Dataset Information

M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

ABSTRACT: Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection status and comparing the release profiles of cytokines GM-CSF, IFN-?, IL-1?, IL-10, IL-12 (p70), IL-2, IL-4, IL-5, IL-6, IL-8, TNF-?, in community controls (CCs) and healthy healthcare workers (HCWs) highly exposed to TB. Among HCWs and CCs, the probability of latent M. tuberculosis (LTB⁺) infection was respectively 5.4 (p?=?0.002) and 3.4 (p?=?0.006) times higher in men than women. The odds ratio of LTB infection was 4 times higher among HCWs in direct contact with active TB patients than other HCW (p?=?0.01). Whole blood supernatant cytokine responses to M. tuberculosis antigens showed differential pro-inflammatory responses between HCWs and CCs. CCs^LTB- had higher IL-1? responses than HCWs^LTB- (p?=?0.002). HCWs^LTB+ had significantly higher IL-8 responses to M. tuberculosis antigens than HCWs^LTB- (p?=?0.003) and CCs^LTB- (p?=?0.015). HCWs^LTB+/- showed weak but positive TNF-? responses to M. tuberculosis antigen stimulation compared to CCs^LTB+/- (p???0.015). Looking at T-helper (1 and 2) responses, HCWs^LTB+ and CCs^LTB+ had significantly higher IFN-? and IL-2 responses compared to HCWs^LTB- and CCs^LTB- (p?LTB+ and CCs^LTB+ than in non-infected CCs^LTB- (p?LTB+ varied based on active TB exposure gradient. HCWs^LTB+ who were highly exposed to active TB (?3?hours per day) had significantly higher IFN-? and IL-8 responses (p???0.02) than HCWs ^LTB+ not in direct contact with active TB patients. HCWs^LTB+ working with active TB patients for 5 to 31 years had a significantly enhanced secretion of proinflammatory cytokines (GM-CSF, IFN-?, IL-1?, IL-2, IL-6, IL-8, IL-12p70, TNF-?) compared to HCWs^LTB- (p?LTB+ than HCWs^LTB-. In conclusion, LTBI individuals controlling the M. tuberculosis infection have an enhanced TB specific Th1-cytokines/proinflammatory response combined with selected Th2 type/anti-inflammatory cytokines induction.

SUBMITTER: Essone PN

PROVIDER: S-EPMC6547719 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

Essone Paulin N PN Leboueny Marielle M Maloupazoa Siawaya Anicet Christel AC Alame-Emane Amel Kévin AK Aboumegone Biyogo Oriane Cordelia OC Dapnet Tadatsin Patrice Hemery PH Mveang Nzoghe Amandine A Essamazokou Dimitri Ulrich DU Mvoundza Ndjindji Ofilia O Padzys Guy-Stéphane GS Agnandji Selidji Todagbe ST Takiff Howard H Gicquel Brigitte B Djoba Siawaya Joel Fleury JF

Scientific reports 20190603 1

Tuberculosis (TB) is the leading cause of death due to an infectious agent, but only a small fraction of those infected develop the disease. Cytokines are involved in the mediation and regulation of immunity, and their secretion patterns may reflect the infection status. To increase our understanding of immune response to M. tuberculosis infection, we conducted a cross-sectional study investigating M. tuberculosis infection status and comparing the release profiles of cytokines GM-CSF, IFN-γ, IL ...[more]

