Treatment Outcomes Of Drug-resistant Tuberculosis Research Articles

Diabetes mellitus affects the treatment outcomes of drug-resistant tuberculosis: a systematic review and meta-analysis

BackgroundBoth tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and affect the absorption and metabolism for anti-TB drugs. Drug-resistant TB (DR-TB) with DM make control TB more difficult.MethodsThis study was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. We searched PubMed, Excerpta Medica Database (EMBASE), Web of Science, ScienceDirect and Cochrance Library for literature published in English until July 2022. Papers were limited to those reporting the association between DM and treatment outcomes among DR-TB and multidrug-resistant TB (MDR-TB) patients. The strength of association was presented as odds ratios (ORs) and their 95% confidence intervals (CIs) using the fixed-effects or random-effects models. This study was registered with PROSPERO, number CRD: 42,022,350,214.ResultsA total of twenty-five studies involving 16,905 DR-TB participants were included in the meta-analysis, of which 10,124 (59.89%) participants were MDR-TB patients, and 1,952 (11.54%) had DM history. In DR-TB patients, the pooled OR was 1.56 (95% CI: 1.24–1.96) for unsuccessful outcomes, 0.64 (95% CI: 0.44–0.94) for cured treatment outcomes, 0.63 (95% CI: 0.46–0.86) for completed treatment outcomes, and 1.28 (95% CI: 1.03–1.58) for treatment failure. Among MDR-TB patients, the pooled OR was 1.57 (95% CI: 1.20–2.04) for unsuccessful treatment outcomes, 0.55 (95% CI: 0.35–0.87) for cured treatment outcomes, 0.66 (95% CI: 0.46–0.93) for treatment completed treatment outcomes and 1.37 (95% CI: 1.08–1.75) for treatment failure.ConclusionDM is a risk factor for adverse outcomes of DR-TB or MDR-TB patients. Controlling hyperglycemia may contribute to the favorite prognosis of TB. Our findings support the importance for diagnosing DM in DR-TB /MDR-TB, and it is needed to control glucose and therapeutic monitoring during the treatment of DR-TB /MDR-TB patients.

The Effect of HIV and Antiretroviral Therapy on Drug-Resistant Tuberculosis Treatment Outcomes in Eastern Cape, South Africa: A Cohort Study.

South Africa has a dual high burden of HIV and drug-resistant TB (DR-TB). We sought to understand the association of HIV and antiretroviral therapy status with TB treatment outcomes. This was a retrospective chart review of 246 patients who began treatment at two DR-TB hospitals in Eastern Cape, South Africa between 2017 and 2020. A categorical outcome with three levels was considered: unfavorable, transferred out, and successful. Descriptive statistics and logistic regression were used to compare the individuals without HIV, with HIV and on antiretroviral therapy (ART), and with HIV but not on ART. Sixty-four percent of patients were co-infected with HIV, with eighty-seven percent of these individuals on ART at treatment initiation. The majority (59%) of patients had a successful treatment outcome. Twenty-one percent of patients transferred out, and an additional twenty-one percent did not have a successful outcome. Individuals without HIV had more than three and a half times the odds of success compared to individuals with HIV on ART and more than ten times the odds of a successful outcome compared to individuals with HIV not on ART (OR 3.64, 95% CI 1.11, 11.95; OR 10.24, 95% CI 2.79, 37.61). HIV co-infection, especially when untreated, significantly decreased the odds of treatment success compared to individuals without HIV co-infection.

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

Predictors of unfavourable treatment outcome in patients diagnosed with drug-resistant tuberculosis in the Torres Strait / Papua New Guinea border region.

