Clinical characteristics and treatment outcome of multidrug-resistant pulmonary tuberculosis complicated with diabetes mellitus

The steadily growing epidemic of diabetes mellitus poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between diabetes mellitus and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the diabetes mellitus-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: (i) whether, when and how to screen for TB in patients with diabetes mellitus and vice versa; (ii) the impact of diabetes mellitus and non-diabetes mellitus hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; (iii) implementation and evaluation of the tuberculosis 'DOTS' model for diabetes mellitus management; and (iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A(1c) (HbA(1c)) for patients with diabetes mellitus. Implementation of this research agenda will benefit the control of both diseases.

The impact of HIV viral suppression on multidrug resistant tuberculosis (MDR-TB) treatment outcomes among people with HIV (PWH) has not been clearly established. Using secondary data from a cluster-randomized clinical trial among people with MDR-TB in South Africa, we examined the effects of HIV viral suppression at MDR-TB treatment initiation and throughout treatment on MDR-TB outcomes among PWH using multinomial regression. This analysis included 1479 PWH. Viral suppression (457, 30.9%), detectable viral load (524, 35.4%), or unknown viral load (498, 33.7%) at MDR-TB treatment initiation were almost evenly distributed. Having a detectable HIV viral load at MDR-TB treatment initiation significantly increased risk of death compared to those virally suppressed (relative risk ratio [RRR] 2.12, 95% CI 1.11–4.07). Among 673 (45.5%) PWH with a known viral load at MDR-TB outcome, 194 (28.8%) maintained suppression, 267 (39.7%) became suppressed, 94 (14.0%) became detectable, and 118 (17.5%) were never suppressed. Those who became detectable (RRR 11.50, 95% CI 1.98–66.65) or were never suppressed (RRR 9.28, 95% CI 1.53–56.61) were at significantly increased risk of death (RRR 6.37, 95% CI 1.58–25.70), treatment failure (RRR 4.54, 95% CI 1.35–15.24), and loss to follow-up (RRR 7.00, 95% CI 2.83–17.31; RRR 2.97, 95% CI 1.02–8.61) compared to those who maintained viral suppression. Lack of viral suppression at MDR-TB treatment initiation and failure to achieve or maintain viral suppression during MDR-TB treatment drives differences in MDR-TB outcomes. Early intervention to support access and adherence to antiretroviral therapy among PWH should be prioritized to improve MDR-TB treatment outcomes.

The impact of HIV viral suppression on multidrug resistant tuberculosis (MDR-TB) treatment outcomes among people with HIV (PWH) has not been clearly established. Using secondary data from a cluster-randomized clinical trial among people with MDR-TB in South Africa, we examined the effects of HIV viral suppression at MDR-TB treatment initiation and throughout treatment on MDR-TB outcomes among PWH using multinomial regression. This analysis included 1479 PWH. Viral suppression (457, 30.9%), detectable viral load (524, 35.4%), or unknown viral load (498, 33.7%) at MDR-TB treatment initiation were almost evenly distributed. Having a detectable HIV viral load at MDR-TB treatment initiation significantly increased risk of death compared to those virally suppressed (relative risk ratio [RRR] 2.12, 95% CI 1.11-4.07). Among 673 (45.5%) PWH with a known viral load at MDR-TB outcome, 194 (28.8%) maintained suppression, 267 (39.7%) became suppressed, 94 (14.0%) became detectable, and 118 (17.5%) were never suppressed. Those who became detectable (RRR 11.50, 95% CI 1.98-66.65) or were never suppressed (RRR 9.28, 95% CI 1.53-56.61) were at significantly increased risk of death (RRR 6.37, 95% CI 1.58-25.70), treatment failure (RRR 4.54, 95% CI 1.35-15.24), and loss to follow-up (RRR 7.00, 95% CI 2.83-17.31; RRR 2.97, 95% CI 1.02-8.61) compared to those who maintained viral suppression. Lack of viral suppression at MDR-TB treatment initiation and failure to achieve or maintain viral suppression during MDR-TB treatment drives differences in MDR-TB outcomes. Early intervention to support access and adherence to antiretroviral therapy among PWH should be prioritized to improve MDR-TB treatment outcomes.

