Background: Several host inflammatory markers have been proposed as biomarkers for diagnosis and treatment response in Tuberculosis (TB), but few studies compare their utility in different demographic, ethnic, and TB endemic settings.Methods: Fifty-four host biomarkers were evaluated in plasma samples obtained from presumed TB cases recruited at the Oslo University Hospital in Norway, and a health center in Cape Town, South Africa. Based on clinical and laboratory assessments, participants were classified as having TB or other respiratory diseases (ORD). The concentrations of biomarkers were analyzed using the Luminex multiplex platform.Results: Out of 185 study participants from both study sites, 107 (58%) had TB, and 78 (42%) ORD. Multiple host markers showed diagnostic potential in both the Norwegian and South African cohorts, with I-309 as the most accurate single marker irrespective of geographical setting. Although study site-specific biosignatures had high accuracy for TB, a site-independent 5-marker biosignature (G-CSF, C3b/iC3b, procalcitonin, IP-10, PDGF-BB) was identified diagnosing TB with a sensitivity of 72.7% (95% CI, 49.8–82.3) and specificity of 90.5% (95% CI, 69.6–98.8) irrespective of geographical site.Conclusion: A 5-marker host plasma biosignature has diagnostic potential for TB disease irrespective of TB setting and should be further explored in larger cohorts.

Background HIV-load decrease and suppression over time is associated with consistent adherence to antiretroviral therapy (ART). Our study aimed to evaluate the difference in viral load and adherence of patients treated with a combination of either Tenofovir (TDF), Lamivudine (3TC) and Efavirenz (EFV) or TDF / Zidovudine (AZT), 3TC and Nevirapine (NVP) regimens at 24 and 48 weeks. Methods A longitudinal study was conducted from May 2016 to June 2017 among 256 HIV infected adult patients who were enrolled at two approved treatment hospitals in Yaoundé, before the start of first-line ART. Whole blood samples were collected using standard operating procedures. HIV-loads were determined by a quantitative RealTime PCR assay. Adherence was evaluated by pharmacy refill data records. Statistical analyses were performed using the PRISM 5.0 software. Results Off the 256 HIV infected patients enrolled, 180 (70%) patients completed the study and 76 (30%) patients were lost to follow-up. The success rate in achieving viral load < 40 copies/ml was 1.8 times higher with the EFV regimen at 24 weeks and was 1.2 times higher in the NVP regimen at 48 weeks. At 48 weeks the treatment failure rate was 12.0 and 40.0% in patients on EFV and the NVP regimen, respectively. The rate of adherence varied in both ART based regimens with 84.0 to 74.0% for EFV and 65.5 to 62.5% for NVP, at 24 and 48 weeks respectively. Conclusion In our study and setting, the rate of viral load decrease was higher in the NVP based regimen than with the EFV regimen. The adherence rate to ART was higher in the EFV regimen, compared to the NVP regimen. This adds to evidence that the EFV regimen is the preferred ART combination for non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Objectives: To evaluate the performance of selected host immunological biomarkers in differentiating tuberculosis (TB) disease from latent TB infection (LTBI) in HIV uninfected and infected individuals enrolled in TB low-burden countries. Design: Participants with TB disease ( N = 85) and LTBI ( N = 150) were recruited from prospective cohorts at hospitals in Norway and Denmark. Plasma concentrations of 54 host markers were assessed by Luminex multiplex immunoassays. Using receiver operator characteristic curves and general discriminant analysis, we determined the abilities of individual and combined biomarkers to discriminate between TB disease and LTBI including when patients were stratified according to HIV infection status. Results: Regardless of the groups compared, CCL1 and IL-2Ra were the most accurate single biomarkers in differentiating TB disease from LTBI. Regardless of HIV status, a 4-marker signature (CCL1 + RANTES + CRP + MIP-1 α) derived from a training set ( n = 155) differentiated TB disease from LTBI in the test set ( n = 67) with a sensitivity of 56.0% (95% CI, 34.9-75.6) and a specificity of 85.7% (95% CI, 71.5-94.6). A 5-marker signature derived from the HIV uninfected group (CCL1 + RANTES + MIP-1 α+ procalcitonin + IP-10) performed in HIV-infected individuals with a sensitivity of 75.0% and a specificity of 96.7% after leave-one-out cross validation. A 2-marker signature (CCL1 + TNF-α) identified in HIVinfected persons performed in HIV-uninfected with a sensitivity and specificity of 66.7% and 100% respectively in the test set. Conclusions: Plasma CCL1 and IL-2Ra have potential as biomarkers for differentiating TB disease from LTBI in low TB burden settings unaffected by HIV infection. Combinations between these and other biomarkers in bio-signatures for global use warrant further exploration.

Background Previous studies have shown that tuberculosis (TB) is a risk factor for chronic airflow limitation. Chronic obstructive pulmonary disease (COPD) is recognized as the result of chronic inflammation, usually related to noxious particles. Post-TB airflow obstruction and tobacco-related COPD have the same functional pathway characterized by persistent airflow limitation. We sought to compare the profile of 29 cytokines in the sputum of subjects with post-TB airflow obstruction and those with COPD related to tobacco. Results The forced expiratory volume in the first second (FEV1) and forced expiratory volume/forced vital capacity (FEV/FVC) ratio were lower in the COPD patients with the history of smoking compared to the post-TB airflow obstruction subgroup. The stages of the disease were more advanced in COPD / tobacco patients. Among the cytokines, IL-1α, IL-1β, MIP-1β, sCD40L and VEGF levels were higher in COPD patients, compared to the controls with p values ​​of 0.003, 0.0001, 0.03, 0.0001 and 0.02 respectively. When the two COPD subgroups were compared, IL-1α, IL-6, TNF-α and IL-8 levels were higher in the COPD patients with the history of tobacco compared to the COPD patients with the history of TB with p-values ​​of 0.031, 0.05, 0.021 and 0.016, respectively. Conclusion COPD related to tobacco is more severe than post-TB airflow obstruction. The pathogenesis of post-TB airflow obstruction appears to involve the cytokines IL-1RA, IL-1α, IL-1β, IL-17, GRO and sCD40L, while COPD related to tobacco involves more cytokines.

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