Drug-resistant tuberculosis (DR-TB) is an ongoing challenge in the Torres Strait Islands (TSI) / Papua New Guinea (PNG) border region. Treatment success rates have historically been poor for patients diagnosed with DR-TB, leading to increased transmission. This study aimed to identify variables associated with unfavourable outcome in patients diagnosed with DR-TB to inform programmatic improvements. A retrospective study of all DR-TB cases who presented to Australian health facilities in the Torres Strait between 1 March 2000 and 31 March 2020 was performed. This time period covers four distinct TB programmatic approaches which reflect Australian and Queensland Government decisions on TB management in this remote region. Univariate and multivariate predictors of unfavourable outcome were analysed. Unfavourable outcome was defined as lost to follow up, treatment failure and death. Successful outcome was defined as cure and treatment completion. In total, 133 patients with resistance to at least one TB drug were identified. The vast majority (123/133; 92%) of DR-TB patients had pulmonary involvement; and of these, 41% (50/123) had both pulmonary and extrapulmonary TB. Unfavourable outcomes were observed in 29% (39/133) of patients. Patients living with human immunodeficiency virus, renal disease or diabetes (4/133; 4/133; 3/133) had an increased frequency of unfavourable outcome (p <0.05), but the numbers were small. Among all 133 DR-TB patients, 41% had a low lymphocyte count, which was significantly associated with unfavourable outcome (p <0.05). We noted a 50% increase in successful outcomes achieved in the 2016-2020 programmatic period, compared to earlier periods (OR 5.3, 95% Confidence Interval [1.3, 20.4]). Being a close contact of a known TB case was associated with improved outcome. While DR-TB treatment outcomes have improved over time, enhanced surveillance for DR-TB, better cross border collaboration and consistent diagnosis and management of comorbidities and other risk factors should further improve patient care and outcomes.

Drug-Resistant Tuberculosis Treatment Outcomes among Children and Adolescents in Karachi, Pakistan.

Significant data gaps exist for children and adolescents with drug-resistant (DR) TB, particularly from high TB incidence settings. This report provides a descriptive analysis of programmatic outcomes among children and adolescents treated for DR-TB in Pakistan. We extracted programmatic data from January 2014 to December 2019 from a tertiary care hospital with specialised child and adolescent DR-TB services. A physician assessed all children and adolescents (0-19 years) with presumptive DR-TB, including details of exposure to DR-TB, medical history, radiology, and laboratory results. All patients received treatment as per national DR-TB management guidelines based on WHO recommendations. There were 262 treatment episodes for 247 patients enrolled during the study period. The median age of the cohort was 16 years (IQR: 13-18 years) with 16 (6.1%) children being under 5 years; 237 (90.5%) patients had pulmonary TB. The majority of the patients (194 or 74.1%) experienced a favourable treatment outcome and 26 (9.9%) died while on treatment. Female patients (78.5%) were more likely to experience favourable outcomes compared to males (64.7%; chi-sqr p-value = 0.02). We found high rates of favourable outcomes in children and adolescents treated for DR-TB. However, there were few young children in our cohort and there was a considerable gender gap that enhanced efforts to diagnose DR-TB in young children and to elucidate and mitigate the reasons for poor outcomes amongst males.

Impacts of Medical Security Level on Treatment Outcomes of Drug-Resistant Tuberculosis: Evidence from Wuhan City, China.

Drug-resistant tuberculosis (DR-TB) is an increasingly serious global issue. DR-TB has a lower success rate and more severe interruption of treatment than ordinary tuberculosis. Incomplete treatment not only reduces recovery rate in DR-TB patients but also increases the spread of DR-TB. Optimizing medical security policies for DR-TB can reduce the economic burden of patients and can thereby improve treatment success rate. Patients with DR-TB who were registered in Wuhan Center for Tuberculosis Control and Prevention from January 2016 to December 2019 were selected as research subjects. General descriptive statistical analysis methods were used in analyzing patients' treatment outcomes and medical security compensation rate. The binary logistic regression was used in analyzing the impacts of medical security level on treatment outcomes of DR-TB. A total of 409 DR-TB patients were included in the study, and the refusal rate was 12.47%. The treatment success rate was only 37.09% for patients who started treatment and had treatment outcomes. The total out-of-pocket expenses (OOPs) per capita for DR-TB patients were 13,005.61 Chinese yuan. The outpatient effective compensation ratio (ECR) of DR-TB patients was only 51.04%. The outpatient ECR of DR-TB with subsidies of public health projects (SPHPs) were nearly 80% higher than those without SPHP. high outpatient ECR helped optimize treatment outcomes (P < 0.001, OR = 1.038). The inpatient ECR had no effect on patients' treatment outcomes (P = 0.158, OR = 0.986). Many DR-TB patients did not receive complete treatment. The key breakthrough point in improving DR-TB treatment outcomes is to optimize the outpatient medical insurance compensation policy. Including the costs of DR-TB in expenses for severe diseases in outpatient care is recommended, and financial investment should be appropriately increased to ensure the high coverage ratio of subsidies for public health projects.

