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Background: Tuberculosis (TB) management continues to be a challenge globally; weakened immunity plays a significant role in the reactivation of TB. There is limited information on hematological parameters in patients with pulmonary TB and its association with outcome. Objectives: We present hematological parameters of newly diagnosed sputum-positive pulmonary TB patients enrolled in a randomized, clinical trial that assessed the efficacy and safety of 3 and 4 regimens using moxifloxacin. Materials and Methods: Blood hematological parameters at baseline, comparison of the baseline and end of treatment values, including the monocytes by lymphocytes ratio (M/L), neutrophil lymphocyte ratio (N/L), and platelet lymphocyte ratio (P/L) between the patients with favorable and unfavorable TB treatment outcome, and among different age group and sex presented in this paper. Results: Among the total 1059 patients, 782 were males, the mean hemoglobin (HB) ± standard deviation (SD) was 11.5 g/dL ± 2.0, the mean white blood cell (WBC) count ± SD was 9800 ± 3009 and the mean platelet count (in lakhs) ± SD was 4.24 ± 1.42 cells/uL. There was an increase from baseline in the mean hemoglobin, eosinophil, and lymphocyte count and a decrease in mean neutrophil, monocyte counts to the end of treatment. There was a decrease in baseline mean total WBC count posttreatment, both in favorable (10,271 cells/uL ± 3007 SD to 6689 cells/uL ± 1837 SD, [P ≤ 0.001]), and unfavorable TB outcome patients. Conclusion: An increase in HB, and a decrease in WBC count, M/L, N/L, and P/L ratio is possible at the end of TB treatment and future studies to correlate blood hematology parameters with TB treatment outcome.

BackgroundNumerous studies indicate a potential protective role of helminths in diabetes mellitus (DM) progression. The complement system, vital for host defense, plays a crucial role in tissue homeostasis and immune surveillance. Dysregulated complement activation is implicated in diabetic complications. We aimed to investigate the influence of the helminth, Strongyloides stercoralis (Ss) on complement activation in individuals with type 2 DM (T2D).MethodologyWe assessed circulating levels of complement proteins (C1q, C2, C3, C4, C4b, C5, C5a, and MBL (Lectin)) and their regulatory components (Factor B, Factor D, Factor H, and Factor I) in individuals with T2D with (n = 60) or without concomitant Ss infection (n = 58). Additionally, we evaluated the impact of anthelmintic therapy on these parameters after 6 months in Ss-infected individuals (n = 60).ResultsSs+DM+ individuals demonstrated reduced levels of complement proteins (C1q, C4b, MBL (Lectin), C3, C5a, and C3b/iC3b) and complement regulatory proteins (Factor B and Factor D) compared to Ss-DM+ individuals. Following anthelmintic therapy, there was a partial reversal of these levels in Ss+DM+ individuals.ConclusionOur findings indicate that Ss infection reduces complement activation, potentially mitigating inflammatory processes in individuals with T2D. The study underscores the complex interplay between helminth infections, complement regulation, and diabetes mellitus, offering insights into potential therapeutic avenues.

Background: Information on genotypic with comparison of phenotypic drug sensitivity test of anti-tuberculosis (TB) has been reported in several studies, which have variable results. The present study aimed to assess the Genotype MTBDRsl version 2.0/Line probe assay (LPA) for the detection of fluoroquinolones (FQ) and aminoglycosides (AMGs) resistance mutations among drug-resistant Mycobacterium TB (MTB) strains and also to compare the patterns of genotypic mutations of gyrA/B, rrs, and eis with mycobacteria growth indicator tube (MGIT 960). Methods: A total of 1416 samples were subjected to Genotype MTBDRsl version 2.0 assay. One hundred and twenty sputum smear positive MTB isolates and 37 sputum smear negative MTB isolates confirmed multiple drug resistance resistant to FQ and AMG by the Genotype MTBDRsl version 2.0 were subjected to phenotypic drug susceptibility testing (DST) were analyzed. Results: The association sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for the resistance detection between MGIT (DST) and the Genotype MTBDRsl version 2.0 assay was significant (P < 0.01) of moxifloxacin (MFX) concentration. Sensitivity and specificity value for kanamycin (KAN) resistance was 76% and 89%; 47% and 94% for capreomycin (CAP); and 60% and 76% for low-level KAN, respectively. Conclusion: Our results indicate that MFX (0.25and 1 μg/mL), KAN (2.5 μg/mL), and CAP (2.5 μg/mL) significantly (P < 0.01) and support the World Health Organization guidance to test FQ and AMG by genotypic test.

