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Journal articlePollock KM, Montamat-Sicotte D, Grass L, et al., 2016,
PD-1 expression and cytokine secretion profiles of Mycobacterium tuberculosis-specific CD4+ T-cell subsets; potential correlates of containment in HIV-TB co-infection
, PLOS One, Vol: 11, ISSN: 1932-6203HIV co-infection is an important risk factor for tuberculosis (TB) providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB)-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI), with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) and expressing CD279 (PD-1) were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL). The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.
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Journal articleSridhar S, Lalvani A, 2015,
Smoking and the Transmission of Tuberculosis <i>Reply</i>
, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 34, Pages: 1138-1138, ISSN: 0891-3668 -
Journal articleNooredinvand HA, Connell DW, Asgheddi M, et al., 2015,
Viral hepatitis prevalence in patients with active and latent tuberculosis
, World Journal of Gastroenterology, Vol: 21, Pages: 8920-8926, ISSN: 1007-9327AIM: To assess the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and association with drug induced liver injury (DILI) in patients undergoing anti-tuberculosis (TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB - either active disease or latent infection - who were due to commence anti-TB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus (HIV) infections - hepatitis B core antigen (HBcAg), hepatitis B surface antigen (HBsAg), hepatitis B e antigen, IgG and IgM antibody to HBcAg (anti-HBc), HCV IgG antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of anti-TB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher’s exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270 (62.9%) had active TB disease and 159 (37.1%) had latent TB infection. 61 (14.2%) patients had isolated anti-HBc positivity, 11 (2.6%) were also HBsAg positive and 7 (1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis (HBsAg or HCV antibody positive; P = 0.023). Similarly the proportion of HBsAg positive patients were significantly greater in the active vs latent TB infection group (10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each
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Journal articleWilliams OM, Abeel T, Casali N, et al., 2015,
Fatal nosocomial transmission of MDR-TB identified through routine genetic analysis and whole genome sequencing
, Emerging Infectious Diseases, Vol: 21, ISSN: 1080-6059 -
Journal articlePollock KM, Montamat-Sicotte DJ, Cooke GS, et al., 2015,
Differences in antigen-specific CD4+ responses to opportunistic infections in HIV infection
, Immunity, Inflammation and Disease, Vol: 3, Pages: 141-153, ISSN: 2050-4527HIV-infected individuals with severe immunodeficiency are at risk of opportunistic infection (OI). Tuberculosis (TB) may occur without substantial immune suppression suggesting an early and sustained adverse impact of HIV on Mycobacterium tuberculosis (MTB)-specific cell mediated immunity (CMI). This prospective observational cohort study aimed to observe differences in OI-specific and MTB-specific CMI that might underlie this. Using polychromatic flow cytometry, we compared CD4+ responses to MTB, cytomegalovirus (CMV), Epstein-Barr virus (EBV) and Candida albicans in individuals with and without HIV infection. MTB-specific CD4+ T-cells were more polyfunctional than virus specific (CMV/EBV) CD4+ T-cells which predominantly secreted IFN-gamma (IFN-γ) only. There was a reduced frequency of IFN-γ and IL-2 (IL-2)-dual-MTB-specific cells in HIV-infected individuals, which was not apparent for the other pathogens. MTB-specific cells were less differentiated especially compared with CMV-specific cells. CD127 expression was relatively less frequent on MTB-specific cells in HIV co-infection. MTB-specific CD4+ T-cells PD-1 expression was infrequent in contrast to EBV-specific CD4+ T-cells. The variation in the inherent quality of these CD4+ T-cell responses and impact of HIV co-infection may contribute to the timing of co-infectious diseases in HIV infection.
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Journal articleLalvani A, Pareek M, Almanza LCB, 2015,
Pre-entry screening for tuberculosis: the need for better evidence
, PATHOGENS AND GLOBAL HEALTH, Vol: 109, Pages: 44-45, ISSN: 2047-7724- Author Web Link
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- Citations: 3
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Journal articleSridhar S, Begom S, Hoschler K, et al., 2015,
Longevity and Determinants of Protective Humoral Immunity after Pandemic Influenza Infection
, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 191, Pages: 325-332, ISSN: 1073-449X- Author Web Link
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- Citations: 19
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Journal articleLalvani A, 2014,
Preventing infectious disease pandemics with T cells
, IMMUNOLOGY, Vol: 143, Pages: 23-23, ISSN: 0019-2805 -
Journal articleSridhar S, Karnani N, Connell DW, et al., 2014,
INCREASED RISK OF <i>MYCOBACTERIUM TUBERCULOSIS</i> INFECTION IN HOUSEHOLD CHILD CONTACTS EXPOSED TO PASSIVE TOBACCO SMOKE
, PEDIATRIC INFECTIOUS DISEASE JOURNAL, Vol: 33, Pages: 1303-1306, ISSN: 0891-3668- Author Web Link
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- Citations: 7
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Conference paperKow KJH, Connell DW, Singanayagam A, et al., 2014,
INTRATHORACIC LYMPH NODE TUBERCULOSIS - A COMPREHENSIVE CLINICAL DESCRIPTION
, Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A157-A158, ISSN: 0040-6376
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