Usefulness of interferon-γrelease assay for the diagnosis of sputum smear-negative pulmonary and extra-pulmonary TB in Zhejiang Province,China

Background:Quick diagnosis of smear-negative pulmonary tuberculosis(TB)and extra-pulmonary TB are urgently needed in clinical diagnosis.Our research aims to investigate the usefulness of the interferon-γrelease assay(IGRA)for the diagnosis of smear-negative pulmonary and extra-pulmonary TB.Methods:We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients(including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients),113 extra-pulmonary TB patients,81 patients with other pulmonary diseases and 100 healthy controls.Blood samples for the TB-Ab test and the TB-IGRA were collected,processed,and interpreted according to the manufacturer’s protocol.Results:The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8%(109 of 120)and 89.6%(241 of 269),respectively.There was no statistically significant difference of its performance between these two sample sets(P>0.05).The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0%(350 of 389)and 87.6%(99 of 113),respectively,which was not significantly different(P>0.05).Conclusions:In this work,the total detection ratio using TB-IGRA was 89.4%,therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.

Performance of Loop-Mediated Isothermal Amplification (LAMP)-Lateral Flow Detection and Xpert MTB/RIF Ultra for Diagnosis of Pulmonary Tuberculosis

Background: Due to the limitations of diagnosis by Xpert MTB/RIF assay, WHO suggests Loop—Mediated Isothermal Amplification (TB-LAMP) instead of sputum-smear microscopy for pulmonary TB diagnosis in patients. Dr. Thongchai Kaewphinit et al. invented a fast TB detection kit called TB d-tect (LAMP-LFD assay). There was no clinical trial to estimate the performance of TB d-tect. Objective: This study was aimed to find the performance of LFD assay and Xpert MTB/RIF ultra for pulmonary TB. Material and methods: A cross-sectional study was conducted. Suggestive pulmonary TB patients were enrolled from June 2020-28 February 2021. Respiratory specimens were collected from each patient and sent for AFB smear, LAMP-LFD assay, Xpert MTB/RIF ultra and culture TB. Result: 139 patients with suspected pulmonary TB were enrolled. 51% of patients were diagnosed with pulmonary tuberculosis. Based on culture TB as a gold standard, the sensitivity and specificity of LAMP-LFD assay were 85.4% (95% CI: 70.8% - 94.4%) and 87.8% (95% CI: 79.6 - 93.5), respectively. The sensitivity and specificity of Xpert MTB/RIF ultra were 95.1% (95% CI: 83.5% - 99.4%) and 74.5% (95% CI: 64.7 - 82.8), respectively. According to ROC curve, it was found that the areas under the curve of LAMP-LFD assay and Xpert MTB/RIF ultra were 0.866 and 0.848, respectively (p = 0.546). Conclusion: The diagnostic sensitivity and specificity of LAMP-LFD assay appeared to be comparable to those of Xpert MTB/RIF ultra. LAMP-LFD assay could be used in resource limiting laboratory.

Clinical Correlates and Drug Resistance in HIV-Infected and -Uninfected Pulmonary Tuberculosis Patients in South India

Objectives: To examine demographics, clinical correlates, sputum AFB (acid fast bacilli) smear grading DOTS (Directly Observed Therapy Short Course) uptake, and drug resistance in a cohort of newly-diagnosed, smear positive pulmonary tuberculosis (TB) patients with respect to HIV status at baseline, and compare smear conversion rates, side effects and mortality after two months. Design: A prospective study among 54 HIV positive and 41 HIV negative pulmonary TB patients. Data were collected via face-to-face interviews, review of medical records, and lab tests. Results: HIVTB co-infected patients, though more symptomatic at baseline, showed more improvement in their symptoms compared to HIV-uninfected TB patients at follow-up. The HIV co-infected group had more prevalent perceived side effects, and sputum smear positivity was marginally higher compared to the HIV negative group at follow-up. Mortality was higher among the HIV-infected group. Both groups had high rates of resistance to first-line anti-tubercular drugs, particularly isoniazid. There was no significant difference in the drug resistance patterns between the groups. Conclusions: Prompt initiation and provision of daily regimens of ATT (Anti-Tubercular treatment) along with ART (Anti-Retroviral treatment) via ART centers is urgently needed in India. As resistance to ART and/or ATT is directly linked to medication non-adherence, the use of counseling, regular reinforcement, early detection and appropriate intervention strategies to tackle this complex issue could help prevent premature mortality and development of resistance in HIV-TB co-infected patients. The high rate of isoniazid resistance might preclude its use in India as prophylaxis for latent TB in HIV infected persons as per the World Health Organization (WHO) guideline.

Association of TNF-α-238G/A and 308 G/A Gene Polymorphisms with Pulmonary Tuberculosis among Patients with Coal Worker’s Pneumoconiosis

Objectives Tumor necrosis factor-α （TNF-α） may play an important role in host＇s immune response to mycobacterium tuberculosis （M. tuberculosis） infection. This study was to investigate the association of TNF-α gene polymorphism with pulmonary tuberculosis （TB） among patients with coal worker＇s pneumoconiosis （CWP）. Methods A case-control study was conducted in 113 patients with confirmed CWP complicated with pulmonary TB and 113 non-TB controls with CWP. They were matched in gender, age, job, and stage of pneumoconiosis. All participants were interviewed with questionnaires and their blood specimens were collected for genetic determination with informed consent. The TNF-α gene polymorphism was determined with polymerase chain reaction of restriction fragment length polymorphism （PCR-RFLP）. Frequency of genotypes was assessed for Hardy-Weinberg equilibrium by chi-square test or Fisher＇s exact probability. Factors influencing the association of individual susceptibility with pulmonary TB were evaluated with logistic regression analysis. Gene-environment interaction was evaluated by a multiplieative model with combined OR. All data were analyzed using SAS version 8.2 software. Results No significant difference in frequency of the TNF-α-308 genotype was found between CWP complicated with pulmonary TB and non-TB controls （2,2=5.44, P=-0.07）. But difference in frequency of the TNF-α-308 A allele was identified between them （2,2-5.14, P=0.02）. No significant difference in frequencies of the TNF-α-238 genotype and allele （P=0.23 and P=0.09, respectively） was found between cases and controls either, with combined （GG and AA） OR of 3.96 （95% confidence interval of 1.30-12.09） at the -308 locus of the TNF-α gene, as compared to combination of the TNF-α-238 GG and TNF-α-308 GG genotypes. Multivariate-adjusted odds ratio of the TNF-α-238 GG and TNF-α-308 GA genotypes was 1.98 （95% CI of 1.06-3.71） for risk for pulmonary TB in patients with CWP. There was a synergic interaction between the TNF-a-308 GG genotype and body mass index （OR=4.92）, as well as an interaction between the TNF-α-308 GG genotype and history of BCG immunization or history of TB exposure. And, the interaction of the TNF-α-238 GG genotype and history of BCG immunization or TB exposure with risk for pulmonary TB in them was also indicated. Conclusions TNF-α-308 A allele is associated with an elevated risk for pulmonary TB, whereas TNF-α-238 A allele was otherwise.