A pilot study with a mixed-methods design was conducted to estimate the time for tuberculosis (TB) treatment initiation and associated factors among children with central nervous system-TB (CNS-TB). A total of 38 children were enrolled for the quantitative component, and 20 in-depth interviews were conducted. The median duration (interquartile range) from onset of symptoms to treatment initiation was 23 (11, 55) days. About 44% and 31% of the children presented with Stage II and Stage III of CNS-TB, respectively. The major reasons for delay were symptoms not taken seriously (50%) and too many referrals (21%). About 89% of the families went into catastrophic health expenditure due to the disease. The treatment delay may be due to both patient delay and health system delay. Tailoring approaches to target the pediatric population could further improve early detection and treatment initiation of CNS-TB.

Introduction: Neonatal sepsis is a leading cause of mortality and morbidity. In spite of using appropriate antibiotics, those who are bacterial culture-negative, still succumb to fungal infection. Fungal sepsis is common in the Neonatal Intensive Care Unit (NICU), especially with invasive procedures and prolonged empirical use of antibiotics. The incidence of fungal infection varies widely across centres, likely due to differences in practice related to modifiable risk factors such as exposure to empiric antibiotics and length of parenteral nutrition. Neonates are at high risk for acquiring infections due to their specific Central Nervous System (CNS) structure as well as functionally immature immune system, causing CNS infection or Intracranial Haemorrhage (ICH) due to sepsis induced coagulopathy. Intracranial haemorrhage in neonates often results in devastating neurodevelopmental outcomes and also results in significant mortality in the neonatal period. Aim: To find the association and outcome of ICH in newborn with fungal sepsis. Materials and Methods: This study was a prospective cohort study conducted at the Department of Paediatrics, Government Kilpauk Medical College, Chennai, Tamil Nadu, India, on neonates admitted in the NICU during the period January 2018 to December 2020. Neonates with a diagnosis of fungal sepsis were identified from blood cultures. They were also subjected to Complete Blood Count (CBC), Capillary Refill Time (CRT), Prothrombin Time (PT), activated Partial Thromboplastin clotting time (aPTT) and cranial ultrasound. Chi-square analysis for descriptive data and Cox Proportional Hazard Regression for survival and non survival neonates and Kaplan-Meier curve analysis were done. Results: Out of total 80 neonates, nine had ICH, 21 neonates had Intraventricular Haemorrhage (IVH) and no haemorrahge in 50 neonates. More the gestational age, lesser were the chances of ICH and the difference was statistically significant (p

Abstract Climate factors such as dew point temperature, relative humidity and atmospheric temperature may be crucial for the spread of tuberculosis. This study was conducted for the first time to investigate the relationship of climatic factors with TB occurrence in an Indian setting. Daily tuberculosis notification data during 2008–2015 were generated from the National Treatment Elimination Program, and analogous daily climatic data were obtained from the Regional Meteorological Centre at Chennai city, Tamil Nadu, India. The decomposition method was adopted to split the series into deterministic and non-deterministic components, such as seasonal, non-seasonal, trend and cyclical, and non-deterministic climate factors. A generalized linear model was used to assess the relation independently. TB disease progression from latent stage infection to active was supported by higher dew point temperature and moderate temperature. It had a significant association with TB progression in the summer and monsoon seasons. The relative humidity may be favored in the winter and post-monsoon. The water tiny dew droplets may support the TB bacterium to recuperate in the environment.

