Sputum Smear Conversion Research Articles

Endogenous reactivation cases identified by whole genome sequencing of Mycobacterium tuberculosis: Exploration of possible causes in Latvian tuberculosis patients

BackgroundThe recurrence of tuberculosis (TB) continues to place a significant burden on patients and TB programs worldwide. Repeated TB episodes can develop either due to endogenous reactivation of previously treated TB or exogenous reinfection with a distinct strain of Mycobacterium tuberculosis (Mtb). Determining the precise cause of the recurrent TB episodes and identifying reasons for endogenous reactivation of previously successfully treated patients is crucial for introducing effective TB control measures. MethodsHere, we aimed to provide a retrospective individual analysis of the clinical data of pulmonary TB patients with assumed endogenous infection reactivation based on WGS results to identify the reasons for reactivation. Patient medical files were reviewed to describe the provoking factors for endogenous reactivation. ResultsIn total, 25 patients with assumed endogenous TB reactivation were included in the study group, and 30 patients with one TB episode during the study period were included in the control group. There were no statistically significant differences identified between studied patient groups in patients age (t(53) = −1.53, p = 0.13), body mass index (t(53) = 0.82, p = 0.42), area of residency (χ2(1;55) = 0.015, p = 0.9), employment status (χ2(1;55) = 0.076, p = 0.78) and presence of comorbidities (χ2(1;55) = 3.67, p = 0.78). Study group patients had statistically significantly more frequently positive sputum smear microscopy results (χ2(1;55) = 8.72, p = 0.0031), longer time to sputum smear (t(31) = −2.2, p = 0.036) and sputum culture conversion (W (55) = 198.5, p = 0.0029). Smoking was statistically significantly (χ2(1;55) = 5.77, p = 0.016) more frequently represented among study group patients. The median treatment duration for drug susceptible TB was 6 months in both in the control group (IQR 6–6) and among study group patients (IQR 6–7.75). The median treatment duration for multidrug-resistant TB was 20 months (IQR 17–23) in the control group and 19 months (IQR 16–19) in the study group patients. ConclusionPositive SSM for acid-fast bacteria, delayed time to sputum smear and sputum culture conversion, smoking, and incomplete therapy in the study group patients with multidrug-resistant TB should be considered as potential reasons for reactivation in recurrent TB patient group in our study.

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.

Protocol for the effectiveness of multimonth refill of antituberculosis drugs (MORAD) on treatment success among people with drug-susceptible tuberculosis in rural eastern Uganda: a non-inferiority randomised trial

IntroductionMultimonth dispensing of antituberculosis (TB) drugs reduces frequent visits and costs associated with longer travel distances to a TB clinic. We will evaluate the effectiveness of multimonth dispensing of anti-TB...

Variants of human DECTIN-1 rs16910526 are linked to differential reactive oxygen species production and susceptibility to tuberculosis

BackgroundDectin-1 is a transmembrane receptor that plays a pivotal role in recognising fungi and Mycobacterium tuberculosis (Mtb). A specific variant, DECTIN-1 rs16910526, results in a truncated receptor that disrupts membrane expression and ligand binding and is clinically associated with recurrent cutaneous mycoses. Previous research has clarified the role of Dectin-1 in boosting immune defenses against mycobacteria by enhancing reactive oxygen species (ROS) production in neutrophils (PMNs). Here, we investigated the association between the rs16910526 variant and Dectin-1 expression in PMNs, as well as intracellular ROS production in response to Mtb. Furthermore, we explored the potential link between the rs16910526 gene variant and TB outcomes in Argentina.MethodsDNA was extracted from blood samples obtained from a cohort of 178 TB patients and healthy subjects (HS) in Argentina. PCR amplification and sequencing were performed to identify the rs16910526 variant. Flow cytometry was utilised to assess Dectin-1 expression on the PMN plasma membrane and to measure intracellular ROS levels, as indicated by the oxidation of DHR123 in response to the Mtb antigen.ResultsPMNs carrying the rs16910526 variant exhibited diminished Dectin-1 expression and ROS production in response to Mtb (p < 0.0001). In a case‒control study, the rs16910526 variant had an allelic frequency of 0.112 in TB patients and 0.051 in HS. Notably, 10 out of 88 HS and 18 out of 62 TB patients harboured the variant (odds ratio [OR]: 2.55 [95% CI 1.1–5.9, p = 0.03]), indicating a potential association with TB disease. Furthermore, TB patients with the rs16910526 variant exhibited a delayed sputum smear conversion time (p < 0.004) and 100% positivity for acid-fast bacilli smears (p < 0.00001).ConclusionOur study identified a significant association between the SNP variant rs16910526 in the DECTIN-1 gene and Dectin-1 expression in the PMN, leading to altered ROS production. The higher frequency of this variant in TB patients compared to HS suggests a possible link with susceptibility to TB disease in Argentina.Graphical

Evaluation of time to sputum smear conversion and its association with treatment outcomes among drug-resistant tuberculosis patients: a retrospective record-reviewing study.