Tuberculosis (TB) treatment success rates are high in China, but there are still a considerable number of cases who have unfavourable treatment outcomes (UTO). We aimed to determine the proportion of TB patients with UTO and to assess whether baseline characteristics that included glycaemic status [normal fasting blood glucose (FBG), transient hyperglycaemia and diabetes mellitus (DM)] and vitamin D status were associated with UTO. Prospective cohort study conducted between November 2015 and July 2016 at six clinics within routine TB services in Jilin province, where persons with TB were consecutively recruited. Data analysis was performed using the chi-squared test and multivariate logistic regression. Of the306 recruited TB patients, 96 (31.4%) had smear-positive pulmonary TB, 187 (61.1%) had smear-negative pulmonary TB and 23 (7.5%) had extrapulmonary TB (EPTB). Of these, 95 (31.1%) had normal blood glucose, 83 (27.1%) had transient hyperglycaemia and 128 (41.8%) had DM. 227 (74.2%) patients had vitamin D deficiency/severe deficiency. There were 125 (40.8%) patients with UTO of whom the majority were lost to follow-up (57.6%) or not evaluated (28.8%). UTO was significantly associated with smear-negative pulmonary TB (P=0.009), EPTB (P<0.001) and DM (P=0.007). The proportion of TB patients with UTO increased with smear-negative pulmonary TB, EPTB and DM. TB programmes need to pay more attention to these issues and ensure intensive patient support to those at risk and early detection of DM.

There is a high burden of both diabetes (DM) and tuberculosis (TB) in China, and this study aimed to assess feasibility and results of screening patients with TB for DM within the routine healthcare setting of six health facilities. Agreement on how to screen, monitor and record was reached in May 2011 at a stakeholders' meeting, and training was carried out for staff in the six facilities in July 2011. Implementation started in September 2011, and we report on 7 months of activities up to 31 March 2012. There were 8886 registered patients with TB. They were first asked whether they had DM. If the answer was no, they were screened with a random blood glucose (RBG) followed by fasting blood glucose (FBG) in those with RBG ≥ 6.1 mm (one facility) or with an initial FBG (five facilities). Those with FBG ≥ 7.0 mm were referred to DM clinics for diagnostic confirmation with a second FBG. Altogether, 1090 (12.4%) patients with DM were identified, of whom 863 (9.7%) had a known diagnosis of DM. Of 8023 patients who needed screening for DM, 7947 (99%) were screened. This resulted in a new diagnosis of DM in 227 patients (2.9% of screened patients), and of these, 226 were enrolled to DM care. In addition, 575 (7.8%) persons had impaired fasting glucose (FBG 6.1 to <7.0 mm). Prevalence of DM was significantly higher in patients in health facilities serving urban populations (14.0%) than rural populations (10.6%) and higher in hospital patients (13.5%) than those attending TB clinics (8.5%). This pilot project shows that it is feasible to screen patients with TB for DM in the routine setting, resulting in a high yield of patients with known and newly diagnosed disease. Free blood tests for glucose measurement and integration of TB and DM services may improve the diagnosis and management of dually affected patients.

Background: Despite the predictor role of the body weight variation on multidrug-resistant tuberculosis (MDR-TB) treatment outcome, little data are available to corroborate this finding. We aimed to study the course of weight in patients with MDR-TB, to identify subgroups of weight evolutions, and to determine factors that influence these evolutions. Methods: Patients treated with a shorter MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 from three major drug-resistance TB centres in Guinea, who had rifampicin resistance, and who were cured or died were analysed. Patients were seen monthly until the end of treatment. Clinical outcome was the Body Mass Index (BMI). We used a linear mixed model to analyze the course of BMI and a latent class mixed model to identify subgroup of BMI evolutions. Findings: Of 232 patients treated for MDR-TB during the study period, only 165 (71%) patients who were cured or died were analysed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3 - 8 visits). Monthly BMI increase was 0·24 (SE 0·02) per kg/m2. Factors that associated with faster BMI progression were cured to MDR-TB treatment (0·24 [SE 0·09] per kg/m2; p = 0·0205), and the absence of lung cavities on X-ray (0·18 [0·06] per kg/m2; p = 0·0068). Two subgroups of BMI evolution were identified: Rapid BMI (n = 121; 85%) and Slow BMI evolution (n = 22; 15%). Patients in the slow increasing BMI group were mostly female (68%) without history of TB treatment (41%) with most severe clinical condition at baseline, characterized by a higher frequency of symptoms including HIV infection (59%), depression (18%), dyspnea (68%), nausea (23%), poor adherence to MDR-TB treatment (64%), lower platelets count, and higher liver SGOT count. These patients had also a longer time to-initial culture conversion delay (log-rank test: p = 0·0087). Interpretation: The available data provide quantitative information on BMI progression of patients with MDR-TB treated with a shorter regimen, and allowed the identification of the subgroup of patients with different BMI evolutions. Furthermore, they emphasize the usefulness of BMI as biomarker to monitor MDR-TB treatment outcome, and allow more efficient use of resources and patient management. Funding Statement: The authors stated: None Declaration of Interests: The authors declare no competing interests in relation with this work. Ethics Approval Statement: The study was approved by the National Ethics Committee for Heath Research (NECHR) attached to the Ministry of Health (Conakry, Guinea).