Background: The routine vaccinations and acquired immunity by other viral infections were believed to be acting as a protective factor against severe COVID-19 outbreaks in some countries. This study is overviewing the relationship of routine BCG, MMR vaccinations and reported MMR disease outbreak with reported COVID-19 infection across the Indian states. Methods: The data on vaccination coverage and respiratory disease infection was obtained from Universal immunization program and Integrated disease surveillance project reports. spearman rank Correlation has been used to assess the relationship of routine vaccination and COVID-19 infection. Results: The result did not find any relationship of routine vaccination with BCG and MMR or exposure to MMR infection on COVID-19 infections in India. Conclusion: The exposure to BCG or MMR vaccination did not have a non specific protection against COVID-19 infection. The results imply that a larger proportion of the Indian population is still vulnerable to COVID-19 infection.

BackgroundThe prevalence of Strongyloides stercoralis infection is estimated to be 30-100 million worldwide, although this an underestimate. Most cases remain undiagnosed due to the asymptomatic nature of the infection. We wanted to estimate the seroprevalence of S. stercoralis infection in a South Indian adult population.MethodsTo this end, we performed community-based screening of 2351 individuals (aged 18-65) in Kanchipuram District of Tamil Nadu between 2013 and 2020. Serological testing for S. stercoralis was performed using the NIE ELISA.ResultsOur data shows a seroprevalence of 33% (768/2351) for S. stercoralis infection which had a higher prevalence among males 36% (386/1069) than among females 29.8% (382/1282). Adults aged ≥55 (aOR = 1.65, 95% CI: 1.25-2.18) showed higher adjusted odds of association compared with other age groups. Eosinophil levels (39%) (aOR = 1.43, 95% CI: 1.19-1.74) and hemoglobin levels (24%) (aOR = 1.25, 95% CI: 1.11-1.53) were significantly associated with S. stercoralis infection. In contrast, low BMI (aOR = 1.15, 95% CI: 0.82-1.61) or the presence of diabetes mellitus (OR = 1.18, 95% CI: 0.83-1.69) was not associated with S. stercoralis seropositivity.ConclusionsOur study provides evidence for a very high baseline prevalence of S. stercoralis infection in South Indian communities and this information could provide realistic and concrete planning of control measures.

BackgroundWe retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission.Methods and findingsData on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among 'survivors' and 'non-survivors'. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 "survivors" and 259 "non-survivors" (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40-70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO23; 3.01 (1.61-5.83), Age ≥50 years;2.52 (1.45-4.43), Pulse Rate ≥100/min: 2.02 (1.19-3.47) and coexisting Diabetes Mellitus; 1.73 (1.02-2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO23-11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as 'OUR-ARDs score' showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85.ConclusionsThe 'OUR ARDs' risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system.

IntroductionDespite the exalted status of sputum mycobacterial load for gauging pulmonary tuberculosis treatment and progress, Chest X-rays supplement valuable information for taking instantaneous therapeutic decisions, especially during the COVID-19 pandemic. Even though literature on individual parameters is overwhelming, few studies have explored the interaction between radiographic parameters denoting severity with mycobacterial burden signifying infectivity. By using a sophisticated approach of integrating Chest X-ray parameters with sputum mycobacterial characteristics, evaluated at all the three crucial time points of TB treatment namely pre-treatment, end of intensive phase and completion of treatment, utilizing the interactive Cox Proportional Hazards model, we aimed to precisely deduce predictors of unfavorable response to TB treatment.Materials and methodWe extracted de-identified data from well characterized clinical trial cohorts that recruited rifampicin-sensitive Pulmonary TB patients without any comorbidities, taking their first spell of anti-tuberculosis therapy under supervision and meticulous follow up for 24 months post treatment completion, to accurately predict TB outcomes. Radiographic data independently obtained, interpreted by two experienced pulmonologists was collated with demographic details and, sputum smear and culture grades of participants by an independent statistician and analyzed using the Cox Proportional Hazards model, to not only adjust for confounding factors including treatment effect, but also explore the interaction between radiological and bacteriological parameters for better therapeutic application.ResultsOf 667 TB patients with data available, cavitation, extent of involvement, lower zone involvement, smear and culture grade at baseline were significant parameters predisposing to an unfavorable TB treatment outcome in the univariate analysis. Reduction in radiological lesions in Chest X-ray by at least 50% at 2 months and 75% at the end of treatment helped in averting unfavorable responses. Smear and Culture conversion at the end of 2 months was highly significant as a predictor (p2 zones, were 3.05 (95% CI: 1.12-8.23) and 1.92 (95% CI: 0.72-5.08) respectively. Patients without cavitation, zonal involvement ConclusionBaseline Cavitation, Opacities occupying >2 zones and 3+ smear grade individually and independently forecasted a poorer TB outcome. The interaction model revealed that Zonal involvement confined to 2 zones, without a cavity and smear grade up to 2+, constituting "minimal disease", had a better prognosis. Radiological clearance >50% along with smear conversion at the end of intensive phase of treatment, observed to be a reasonable alternative to culture conversion in predicting a successful outcome. These parameters may potentially take up key positions as stratification factors for future trials contemplating on shorter TB regimens.