Comparison of treatment outcome definitions in drug-resistant tuberculosis patients with high incidence of acquired second-line drug resistance.

Background Simplified drug-resistant tuberculosis (DR-TB) treatment outcome definitions, mostly centred around receipt of treatment and sputum culture status at 6 months after treatment initiation, have been proposed, but have not been widely evaluated in resource-limited settings. Objectives To compare DR-TB treatment outcomes, as defined by the World Health Organization (WHO) at the time of treatment, with simplified definitions. Methods We performed retrospective folder reviews of a cohort of 246 South African DR-TB patients, most of whom developed second-line drug resistance. Sequential treatment outcomes were assigned retrospectively using both simplified Tuberculosis Network European Trials Group (TBNET)-based and 2013 WHO-based definitions. Results Of 246 patients, 40% were HIV-positive, and 88% developed second-line drug resistance. Patients were observed for a median of 38 (interquartile range 24 - 63) months from DR-TB treatment initiation. Using WHO-based definitions, 93% of patients had >1 sequential outcome, whereas with simplified definitions, 25% of patients had >1 outcome. Fewer outcomes of cure (3% v. 9%) and more outcomes of treatment failure (42% v. 22%) were assigned using simplified definitions. Conclusion Simplified outcome definitions applied to real-world patients with long, often complex treatment histories resulted in underestimating cures and overestimating treatment failures compared with WHO-based definitions. Simplified definitions may identify more individuals at higher risk for treatment failure than WHO-based definitions, but without consistent programmatic follow-up it may be difficult to distinguish cure, failure and loss to follow-up.

Impacts of clofazimine on the treatment outcomes of drug-resistant tuberculosis

BackgroundThe purpose of this research was to evaluate the effect of clofazimine on drug-resistant tuberculosis treatment outcomes. MethodsA systematic search was conducted in the PubMed, Web of Science and EMBASE databases to identify eligible studies published up to July 10, 2021. The search terms were as follows: “clofazimine,” “tuberculosis,” “multidrug resistant tuberculosis” or “extensively drug resistant tuberculosis” and their synonyms or similar words. Two researchers independently screened the titles, abstracts, and full texts for inclusion. Meta-analysis was performed with Stata version 16.0 (Stata Corp., College Station, Texas, USA). Risk ratios (RRs) with 95% CIs were calculated to evaluate the treatment outcome. ResultsEight studies including 3219 participants were included in the meta-analysis. The meta-analysis found that the rates of treatment completion was higher in patients receiving clofazimine-containing regimens than in those not receiving clofazimine-containing regimens (RR: 1.185 (1.060–1.325), P = 0.003). Significant reduction in treatment failure (RR: 0.598 (0.473–0.756), P < 0.001) was found in the clofazimine treatment group. The subgroup analyses of randomized controlled trials (RCTs) found a higher rates of favorable outcomes, treatment completion and cure in the clofazimine group than in the control group (RR: 1.203 (1.029–1.407), P = 0.020; RR: 3.167 (2.043–4.908), P < 0.001; and RR: 1.251 (1.031–1.518), P = 0.023, respectively). Patients receiving clofazimine had a lower risk of treatment failure than those not receiving clofazimine (RR: 0.529 (0.454–0.616), P < 0.001). However, clofazimine treatment did not have a statistically significant effect on all-cause mortality in RCTs. ConclusionsThis study demonstrated that compared with patients who do not receive clofazimine, this drug has the potential to achieve a higher favorable outcome, treatment completion and cure rates, and a lower treatment failure risk among drug-resistant tuberculosis cases.

Impact of Treatment Supporters on the Treatment Outcomes of Drug Resistant-Tuberculosis (DR-TB) Patients: A Retrospective Cohort Study.