Background: This study examined the time to sputum smear and culture conversion and determinants of conversion, as well as variables associated with treatment outcomes among drug-resistant pulmonary tuberculosis (DR-PTB) cases. Methods: The electronic database and written medical records of patients were utilized to assess the sociodemographic, clinical, microbiological, and treatment characteristics and outcomes of study participants. Results: Among 736 patients with pulmonary tuberculosis (PTB), the mean age was 36.5 ± 16.5years, with males comprising 53.4% and a mean weight of 47.76 ± 11.97kg. The median time period for sputum smear conversion and sputum culture conversion was a month. The first-month culture conversion (p < 0.001, aOR = 5.817, and 95% CI = 3.703-9.138) was the determinant of sputum smear conversion and receiver operating curve analysis with AUC = 0.881, 95% CI = 0.855-0.907, and p < 0.001, which showed a high level of predictive ability for the regression model for the initial sputum smear conversion. However, the first-month sputum conversion (p < 0.001, aOR = 7.446, and 95% CI = 4.869-11.388) was attributed to sputum culture conversion, and the model has shown excellent predictive ability for regression with ROC curve analysis demonstrating AUC = 0.862, 95% CI = 0.835-0.889, and p < 0.001. A total of 63.2% of patients showed favorable treatment outcomes, with 63.1% of cases achieving treatment-cured status. The previous use of SLD, history of smoking, duration of illness ≤ 1 year, extensively drug-resistant tuberculosis, and first-month sputum conversion were the variables attributed to favorable treatment outcomes observed in drug-resistant pulmonary tuberculosis cases. ROC curve analysis with AUC = 0.902, 95% CI = 0.877-0.927, and p < 0.001) has shown outstanding ability for regression model prediction for the variables influencing treatment outcomes. Conclusions: Within 2months of treatment, most patients had converted their sputum cultures and sputum smears. The determinants of early sputum smear and sputum culture conversion, as well as favorable treatment outcomes, were identified. These factors should be considered during the design and implementation of effective strategies for drug-resistant tuberculosis control programs.

IJCM_276A: Determinants of Delayed Sputum Conversion among Tuberculosis Patients in Malappuram District: A Case Control Study

Background: Treatment of drug-sensitive TB consists of an intensive phase of 2 months followed by a continuation phase of 4 months. After completion of intensive phase of therapy, sputum AFB smear microscopy is repeated and presence of smear conversion is suggested as a significant early predictor of treatment effectiveness. Delay in sputum conversion will lead to prolongation of the period of time that patients remain contagious. Objectives: To study the determinants of delayed sputum conversion among Tuberculosis patients in Malappuram district Methodology: A Case control study was conducted among tuberculosis patients residing in Malappuram district of Kerala and registered under NTEP in District Tuberculosis Centre (DTC), Manjeri, Malappuram. After satisfying inclusion and exclusion criteria, 90 tuberculosis patients who failed to achieve sputum smear negativity after completion of 2 months of intensive phase multi drug therapy were taken as cases. Another 90 tuberculosis patients those who achieved sputum smear negativity after completion of 2 months of intensive phase therapy were selected as control group. Data was collected by interview method. Results: Patients with lower socio-economic status (OR = 3.59, 95% CI 1.92- 6.73), low BMI or underweight (OR = 1.98, 95% CI 1.1 - 3.6), multiple symptoms (OR= 5.50, 95% CI 1.98 - 15.28), increased duration of symptoms (OR=4.54, 95% 2.24-9.19), co-morbid condition of diabetes mellitus (OR = 2.25, 95% CI 1.24 - 4.09) are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Conclusion: Patients with lower socio-economic status, low BMI or underweight, multiple symptoms, increased duration of symptoms, co-morbid condition of diabetes mellitus are at statistically significant risk of delay in sputum smear conversion after intensive phase of anti-tubercular therapy. Treating physicians and public health experts should give special attention to TB patients with these risk factors.

