Predictors of weight loss during the intensive phase of tuberculosis treatment in patients with drug-susceptible pulmonary tuberculosis in South India.

BACKGROUND: Tuberculosis (TB) is well-known for causing wasting. Patients on treatment gain weight and weight loss is associated with unfavorable treatment outcomes. There is limited description of weight loss and its predictors during intensive treatment phase. The objective of this study was to assess the predictors of weight loss during intensive phase and to see if there is any association exists with sputum conversion at the end of intensive phase of treatment. METHODS: Data collected as a part of the prospective TB cohort (Regional Prospective Observational Research for TB India Phase 1) conducted in Pondicherry, Cuddalore and Viluppuram districts of Tamil Nadu were used for this study. Sputum smear and body weight comparison were made in the baseline and at the end of second month of treatment. RESULTS: In all, 726 participants had weight measurements at the two time points and 18.7% had weight loss; mean weight lost being 2.3 kg (SD 3.05). Mean weight loss was more among males (2.4 kg, SD 3.2), diabetics (2.8 kg, SD 3.9) and alcoholics (2.1 kg, SD 2.4). Alcohol consumption was the only predictor of weight loss after adjusting for age, diabetes, marital status and BMI (aRR 1.52, P 0.02). Weight loss was not associated with sputum conversion at the end of second month. CONCLUSIONS: Alcohol use emerged as the major predictor for weight loss during intensive phase.

Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study.

Rationale: Bedaquiline and delamanid offer the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). With this treatment, however, some patients remain at high risk for an unfavorable treatment outcome. The endTB Observational Study is the largest multicountry cohort of patients with rifampin-resistant TB or MDR-TB treated in routine care with delamanid- and/or bedaquiline-containing regimens according to World Health Organization guidance.Objectives: We report the frequency of sputum culture conversion within 6 months of treatment initiation and the risk factors for nonconversion.Methods: We included patients with a positive baseline culture who initiated a first endTB regimen before April 2018. Two consecutive negative cultures collected 15 days or more apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.Measurements and Main Results: A total of 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%), or both (10%). Of these, 939 (85%) experienced culture conversion within 6 months. In adjusted analyses, patients with HIV had a lower probability of conversion (0.73; 95% confidence interval [CI], 0.62-0.84) than patients without HIV (0.84; 95% CI, 0.79-0.90; P = 0.03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0.68; 95% CI, 0.57-0.79) relative to patients without either (0.89; 95% CI, 0.84-0.95; P = 0.0004). Hepatitis C infection, diabetes mellitus or glucose intolerance, and baseline resistance were not associated with conversion.Conclusions: Frequent sputum conversion in patients with rifampin-resistant TB or MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.

Redevelopment after spontaneous sputum conversion in noncavitary nodular bronchiectatic Mycobacterium avium complex lung disease.

BACKGROUND: Although spontaneous sputum conversion can occur in noncavitary nodular bronchiectatic (NC-NB) Mycobacterium avium complex lung disease (MAC-LD), little is known about redevelopment after spontaneous conversion. We investigated the redevelopment phenomenon after spontaneous sputum conversion in patients with NC-NB MAC-LD. MATERIAL AND METHODS: Among patients diagnosed with NC-NB MAC-LD between 2000 and 2013, 140 patients who experienced spontaneous sputum conversion, and whose follow-up duration after conversion was ≥6 months, were enrolled at a tertiary referral center in South Korea. Their medical records were retrospectively reviewed. RESULTS: Of the 140 patients, 34 (24.3%) underwent redevelopment during the median follow-up period of 71.0 months (interquartile range [IQR], 58.8-87.5). Redevelopment occurred at a median interval of 25.0 months (IQR, 11.5-41.8) after spontaneous sputum conversion. The mean age of the 34 patients with redevelopment was 63.6 years, and 73.5% were women. No statistically significant differences in clinical characteristics were noted between the 34 patients with redevelopment and those with persistent conversion. Among the 34 patients with redevelopment, 6 received treatment at a median interval of 8 months (IQR, 1.5-16.8) after redevelopment. No significant differences in clinical characteristics were noted between the six treated and 28 untreated patients. CONCLUSION: At least approximately 24% of patients with spontaneous sputum conversion in NC-NB MAC-LD had redevelopment, and a portion of them required treatment. These findings suggest that long-term follow-up is necessary for patients with NC-NB MAC-LD, even those who experience spontaneous sputum conversion.