Background: Drug resistant-tuberculosis (DR-TB) patients are provided universal drug susceptibility testing (UDST), anti-TB drugs for the treatment of DR-TB, nutritional support (Nikshay Poshan Yojana - the financial incentive of rupees five hundred per month for each notified DR-TB patient for the duration for which the patient is on anti-TB drugs) by the Government of India.Methods: This retrospective cohort record-based study was conducted in DR-TB patients. Some 1095 DR-TB patients who have initiated treatment at Nodal DR-TB Centre, Darbhanga Medical College and Hospital (DMCH), Darbhanga, and continued their anti-TB drugs at home blocks were followed till their treatment outcome was known. Data were analyzed by statistical experts of DMCH.Results: Treatment supporters comprised 688 (62.83%) females and 407 (37.17%) males. Different types of treatment supporters noted were accredited social health activists (ASHAs) 622 (56.80%), family members 365 (33.33%), and community health workers 108 (09.86%). Treatment outcome as transfer out was observed in 08 (1.29%), 10 (2.74%), and 13 (12.03%) cases among ASHAs, family members, and community health workers, respectively [statistically significant (p < 0.0001)].Conclusion: ASHAs proved to be the best treatment supporters in comparison to both family members and community health workers for multi-drug resistant TB (MDR/RR-TB) patients.

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BackgroundPeople with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India.MethodsThis is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care.ResultsDuring the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0–36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014).ConclusionIn our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Treatment outcomes of drug-resistant tuberculosis in people living with HIV in Odesa province, Ukraine, 2014-2016.

Odesa province has the highest TB/HIV prevalence in Ukraine, exceeding the total prevalence in the country by 3 times. The objective of this study was to investigate the unfavorable treatment outcomes and associated factors in patient with drug-resistant (DR) TB in people living with HIV (PLH) in Odesa. A cohort study with secondary data analysis was conducted among 373 PLH with confirmed pulmonary DR TB for 2014-2016. About 2/3rd of the cohort were males from urban areas. Mean age and CD4 counts were 39 and 203, respectively. The overall treatment success was 44.2% with the most unfavorable treatment outcomes being observed in extensively and pre-extensively drug resistant (XDR and PreXDR) TB. The mean time between the results of GeneXpert (manufactured by Cepehid) and DR TB treatment based on GeneXpert was 1.3 days. However, the mean time between DR TB treatment based on GeneXpert and results of drug susceptibility test (DST) was 37.0 days referring to a late reporting of DST and to a late adjustment of previously prescribed treatment. The factors associated with the treatment unfavorable outcome included XDR and Pre-XDR TB, lack of antiretroviral treatment (ART), contrimoxazole preventive therapy (CPT) and CD4 test. The rate of successful DR TB treatment in PLH in Odesa remains low. The delayed reporting of DST contributes to lack of timely adjusted treatments. XDR and Pre-XDR TB, lack of ART and CPT are associated with unfavorable treatment outcomes. Additional studies would help to understand the temporal relationship between CD4 test and treatment outcomes.

Impacts of social support on the treatment outcomes of drug-resistant tuberculosis: a systematic review and meta-analysis

ObjectiveTo assess the effectiveness of social support on treatment success promotion or lost to follow-up (LTFU) reduction for patients with drug-resistant tuberculosis (DR-TB).DesignWe searched Pubmed, Web of Science, Embase, Scopus...

Treatment outcomes of drug-resistant tuberculosis in the Netherlands, 2005\u20132015