BackgroundTreatment outcomes of multidrug-resistant tuberculosis (MDR TB) remain poor, particularly for fluoroquinolone-resistant (FQ-R) MDR TB. The aim of this study was to determine treatment outcomes and factors associated with failure of MDR TB treatment, focusing on FQ resistance.MethodsMedical records were retrospectively reviewed of patients diagnosed and treated for MDR TB from January 2005 through December 2017 at Severance Hospital, South Korea.ResultsOf a total of 129 patients with MDR TB, 90 (69.8%) cases were FQ-sensitive (FQ-S) and 39 (30.2%) were FQ-R. FQ-R MDR TB was associated with more severe clinical symptoms, including cavitary lesions and bilateral disease, and tended to require treatment with a greater number of drugs for a longer period of time than FQ-S MDR TB. Linezolid (51.3% vs 7.8%, P < .001), bedaquiline (20.5% vs 8.9%, P = .083), and delamanid (10.3% vs 5.6%, P = .452) were more frequently used in FQ-R cases. Overall, 95/124 patients (76.6%) had favorable treatment outcomes, and we did not detect a significant difference between FQ-R and FQ-S (FQ-S 65/87, 74.7%, vs FQ-R 30/37, 81.1%; P = .443). Old age, low body mass index, smoking, and malignancy—but not FQ resistance or extensively drug-resistant (XDR) TB—were associated with poor clinical outcomes.ConclusionsOverall, 76.6% of MDR TB patients had successful treatment outcomes. Effective drug combinations and appropriate use of new drugs may improve treatment outcomes of FQ-R MDR and XDR TB. Poor clinical outcomes were more related to the patients’ general condition rather than FQ resistance or XDR.

Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District

After several changes in treatment modalities, it is time to re-evaluate treatment outcomes of multidrug-resistant tuberculosis (MDR-TB). To evaluate treatment outcomes, elucidate changes in outcomes over time and identify predictors of treatment success for MDR-TB. Patients diagnosed with MDR-TB at a tertiary referral centre in South Korea between January 2006 and December 2010 were included. Treatment modalities and outcomes were assessed. Predictors of treatment success were analysed using multiple logistic regression. The treatment modalities and outcomes of these patients were compared with those of MDR-TB patients between January 1996 and December 2005. Of the 123 MDR-TB patients diagnosed during the later study period, treatment was successful in 103 (83.7%). Extensive drug resistance (OR 0.31, P = 0.044) and additional resistance to fluoroquinolones (OR 0.23, P = 0.039) were inversely associated with treatment success. The treatment success rate improved from 53.5% in 1996-2000 to 68.8% in 2001-2005 and 83.7% in 2006-2010 (P < 0.001). Improved outcomes were accompanied with more frequent use of later-generation fluoroquinolones and linezolid and less frequent surgical resection. Treatment outcomes for MDR-TB improved at a tertiary referral centre in South Korea. The improvement was associated with more frequent use of later-generation fluoroquinolones and linezolid.