The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis.

BACKGROUND: The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes. METHODS: This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events. RESULTS: Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments. CONCLUSIONS: Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.

The Prevalence of Absolute and Functional Iron Deficiency Anemia in New Cases of Smear-positive Pulmonary Tuberculosis and Their Sputum Conversion Rate at the End of Intensive Tuberculosis Treatment Phase.

About one third of the population is infected with tuberculosis (TB). On the other hand, iron deficiency is the most common micronutrient deficiency in the world. A number of studies have documented anemia in patients with TB, however, this study aimed to assess the prevalence of iron deficiency anemia (IDA) in patients with acid-fast bacilli (AFB) sputum smear-positive, and sputum conversion in these two groups of patients with absolute and functional IDA at the end of the second month of anti-TB therapy in Zahedan, Iran. The results of this study revealed that 91 out of 198 (45.9%) sputum positive pulmonary TB patients were anemic, and among those 72 (79.1%) had iron deficiency anemia. The overall prevalence of IDA in this study was 36.3%. In 72 patients with IDA, 54 (75%) had functional while the remainder had absolute IDA 18 (25%). Twenty-one out of 72 (29.2%) of patients with IDA remained sputum positive and among 126 non IDA patients 47 (37.3%) had positive sputum smear at the end of intensive TB treatment phase (p=0.278). Approximately, less than half of patients with tuberculosis had anemia among them 79% had iron deficiency anemia. The frequency of functional IDA was three times more than absolute IDA. There was no statistically significant difference in sputum conversion between two groups of IDA and non-IDA patients after intensive phase of anti-TB therapy.

Influence of Micronutrient Consumption by Tuberculosis Patients on the Sputum Conversion Rate: A Systematic Review and Meta-analysis Study.

BACKGROUND: infectious disease is one of the global health challenge in the world, including tuberculosis. Some factors significantly associated with increased treatment success, including the duration of treatment or treatment compliance, use more than three sensitive drugs, individualized regimen, and weight-related to micronutrient. METHODS: a systematic review and meta-analysis study of randomized control trial studies conducted and reported by preferred reporting items for systematic reviews and meta-analyses. The primary data source was online publications, consist of three bases data, which subscribed by Universitas Indonesia, they are Proquest, EBSCO CINAHL, EBSCO Dentistry. Risk of bias was assessed using the Cochrane risk-of-bias tool, and data were analyzed using Review Manager 2015. RESULTS: there were eight full paper rates as relevant studies. There was a significant difference of effect among the intervention group compared the control group (or placebo group). RR of the pooled estimate was 1.12 (95% CI: 1.06 - 1.18) with heterogeneity study 36%. While, the poled calculated based on type of micronutrient from seven studies showed there was no difference of sputum conversion between Vitamin D and placebo group (RR-1.05, 95% CI 0.99 - 1.12) with heterogeneity study 0% and a significant result seems among Zinc and Retinol intervention (RR=1.21, 95% CI 1.09 - 1.35) with heterogeneity study 40%. CONCLUSION: micronutrient intervention during tuberculosis treatment has a positive effect toward to sputum conversion among patient. Zinc and retinol influence sputum conversion while vitamin D did not.

Depressed Gamma Interferon Responses and Treatment Outcomes in Tuberculosis Patients: a Prospective Cohort Study.