Meta-analysis is the combination of results from various independent studies. In a meta-analysis, combining survival data from different clinical trials, an important issue is the possible heterogeneity between trials. Such inter-trial variation can not only be explained by heterogeneity of treatment effects across trials but also by heterogeneity of their baseline risk. In addition, one might examine the relationship between magnitude of the treatment effect and the underlying risk of the patients in the different trials. However, the need for medical research and clinical practice to be based on the totality of relevant and sound evidence has been increasingly recognized. In this paper, we review the advances of meta-analysis using clinical trials TB data. This paper examines sixteen reporting results of randomized clinical trials conducted in a particular centre at consecutive periods. Every study pools that the results from the relevant trials in order to evaluate the efficacy of a certain treatment between cases and control. There is a need for empirical effort comparing random effects model with the fixed effects model in the calculation of a pooled relative risk in the meta-analysis in systematic reviews of randomized controlled clinical trials. We review heterogeneity and random effects analyses and assessing bias within and across studies. We compare the two approaches with regards to statistical significance, summary relative risk, and confidence intervals. [ABSTRACT FROM AUTHOR]

The optimal duration of preventive therapy for tuberculosis (TB) among HIV-infected persons in TB-endemic countries is unknown.An open-label randomized clinical trial was performed and analyzed for equivalence. Seven hundred and twelve HIV-infected, ART-naïve patients without active TB were randomized to receive either ethambutol 800 mg and isoniazid 300 mg daily for six-months (6EH) or isoniazid 300 mg daily for 36-months (36H). Drugs were dispensed fortnightly and adherence checked by home visits. Patients had chest radiograph, sputum smear and culture performed every six months, in addition to investigations if they developed symptoms. The primary endpoint was incident TB while secondary endpoints were all-cause mortality and adverse events. Survival analysis was performed on the modified intent to treat population (m-ITT) and rates compared.Tuberculosis developed in 22 (6.4%) of 344 subjects in the 6EH arm and 13 (3.8%) of 339 subjects in the 36H arm with incidence rates of 2.4/100 py (95%CI- 1.4-3.5) and 1.6/100 py (95% CI-0.8-3.0) with an adjusted rate ratio (aIRR) of 1.6 (0.8-3.2). Among TST-positive subjects, the aIRR of 6EH was 1.7 (0.6-4.3) compared to 36H, p = 0.8. All-cause mortality and toxicity were similar in the two arms. Among 15 patients with confirmed TB, 4 isolates were resistant to isoniazid and 2 were multidrug-resistant.Both regimens were similarly effective in preventing TB, when compared to historical incidence rates. However, there was a trend to lower TB incidence with 36H. There was no increase in isoniazid resistance compared to the expected rate in HIV-infected patients. The trial is registered at ClinicalTrials.gov, NCT00351702.

A letter to the editor is presented in response to an article about the sensitivity and specificity of combination testing algorithms for human immunodeficiency virus (HIV) in a tuberculosis health facility.