BackgroundSince in low incidence TB countries population migration and complex treatment of drug-resistant tuberculosis (DR-TB) patients are major issues, we aimed to analyse patient risk factors associated with the incidence of poor outcome of TB treatment among DR-TB patients in the Netherlands.MethodsThis retrospective cohort study included adult patients with confirmed DR-TB treated from 2005 to 2015. We obtained data from a nationwide exhaustive registry of tuberculosis patients in the Netherlands. Predictors for unsuccessful TB treatment (defaulted and failed treatment) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 10,303 registered TB patients, 545 patients with DR-TB were analysed. Six types of DR-TB were identified from the included patients, i.e. isoniazid mono- or poly-resistance (68%); rifampicin mono- or poly-resistance (3.1%); pyrazinamide mono-resistance (8.3%); ethambutol mono-resistance (0.1%); multidrug-resistance (18.9%); and extensively drug-resistance (0.7%). The majority of patients were foreign-born (86%) and newly diagnosed TB (89%) patients. The cumulative incidence of unsuccessful treatment and mortality were 5 and 1%, respectively. Among all DR-TB cases, patients with Multi Drug-Resistant Tuberculosis (MDR-TB) (OR 4.43; 95%CI 1.70–11.60) were more likely to have unsuccessful treatment, while miliary and central nervous system TB (OR 15.60; 95%CI 2.18–111.52) may also be predictors for TB mortality. Additionally, patients with substance abuse and homelessness tend to have unsuccessful treatment.ConclusionsIn recent years, we identified a low incidence of DR-TB as well as the poor outcome of DR-TB treatment. The majority of cases were primary drug-resistant and foreign-born. To further improve treatment outcome, special attention should be given to the high-risk DR-TB patients.

What will it take to eliminate drug-resistant tuberculosis?

Drug-resistant tuberculosis (DR-TB) is challenging to diagnose, treat, and prevent, but this situation is slowly changing. If the world is to drastically reduce the incidence of DR-TB, we must stop creating new DR-TB as an essential first step. The DR-TB epidemic that is ongoing should also be directly addressed. First-line drug resistance must be rapidly detected using universal molecular testing for resistance to at least rifampin and, preferably, other key drugs at initial TB diagnosis. DR-TB treatment outcomes must also improve dramatically. Effective use of currently available, new, and repurposed drugs, combined with patient-centered treatment that aids adherence and reduces catastrophic costs, are essential. Innovations within sight, such as short, highly effective, broadly indicated regimens, paired with point-of-care drug susceptibility testing, could accelerate progress in treatment outcomes. Preventing or containing resistance to second-line and novel drugs is also critical and will require high-quality systems for diagnosis, regimen selection, and treatment monitoring. Finally, earlier detection and/or prevention of DR-TB is necessary, with particular attention to airborne infection control, case finding, and preventive therapy for contacts of patients with DR-TB. Implementing these strategies can overcome the barrier that DR-TB represents for global TB elimination efforts, and could ultimately make global elimination of DR-TB (fewer than one annual case per million population worldwide) attainable. There is a strong cost-effectiveness case to support pursuing DR-TB elimination; however, achieving this goal will require substantial global investment plus political and societal commitment at national and local levels.

Treatment outcomes of drug resistant tuberculosis patients in Morocco: multi-centric prospective study

BackgroundDrug resistant tuberculosis is a major public health problem in Morocco and worldwide. Treatment outcome of drug resistant tuberculosis is poor and requires a long period of treatment with many toxic and expensive antituberculosis drugs. The aim of this study is to evaluate treatment outcomes of drug resistant tuberculosis and to determine predictors of poor treatment outcomes in a large region of Morocco.MethodsIt is a multi-centric observational cohort study conducted from January 01, 2014 to January 01, 2016. A questionnaire was established to collect data from clinical charts of patients with confirmed resistant TB. The study was carried out in all the 11 centers located in the Rabat-Salé-Kénitra region of Morocco where drug resistant tuberculosis is treated. Treatment outcomes were reported and the definitions and classifications of these outcomes were defined according to the WHO guidelines. Univariate and multivariate logistic regression were conducted to determine factors associated with poor drug resistant tuberculosis treatment outcomes in Morocco.ResultsIn our study, 101 patients were treated for drug resistant tuberculosis between January 01, 2014 and January 01, 2016. Patients’ age ranged from 9.5 to70 years; 72patients (71.3%) were male and 80 patients (79.2%) were living in urban areas. Thirty two patients were smokers, 74 patients had multidrug-resistant tuberculosis, 25 patients had rifampicin resistance and 2 patients had isoniazid resistance. Treatment outcomes of tuberculosis patients were as follows: 45 patients were cured (44.5%), 9 completed treatment (8.9%), 5 patients died before completing the treatment, 35 patients were lost to follow up (34.6%) and 7 patients had treatment failure. In the multivariate analysis, being a smoker is an independent risk factor for poor treatment outcomes, (p-value = 0.015, OR = 4.355, IC [1.327–14.292]).ConclusionTreatment success outcomes occurred in more than half of the cases, which is lower than the World Health Organization target of at least a 75% success rate. A significant number of patients abandoned their treatment before its completion. These dropouts are a serious public health hazard that needs to be addressed urgently.