Immunosuppression induced by Mycobacterium tuberculosis is important in the pathogenesis of active tuberculosis (TB). However, the impact of depressed TB-specific and non-TB-specific gamma interferon (IFN-γ) response on the treatment outcomes of TB patients remains uncertain. In this prospective cohort study, culture- or pathology-proven active TB patients were enrolled and QuantiFERON-TB Gold In-Tube (QFT-GIT) assays were performed before the initiation of anti-TB treatment. TB-specific IFN-γ responses (TB antigen tube subtracted from the nil tube) and non-TB-specific IFN-γ responses (mitogen tube subtracted from the nil tube) were measured and associated with treatment outcomes, including 2-month culture conversion and on-treatment mortality. A total of 212 active TB patients were included in the analysis. We observed a close correlation between decreased lymphocyte count and lower non-TB-specific IFN-γ responses but not TB-specific IFN-γ responses. Patients with lower non-TB-specific IFN-γ responses had lower 2-month culture conversion rate (71.1% versus 84.7%, respectively; P = 0.033) and higher on-treatment mortality (22.6% versus 5.7%, respectively; P = 0.001) than those with higher non-TB-specific IFN-γ responses. In multivariate analysis, depressed non-TB-specific IFN-γ response was an independent factor associated with 2-month sputum culture nonconversion (odds ratio [OR], 2.49; 95% CI [95% confidence interval], 1.05 to 5.90) and on-treatment mortality (hazard ratio [HR], 2.76; 95% CI, 1.15 to 6.62). In contrast, depressed TB-specific IFN-γ responses were significantly associated with higher on-treatment mortality in univariate analysis but not in multivariate analysis. Our findings suggest that depressed non-TB-specific responses, but not TB-specific IFN-γ responses, as measured by QFT-GIT before the initiation of anti-TB treatment, were significantly associated with worse treatment outcomes in TB patients.

Efficacy of Vitamin D supplementation in achieving an early Sputum Conversion in Smear positive Pulmonary Tuberculosis.

OBJECTIVE: To determine the efficacy of Vitamin D supplementation in achieving an early sputum conversion in vitamin D deficient smear positive pulmonary tuberculosis patients. METHODS: This randomized clinical trial was done at Mayo hospital Lahore from November 2015 to August 2016. One hundred twenty patients with sputum smear positive pulmonary tuberculosis were selected and randomized to Group-A (taking anti-tuberculous therapy (ATT) only) and Group-B (taking ATT with Vitamin D supplementation). Four doses of100,000 IU of Vitamin D injection intramuscularly were given after every 14 days during intensive-phase. Sputum examination was repeated at 2nd, 4th, 6th, 8th, 10th and 12th weeks. Efficacy of treatment in terms of early sputum conversion between both groups was tested using Chi square and independent sample t-test was applied to compare mean values of serum vitamin D before and after treatment. P-value ≤ 0.05 was considered as significant. RESULTS: The mean age of patients was 37.18±6.81 years in Group-A and 39.02±7.56 years in Group-B. There were 63 (52.50%) males and 57 (47.50%) females. The mean serum Vitamin D was 17.07±1.44 in Group-A and 17.23±2.37 in Group-B at baseline and at 12th week, the levels were 21.77±2.23 in Group-A and 29.24±0.72 in Group-B. In Group-A, 7 (11.7%) patients showed positive sputum examination and in Group-B, only one (1.7%) patient had positive sputum examination at 12th week. The difference was statistically significant (p-value= 0.028). CONCLUSION: Four doses of intramuscular vitamin D given after every 14 days corrected vitamin D deficiency and improved the rate of sputum smear conversion in patients of pulmonary tuberculosis.

Sputum culture conversion with moxifloxacin-containing regimens in the treatment of patients with newly diagnosed sputum-positive pulmonary tuberculosis in South India.

