Increased Neuronal Expression of the Early Endosomal Adaptor APPL1 Replicates Alzheimer's Disease-Related Endosomal and Synaptic Dysfunction with Cholinergic Neurodegeneration.

Endosomal system dysfunction within neurons is a prominent early feature of Alzheimer's disease (AD) pathology. Multiple AD risk factors are regulators of endocytosis and known to cause hyperactivity of the early endosome small GTPase rab5, resulting in neuronal endosomal pathway disruption and cholinergic neurodegeneration. Adaptor protein containing Pleckstrin homology domain, Phosphotyrosine binding domain, Leucine zipper motif (APPL1), an important rab5 effector protein and signaling molecule has been shown in vitro to interface between endosomal and neuronal dysfunction through a rab5-activating interaction with the BACE1-generated C-terminal fragment of amyloid precursor protein (APP-βCTF), a pathogenic APP fragment generated within endosomal compartments.

Characteristics of children and adolescents with multidrug-resistant and rifampicin-resistant tuberculosis and their association with treatment outcomes: a systematic review and individual participant data meta-analysis.

Background: There are few data on the treatment of children and adolescents with multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis, especially with more recently available drugs and regimens. We aimed to describe the clinical and treatment characteristics and their associations with treatment outcomes in this susceptible population.

Methods: We conducted a systematic review and individual participant data meta-analysis.

TB-vaccines: Current status & challenges.

Tuberculosis continues to be among the leading causes of morbidity as well as mortality. It is appreciated that our aim of eliminating TB in the foreseeable future will not be realized until we have a new vaccine with significant efficacy among diverse populations and all age-groups. Although impressive strides have been made in more refined development of new TB vaccines based on learnings from past experiences, the substitute or a booster vaccine for the BCG vaccine is not available yet.

Assessing the impact of COVID-19 management on the workload of human resources working in India's National Tuberculosis Elimination Program.

Background: In 1993, WHO declared tuberculosis (TB) as a global health emergency considering 10 million people are battling TB, of which 30% are undiagnosed annually. In 2020 the COVID-19 pandemic took an unprecedented toll on health systems in every country. Public health staff already engaged in TB control and numerous other departments were additionally tasked with managing COVID-19, stretching human resource (HR) capacity beyond its limits.

Facilitators and Barriers for Private Health Sector Engagement for TB Care in India: A Systematic Review and Meta-Synthesis of Qualitative Research.

Introduction: Private sector engagement is recognized as one of the most critical interventions to achieve the End TB goals in India. We conducted a systematic review and a meta-synthesis of qualitative studies to identify the barriers and facilitators for private sector engagement in TB care in India.

Methods: A systematic search in electronic databases was done.

Test and Treat Model for Tuberculosis Preventive Treatment among Household Contacts of Pulmonary Tuberculosis Patients in Selected Districts of Maharashtra: A Mixed-Methods Study on Care Cascade, Timeliness, and Early Implementation Challenges.

Tuberculosis preventive treatment (TPT) is an important intervention in preventing infection and reducing TB incidence among household contacts (HHCs). A mixed-methods study was conducted to assess the "Test and Treat" model of TPT care cascade among HHCs aged ≥5 years of pulmonary tuberculosis (PTB) patients (bacteriologically/clinically confirmed) being provided TPT care under Project Axshya Plus implemented in Maharashtra (India). A quantitative phase cohort study based on record review and qualitative interviews to understand the challenges and solutions in the TPT care cascade were used.

Effect of delamanid on interim outcomes of bacteriological conversion amongst pediatric drug resistant tuberculosis cases in India.

Aim: To determine the bacteriological conversion rate after 6 months of Delamanid (DLM) based treatment in children with drug-resistant tuberculosis (DR-TB) and determine factors associated with bacteriological conversion.

Methods: This is a descriptive retrospective study done in children between the age of 6-17 years with DR-TB who received DLM-based therapy from October 2018 to May 2021. The drug resistance pattern of TB was detected using Xpert RIF/MTB and phenotypic drug sensitivity testing (DST) on TB-MGIT culture reports.

Patient adherence to tuberculosis treatment in the Indian subcontinent: systematic review and meta-synthesis of qualitative research.

Objectives: How well patients adhere to their tuberculosis (TB) treatment influences their recovery and development of drug resistance, but influences on adherence are multiple and often competing. We synthesised qualitative studies from our setting in the Indian subcontinent to understand the dimensions and dynamics involved to help inform service provision.

Design: Qualitative synthesis comprising inductive coding, thematic analysis and forming a conceptual framework.

Building communities of practice through case-based e-learning to prevent and manage TB among people living with HIV-India.

Background: Co-management of HIV-TB coinfection remains a challenge globally. Addressing TB among people living with HIV (PLHIV) is a key priority for the Government of India (GoI). In 2016, GoI implemented single-window services to prevent and manage TB in PLHIV.

Strategies to detect and manage latent tuberculosis infection among household contacts of pulmonary TB patients in high TB burden countries - a systematic review and meta-analysis.

Objective: To summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high-TB burden countries.

Methods: PubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol-driven (PROSPERO-CRD42021208715).

Estimation of tuberculosis incidence at subnational level using three methods to monitor progress towards ending TB in India, 2015-2020.

