with unfavorable treatment outcomes among people with MDR-TB in Sierra Leone.MethodsWe conducted a cross-sectional study to analyze hospital-based MDR-TB data from 2017 to 2021. Demographic, clinical, and treatment outcome data were extracted from the main MDR-TB referral hospital database. We defined unfavorable outcomes as patients who died, were lost to follow-up, or defaulted. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to identify predictors of the outcomes of MDR-TB treatment.ResultsBetween 2017 and 2021, 628 people with MDR-TB were reported at Lakka Hospital; 441 (71%) were male, with a median age of 25 years (interquartile ranges: 17–34). Clinically, 21% of the 628 MDR-TB patients were HIV positive, and 413 were underweight (66%). 70% (440) of MDR-TB patients received tuberculosis treatment. The majority of patients, 457 (73%), were treated with a short treatment regimen, and 126 (20%) experienced unfavorable outcomes. Age 45 years or younger (aOR = 5.08; CI:1.87–13.82), 21–45 years (aOR = 2.22; CI:140–3.54), tuberculosis retreatment (aOR = 3.23; CI:1.82–5.73), age group, HIV status (aOR = 2.16; CI:1.33–3.53), and malnourishment status (aOR = 1.79; CI:1.12–2.86) were significantly associated with unfavorable treatment outcomes for DR-TB patients.ConclusionThis analysis revealed a high proportion of unfavorable treatment outcomes among MDR-TB patients in Sierra Leone. Malnourishment, TB retreatment, HIV coinfection, and age 45 years or younger were associated with unfavorable outcomes of MDR-TB treatment. Increasing patients’ awareness, mainly among young people, heightens treatment adherence and HIV monitoring by measuring the amount of HIV in patient blood, which can reduce adverse treatment outcomes in Sierra Leone and other sub-Saharan African countries.

Mental Health Impacts of Multidrug-Resistant Tuberculosis in Patients and Household Contacts: A Mixed Methods Study.

Multidrug-resistant tuberculosis (MDR-TB) patients experience disproportionately worse mental health, with implications for adherence, outcomes, and families. Comprehensive assessments of comorbid depression/anxiety and related factors remain limited. This study aimed to assess the prevalence, predictors, and qualitative experiences of depression and anxiety in MDR-TB patients and household contacts. A sequential explanatory mixed methods study was conducted in Gujarat, India, with 403 smear-positive MDR-TB patients and 403 contacts. The quantitative phase administered structured questionnaires on sociodemographic factors, clinical history, depression/anxiety symptoms, and psychosocial stressors (like stigma and social support). Logistic regression models were used. The qualitative phase included in-depth interviews with 30 purposively sampled patients for thematic content analysis. Results were integrated to contextualize quantitative findings. High rates of depression (37.5%, n = 151) and anxiety (45.2%, n = 182) were documented among the MDR-TB patients, significantly greater than household contacts (20.1%, n = 81and 25.1%, n = 101, respectively). For depression, older age (adjusted odds ratio (AOR) 2.03, 95% CI 1.01-4.05), female gender (AOR 2.5, 95% CI 1.1-6.0), divorced/widowed status (AOR 3.8, 95% CI 1.1-8.0), financial constraints, substance abuse (AOR 1.7, 95% CI 1.1-2.7), greater disease severity (AOR 1.8, 95% CI 1.5-2.2), medication side effects (AOR 2.4, 95% CI 1.2-4.6), and perceived stigma (AOR 3.2, 95% CI 1.1-5.3) emerged as significant risk factors. For anxiety, significant predictors were less social support (AOR 0.81, 95% CI 0.71-0.86), higher perceived stigma (AOR 2.2, 95% CI 1.1-6.3), greater disease severity (AOR 2.6, 95% CI 1.3-4.0), and more medication side effects (AOR 3.3, 95% CI 1.1-5.5). Prominent themes included psychological impacts like depression and anxiety, experiences of stigma and caretaking challenges, and recommendations for comprehensive patient support services. MDR-TB patients experience a substantially higher dual disease burden of depression and anxiety, elevating the risk for adverse outcomes and transmission. Improving psychosocial support is vital to patient-centric care pathways for vulnerable groups. Mixed methods provide comprehensive evidence to inform integrated physical and mental health services.

Modelling Time to Recovery from Multidrug Resistant Tuberculosis in Southern Ethiopia

Introduction: Multidrug resistant tuberculosis (MDR-TB) is a global heath threat, resistant to key anti-TB drugs. It is ranked among the top 10 causes of death worldwide. Therefore, the current study investigated time to recovery from MDR-TB in southern Ethiopia. Data, Materials and Methods: Restrospective data from selected hospitals in SNNPR (January 2016 to December 2021) were analyzed. A cluster sample of 301 MDR-TB patients (131 NEMMCH, 121 BH, 49 AGH) was considered. Results: Among the 301 cases, 116 (38.5%) were censored. While 185 (61.5%) were recovered. Parametric shared frailty models were employed to account unobserved heterogeneity among the Hospitals and patients and AFT models were employed. the median recovery time of MDR-TB is 22 months. The clustering effect of frailty model was hospitals. Weibull-gamma shared frailty model was appropriate for this data. Conclusion: The final model showed that males have higher recovery rates than females. Extra pulmonary MDR-TB and Urban residency correleted with longer recovery times. The recovery rate increases with increasing baseline weight, education level, and occupation. But, the recovery rate decreases with smoking, co-morbidities, previous drug history, history of TB, and alcohol use Recommendation: All concerned bodies should be cognizant on the risk factors of MDR-TB in SNNP region By providing on early case detection and appropriate treatment of drug-susceptible MDR-TB, since it is essential to shorten the recovery time of MDR-TB patients in line with WHO guidelines

Evaluation of MeltPro Assay in Identification of Second-Line Injectable Drug Resistance in Multidrug-Resistant Tuberculosis Isolates.

We compared the MeltPro assay to whole-genome sequencing (WGS) to investigate the molecular characterization of second-line injectable drug (SLID) resistance in multidrug-resistant tuberculosis (MDR-TB) isolates in Chongqing, China. A total of 122 MDR-TB patient isolates were collected between March 2019 and June 2020 from Chongqing Municipality, China. Conventional drug-susceptibility testing was performed using the proportion method, followed to generate minimum inhibitory concentrations (MICs) of SLIDs determined by microplate alamarblue assay. All strains were subjected to both MeltPro and WGS assays. Among 122 MDR-TB isolates, 30 (24.6%), 22 (18.0%), and 14 (11.5%) were resistant to kanamycin (KM), amikacin (AM), and capreomycin (CM), respectively. Of the 31 SLID-resistant isolates, 24 (77.4%, 24/31) isolates harbored mutations in the rrs gene, with the most prevalent mutations in rrs A1401G (22/24, 91.7%). Mutation in rrs A1401G was associated with high levels of resistance to KM (MIC, ≥40 μg/mL) and AM (MIC, ≥64 μg/mL), but disparities in CM-resistance levels. Using phenotypic drug-susceptibility testing as gold standard, we found that the overall sensitivity of MeltPro and WGS was 87.1% and 90.32% and specificity 100% and 97.8%, respectively. Seven isolates had discordant results between phenotypic and genotypic resistance of SLIDs. MeltPro is a promising diagnostic tool for accurate identification of SLID-resistant MTB isolates with mutations in the rrs and eis genes. There was a disparity between MeltPro with WGS results in the proportion of heterogeneous drug-resistant bacteria with rrs mutation and limited probes. Resistance mechanisms other than genetic mutations will affect the consistency of MeltPro and WGS with phenotypic drug-susceptibility results.