Mortality in multidrug-resistant (MDR) tuberculosis-human immunodeficiency virus (HIV) coinfection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR tuberculosis-HIV-coinfected patients on ART to those in patients with MDR tuberculosis alone. This observational study enrolled culture-confirmed MDR tuberculosis patients with and without HIV in South Africa between 2011 and 2013. Participants received standardized MDR tuberculosis and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival. Among 206 participants, 150 were HIV infected, 131 (64%) were female, and the median age was 33 years (interquartile range [IQR], 26-41). Of the 191 participants with a final MDR tuberculosis outcome, 130 (73%) were cured or completed treatment, which did not differ by HIV status (P = .50). After 2 years, CD4 count increased a median of 140 cells/mm3 (P = .005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; P = .34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm3 (adjusted hazards ratio, 15.6; 95% confidence interval, 4.4-55.6). Survival and treatment outcomes among MDR tuberculosis-HIV individuals receiving concurrent ART approached those of HIV-uninfected patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm3. These findings provide critical evidence to support concurrent treatment of MDR tuberculosis and HIV.

Introduction: multidrug-resistant tuberculosis (MDR-TB) defined as resistance to isoniazid and rifampicin, has become a major threat to the control of TB across the globe. This study aimed to determine the risk factors and treatment outcomes of Drug-resistant tuberculosis (DR-TB) patients attending Ndola Teaching Hospital (NTH) in Ndola, Zambia. Methods: we conducted a case control study among DR-TB patients treated at NTH from 2018 - 2020. Medical records of selected MDR-TB cases and drug susceptible TB controls were included. Treatment outcomes of MDR-TB patients were recorded. The multivariable logistic regression was used to evaluate associations between risk factors and MDR-TB infection. Odds ratios and their 95% confidence intervals were reported. Results: the mean age for the study was 36.67±9.94, and males were the majority 156(70.9%). Those with HIV were 123(55.9%), and contact with DR-TB patients were 61(27.7%). A total of 110 cases and 110 controls were selected for this study. The multivariable logistic regression model indicated a strong association between a family size of 1-5 and occurrence of MDR-TB (aOR (adjusted odds ratio): 1.44, 95% CI (confidence interval), 0.74-2.79; p=0.028*). There was also a strong association between contact with TB patient and MDR-TB (aOR: 1.67, 95% CI 0.56-4.92, p=0.033*). The analysis indicated that living in the rural area had a negative association with MDR-TB development (aOR: 0.42, 95% CI 0.19- 0.91, p=0.025*). There was also a negative association between history of previous treatment and developing MDR-TB (aOR: 0.32, 95% CI 0.17-0.61, p&lt;0.001*), as well as that between contact with MDR-TB patient and MDR-TB development (aOR: 0.50, 95% CI 0.16-1.52, p=0.010*). The study further found that of the 110 MDR-TB patients treated, 73.6% had a successful treatment outcome, and 26.4% had an unsuccessful treatment outcome. Conclusion: the study found that smaller family size and contact with TB patients were significant risk factors for developing MDR-TB, while living in rural areas, having a history of previous TB treatment, and contact with MDR-TB patients were negatively associated with its occurrence. A notable proportion of unsuccessful treatment outcome of some cases underscores the need for strengthened patient-centered care, adherence support, and equitable access to healthcare across both rural and urban settings.

Background: People with diabetes mellitus (DM) have a higher risk for drug-resistant tuberculosis (DR-TB). DR-TB patients with comorbidity of DM were also vulnerable to experience adverse effects of DR-TB treatment. Management of DR-TB with comorbidity of DM is complicated. Also, DM may affect TB response treatment and cause more adverse effects. Objectives: This study was conducted on DR pulmonary TB (DR-PTB) patients to evaluate the effect of DM on adverse effects, especially renal function impairment and audiology impairment, as well as treatment outcomes due to treatment regimens containing kanamycin. Methods: A retrospective study was conducted from 2016 to 2017 at Dr. Soetomo Hospital. Patients who received DR-TB regimens containing kanamycin were included in this study. HbA1c &gt;7 was used to define DM. The adverse effects in this study were impaired renal function (increased serum creatinine) and audiology impairment. Results: Patients who experienced increased serum creatinine were 28/82 (34.1%) with DM and 20/120 (16.7%) without DM, audiology impairment were 22/82 (26.8%) with DM and 19/120 (15.8%) without DM, and unfavorable outcome were 37/82 (45%) with DM and 46/120 (38%) without DM. Moreover, DM is associated with adverse effects and treatment outcomes. Patients with DM have a risk ratio (RR) for increased serum creatinine, audiology impairment, and unfavorable outcome with RR 2.049 (95% CI: 1.242 – 3.379), RR 1.694 (95% CI: 0.982 – 2.925), and RR 1.177 (95% CI: 0.847 – 1.636), respectively. Conclusions: Diabetes mellitus increases the risk of adverse effects, increased serum creatinine, and audiology impairment. Also, it increases the risk of unfavorable treatment outcomes in patients with DR-PTB who receive DR-TB regimens containing kanamycin.

