1976 research outputs found
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Low-complexity manual nucleic acid amplification tests for pulmonary tuberculosis in children.
Full text linkAccurate and prompt diagnosis of tuberculosis in children is challenging due to non-specific clinical presentation and the low bacillary load of samples. Low-complexity manual nucleic acid amplification tests (LC-mNAATs) such as loop-mediated isothermal amplification (TB-LAMP) are World Health Organization (WHO)-recommended rapid molecular diagnostic tests. Even in resource-limited settings, they
have good diagnostic accuracy in adults
Efficacy & safety of high-dose rifampicin in pulmonary tuberculosis: A systematic review & meta-analysis
Full text linkEvidence suggests that higher doses of rifampicin aid in faster culture conversion, but its effects on unfavourable outcomes are unclear. We aimed to synthesise evidence on the
efficacy and safety of high-dose rifampicin (>15 mg/kg) containing anti-tuberculosis regimen compared to a regimen with standard dose of rifampicin in adults with pulmonary tuberculosis
Editorial: Monocyte heterogeneity and plasticity
Full text linkMonocytes are innate immune cells that are formed in the bone marrow before being released into the blood (1). They differentiate in the circulation with three major monocyte subsets identified in humans: classical, intermediate and non-classical (2). While the subsets show phenotypic and functional differences (3–5), there is also considerable heterogeneity within each subset (6). In addition, monocytes exhibit plasticity, responding to factors in their environment (7). These functional modifications highlight the ability of monocytes to play a unique role in homeostasis and disease, even before their migration and differentiation in the tissue
Unraveling the Dynamics of Human Filarial Infections: Immunological Responses, Host Manifestations, and Pathogen Biology
Full text linkLymphatic filariasis (LF), or elephantiasis, is a neglected tropical disease caused by filarial worms, primarily Wuchereria bancrofti, transmitted through mosquito bites. It often begins in childhood but may not show symptoms until later, leaving many individuals asymptomatic for long periods. LF disrupts the lymphatic system, causing severe swelling in the limbs and genitals, leading to deformities and disabilities. The World Health Organization estimates that around 51 million people are affected globally, with 36 million suffering from chronic conditions like lymphedema and hydrocele. In 2021, approximately 882.5 million people in 44 countries required preventive chemotherapy, making LF the second leading parasitic cause of disability, significantly impacting socioeconomic status. The immune response to filarial parasites is complex, involving both innate AcademicEditor: AndrewW. Taylor-Robinson Received: 17January2025 Revised: 19February2025 Accepted: 20February2025 Published: 25 February2025 Citation: Rajamanickam,A.;Babu,S. UnravelingtheDynamicsofHuman Filarial Infections: Immunological Responses, HostManifestations, and PathogenBiology. Pathogens 2025, 14, 223. https://doi.org/10.3390/ pathogens14030223 Copyright: ©2025bytheauthors. Licensee MDPI,Basel,Switzerland. This article is an open access article distributed under the termsand conditions of the Creative Commons Attribution (CC BY)license (https://creativecommons.org/ licenses/by/4.0/). and adaptive immune cells. A key feature of LF immunology is the antigen-specific Th2 response, expansion of IL-10-producing CD4+ T cells, and a muted Th1 response. This T cell hypo-responsiveness is crucial for sustaining long-term infections with high parasite densities. While the correlates of protective immunity are not fully understood—due in part to a lack of suitable animal models—T cells, particularly CD4+ Th2 cells, and B cells, play essential roles in immune protection. Moreover, host immune responses contribute to the disease’s pathological manifestations. A failure to induce T cell hypo-responsiveness can lead to exaggerated inflammatory conditions such as lymphedema, hydrocele, and elephantiasis. Filarial infections also induce bystander effects on various immune responses, impacting responses to other infectious agents. This intricate immune interplay offers valuable insights into the regulation of immune responses to chronic infections. This review explores recent immunological research on lymphatic filarial worms, highlighting their effects on both innate and adaptive immune responses in humans and the mechanisms underlying this neglected tropical disease
Phenotypic and genotypic characterization of Mycobacterium tuberculosis pyrazinamide resistance—India, 2018–2020
Full text linkPyrazinamide (PZA) is a key first-line antituberculosis drug that plays an important role in eradicating persister Mycobacterium tuberculosis (TB) bacilli and shortening
the duration of tuberculosis treatment. However, PZA-resistance is on the rise, particularly among persons with multidrug-resistant (MDR) tuberculosis. This nationwide study was conducted to explore the prevalence of mutations conferring PZA resistance, catalogue mutation diversity, investigate the associations of PZA resistance with specific lineages, examine co-resistance to 13 first- and second�line drugs, and evaluate the diagnostic accuracy of sequencing pncA and panD genes for predicting PZA resistance. Whole genome sequencing was performed on 2,207 M. tuberculosis isolates from 25 States and 4 Union Territories of India.