BACKGROUND: Rapid sputum culture conversion at 2 months indicates the sterilizing capacity and potential of regimens to shorten duration of tuberculosis treatment. We compared results of sputum culture conversion by moxifloxacin and control regimens and identified factors affecting sputum culture positivity after 2 months of treatment. METHODS: Human immunodeficiency virus-uninfected adults with newly diagnosed smear-positive pulmonary tuberculosis were randomized to receive a 3- or 4-month moxifloxacin regimen (moxifloxacin [M], isoniazid [H], rifampicin [R], pyrazinamide [Z], ethambutol [E]) or the control regimen (RHZE thrice weekly). Bacteriological assessments were done at 15, 30, 45, and 60 days of treatment. Because all patients in the moxifloxacin groups received 2 months of daily RHZEM, they were grouped together for analysis. Statistical methods included χ(2) test and logistic regression analysis. RESULTS: Sputum culture conversion was analyzed in 780 (616 in the moxifloxacin group and 164 in the control group) of 801 enrolled patients. Ninety-five percent of 590 patients in the moxifloxacin group and 81% of 151 patients in the control group had negative sputum cultures at month 2 (P < .001). The control regimen, age (≥35 years), initial sputum culture grade (2+ or 3+), and male sex were significantly associated with higher odds of positive sputum cultures at 2 months. CONCLUSIONS: A 5-drug daily regimen with moxifloxacin results in significantly higher sputum culture conversion in the first 2 months compared with a thrice-weekly, 4-drug regimen in patients with newly diagnosed sputum-positive pulmonary tuberculosis.

Homeopathic treatment in addition to standard care in multi drug resistant pulmonary tuberculosis: a randomized, double blind, placebo controlled clinical trial.

BACKGROUND: Multi drug resistant-tuberculosis (MDR-TB) [resistant to Isoniazid and Rifampicin] is a major global public health problem. In India the incidence is rising in spite of implementation of Revised National Tuberculosis Control Program. Standard MDR-TB drugs are second generation antibiotics taken for 24-27 months. The present study was undertaken to evaluate the efficacy of add on homeopathic intervention to the standard MDR-TB regimen (SR). METHODS: A randomized, double blind, placebo controlled study was conducted from 2003 to 2008. 120 diagnosed MDR-TB patients (both culture positive and negative) were enrolled and randomized to receive Standard Regimen + individualized homeopathic medicine (SR + H) or Standard Regimen + identical placebo (SR + P). The medicines have been used in infrequent doses. The outcome measures were sputum conversion, changes in chest X-ray (CXR), hemoglobin, erythrocyte sedimentation rate (ESR), weight gain, and clinical improvement. RESULTS: There was an improvement in all the outcome measures as per intention to treat (ITT) and per protocol (PP) analyses. ITT analyses revealed sputum culture conversion from positive to negative in 23 (38.3%) in SR + H; 23 (38.3%) patients in SR + P group; (p = 0.269) and 27 (55.1); 21 (42.8%), p = 0.225 as PP analyses. The mean weight gain in SR + H group was 2.4 ± 4.9 and in SR + P was 0.8 ± 4.4; [p = 0.071], reduction in ESR in SR + H was -8.7 ± 13.2; SR + P was 3.9 ± 15.4 [p = 0.068]. The mean increase in hemoglobin was by 0.6 ± 1.7 in SR + H & 0.3 ± 2.3 [p = 0.440] in SR + P group at 95% confidence interval. Statistically significant improvement was seen in CXR in 37 (61.7%) in SR + H and 20 (33.3%) patients in SR + P group (p = 0.002). Subgroup analyses of culture positive patients showed statistically significant improvement in CXR (p = 0.0005), weight gain (p = 0.026), increase in hemoglobin (p = 0.017) and reduction in ESR (p = 0.025) with add on homeopathy. The cure rate was 11.4% more in SR + H group as compared to placebo group. Change in sputum culture conversion, was not statistically significant. CONCLUSION: Add on homeopathy in addition to standard therapy appears to improve outcome in MDR-TB. Larger scale studies using a standardized homeopathic treatment regime should be conducted.

A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation.

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7.3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34.4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0.61; 95 % confidence intervals (95 % CI), (0.44-0.84) and 0.67, 95 % CI (0.53-0.84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0.41; 95 % CI, (0.23-0.73)) and 48 % (aHR, 0.52; 95 % CI, (0.35-0.79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

A study on factors influencing delayed sputum conversion in newly diagnosed pulmonary tuberculosis based on bacteriology and genomics.

