BackgroundDevelopment of new tuberculosis (TB) drugs and alternative treatment strategies are urgently required to control the global spread of TB. Previous results have shown that vitamin D3 (vitD3) and 4-phenyl butyrate (PBA) are potent inducers of the host defense peptide LL-37 that possess anti-mycobacterial effects.ObjectiveTo examine if oral adjunctive therapy with 5,000IU vitD3 or 2x500 mg PBA or PBA+vitD3 to standard chemotherapy would lead to enhanced recovery in sputum smear-positive pulmonary TB patients.MethodsAdult TB patients (n = 288) were enrolled in a randomized, double-blind, placebo-controlled trial conducted in Bangladesh. Primary endpoints included proportions of patients with a negative sputum culture at week 4 and reduction in clinical symptoms at week 8. Clinical assessments and sputum smear microscopy were performed weekly up to week 4, fortnightly up to week 12 and at week 24; TB culture was performed at week 0, 4 and 8; concentrations of LL-37 in cells, 25-hydroxyvitamin D3 (25(OH)D3) in plasma and ex vivo bactericidal function of monocyte-derived macrophages (MDM) were determined at week 0, 4, 8, 12 and additionally at week 24 for plasma 25(OH)D3.ResultsAt week 4, 71% (46/65) of the patients in the PBA+vitD3-group (p = 0.001) and 61.3% (38/62) in the vitD3-group (p = 0.032) were culture negative compared to 42.2% (27/64) in the placebo-group. The odds of sputum culture being negative at week 4 was 3.42 times higher in the PBA+vitD3-group (p = 0.001) and 2.2 times higher in vitD3-group (p = 0.032) compared to placebo. The concentration of LL-37 in MDM was significantly higher in the PBA-group compared to placebo at week 12 (p = 0.034). Decline in intracellular Mtb growth in MDM was earlier in the PBA-group compared to placebo (log rank 11.38, p = 0.01).ConclusionAdjunct therapy with PBA+vitD3 or vitD3 or PBA to standard short-course therapy demonstrated beneficial effects towards clinical recovery and holds potential for host-directed-therapy in the treatment of TB.Trial Registrationclinicaltrials.gov NCT01580007

COVID-19 vaccines are indispensable, with the number of cases and mortality still rising, and currently no medicines are routinely available for reducing morbidity and mortality, apart from dexamethasone, although others are being trialed and launched. To date, only a limited number of vaccines have been given emergency use authorization by the US Food and Drug Administration and the European Medicines Agency. There is a need to systematically review the existing vaccine candidates and investigate their safety, efficacy, immunogenicity, unwanted events, and limitations. The review was undertaken by searching online databases, i.e., Google Scholar, PubMed, and ScienceDirect, with finally 59 studies selected. Our findings showed several types of vaccine candidates with different strategies against SARS-CoV-2, including inactivated, mRNA-based, recombinant, and nanoparticle-based vaccines, are being developed and launched. We have compared these vaccines in terms of their efficacy, side effects, and seroconversion based on data reported in the literature. We found mRNA vaccines appeared to have better efficacy, and inactivated ones had fewer side effects and similar seroconversion in all types of vaccines. Overall, global variant surveillance and systematic tweaking of vaccines, coupled with the evaluation and administering vaccines with the same or different technology in successive doses along with homologous and heterologous prime-booster strategy, have become essential to impede the pandemic. Their effectiveness appreciably outweighs any concerns with any adverse events.

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Background In the ongoing pandemic situation of COVID-19, serological tests can complement the molecular diagnostic methods, and can be one of the important tools of sero-surveillance and vaccine evaluation. Aim To develop and evaluate a rapid SARS-CoV-2 specific ELISA for detection of anti-SARS-CoV2 IgG from patients’ biological samples. Methods In order to develop this ELISA, three panels of samples (n = 184) have been used: panel 1 (n = 19) and panel 2 (n = 60) were collected from RT-PCR positive patients within 14 and after 14 days of onset of clinical symptoms, respectively; whereas panel 3 consisted of negative samples (n = 105) collected either from healthy donors or pre-pandemic dengue patients. As a capturing agent full-length SARS-CoV2 specific recombinant nucleocapsid was immobilized. Commercial SARS-CoV2 IgG kit based on chemiluminescent assay was used for the selection of samples and optimization of the assay. The threshold cut-off point, inter-assay and intra-assay variations were determined. Results The incubation/reaction time was set at a total of 30 minutes with the sensitivity of 84% (95% confidence interval, CI, 60.4%, 96.6%) and 98% (95% CI, 91.1%, 100.0%), for panel 1 and 2, respectively; with overall 94.9% sensitivity (95% CI 87.5%, 98.6%). Moreover, the clinical specificity was 97.1% (95% CI, 91.9%, 99.4%) with no cross reaction with dengue samples. The overall positive and negative predictive values are 96.2% (95% CI 89.2%, 99.2%) and 96.2% (95% CI, 90.6% 99.0%), respectively. In-house ELISA demonstrated 100% positive and negative percent agreement with Elecsys Anti-SARS-CoV-2, with Cohen’s kappa value of 1.00 (very strong agreement), while comparing 13 positive and 17 negative confirmed cases. Conclusion The assay is rapid and can be applied as one of the early and retrospective sero-monitoring tools in all over the affected areas.

BackgroundWe have previously shown that 8 weeks’ treatment with phenylbutyrate (PBA) (500mgx2/day) with or without vitamin D3 (vitD3) (5000 IU/day) as host-directed therapy (HDT) accelerated clinical recovery, sputum culture conversion and increased expression of cathelicidin LL-37 by immune cells in a randomized, placebo-controlled trial in adults with pulmonary tuberculosis (TB). In this study we further aimed to examine whether HDT with PBA and vitD3 promoted clinically beneficial immunomodulation to improve treatment outcomes in TB patients.MethodsCytokine concentration was measured in supernatants of peripheral blood mononuclear cells (PBMC) from patients (n = 31/group). Endoplasmic reticulum stress-related genes (GADD34 and XBP1spl) and human beta-defensin-1 (HBD1) gene expression were studied in monocyte-derived-macrophages (MDM) (n = 18/group) from PBMC of patients. Autophagy in MDM (n = 6/group) was evaluated using LC3 expression by confocal microscopy.ResultsA significant decline in the concentration of cytokines/chemokines was noted from week 0 to 8 in the PBA-group [TNF-α (β = − 0.34, 95% CI = − 0.68, − 0.003; p = 0.04), CCL11 (β = − 0.19, 95% CI = − 0.36, − 0.03; p = 0.02) and CCL5 (β = − 0.08, 95% CI = − 0.16, 0.002; p = 0.05)] and vitD3-group [(CCL11 (β = − 0.17, 95% CI = − 0.34, − 0.001; p = 0.04), CXCL10 (β = − 0.38, 95% CI = − 0.77, 0.003; p = 0.05) and PDGF-β (β = − 0.16, 95% CI = − 0.31, 0.002; p = 0.05)] compared to placebo. Both PBA- and vitD3-groups showed a decline in XBP1spl mRNA on week 8 (p < 0.03). All treatment groups demonstrated increased LC3 expression in MDM compared to placebo over time (p < 0.037).ConclusionThe use of PBA and vitD3 as adjunct therapy to standard TB treatment promoted favorable immunomodulation to improve treatment outcomes.Trials registrationThis trial was retrospectively registered in clinicaltrials.gov, under identifier NCT01580007.Electronic supplementary materialThe online version of this article (10.1186/s12879-018-3203-9) contains supplementary material, which is available to authorized users.