Objectives: We verified subnational (state/union territory (UT)/district) claims of achievements in reducing tuberculosis (TB) incidence in 2020 compared with 2015, in India.

Design: A community-based survey, analysis of programme data and anti-TB drug sales and utilisation data.

Setting: National TB Elimination Program and private TB treatment settings in 73 districts that had filed a claim to the Central TB Division of India for progress towards TB-free status.

Active Case Finding for Tuberculosis in India: A Syntheses of Activities and Outcomes Reported by the National Tuberculosis Elimination Programme.

India launched a national community-based active TB case finding (ACF) campaign in 2017 as part of the strategic plan of the National Tuberculosis Elimination Programme (NTEP). This review evaluated the outcomes for the components of the ACF campaign against the NTEP's minimum indicators and elicited the challenges faced in implementation. We supplemented data from completed pretested data proformas returned by ACF programme managers from nine states and two union territories (for 2017-2019) and five implementing partner agencies (2013-2020), with summary national data on the state-wise ACF outcomes for 2018-2020 published in annual reports by the NTEP.

Whole-Genome Sequencing to Identify Missed Rifampicin and Isoniazid Resistance Among Tuberculosis Isolates-Chennai, India, 2013-2016.

India has a high burden of drug-resistant tuberculosis (DR TB) and many cases go undetected by current drug susceptibility tests (DSTs). This study was conducted to identify rifampicin (RIF) and isoniazid (INH) resistance associated genetic mutations undetected by current clinical diagnostics amongst persons with DR TB in Chennai, India. Retrospectively stored 166 DR TB isolates during 2013-2016 were retrieved and cultured in Löwenstein-Jensen medium.

Engaging with the private healthcare sector for the control of tuberculosis in India: cost and cost-effectiveness.

Background: The control of tuberculosis (TB) in India is complicated by the presence of a large, disorganised private sector where most patients first seek care. Following pilots in Mumbai and Patna (two major cities in India), an initiative known as the 'Public-Private Interface Agency' (PPIA) is now being expanded across the country. We aimed to estimate the cost-effectiveness of scaling up PPIA operations, in line with India's National Strategic Plan for TB control.

Recovering from the Impact of the Covid-19 Pandemic and Accelerating to Achieving the United Nations General Assembly Tuberculosis Targets.

In 2020, the novel COVID-19 pandemic replaced TB as the world's top cause of death from an infectious disease. The October 21, 2020 the UN Secretary-General report on progress towards implementation of the UNHLM political declaration on TB stresses that although high-level commitments and targets had galvanized global and national progress towards ending TB, urgent and more ambitious investments and actions were required, especially in lieu of the COVID-19 pandemic where associated public health measures and travel restrictions, have disrupted health services universally. The report sets out 10 priority recommendations to get the world on track to reach agreed targets by 2022.

The Interplay of Host Lysosomes and Intracellular Pathogens.

Lysosomes are an integral part of the intracellular defense system against microbes. Lysosomal homeostasis in the host is adaptable and responds to conditions such as infection or nutritional deprivation. Pathogens such as () and avoid lysosomal targeting by actively manipulating the host vesicular trafficking and reside in a vacuole altered from the default lysosomal trafficking.

Evolutionary journey of programmatic services and treatment outcomes among drug resistant tuberculosis (DR-TB) patients under National TB Elimination Programme in India (2005-2020).

India, with one-fourth of global burden of tuberculosis as well as multidrug-resistant TB, made bold commitment to end TB by 2025. There is no documented comprehensive review of the evolutionary journey of India's DRTB service expansion and changes in the treatment outcome so far. The current document presents evolution and journey of programmatic services and the progress in treatment outcomes among DRTB patients since 2005 with efforts cum challenges in nationwide scale-up of evidence-based policies and services, opportunities and future prospects for universalizing quality care - an essential ingredient to end TB in India.

The paradigm shift in the approach to management of latent tuberculosis infection in high tuberculosis burden countries.

: Addressing the reservoir of Latent Tuberculosis Infection (LTBI) is critical to TB elimination because if left untreated LTBI can progress to active TB disease. This additional burden can prevent achieving the global targets of TB elimination. Management of LTBI has been a low priority target for National TB Elimination Programs (NTEP) due to various challenges in the field settings.

Mycobacterium tuberculosis polyclonal infections through treatment and recurrence.

Background: Mixed/polyclonal infections due to different genotypes are reported in Tuberculosis. The current study was designed to understand the fate of mixed infections during the course of treatment and follow-up and its role in disease pathogenesis.

Methods: Sputum samples were collected on 0,1,2,3,6,12 and 24 months from 157 treatment-naïve patients, cultures subjected to Drug-Susceptibility-testing (MGIT 960), spoligotyping, MIRU-VNTR and SNP genotyping.

Heterogeneity in the endocytic capacity of individual macrophage in a population determines its subsequent phagocytosis, infectivity and subcellular trafficking.

Phagocytosis is a complex cellular uptake process involving multiple distinct steps of cargo recognition, uptake, phagosome maturation and eventual phagolysosome resolution. Emerging literature shows that heterogeneity of phagocytosis at multiple steps at a single cell level influences the population outcome. However, the determinants of phagocytic heterogeneity are not clear.