Conversion of sputum from positive to negative is one of the indicators to evaluate the efficacy of anti-tuberculosis treatment (ATT). We investigate the factors associated with delayed sputum conversion after 2 or 5 months of ATT from the perspectives of bacteriology and genomics. A retrospective study of sputum conversion in sputum positive 1782 pulmonary tuberculosis (PTB) was conducted from 2021 to 2022 in Beijing, China. We also designed a case-matched study including 24 pairs of delayed-sputum-conversion patients (DSCPs) and timely-sputum-conversion patients (TSCPs), and collect clinical isolates from DSCPs before and after ATT and initial isolates of TSCPs who successfully achieved sputum conversion to negative after 2 months of ATT. A total of 75 strains were conducted drug sensitivity testing (DST) of 13 anti-TB drugs and whole-genome sequencing (WGS) to analyze the risk factors of delayed conversion and the dynamics changes of drug resistance and genomics of Mycobacterium tuberculosis (MTB) during ATT. We found TSCPs have better treatment outcomes and whose initial isolates show lower levels of drug resistance. Clinical isolates of DSCPs showed dynamically changing of resistance phenotypes and intra-host heterogeneity. Single nucleotide polymorphism (SNP) profiles showed large differences between groups. The study provided insight into the bacteriological and genomic variation of delayed sputum conversion. It would be helpful for early indication of sputum conversion and guidance on ATT.

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.

Introduction: 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. Method: 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). Results: 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. Conclusion: 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.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Time to sputum conversion in patients with pulmonary tuberculosis: A score to estimate the infectious period.

Introduction: Patients with pulmonary tuberculosis (PTB) disease and positive sputum cultures are the main source of infection. Culture conversion time is inconsistent and defining the length of respiratory isolation is challenging. The objective of this study is to develop a score to predict the length of isolation period. Methods: A retrospective study was carried out to evaluated risk factors associated with persistent positive sputum cultures after 4 weeks of treatment in 229 patients with PTB. A multivariable logistic regression model was used to determinate predictors for positive culture and a scoring system was created based on the coefficients of the final model. Results: Sputum culture was persistently positive in 40.6%. Fever at consultation (1.87, 95% CI:1.02-3.41), smoking (2.44, 95% CI:1.36-4.37), >2 affected lung lobes (1.95, 95% CI:1.08-3.54), and neutrophil-to-lymphocyte ratio > 3.5 (2.22, 95% CI:1.24-3.99), were significantly associated with delayed culture conversion. Therefore, we assembled a severity score that achieved an area under the curve of 0.71 (95% CI:0.64-0.78). Conclusions: In patients with smear positive PTB, a score with clinical, radiological and analytical parameters can be used as a supplemental tool to assist clinical decisions in isolation period.

Recurrent pulmonary tuberculosis after treatment success: a population-based retrospective study in China.

OBJECTIVES: Post-treatment recurrence remains a challenge for the global control of tuberculosis (TB). This study investigated longitudinal data on pulmonary TB recurrence rates and risk factors for recurrence among successfully treated smear-positive tuberculosis cases in China. METHODS: Between 1st January 2009 and 31st December 2016 we evaluated 33 441 treatment-naïve patients diagnosed with sputum-smear-positive, non-multidrug-resistant TB in Hangzhou, China. We included the data of 9828 patients with TB who were treated successfully. RESULTS: A total of 4.9% of the cases were recurrent (479/9828), identified within a median observation period lasting 1565 days. Altogether, 51.1% (245/479) of the recurrences occurred within 1 year. The cumulative 2- and 5-year recurrence rates were 3.90% (95% confidence interval (CI) 3.3-4.5%) and 5.4% (95%CI 4.8-6.0%), respectively. Prolonged treatment (over 7 months) occurred in 64.7% (6363/9828), with a median treatment duration of 242 days (interquartile range 195-348 days). Male sex (adjusted hazard ratio (aHR) (95%CI) 1.61 (1.30-2.00), p < 0.001), age 60 years old or older (aHR (95%CI) 2.03 (1.70-2.44), p < 0.001), pulmonary cavity (aHR (95%CI) 1.51 (1.25-1.82), p < 0.001) and sputum positivity at 2 months (aHR (95%CI) 1.39 (1.05-1.81), p 0.02) all increased the risk of TB recurrence. Prolonged treatment was associated with reduced TB recurrence (aHR (95%CI) 0.73 (0.61-0.88), p 0.001). CONCLUSIONS: Recurrence remains a problem for successfully treated patients with sputum-smear-positive pulmonary TB, especially those with independent risk factors. Further analysis of prolonged treatment is required.

