Dataset Information

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis.

ABSTRACT: Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk. We performed two case-control studies (in the United States and Brazil) among HIV-seronegative adults with previous EPTB (n = 9; 25), previous pulmonary TB (n = 7; 25), latent M. tuberculosis (Mtb) infection (n = 11; 25), and uninfected TB contacts (n = 10; 25). We assessed the frequency of dual CD4+ interferon-γ and tumor necrosis factor-α responses after stimulation with overlapping Mtb peptides from ESAT-6 or CFP-10, or gamma-irradiated Mtb H37Rv, proliferative responses to Mtb antigens, T-regulatory cell (Treg) frequency and phenotype. In both study populations, individuals with prior EPTB had the highest frequency of intracellular cytokine-producing cells in response to Mtb antigens (p < 0.05; p <.0001). Persons with prior EPTB in Brazil had the highest levels of CD4 proliferation to Mtb antigens (p < 0.0001), and the highest expression of CD39 on Tregs (p < 0.0001). Individuals with treated EPTB maintained high frequencies of Mtb-specific memory responses and active Treg cells, suggesting that susceptibility to EPTB occurs despite the ability to develop and maintain enhanced adaptive immune responses.

SUBMITTER: Barreto-Duarte B

PROVIDER: S-EPMC7774017 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis.

Barreto-Duarte Beatriz B Sterling Timothy R TR Fiske Christina T CT Almeida Alexandre A Nochowicz Cynthia H CH Smith Rita M RM Barnett Louise L Warren Christian C Blackman Amondrea A Lapa E Silva Jose Roberto JR Andrade Bruno B BB Kalams Spyros A SA

Frontiers in immunology 20201217

Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk. We performed two case-control studies (in the United States and Brazil) among HIV-seronegative adults with previous EPTB (n = 9; 25), previous pulmonary T ...[more]

PMID: 33391271

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Project description:BackgroundWith the widespread use of rifampicin and isoniazid, bacterial resistance has become a growing problem. Additionally, the lack of relevant baseline information for the frequency of drug-resistant tuberculosis (TB) gene mutations is a critical issue, and the incidence of this infection in the city of Changchun has not investigated to date. However, compared with the slow traditional methods of drug susceptibility testing, recently developed detection methods, such as rifampicin and isoniazid resistance-related gene chip techniques, allow for rapid, easy detection and simultaneous testing for mutation frequency and drug resistance.MethodsIn this study, the rifampicin and isoniazid resistance-related gene mutation chip method was employed for an epidemiological investigation. To assess the gene mutation characteristics of drug-resistant TB and evaluate the chip method, we tested 2143 clinical specimens from patients from the infectious diseases hospital of Changchun city from January to December 2016. The drug sensitivity test method was used as the reference standard.ResultsThe following mutation frequencies of sites in the rifampicin resistance gene rpoB were found: Ser531Leu (52.6%), His526Tyr (12.3%), and Leu511Pro (8.8%). The multidrug-resistance (MDR)-TB mutation frequency was 34.7% for rpoB Ser531Leu and katG Ser315Thr, 26.4% for rpoB Ser531Leu and inhA promoter - 15 (C → T), and 10.7% for rpoB His526Tyr and katG Ser315Thr. In addition, drug susceptibility testing served as a reference standard. In previously treated clinical cases, the sensitivity and specificity of GeneChip were 83.1 and 98.7% for rifampicin resistance, 79.9 and 99.6% for isoniazid resistance, and 74.1 and 99.8% for MDR-TB.ConclusionsOur experimental results show that the chip method is accurate and reliable; it can be used to detect the type of drug-resistant gene mutation in clinical specimens. Moreover, this study can be used as a reference for future research on TB resistance baselines.

Project description:BackgroundPersistent respiratory symptoms and radiographic abnormalities are common among individuals previously treated for tuberculosis (TB) and may contribute to misdiagnosis and incorrect treatment when they seek care. We sought to determine if clinical and radiographic characteristics differed among previously treated, presumptive TB patients according to their current TB disease status.MethodsAdults (>18 years of age) seeking care at a public health facility in Lusaka, Zambia were systematically evaluated for active TB using symptom screening and chest X-ray. All patients with presumptive TB submitted a sputum sample for microbiological TB testing. Patients who reported a prior history of TB treatment were included in the present analysis. 'Confirmed TB' was defined by the detection of TB using Xpert Ultra and/or liquid culture, while 'possible TB' was defined by the receipt of TB treatment without a positive Xpert Ultra or culture result. We evaluated the positive predictive value (PPV) of clinical symptoms and radiographic features for active TB alone and in combination.ResultsOf 740 presumptive TB patients, 144 (19%) had been previously treated for active TB. Of these, 19 (13%) patients had confirmed TB, 14 (10%) had possible TB, and 111 (77%) had no pulmonary TB. Overall, 119 (83%) patients had ≥1 current respiratory symptom-this did not differ according to current TB disease classification (95%, 93%, 79%; p = 0.23). Sixty-one patients (56%) had radiographic abnormalities suggestive of active TB and such findings were more common among patients with confirmed or possible TB compared to those without TB (93%, 71%, vs. 47%; p = 0.002). Most patients (n = 91, 83%) had at least one radiographic abnormality-no difference by current TB classification was observed (93%, 100%, 79%; p = 0.08). The PPV of any current respiratory symptom, active TB radiographic finding, or any radiographic abnormality for TB was 13% (95%CI: 7-21%), 21% (95%CI: 12-34) and 14% (95%CI: 9-23), respectively; combining clinical and radiographic characteristics did not significantly improve the PPV for active TB.ConclusionsAmong presumptive TB patients previously treated for TB, respiratory symptoms and radiographic abnormalities were common and poorly differentiated those with current active TB from those without current active TB. Reliance on clinical and radiographic characteristics alone in this patient population may result in substantial overtreatment and therefore, microbiological investigations should be used to inform TB treatment decisions whenever possible.

Dataset Information

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis.

Publications

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis.

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