Negative effects of undernutrition on sputum smear conversion and treatment success among retreatment cases in Uganda: A quasi-experimental study

RationaleThe causal relationship between undernutrition and response to anti-tuberculosis (TB) treatment and TB treatment outcomes among people with retreatment TB is understudied. ObjectiveTo evaluate the effect of undernutrition on treatment success and sputum smear conversion among people with retreatment drug-susceptible TB in Kampala, Uganda. MethodsWe conducted a quasi-experimental study utilizing propensity score weighting among people with retreatment drug-susceptible TB aged ≥ 15 years treated between 2012 and 2022 in Kampala. The primary exposure was undernutrition assessed using the mid-upper arm circumference at the time of TB diagnosis. The primary outcome was treatment success defined as cure or treatment completion at month 6. Sputum smear conversion was the secondary outcome and was measured as a change in sputum smear status from positive to negative at months 2, 5, and 6. We estimated the causal effect of undernutrition on the outcomes using a propensity-score weighted modified Poisson regression model with robust error variance. Measurements and main resultsOf the 605 participants, 432 (71.4 %) were male, 215 (35.5 %) were aged 25–34 years, 427 (70.6 %) had bacteriologically confirmed pulmonary TB, 133 (22.0 %) were undernourished and 398 (65.8 %) achieved treatment success. Of participants with bacteriologically confirmed pulmonary TB, 232 (59.0 %), 327 (59.3 %), and 360 (97.6 %) achieved sputum smear conversion at months 2, 5, and 6, respectively. Undernutrition reduced treatment success (RR 0.42, 95 % CI 0.32–0.55) as well as sputum smear conversion at months 2 (RR 0.45, 95 % CI 0.42–0.49) and 5 (RR 0.46, 95 % CI 0.43–0.51) but not month 6 (RR 0.99, 95 % CI 0.97–1.02). ConclusionUndernutrition negatively impacts treatment outcomes. Therefore, nutritional assessment should be an integral component of TB care, with nutritional counseling and support offered to those undernourished to optimize their TB treatment response and outcomes.

Association of vitamin D with HIV infected individuals, TB infected individuals, and HIV-TB co-infected individuals: a systematic review and meta-analysis.

Vitamin D deficiency (VDD) is a worldwide disease. VDD is also associated with an increased risk of HIV-related comorbidities and mortality, and patients have a tendency to develop active tuberculosis compared to those with latent tuberculosis infection. Vitamin D supplementation may modulate HIV replication, improve TB inflammation and reduce progression of HIV-TB co-infection. We meta-analyzed individual participant data from cohort studies, cross-sectional study, and RCTs of vitamin D in HIV group, TB group, and HIV-TB group. The primary outcomes were differences in vitamin D level and VDD prevalence between three groups, the secondary outcomes were CD4 count, HIV viral load, time to sputum smear conversion, time to culture conversion, relapse, morality, and TB score. For vitamin D levels, the overall mean difference (MD) between HIV group and TB group was -0.21 (95% CI, -20.80-20.38; p = 0.9, I2 = 84%), HIV group and HIV-TB group was 0.87 (95% CI, -11.45-13.20; p = 0.89, I2 = 87%), and TB group and HIV-TB group was 1.17 (95% CI, -5.21-7.55; p = 0.72, I2 = 85%). For vitamin D deficiency prevalence, the overall odds ratio (OR) for HIV group versus TB group was 1.23 (95% CI, 0.46-3.31; p = 0.68; I2 = 70%), HIV group versus HIV-TB group was 1.53 (95% CI, 1.03-2.29; p = 0.04; I2 = 0%), and TB group versus HIV-TB group was 0.85 (95% CI, 0.61-1.20; p = 0.36; I2 = 22%). In HIV-TB group, the overall OR for vitamin D group versus placebo group was 0.78 (95% CI, 0.34-1.67; p = 0.52; I2 = 60%). Our findings indicated that there were no variations in vitamin D levels between three groups. The prevalence of vitamin D deficiency was higher in the HIV-TB group than in the HIV group. Additionally, the administration of vitamin D supplements did not have obvious impact on CD4 count and viral load. Likewise, vitamin D had no effect on time to sputum smear conversion, time to culture conversion, relapse, 12-month morality, and TB score.

VITAMIN C AS AN ADD ON SUPPLEMENTATION TO STANDARD ANTITUBERCULAR TREATMENT IMPROVES SPUTUM SMEAR CONVERSION IN NEWLY DIAGNOSED DRUG SENSITIVE PULMONARY TUBERCULOSIS PATIENTS

Objective: This study was aimed to evaluate the effect of oral supplementation of Vitamin C along with standard anti-tubercular (anti-TB) drugs on the sputum smear conversion in newly diagnosed pulmonary tuberculosis (TB) patients. Methods: This was a prospective, observational study in which 49 newly diagnosed pulmonary TB patients were given oral vitamin C supplementation along with standard anti-TB treatment during the intensive phase (2 months) of the treatment. An examination of the sputum smear at the end of the intensive phase of anti-tubercular treatment was done. At the end of the intensive phase, a comparison was done between the results of the sputum smear examination of the study population and the TB patients of the general population from the same locality who were receiving only standard anti-TB treatment and not add on Vitamin C supplementation. Results: The comparison between the results of the study population (sputum conversion–100%) with those of the general population (sputum conversion–92.47%) shows a significant difference between both populations with p&lt;0.05 (p=0.041). Conclusion: This study showed that Vitamin C supplementation as an add-on therapy to the existing standard anti-TB treatment improves sputum smear conversion and decreases disease activity to a greater extent than routine standard anti-TB treatment alone.