High Pretreatment Level of Neutrophil to Lymphocyte Ratio, Monocyte to Lymphocyte Ratio and Other Factors Associated with Delayed Sputum Conversion in Patients with Pulmonary Tuberculosis.

Introduction: Patients with delayed intensive phase sputum conversion have a higher risk of multidrug resistant-tuberculosis (MDR-TB) and poorer treatment outcomes. Both, host (immune response and comorbidity) and pathogen factors play important roles in determining sputum conversion after treatment initiation. Impaired host immune response, especially the cellular components, as defined by the increased pre-treatment level of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and other additional factors, were associated with severe active TB. Purpose: To evaluate whether impaired immune responses (high pre-treatment level of NLR and MLR) and other factors associate with delayed sputum conversion at the end of the intensive phase treatment. Patients and Methods: This was a case-control study from 2016 to 2020, which retrospectively analyzed the pre-treatment level of NLR, MLR and other factors among patients with new cases of pulmonary tuberculosis (PTB). Results: A total of 62 patients (31 cases and 31 control). The cut-off value of high pretreatment level of NLR and MLR was 5.065 and 0.585, respectively. Bivariate analysis showed that pretreatment NLR ≥5.065 (OR 8.23, CI 95% 2.48-27.32, p < 0.001), MLR ≥0.585 (OR 10.18, 95% CI 3.13-33.18, p < 0.001) and BMI <18.5 (OR 2.91, 95% CI 1.03-8.20, p = 0.041) were associated with an increased risk of delayed sputum conversion. Multivariate analysis, however, showed that pretreatment NLR ≥5.065 was not significantly associated with delayed sputum conversion (AOR 3.370, 95% CI 0.71-15.91, p value 0.125). A high pretreatment of MLR (AOR 30.802, 95% CI 3.22-287.55, p value 0.003) and lower BMI (AOR 10.942, 95% CI 1.121-98.563, p value 0.033) were significantly associated with an increased risk of delayed intensive phase sputum conversion. Conclusion: High MLR pretreatment and a low BMI were significantly associated with an increased risk of delayed sputum conversion at the end of the PTB intensive phase treatment. High NLR pretreatment, smoking, diabetes, and HIV were not associated with sputum conversion.

Transient Impact of Dysglycemia on Sputum Conversion among Smear-Positive Tuberculosis Patients in a Tertiary Care Facility in Ghana.

BACKGROUND: Apart from increasing the risk of tuberculosis (TB), diabetes may be associated with more severe disease and lower rates of sputum conversion among TB patients. METHODS: We conducted a baseline cross-sectional study with a longitudinal follow-up of newly diagnosed smear-positive TB patients for 6 months. Sputum conversion rates between those with dysglycemia and those without were compared at 2 months (end of the intensive phase) and 6 months (end of the treatment). Descriptive statistics and logistic regression were computed to assess factors associated with dysglycemia as well as sputum conversion. RESULTS: A significantly higher proportion of normoglycemic patients had negative sputum compared with those with dysglycemia (83% vs 67%, P-value < .05) at 2 months but not at 6 months (87% vs 77%, P-value > .05). After controlling for age group and adjusting for other covariates, patients with dysglycemia were 66% less likely to convert sputum than those with normoglycemia. Females were at least 7 times more likely than males and those with high waist-to-hip ratio (WHR) of 88% were less likely compared with those with low WHR for sputum conversion at 2 months, respectively. At 6 months, females (compared with males) and those with high WHR (compared with those with normal WHR) were at over 9 times increased odds and 89% less likely for sputum conversion, respectively. CONCLUSION: A significantly lower proportion of smear-positive TB patients with dysglycemia converted to smear negative after 2 months of treatment but not at the end of the treatment, thus suggesting a transient impact of dysglycemia on sputum conversion.