The majority of phenotypically PZA-resistant isolates (77%) harbored 171 distinct mutations in pncA; however, a small number of mutations in panD, rpsA and clpC1 were also observed. A set of novel mutations associated PZA resistance
was uncovered, along with an additional 143 PZA resistance-conferring mutations in pncA based on application of WHO-endorsed grading rules. PZA resistance was predominately observed in Lineage 2 and eight lineage-specific resistance
markers were identified. Mutations distributed across pncA correlate to 94% of PZA resistance and were the predominant drivers of phenotypic resistance; evidence generated herein substantiates sequencing the entire gene and promoter for
comprehensive genotypic-based prediction of PZA resistance. This work provides key insights into the scope of PZA-resistance in India, a high drug-resistant TB burden country, and can support the effectiveness of TB prevention and control effort
Enhancing diagnostic efficiency of pyrazinamide resistance in Mycobacterium tuberculosis via modified MGIT assay and genotypic correlation
Full text linkPyrazinamide (PZA) plays a crucial role in the treatment of both active and latent tuberculosis, particularly in regimens designed to treat drug-resistant TB. However, diagnosing resistance to PZA poses challenges for managing TB, highlighting the need for accurate detection methods. This study aims to address the challenges in detecting PZA resistance by modifying the standard MGIT960 PZA drug susceptibility testing method by optimizing the inoculum dilution. Briefly, three MGIT DST versions were evaluated: the standard method, the reduced inoculum (RI) method employing a 1:20 inoculum dilution and the sparse dilution (SD) method using a 1:50 dilution of the inoculum for growth control tube, while the undiluted MGIT positive culture was used for the PZA test tube. The SD MGIT DST approach minimized the number of false-resistant PZA results to (31/401) 7.7 % against 27 % by standard MGIT DST and 11.7 % by RI MGIT DST approach, thereby reducing the false-positivity rate by 19.3 %. Targeted sequencing of pncA gene identified mutations in only 14/401 isolates (3.5 %). Whole genome sequencing (WGS) of the 31 phenotypically resistant isolates identified resistance -associated mutations in pncA gene (45 %), panD (9.6 %), mas (12.9 %), glpK (3.2 %), and lprG (3.2 %), and others efflux associated genes like Rv1258c (3.2 %), Rv0191c (3.2 %), and Rv3008 (6.45 %), except for 4 isolates, for which no mutations were detected in the target genes. These genes are involved in various resistance mechanisms including cell wall synthesis, metabolic pathways, and drug tolerance, which are essential for PZA efficacy. Notably, new mutations in glpK and mas were detected in isolates with wild-type pncA and were absent in the sensitive isolates. Our study substantiates the improvement of phenotypic testing methods and enhances the detection of PZA resistance even in resource-limited settings and direct research towards improving the diagnostic accuracy in TB drug resistance management
Health related quality of life of tuberculosis patients in South India: A longitudinal assessment study.
Full text linkIn India, there is no information on health related quality of life (HRQoL) of patients with drug sensitive tuberculosis (TB) using a longitudinal design that includes post-
treatment period. This study is the first of its kind in India to assess HRQoL of TB patients from a longitudinal prospective and to identify the factors associated with
changes in HRQo
Prediction of mortality and prioritisation to tertiary care using the ‘OUR-ARCad’ risk score gleaned from the second wave of COVID-19 pandemic—A retrospective cohort study from South India
Full text linkJudicious utilisation of tertiary care facilities through appropriate risk stratification assumes priority, in a raging pandemic, of the nature of delta variant-predominated second wave of COVID-19 pandemic in India. Prioritisation of tertiary care, through a scientifically validated risk score, would maximise recovery without compromising individual safety, but importantly without straining the health system
Generalized estimating equations for modeling cluster randomized trial data on smoking cessation among tuberculosis patients.
No full textThere is a paucity of studies applying Generalized Estimating Equations (GEE) for longitudinal analysis of smoking cessation outcomes within the framework of a cluster
randomized trial, especially among tuberculosis (TB) patients. In this study, a GEE model which accounts for repeated measures and cluster-level effects was imple�mented to identify factors associated with smoking cessation among TB patients. The data included 375 TB patients who were smokers and given TB treatment during 2013–2016 in Kanchipuram and Villupuram districts under a cluster randomized trial.GEE modeling provided robust, population-averaged estimates while accounting for intra-cluster correlation, confirming the sustained impact of these interventions. The model demonstrated that smoking cessation interventions, when integrated with TB treatment, had an impact on cessation outcomes in these populations
Drug-resistant tuberculosis treatment outcomes among Saharia: a marginalized community of Madhya Pradesh, India
Full text linkFew attempts have been made to explore the drug-resistant tuberculosis (DR-TB) outcomes and associated factors among underprivileged communities. This study aimed to determine DR-TB treatment out- comes and associated factors in the Saharia tribal group (TGs), a community with a high TB burden in Madhya Pradesh, India