Despite advancements in detection and treatment, tuberculosis (TB), an infectious illness caused by the Mycobacterium TB bacteria, continues to pose a serious threat to world health. The TB diagnosis phase includes a patient's medical history, physical examination, chest X-rays, and laboratory procedures, such as molecular testing and sputum culture. In artificial intelligence (AI), machine learning (ML) is an advanced study of statistical algorithms that can learn from historical data and generalize the results to unseen data. There are not many studies done on the ML algorithm that enables the prediction of treatment success for patients with pulmonary TB (PTB). The objective of this study is to identify an effective and predictive ML algorithm to evaluate the detection of treatment success in PTB patients and to compare the predictive performance of the ML models. In this retrospective study, a total of 1236 PTB patients who were given treatment under a randomized controlled clinical trial at the ICMR-National Institute for Research in Tuberculosis, Chennai, India were considered for data analysis. The multiple ML models were developed and tested to identify the best algorithm to predict the sputum culture conversion of TB patients during the treatment period. In this study, decision tree (DT), random forest (RF), support vector machine (SVM) and naïve bayes (NB) models were validated with high performance by achieving an area under the curve (AUC) of receiver operating characteristic (ROC) greater than 80%. The salient finding of the study is that the DT model was produced as a better algorithm with the highest accuracy (92.72%), an AUC (0.909), precision (95.90%), recall (95.60%) and F1-score (95.75%) among the ML models. This methodology may be used to study the precise ML model classification for predicting the treatment success of TB patients during the treatment period., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ahamed Fayaz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The National Tuberculosis Elimination Programme (NTEP) of the Government of India has strived to control tuberculosis (TB) in the country through various interventions. Understanding the trends of resistance patterns may provide insights into the effectiveness of TB control activities in the country., Methods: A total of 31,144 clinical samples were received from 2013 to 2022 from presumptive drug-resistant TB patients. All the specimens were decontaminated and subjected to the line probe assay for detection of resistance to rifampicin and isoniazid. Mycobacterium tuberculosis (MTB) was detected in 28,814 samples. Autoregressive integrated moving average model (ARIMA) was fitted to assess the trend over time., Results: A decreasing trend in multi-drug resistant TB from 19 % in 2013 to 4 % in 2022 was seen. A decreasing trend in rifampicin monoresistance from 11.2 % in 2013 to 1.5 % in 2022 was seen, though there was an increase in resistance in 2017. No significant decreasing trends were seen in the proportion of isoniazid monoresistance from 8.3 % in 2013 to 7 % in 2022., Conclusion: The findings are encouraging, and to a considerable extent, affirm that India is well on track with regard to the goal of TB elimination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Background: Tuberculosis (TB) lymphadenitis is the most common form of extra-pulmonary TB, and the treatment duration is six months. This non-inferiority based randomized clinical trial in South India evaluated the efficacy and safety of a four-month ofloxacin containing regimen in tuberculosis lymphadenitis (TBL) patients., Methods: New, adult, HIV-negative, microbiologically and or histopathologically confirmed superficial lymph node TB patients were randomized to either four-month oflaxacin containing test regimen [ofloxacin (O), isoniazid (H), rifampicin (R), pyrazinamide (Z) -2RHZO daily/ 2RHO thrice-weekly] or a six-month thrice-weekly control regimen (2HRZ, ethambutol/4RH). The treatment was directly observed. Clinical progress was monitored monthly during and up to 12 months post-treatment, and thereafter every three months up to 24 months. The primary outcome was determined by response at the end of treatment and TB recurrence during the 24 months post-treatment., Results: Of the 302 patients randomized, 298 (98.7%) were eligible for modified intention-to-treat (ITT) analysis and 294 (97%) for per-protocol (PP) analysis. The TB recurrence-free favourable response in the PP analysis was 94.0% (95% CI: 90.1-97.8) and 94.5% (95% CI: 90.8-98.2) in the test and control regimen respectively, while in the ITT analysis, it was 92.7% and 93.2%. The TB recurrence-free favourable response in the test regimen was non-inferior to the control regimen 0.5% (95% CI: -4.8-5.9) in the PP analysis based on the 6% non-inferiority margin. Treatment was modified for drug toxicity in two patients in the test regimen, while one patient had a paradoxical reaction., Conclusion: The 4-month ofloxacin containing regimen was found to be non-inferior and as safe as the 6-month thrice-weekly control regimen., (© 2024. The Author(s).)