BackgroundAlthough the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure.MethodsWe reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes.ResultsOf 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52).ConclusionsFavorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.

Background & objectives:The increase in the burden of multidrug-resistant tuberculosis (MDR-TB) is a matter of grave concern. The present study was undertaken to describe MDR-TB treatment outcome trends in Delhi and their epidemiological correlates, to assess the adequacy of treatment records and to also generate evidence towards influencing and improving practices related to the MDR-TB control programme.Methods:A retrospective record-based study (2009-2014) was conducted in three major drug resistance TB treatment centres of Delhi. Treatment outcomes and adverse effects were extracted from the existing programme records including patients’ treatment cards and laboratory registers.Results:A total of 2958 MDR-TB patients were identified from the treatment cards, of whom 1749 (59.12%) were males. The mean (±standard deviation) age was 30.56±13.5 years. Favourable treatment outcomes were reported in 1371 (53.28%) patients, but they showed a declining trend during the period of observation. On binomial logistic regression analysis, patients with age ≥35 yr, male sex and undernourishment (body mass index <18.5) at the time of treatment initiation had a significantly increased likelihood of unfavourable MDR-TB treatment outcome (P<0.001).Interpretation & conclusions:The study showed an increasing burden of MDR-TB patients, especially in the young population with increased risk of transmission posing a major challenge in achieving TB elimination targets.

IntroductionThe emergence of MDR-TB remained a major public health threat particularly in developing countries. With increased prevalence and complexity of treatment, the burden of MDR-TB challenged the country. It is of an important; the epidemiology of drug resistant TB is not well understood. There are few studies conducted to assess the prevalence, determinants and treatment outcome of MDR-TB with inconclusive finding. Therefore, we aimed to conduct a systematic review and meta-analysis on Epidemiology of MDR-TB in Ethiopia, So that policy makers and other stalk holders could have pooled evidence on the problem to make a decision.MethodsThe review was conducted through a systematic literature search of articles published between 1997 and 2017. Five bibliographic databases and libraries: PubMed/Medline, Global Health Database, Embase, the Cochrane Library, and African Index Medicus were used. After cleaning and sorting, analysis was performed using STATA version 11. The pooled rate of MDR-TB prevalence, determinants and treatment outcome was estimated with a random-effects model. Heterogeneity was assessed by the I2 and publication bias through funnel plot.ResultsThe 34 studies that were retained for final analysis enrolled a total of 7461 TB or MDR-TB patients. We found that 2.18% (95% CI 1.44–2.92%) of newly diagnosed and 21.07% (95% CI 11.47–30.67%) of previously treated patients have MDR-TB with overall prevalence of 7.24% (95% CI 6.11–8.37). History of previous treatment is the major determinant (pooled OR = 4.78 (95% CI 3.16–6.39)), while contact history and adherence also contributed. In this review the pooled death computed among 5 articles showed that 12.25% (95% CI 9.39–15.11%) of MDR-TB patients were died in the course of treatment. Complication, drug side effects and HIV infection were the main determinants for the death.Conclusion and recommendationThe prevalence is by far higher than the previous reports. It is mainly associated with history of previous treatment along with contact history. However, the treatment outcomes are comparable with previous studies, yet it is a concern. Comorbidities, drug side effects and HIV sero-positivity were the determinants. Thus, proper treatment of drug susceptible TB and early detection and treatment of MDR-TB before complication develops along with prevention of drug side effect and contacts with MDR-TB cases are very important.