PMID: 31160610

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Project description:BackgroundMozambican healthcare workers have high rates of latent and active tuberculosis, but occupational screening for tuberculosis is not routine in this setting. Furthermore, the specificity of tuberculin skin testing in this population compared with interferon gamma release assay testing has not been established.MethodsThis study was conducted among healthcare workers at Maputo Central Hospital, a public teaching quaternary care hospital in Mozambique. With a cross sectional study design, risk factors for tuberculosis were assessed using multivariable logistic regression. The care cascade is reported for participants who were prescribed six months of isoniazid preventive therapy for HIV or highly reactive testing for latent tuberculosis infection. The agreement of interferon-gamma release assay results with positive tuberculin skin testing was calculated.ResultsOf 690 screened healthcare workers, three (0.4%) had active tuberculosis and 426 (61.7%) had latent tuberculosis infection. Less education, age 35-49, longer hospital service, and work in the surgery department were associated with increased likelihood of being tuberculosis infected at baseline (p <?0.05). Sex, Bacillus Calmette-Guerin vaccination, HIV, outside tuberculosis contacts, and professional category were not. Three new cases of active tuberculosis developed during the follow-up period, two while on preventive therapy. Among 333 participants offered isoniazid preventive therapy, five stopped due to gastrointestinal side effects and 181 completed treatment. For HIV seropositive individuals, the agreement of interferon gamma release assay positivity with positive tuberculin skin testing was 50% among those with a quantitative skin test result of 5-10?mm, and among those with a skin test result ?10?mm it was 87.5%. For HIV seronegative individuals, the agreement of interferon gamma release assay positivity with a tuberculin skin test result of 10-14?mm was 63.6%, and for those with a quantitative skin test result ?15?mm it was 82.2%.ConclusionsThere is a high prevalence of tuberculosis infected healthcare workers at Maputo Central Hospital. The surgery department was most heavily affected, suggesting occupational risk. Isoniazid preventive therapy initiation was high and just over half completed therapy. An interferon gamma release assay was useful to discern LTBI from false positives among those with lower quantitative tuberculin skin test results.

Project description:BackgroundGiven that there is no rapid and effective method for distinguishing active tuberculosis (ATB) from latent tuberculosis infection (LTBI), the discrimination between these two statuses remains challenging. This study sought to investigate the value of nutritional indexes and tuberculosis-specific antigen/phytohemagglutinin ratio (TBAg/PHA ratio) for distinguishing ATB from LTBI.MethodsParticipants were consecutively recruited based on positive T-SPOT.TB results between January 2018 and January 2020. ATB was diagnosed by positive mycobacterial culture and/or positive GeneXpert MTB/RIF, with clinical symptoms and radiological characteristics suggestive of ATB. Individuals with positive T-SPOT.TB but without the evidence of ATB were defined as LTBI. Patients younger than 17 years and undergoing anti-TB treatment were excluded.ResultsA total of 709 (312 ATB and 397 LTBI) and another 309 (120 ATB and 189 LTBI) subjects were respectively recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort). The level of prealbumin was significantly lower in ATB than in LTBI. With a cut-off value of 139 mg/L, the sensitivity and specificity of prealbumin in distinguishing ATB from LTBI were 50.96% (45.41%-56.51%) and 91.69% (88.97%-94.40%). Meanwhile, TBAg/PHA ratio was found statistically higher in ATB compared with LTBI. If using the threshold of 0.29, the sensitivity and specificity of TBAg/PHA ratio were 65.71% (60.44%-70.97%) and 90.93% (88.11%-93.76%), respectively. Moreover, the combination of prealbumin and TBAg/PHA ratio (obtaining by diagnostic model) yielded better specificity (90.18%, [87.25%-93.10%]) and sensitivity (87.18%, [83.47%-90.89%]), while the clinical utility index (CUI) positive and CUI negative were respectively 0.76 and 0.81. After anti-TB treatment, TBAg/PHA ratio was declined while the level of prealbumin was restored (Wilcoxon test, P < 0.001). Furthermore, the performance of diagnostic model obtained in Qiaokou cohort was confirmed in Caidian cohort.ConclusionsThe diagnostic model based on combination of prealbumin and TBAg/PHA ratio is a rapid and accurate tool for discriminating ATB from LTBI.

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M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

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M. tuberculosis infection and antigen specific cytokine response in healthcare workers frequently exposed to tuberculosis.

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