Impact of Xpert MTB/RIF and decentralized care on linkage to care and drug-resistant tuberculosis treatment outcomes in Johannesburg, South Africa

BackgroundIn 2011, South Africa improved its ability to test for rifampicin-resistant TB (RR-TB) by introducing GeneXpert MTB/RIF. At the same time, the South African National TB program adopted a policy decentralized, outpatient treatment for drug resistant (DR-) TB. We aim to analyze the impact of these changes on linkage to care and DR-TB treatment outcomes.MethodsWe retrospectively matched adult patients diagnosed with laboratory-confirmed RR-TB in Johannesburg from 07/2011–06/2012 (early cohort) and 07/2013–06/2014 (late cohort) with records of patients initiating DR-TB treatment at one of the city’s four public sector treatment sites. We determine the proportion of persons diagnosed with RR-TB who initiated DR-TB treatment and report time to treatment initiation (TTI) before and after the implementation of Xpert MTB/RIF roll-out in Johannesburg, South Africa. We conducted a sub-analysis among those who initiated DR-TB treatment at the decentralized outpatient DR-TB centers to determine if delays in treatment initiation have a subsequent impact on treatment outcomes.ResultsFive hundred ninety four patients were enrolled in the early cohort versus 713 in the late cohort. 53.8 and 36.8% of patients were diagnosed with multi-drug resistant TB in the early and late cohorts, respectively. The proportion of RR-TB confirmed cases diagnosed by Xpert MTB/RIF increased from 43.4 to 60.5% between the early and late cohorts, respectively. The proportion who initiated treatment increased from 43.1% (n = 256) to 60.3% (n = 430) in the late cohort. Pre-treatment mortality during the early and the late cohort reduced significantly from 17.5 to 5.8% while lost to follow-up remained high.Although TTI reduced by a median of 19 days, from 33 days (IQR 12–52) in the early cohort to 14 days (IQR 7–31) in the late cohort, this did not translate to improved treatment outcomes and we found no difference in terms of treatment success or on-treatment mortality for those that initiated without delay vs. those that deferred initiation.ConclusionPre-treatment mortality reduced significantly during late Xpert MTB/RIF coverage but there was no significant difference after treatment was initiated. Despite improvements there is still a significant diagnosis and treatment gap for patients diagnosed with RR-TB and improving treatment outcomes remains critical.

Did diabetes mellitus affect treatment outcome in drug-resistant tuberculosis patients in Pakistan from 2010 to 2014?

Settings: All hospitals managing drug-resistant tuberculosis (DR-TB) according to national guidelines in Pakistan. Objectives: To assess the effect of diabetes mellitus (DM) and factors associated with unfavourable outcomes in DR-TB. Methods: A cross-sectional study based on a retrospective record review of patients enrolled on DR-TB treatment from 2010 to 2014 in Pakistan. DR-TB data reported to Pakistan's National TB Control Programme on a monthly basis were used for the study. Result: Among 5811 patients enrolled on second-line drugs, 8.8% had DM. Overall, 68.9% had favourable outcomes. No association was found between DM and DR-TB treatment outcomes (risk ratio 0.90, 95%CI 0.74-1.05). Unfavourable outcomes were more frequent among DR-TB patients with human immunodeficiency virus (HIV) co-infection (OR 11.58, 95%CI 2.20-60.72), extensively drug-resistant TB patients (OR 5.36, 95%CI 1.00-28.72), patients with exposure to both first-line and second-line anti-tuberculosis drugs (OR 2.45, 95%CI 1.21-4.97) and those with a previous history of treatment in the private sector (OR 1.53, 95%CI 1.16-2.02). Conclusion: Although there were limitations to correctly measuring DM and its management, DM appears not to be a risk factor for unfavourable outcomes in DR-TB patients in our study. DR-TB and HIV co-infection, second-line drug resistance and history of treatment in the private sector were nevertheless more frequently associated with adverse outcomes.