Comparison of Sputum Evaluation Conversion of Pulmonary TB patients with DM and non-DM in High Burden Setting

ABSTRACT&#x0D; Background&#x0D; Tuberculosis (TB) remains a global health problem and is one of the leading causes of death worldwide. By 2022, an estimated 10 million people will suffer from TB worldwide. Based on data from the Global Tuberculosis Report in 2022, Indonesia ranks second as a high-burden country in the world after India. An estimated 1.5 million people die from tuberculosis, becoming the 13th leading cause of death worldwide and the second most deadly infectious disease after COVID-19.&#x0D; Currently, many new cases of TB are influenced by several risk factors, one of which is Diabetes Mellitus (DM). Pulmonary TB is a potential opportunistic infection for people with Diabetes Mellitus. TB patients with DM are at risk of sputum conversion failure after TB treatment, 1.69 times higher risk of treatment failure, 1.24 times higher risk of anti-TB drug resistance, 3.89 times higher risk of relapse, and 4.95 times higher risk of death during treatment compared to TB patients.&#x0D; Aim of Study&#x0D; To evaluate the sputum smear conversion results at the end of the second month of treatment of patients with Tuberculosis with Diabetes Mellitus (TB-DM) and Tuberculosis Non-Diabetes Mellitus (TB-NDM).&#x0D; Methods&#x0D; This research was analytical with a retrospective cohort design by taking secondary data from the Tuberculosis Information System (SITB). The data were recorded in SITB and registered as TB patients undergoing Anti-Tuberculosis Drug treatment and screening for Diabetes Mellitus in all districts in West Nusa Tenggara Province in 2022.&#x0D; Results&#x0D; Among 200 patients with TB in this study, male patients dominated 62% of TB patients. TB patients are mostly found in the age group 46-55 years with 28,5%. Generally, TB patients come from Mataram, with an 18% percentage. Most TB patients were diagnosed using GeneXpert (80,5%). The sputum conversion rate at the end intensive phase in TB-DM patients reached 95%, while in TB-NDM patients, only 85%. The comparative test showed a significant difference between the AFB Sputum Evaluation conversion results between TB patients and those without DM (p-value: 0.018, p&lt;0.05).&#x0D; Conclusion &#x0D; There is a significant difference between the AFB Sputum Evaluation conversion results between TB patients and those without DM.&#x0D; &#x0D; Keywords : Diabetes, diabetes mellitus, sputum conversion, tuberculosis, TB, DM

SOCIO-DEMOGRAPHIC PROFILE AND BODY MASS INDEX OF PATIENTS WITH PULMONARY TUBERCULOSIS AND THEIR TREATMENT OUTCOME IN A TERTIARY CARE CENTRE KERALA

Introduction: Tuberculosis (TB) is a communicable disease that is a major cause of ill health and one of the leading causes of death worldwide. Several socio-demographic factors contributing towards the increasing incidence and development of TB are age, gender, socioeconomic status, smoking, alcoholism, drug addiction, living conditions, literacy, family history, overcrowding, poor sanitation, poor ventilation, malnutrition, occupation. Primary Objectives: To evaluate the socio-demographic profile and body mass index (BMI) of patients with pulmonary tuberculosis and their treatment outcome. Secondary Objectives: 1. To assess the relationship between low SES and new smear positive PTB. 2. To assess malnutrition among diagnosed PTB patients. 3. To know how malnutrition and low SES affect the treatment outcome 4. To assess nutritional status of patients before and after treatment 5. To evaluate the relationship between co morbidity and treatment outcome. Methods: This is a prospective study done in 360 new sputum-positive pulmonary tuberculosis patients attending the department of respiratory medicine, GMC Kannur over 1 year. After full filling the inclusion and exclusion criteria data was collected and the results were organized and analyzed statistically. Results: The total sample size was 360. 29.2%, belonging to 41-50 years with the male preponderance of male: female ratio = 1.7:1. Regarding the socio-demographic profile, 93.3% were natives, and 72.2% were married. 81.9% belonged to the lower caste, 94.7% had nuclear families, with small-sized families of percentage 70, and most of them, 87.2% resided in pucca houses. The majority of cases had a primary level of education and the literacy rate was only 1.9%. 43.3% of Sputum-positive patients were from low SES. Malnutrition (BMI&lt;18.5Kg/m2) was seen in 58% of patients and there was a significant increase in BMI (p&lt; 0.001) after treatment completion. The majority of patients had DM (38.9%).There was statistically significant clearance in CXR after treatment completion (p &lt;0.001). It was found that DM, smoking and CXR shadows can lead to reduced sputum smear conversion and it was statistically significant with statistical significance as follows: DM – OR=0.367,95%CI of OR is 0.181-0.742, p-value- .004, CXR shadows: OR=0.190,95% CI of OR- 0.079-0.460, p value-0.001, current smokers: p value-0.006. Conclusion: In the current study, the majority of patients was having undernutrition (BMI&lt;18.5Kg/m2) and low SES. The nutritional status was improved after treatment completion. Sputum smear conversion at the end of 2 months, which is a key indicator of infectivity, was affected by patients smoking status, DM, and CXR shadow. Hence, education, awareness, smoking cessation, adequate nutritional support, DM control are necessary for control of TB and for achieving the national target.