Treatment outcomes of Gene Xpert positive tuberculosis patients in KwaMashu Community Health Centre, KwaZulu-Natal, South Africa: A retrospective review.

BACKGROUND: We sought to investigate the relationship between tuberculosis (TB) treatment outcomes and its predictors in the KwaMashu region in KwaZulu-Natal (KZN). This area is currently a hotbed for TB and human immunodeficiency virus (HIV) co-infection. METHOD: A retrospective study design was adopted to characterise adult patients diagnosed with Gene Expert (GXP) positive pulmonary TB from 01 January 2016 to 31 December 2017. Tuberculosis treatment outcomes were assessed after two months and five months according to the standard World Health Organization (WHO) criteria. Multiple logistic regression analysis was used to calculate the odds ratio (OR) of the possible determinants associated with unsuccessful treatment outcomes. RESULTS: Amongst the 596 patients diagnosed, 57.4% (95% confidence interval [CI]: 53.3-61.4; 342 of 596) had successful treatment outcomes. Of these reported cases, 88.89% (85.1-92.0; 304 of 342) were cured. For the unsuccessful treatment outcomes, 52.4% (46.0-58.6; 133 of 254) patients were lost to follow-up, 20.9% (16.0-26.4; 53 of 254) failed treatment, 1.2% (0.2-3.4; 3 of 254) died and 25.6% (20.3-31.4; 65 of 254) of the patients could not be accounted for. Patients with unknown HIV status were more likely to have unsuccessful treatment outcomes (adjusted OR [aOR] = 4.94 [1.83-13.36]). Patients who had sputum conversion at 2 months (aOR = 1.94 [1.27-2.96]) were significantly more likely to exhibit unsuccessful treatment outcomes. CONCLUSION: Treatment success rate was 57.4% which was below the target set by the WHO. This underscores the urgent need to strengthen treatment adherence strategies to improve outcomes, especially in high HIV burden settings.

Changes of serum adenosine deaminase level in new cases of pulmonary tuberculosis before and after intensive phase treatment.

BACKGROUND AND OBJECTIVES: Tuberculosis (TB) continues to be a public health crisis with an estimated 10 million people developing TB disease in 2017. Adenosine deaminase (ADA) level in serum and pleural fluid as a biomarker may be used to diagnose pulmonary TB (PTB), but it is not always easy to obtain those samples at the end of treatment. This study was conducted to analyze the changes of serum ADA level in the new case of PTB patients with acid-fast bacilli (AFB) smear-positive sputum and sputum conversion status as treatment monitoring in PTB patients. MATERIALS AND METHODS: This was a prospective observational analytic study conducted in Dr. Soetomo General Hospital, Surabaya, from January 2018 to May 2018. Participants were all new cases of PTB patients with AFB smear-positive sputum, and a positive rapid molecular test for Mycobacterium tuberculosis. Blood serums were taken at the same time on the 1st day of TB treatment and also taken at the end of intensive phase treatment to analyze the changes of serum ADA level. RESULTS: There were 26 TB patients and 26 healthy control people. Serum ADA level at the beginning of TB treatment was higher than the level at the end of intensive phase treatment. There was a significant difference between serum ADA level before and after the intensive phase of TB treatment (P < 0.001). CONCLUSIONS: The examination of serum ADA levels can be used to evaluate the PTB treatment response.