Opportunities and Challenges for Host-Directed Therapies in Tuberculosis.

Tuberculosis (TB) ranks alongside the human immunodeficiency virus (HIV) as cause of death due to an infectious disease. Recently, host-targeted therapies (HDT) have gained attention as a means to shorten the course of treatment of drug-sensitive TB, improve treatment outcomes of drug-resistant TB and generally improve the efficacy and preserve or restore lung architecture of TB patients. It has been suggested that supplementing anti-TB therapy with host response modulators will augment standard TB treatment by overcoming antibiotic resistance in pathogenic strains of Mycobacterium tuberculosis (Mtb) and related species, thus aiding in killing non-replicating bacilli. The aim of this review is to examine pulmonary delivery strategies that can enhance the safety as well as efficacy of HDT against pulmonary TB. We reviewed literature in the public domain and revisited our own results on inhaled HDT to arrive at broad conclusions. HDT can be viewed as a strategy to evoke one or more of the following macrophage responses: (i) soluble, intracellular factors such as free radicals and antimicrobial peptides; (ii) soluble extracellular signals like cytokines, chemokines, prostaglandins, lipids, etc.; (iii) organelles and assemblies such as phagolysosomes or the inflammasome; (iv) Autophagy, via mTOR/S6 Kinase; and (v) apoptosis via caspases, bcr/abl products, etc. All of these may be optimally addressed using drugs approved for other uses. Deployment of HDT in TB may be optimally achieved through macrophage-targeted inhaled delivery systems.

Diagnosis and management of drug-resistant tuberculosis in South African adults

Detection of drug-resistant tuberculosis (DR-TB) increases each year in South Africa (SA). Most cases result from airborne transmission of already resistant TB strains. Epidemic control relies on rapid diagnosis and initiation of effective treatment to reduce the period of infectiousness and ongoing transmission. The rapid diagnostic test, Xpert MTB/RIF, has replaced smear microscopy for routine screening of all cases of presumptive TB in SA. Xpert also detects rifampicin (RIF) resistance, an indicator of more extensive drug resistance, allowing rapid initiation of effective secondline treatment. Definitive diagnosis of DR-TB relies on laboratory confirmation of MTB, along with drug-susceptibility testing (DST) using culture-based (phenotypic) and/or molecular (genotypic) techniques. A standardised treatment regimen, consisting of five (or six) drugs (pyrazinamide, (ethambutol), kanamycin, moxifloxacin, ethionamide, terizidone), is offered to individuals following initial diagnosis of RIF resistance. Treatment regimens are individualised if and when molecular mutation details and second-line DST results indicate more extensive second-line drug resistance. DR-TB treatment outcomes are poor owing to death, and interruption and failure of current treatment. Reliable access to newer, more effective drugs within shorter, more tolerable regimens is desperately needed to improve the chance of a cure for DR-TB patients.

Drug-Resistant Tuberculosis Treatment Complicated by Antiretroviral Resistance in HIV Coinfected Patients: A Report of Six Cases in Lesotho

Treating drug-resistant tuberculosis (DR-TB) is particularly challenging in high human immunodeficiency virus (HIV) prevalence settings. Neither antiretroviral resistance testing nor viral load monitoring is widely available in sub-Saharan Africa, and antiretroviral resistance can complicate the clinical management for DR-TB/HIV coinfected patients. We describe six cases of antiretroviral resistance in DR-TB patients with HIV coinfection in Lesotho. Two patients died before or immediately after antiretroviral resistance was detected by genotyping; the remaining four patients were switched to effective antiretroviral therapy (ART) regimens. Favorable DR-TB treatment outcomes in coinfected patients require successful management of their HIV infection, including treatment with an effective ART regimen. Coinfected patients undergoing DR-TB treatment may require closer monitoring of their response to ART, including routine viral load testing, to ensure that they receive an effective ART regimen concurrent with DR-TB treatment.