Glycemic Control Effect on Acid-Fast Bacteria Conversion in Diabetic Patients with Tuberculosis

Background Diabetic people have a 2-3 times higher risk of tuberculosis than non-diabetic people. Immunocompromised conditions due to diabetes increase the risk of therapeutic failure and delayed sputum conversion, which may cause by poor glycemic control. This study was conducted to determine the glycemic control effect on AFB conversion in diabetic patients with tuberculosis. Methods A cross-sectional study has been conducted on 100 diabetic patients with the new emergence of pulmonary tuberculosis. All patients were in intensive phase treatment of tuberculosis for two months at Bhayangkara R. Said Sukanto's Hospital. Data collected from medical records were random blood glucose level, percentage of random blood glucose decrement, HbA1C, and the microscopic AFB sputum smear. Fisher exact test analysis was conducted to determine the effect of random blood glucose level, percentage of blood glucose decrement and HbA1C to AFB smear results using SPSS V25.0 software for Windows with a significance level of 0.05. Results The analysis between glycemic control and AFB sputum smear conversion using random blood glucose, percentage of random blood glucose decrement and HbA1C showed a p-value of 0.000, indicating a significant relationship (p&lt;0.05), so it showed that glycemic control affects AFB sputum smear conversion. Conclusions A significant relationship exists between glycemic control and AFB-negative conversion in patients with DM and TB. RBG showed the best sensitivity and specificity as a glycemic control parameter compared to others.

Early efficacy of individual regimens containing bedaquiline in patients with drug resistant tuberculosis

Objective: To evaluate early efficacy of sputum conversion within 6 months of individual regimens containing bedaquiline in patients with drug resistant tuberculosis. Methods: We conducted a retrospective study among patients with drug resistant tuberculosis who were receiving individual regimens containing bedaquiline. The primary outcome was sputum conversion of both smear and culture within 6 months of treatment. We used medical records of drug resistant tuberculosis patients from January 2020 to December 2021. The study was conducted at Dr. Soetomo Hospital, Indonesia from August to October 2022. Results: In this study, 44 eligible drug resistant tuberculosis patients were initiated on regimens containing bedaquiline. There were 52.3% males and the median age was 45.5 years. The rates of previous treatment (70.5%) and lung cavity (36.4%) were high. The most common companion drugs included clofazimine, cycloserine, levofloxacin, and linezolid. Sputum smear and culture conversion was seen in 79.4% and 82.1% at the 2nd month, respectively. More than 97% patients had smear and culture conversion at the end of 6 months. Conclusions: Among drug resistant tuberculosis patients, individual regimens containing bedaquiline were associated with high rates of smear and culture conversion at the end of 6 months. Early efficacy of regimens containing bedaquiline can be used to predict cure rate at the end of treatment.

Prevention of relapse in drug sensitive pulmonary tuberculosis patients with and without vitamin D3 supplementation: A double blinded randomized control clinical trial.

