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Haldar, P.

Publications and source records attributed to Haldar, P..

4 recordsLinked to original sources

Twenty-four hour face mask sampling in pulmonary tuberculosis reveals three distinct patterns of bacterial aerosol production dissociated from conventional markers of transmission risk.

Rationale: Although tuberculosis (TB) is transmitted by Mycobacterium tuberculosis (Mtb) in aerosols, little is known of the dynamic characteristics of spontaneous output of bacilli in this form. We have developed and implemented a mask aerosol sampling system (MASS) for longitudinal capture and study of spontaneous aerosol.\n\nObjective: To determine patterns of Mtb output in aerosols, captured using the MASS over 24 hours and their association with existing criteria used to assess transmission risk in patients with pulmonary TB.\n\nMethods: Twenty-four hospitalised patients with newly diagnosed pulmonary TB recruited in Pretoria, South Africa, wore FFP1 masks for one hour out of every three for 24 hours. Aerosol was captured in a gelatine filter processed for Mtb quantitation by PCR. Serial sputum was collected and objective cough frequency monitoring performed over the same period.\n\nMeasurements and Main Results: Mtb was detected in 86.5% of 192 mask samples and 20.7% of 38 assessable sputum samples obtained from the cohort. Mtb was detected by MASS in all but two patients. Three dynamic patterns of expression were identifiable in Mtb aerosol producers: i. variable high; ii. consistent; and iii. variable low. No diurnal variation was apparent and there was no correlation between mask Mtb and either sputum Mtb levels or cough frequency. Sputum smear status, culture time to positivity and chest radiographic characteristics also failed to associate with MASS bacillary output.\n\nConclusions: Conventional markers of tuberculosis case infectivity do not predict bacillary aerosols detected by the MASS. The MASS provides a novel, non-invasive tool for tuberculosis diagnosis and control.

microbiology

Clinico-Demographic trend of HIV-positive cases and sero-discordance at a secondary level hospital in Haryana, North India- programmatic implications for a low HIV prevalence State.

BackgroundAppropriate programmatic intervention for HIV Care and Treatment in a low prevalence state requires local level analysis of programme data. Data generated at an Integrated Counseling and Testing Centre (ICTC) may provide crucial information to understand the epidemiology of the disease in a particular region. There is paucity of information on HIV epidemiology at sub-district level in a low HIV prevalence State of India.\n\nMethodsA secondary analysis of the records from January to December for the years, 2009 through 2014 was conducted among clients who tested HIV positive at the ICTC of a sub-district hospital in Haryana, North India.\n\nResultsA total of 199 individuals were tested HIV positive of whom 121 (61%) were males. By age-group, 8, 8, 178, and 5 individuals were respectively in <5, 5-18, 18-59 and >60 years of age. Over years from 2009 through 2014, 11, 12, 30, 37, 51 and 58 people tested HIV positive, with no sigfinicant sex difference (chi2 p =0.929). Statistically non-significant increase of 18-59 years individuals was observed, from zero in 2009 to 5 in 2014. Major route of transmission was heterosexual (80%), followed-by, parent-to-child (5%), Blood Transfusion (1.5%), MSM (1%) and FSW (0.5%). One third each, were self-referred, from government facility; 16% from tuberculosis clinic. Median CD4 count in 2014, was 392. Serodiscordance rate spouses of HIV positive females was 17%, of males was 33%.\n\nConclusionAnalysis of programme data at a sub-district ICTC could highlight emerging trend even in a low HIV prevalence state.

epidemiology

Differential expression of an alternative splice variant of IL-12Rβ1 impacts early dissemination in the mouse and associates with disease outcome in both mouse and humans exposed to tuberculosis

Experimental mouse models of TB suggest that early events in the lung impact immunity. Early events in the human lung in response to TB are difficult to probe and their impact on disease outcome is unknown. We have shown in mouse that a secreted alternatively-spliced variant of IL-12R{beta}1, lacking the transmembrane domain and termed {Delta}TM-IL-12R{beta}1, promotes dendritic cell migration to the draining lymph node, augments T cell activation and limits dissemination of M. tuberculosis (Mtb). We show here that CBA/J and C3H/HeJ mice (both highly susceptible to Mtb) express higher levels of {Delta}TM-IL-12R{beta}1 than resistant C57BL6 mice and limit early dissemination of Mtb from the lungs. Both CD11c+ cells and T cells express {Delta}TM-IL-12R{beta}1 in humans, and mice unable to make {Delta}TM-IL-12R{beta}1 in either CD4 or CD11c expressing cells permit early dissemination from the lung. Analysis of publically available blood transcriptomes indicates that pulmonary TB is associated with high {Delta}TM-IL-12R{beta}1 expression and that of all IL-12 related signals, the {Delta}TM-IL-12R{beta}1 signal best predicts active disease. {Delta}TM-IL-12R{beta}1 expression reflects the heterogeneity of latent TB infection and has the capacity to discriminate between latent and active disease. In a new Chinese TB patient cohort, {Delta}TM-IL-12R{beta}1 effectively differentiates TB from latent TB, healthy controls and pneumonia patients. Finally, {Delta}TM-IL-12R{beta}1 expression drops in drug-treated individuals in the UK and China where infection pressure is low. We propose that {Delta}TM-IL-12R{beta}1 regulates early dissemination from the lung and that it has diagnostic potential and provides mechanistic insights into human TB.

immunology

A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection

Whole blood transcriptional signatures distinguishing active tuberculosis patients from asymptomatic latently infected individuals exist. Consensus has not been achieved regarding the optimal reduced gene sets as diagnostic biomarkers that also achieve discrimination from other diseases. Here we show a blood transcriptional signature of active tuberculosis using RNA-Seq, confirming microarray results, that discriminates active tuberculosis from latently infected and healthy individuals, validating this signature in an independent cohort. Using an advanced modular approach, we utilise information from the entire transcriptome, which includes over-abundance of type I interferon-inducible genes and under-abundance of IFNG and TBX21, to develop a signature that discriminates active tuberculosis patients from latently infected individuals, or those with acute viral and bacterial infections. We suggest methods targeting gene selection across multiple discriminant modules can improve development of diagnostic biomarkers with improved performance. Finally, utilising the modular approach we demonstrate dynamic heterogeneity in a longitudinal study of recent tuberculosis contacts.

immunology