The immunomodulatory effects of vitamin D are widely recognized and a few studies have been conducted to determine its utility in the treatment of tuberculosis, with mixed results. This study was conducted to see if vitamin D supplementation in patients with active pulmonary tuberculosis (PTB) in the Indian population contributed to sputum smear and culture conversion as well as the prevention of relapse. This randomized double-blind placebo-controlled trial was conducted in three sites in India. HIV negative participants aged 15-60 years with sputum smear positive PTB were recruited according to the Revised National Tuberculosis Control Program guidelines and were randomly assigned (1:1) to receive standard anti-tubercular treatment (ATT) with either supplemental dose of oral vitamin D3 (60,000 IU/sachet weekly for first two months, fortnightly for next four months followed by monthly for the next 18 months) or placebo with same schedule. The primary outcome was relapse of PTB and secondary outcomes were time to conversion of sputum smear and sputum culture. A total of 846 participants were enrolled between February 1, 2017 to February 27, 2021, and randomly assigned to receive either 60,000 IU vitamin D3 (n = 424) or placebo (n = 422) along with standard ATT. Among the 697 who were cured of PTB, relapse occurred in 14 participants from the vitamin D group and 19 participants from the placebo group (hazard risk ratio 0.68, 95%CI 0.34 to 1.37, log rank p value 0.29). Similarly, no statistically significant difference was seen in time to sputum smear and sputum culture conversion between both groups. Five patients died each in vitamin D and placebo groups, but none of the deaths were attributable to the study intervention. Serum levels of vitamin D were significantly raised in the vitamin D group as compared to the placebo group, with other blood parameters not showing any significant difference between groups. The study reveals that vitamin D supplementation does not seem to have any beneficial effect in the treatment of PTB in terms to the prevention of relapse and time to sputum smear and culture conversion. CTRI/2021/02/030977 (ICMR, Clinical trial registry-India).

Prevalence and associated factors of delayed sputum smear conversion in patients treated for smear positive pulmonary tuberculosis: A retrospective follow up study in Sabah, Malaysia.

Tuberculosis remains a major health problem globally and in Malaysia, particularly in the state of Sabah. Delayed sputum conversion is associated with treatment failure, drug-resistant tuberculosis and mortality. We aimed to determine the prevalence of delayed sputum conversion among smear positive pulmonary tuberculosis (PTB) patients and its associated factors in Sabah, Malaysia. A retrospective follow up study on all patients newly diagnosed with smear positive pulmonary tuberculosis from 2017 to 2019 was conducted at three government health clinics in Sabah, utilizing data from a national electronic tuberculosis database and medical records. Descriptive statistics and binary logistic regression were applied for data analysis. The outcome of the study was the sputum conversion status at the end of the two-month intensive treatment phase with either successful conversion to smear negative or non-conversion. 374 patients were included in the analysis. Our patients were generally younger than 60 years old with no medical illness and varying proportions of tuberculosis severity as judged by radiographic appearance and sputum bacillary load upon diagnosis. Foreigners constituted 27.8% of our sample. 8.8% (confidence interval: 6.2-12.2) did not convert to smear negative at the end of the intensive phase. Binary logistic regression showed that older patients ≥60 years old (adjusted odds ratio, AOR = 4.303), foreigners (AOR = 3.184) and patients with higher sputum bacillary load at diagnosis [2+ (AOR = 5.061) and 3+ (AOR = 4.992)] were more likely to have delayed sputum smear conversion. The prevalence of delayed sputum conversion in our study was considerably low at 8.8% with age ≥60 years old, foreigners and higher pre-treatment sputum bacillary load associated with delayed conversion. Healthcare providers should take note of these factors and ensure the patients receive proper follow up treatment.

Diagnosis and Treatment Pathway of MDR/RR-TB in Taizhou, Zhejiang Province, China

This study aims to understand MDR/RR-TB patients' experience from seeking TB-related health care to diagnosis and treatment completion, as well as the social determinants with the waiting time for DST and treatment, pre-treatment attrition, and treatment outcome based on a retrospective cohort study. Univariate and multi-variate logistic regressions were used to analyze the associated factors. The median time of waiting time for DST and treatment was 24.00 and 30.00 days, respectively. Non-residential patients (aOR: 2.89, 95% CI: 1.14-7.70), registered before 2018 (aOR: 19.93, 95% CI: 8.99-48.51), first visited a county-level hospital (aOR: 4.65, 95% CI: 1.08-21.67), sputum smear-negative (aOR: 3.54, 95% CI: 1.28-10.16), and comorbid with pneumoconiosis (aOR: 7.10, 95% CI: 1.23-47.98) had a longer DST delay. The pre-treatment attrition was 26.9% (82/305). Elderly, non-residential patients and patients registered before 2018 were more likely to refuse MDR/RR treatment. However, in housekeeping/unemployment and farmer/fisherman, recurrent patients tended to take therapeutic measures actively. The successful treatment rate was 62.1% (105/169). Elderly, comorbidity with diabetes and sputum smear conversion time >1 month may lead to poorer outcomes. Immediate interventions should be taken to smooth diagnosis and treatment pathways and improve the social protections further so as to encourage patients to cooperate with the treatment actively.

Patient-reported usability and satisfaction with electronic medication event reminder and monitor device for tuberculosis: a multicentre, randomised controlled trial

The success of a tuberculosis digital adherence technology relies on patients' satisfaction with and the usability of the technology. This study aimed to evaluate treatment satisfaction and usability of a digital medication event reminder and monitor (MERM) device for patients with tuberculosis to address the prespecified secondary endpoint of the SELFTB trial. In this multicenter, randomised controlled trial, adults (≥18 years) with new or previously treated, bacteriologically-confirmed, drug-sensitive pulmonary tuberculosis who were eligible to start anti-tuberculosis therapy were recruited from 10 healthcare facilities in Ethiopia. With a computer-generated random number sequence, participants were randomly assigned 1:1 to receive a 15-day tuberculosis medication supply dispensed with an evriMED500® MERM device to self-administer and return every 15 days or the standard in-person DOT. Both arms were followed throughout the standard two-month intensive treatment phase. Treatment was based on the WHO-recommended two-month fixed-dose-combination of first-line anti-tuberculosis drug delivered as a single daily dose (2RHZE). Treatment Satisfaction Questionnaire for Medication version 4 (TSQM 1.4©) was used to measure and compare treatment satisfaction between arms. Adapted System Usability Scale (SUS) was used to assess the usability of the device, with emphasis on ease of use, challenges, benefits, motivation, popularity, and recommendation. The findings were correlated with adherence and clinical endpoints including sputum smear conversion and IsoScreen urine isoniazid test results. This trial is registered with ClinicalTrials.gov, NCT04216420. Between June 2, 2020, and June 15, 2021, 337 patients were screened for eligibility, of whom 109 participants enrolled and completed the satisfaction [control (n=57) and intervention (n=52) arms] and usability [intervention arm (n=52)] questionnaires. TSQM 1.4© geometric mean scores were: Effectiveness 73.25 [geometric standard deviation (GSD) 1.28], Side Effects 100, Convenience 63.31 (GSD 1.45), and Global Satisfaction 77.29 (GSD 1.25). TSQM score was significantly higher in the intervention vs the control: Effectiveness [85.78 vs 63.43, 95% CI 1.35 (1.26-1.45), p<0.001], Convenience [85.41 vs 48.18, 95% CI 1.77 (1.63-1.93), p<0.001], and Global Satisfaction [90.19 vs 67.11, 95% CI 1.34 (1.26-1.43), p<0.001]. There were significant associations between Global Satisfaction and medication adherence (p=0.017). Average SUS score was 97.45%, which was close to the best imaginable SUS value of 100%. Likelihood to Recommend (LTR) value was ≥9, on a scale of 0-10, for 90.4% of MERM users, yielding higher net promoters. There was no significant association between usability and medication adherence (p=0.691). Our findings suggested that treatment satisfaction scores were superior in the intervention vs control arms and across the domains of Effectiveness, Convenience, and Global Satisfaction. There was excellent usability of the MERM device and a significantly higher number of users likely to promote the device. High tuberculosis burden countries may transform patient-centered care through ongoing evaluation and scale-up of digital health innovations. U.S. National Institute of Health (NIH) Fogarty International Center and National Institute of Allergy and Infectious Diseases (D43 TW009127) and the Emory Center for AIDS Research (P30 AI050409).

Treatment outcomes of extended versus nonextended intensive phase in pulmonary tuberculosis smear positive patients with delayed sputum smear conversion: A retrospective cohort study at primary care clinics in Kota Kinabalu.

Delayed sputum smear conversion in patients with smear-positive pulmonary tuberculosis is a crucial problem at primary care clinics in Sabah resulting in poor treatment outcomes. This study aimed to compare the treatment outcomes between extended and nonextended intensive phase treatments among patients with delayed sputum smear conversion and to identify the factors associated with unsuccessful treatment outcomes. This retrospective cohort study was conducted using data from a Malaysian tuberculosis registry, medical records and clinic referral emails from five primary care clinics in Kota Kinabalu from January 2014 to December 2018. A total of 163 patients with delayed sputum smear conversion were selected and divided into cohort groups: 90 patients received 3 months of intensive phase treatment (extended intensive phase), and 73 patients received 2 months of intensive phase treatment (non-extended intensive phase). Of the 163 patients, 33.7% had unsuccessful treatment outcomes (25.2% had treatment failure; 0.6% died; 3.7% defaulted; and 4.3% transferred out), and 3.7% had relapse. There were no significant differences in the prevalence of unsuccessful treatment outcomes (37.6% vs 28.6%, OR=1.51, CI=0.77-2.94, P=0.226) and relapse (2.2% vs 5.7%, 0R=0.36, CI=0.65-2.04, P=0.404) between the extended and non-extended intensive phase groups. High sputum acid-fast bacilli grade (AFB) at 2 months, drug resistance and lack of directly observed treatment, short-course supervision (DOTS) were associated with unsuccessful treatment outcomes. Extended intensive phase treatment in patients with delayed sputum smear conversion does not prevent unsuccessful treatment outcomes and relapse.

Impact of anemia on sputum smear conversion and treatment outcomes among newly diagnosed tuberculosis patients in Southern India.

Tuberculosis (TB) is a leading cause of mortality worldwide. The higher prevalence of anemia among TB patients is concerning due to its association with delayed sputum conversion and poor treatment outcomes. The present study aimed to evaluate the association of anemia with sputum smear conversion and treatment outcomes among TB patients. In a prospective community-based cohort study, TB patients were recruited from 63 primary health centers in the district. Blood samples were collected at baseline, at 2 months, and at the end of 6 months. Data were analyzed using SPSS software version 15. Out of 661 patients recruited, anemia was observed among 503 (76.1%) participants. Prevalence of anemia was more among males 387 (76.9%) than 116 (23.1%) females. Out of 503 anemic patients, 334 (66.4%) had mild, 166 (33.0%) had moderate, and 3 (0.6%) had severe anemia at baseline. At 6-month treatment completion, 16 (6.3%) were still anemic. Among 503 anemic patients, 445 (88.4%) were given iron supplements and remaining 58 (11.6%) were managed with diet modifications. After completion of TB treatment, 495 (98.4%) patients had favorable treatment outcomes, whereas 8 (1.6%) patients had died. Severe anemia was not associated with poor outcomes. The presence of anemia among newly diagnosed TB patients, especially pulmonary TB was high. Increased risk of anemia was noted among males who were alcohol and tobacco consumers. There was no significant association between the presence of anemia and sputum conversion from baseline to 6 months of treatment completion.

Sputum smear conversion and treatment outcomes among drug-resistant pulmonary tuberculosis patients in eastern Ethiopia: A 9-years data analysis.

Drug-resistant tuberculosis (DR-TB) has become a public health problem throughout the world and about one-third of deaths were attributed to DR-TB from antimicrobial resistance which contributes to 10% of all TB deaths. Sub-Saharan Africa, particularly Ethiopia accounts for a significant number of TB cases. However, the scanty evidence on DR-TB contributing factors could affect the level of this deadly case tackling program. Therefore, this study aimed to assess the factors affecting sputum smear conversion and treatment outcomes among patients with DR-TB in Health facilities in Eastern Ethiopia. A cross-sectional study design was employed from 10 October to 10 November 2021, in the health facilities providing DR-TB services in Harari Region and Dire Dawa city administration. The medical records of 273 DR-TB patients from 10 January 2013 to 27 December 2021, were reviewed using structured checklists. Data were entered into Epidata 3.1 version and exported to STATA 14 version for analysis. The outcome variables were Initial Sputum conversion (converted vs. not-converted) and treatment outcome (Unfavorable vs. Favorable). Sputum examination was performed using both Acid-fast bacillus (AFB) smear microscopy and Löwenstein-Jensen (LJ) culture technique. A binary logistic regression analysis was used to assess the association of independent variables with the first month sputum smear conversion, while a conditional logistic regression model was used to assess the association of treatment outcome with explanatory variables. The associations were reported using adjusted odds ratios (AORs) at a 95% confidence interval. A total of 273 DR-TB patients were included in this study. The unfavorable DR-TB treatment outcome was significantly associated with the history of chewing khat (AOR = 4.38, 95% CI = 1.62, 11.84), having bilateral lung cavity on baseline chest X-ray (AOR = 12.08, 95% CI = 1.80, 2.57), having greater than 2+ smear result at baseline (AOR = 3.79, 95% CI = 1.35, 10.59), and poor adherence (AOR = 2.9, 95% CI = 1.28, 6.82). The sputum smear non-conversion at first month was significantly associated with being Human Immune Virus (HIV)-negative (AOR = 0.37, 0.17, 0.82), having low baseline BMI (AOR = 0.54, 95% CI = 0.29, 0.97), baseline culture > 2++ (AOR = 0.15, 95% CI = 0.05, 0.49) and having greater than 2+ sputum smear result (AOR = 0.09, 95% CI = 0.012, 0.67). Patients with normal chest X-ray at baseline had 3.8 times higher chance of sputum smear conversion on first month (AOR = 3.77, 1.11, 12.77). The overall initial sputum smear conversion and the treatment success rate among DR-TB patients were 52.75 and 66.30%, respectively. The Baseline underweight, HIV-negative, baseline smear > 2+, baseline culture > 2++, and clear lung on baseline X-ray were associated with smear conversion and history of khat chewing, bilateral lung cavity at baseline, having greater than 2+ smear results at baseline, and patients with poor treatment adherence had hostile treatment outcomes. So, strengthening and implementing nutrition assessment and patient counseling during directly observed therapies (DOTs) service and drug compliance could result in early sputum conversion and better treatment outcomes. DR-TB patients with high bacterial load and abnormal lungs on radiologic examination at baseline could need special attention during their course of treatment.