Serum biomarkers for monitoring response to tuberculosis treatment: an assessment of the effect of different covariates among slow and fast treatment responders.

INTRODUCTION: The long duration of tuberculosis treatment, as well as the 2-year post-treatment follow-up period often required for predicting relapse, present a hindrance to drug development and treatment monitoring efforts. Therefore, there is need for treatment response biomarkers to inform treatment time shortening, clinical decision-making, and inform clinical trials. OBJECTIVES: To assess the abilities of serum host biomarkers to predict treatment response among active PTB patients. METHODS: Active pulmonary TB patients (n = 53) as confirmed by sputum MGIT culture were enrolled at a TB treatment centre in Kampala, Uganda. We evaluated concentrations of 27 serum host biomarkers at baseline, month 2, and month 6 following the initiation of anti-tuberculosis treatment using the luminex platform for their ability to predict sputum culture status at month-2 post treatment initiation. RESULTS: There were significant differences in concentrations of IL1ra, IL1ß, IL6, IP10, MCP-1, and IFNγ during treatment. A bio-signature comprising TTP, TNFα, PDGF-BB, IL9, and GCSF best predicted month 2 culture conversion with sensitivity and specificity of 82% (95% CI; 66 -92% and 57 -96% respectively). Slow anti-TB treatment responders had higher pro-inflammatory marker levels during treatment. The strongest correlation was observed between VEGF and IL12p70 (0.94), IL17A and basic FGF (0.92), basic FGF, and IL2 (0.88), and IL10 with IL17A (0.87). CONCLUSION: We identified host biomarkers that predicted early response to PTB treatment, which may be valuable in future clinical trials and treatment monitoring. Similarly, strong correlations between biomarkers provide options for biomarkers substitutions during the development of treatment response monitoring tools or point of care tests.

Antimicrobial susceptibility surveillance and antimicrobial resistance in Neisseria gonorrhoeae in Africa from 2001 to 2020: A mini-review.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG), compromising gonorrhea treatment, is a global public health concern. Improved, quality-assured NG AMR monitoring at the global level is essential. This mini-review examined NG AMR susceptibility surveillance and AMR data from the African continent from 2001 to 2020. Eligible peer-reviewed publications (n = 30) containing NG AMR data for antimicrobials currently recommended for gonorrhea treatment were included. Overall, very limited NG surveillance and AMR data was available. Furthermore, the NG AMR surveillance studies varied greatly regarding surveillance protocols (e.g., populations and samples tested, sample size, antimicrobials examined), methodologies (e.g., antimicrobial susceptibility testing method [agar dilution, minimum inhibitory concentration (MIC) gradient strip test, disc diffusion test] and interpretative criteria), and quality assurance (internal quality controls, external quality assessments [EQA], and verification of AMR detected). Moreover, most studies examined a suboptimal number of NG isolates, i.e., less than the WHO Global Gonococcal Antimicrobial Surveillance Program (GASP) and WHO Enhanced GASP (EGASP) recommendations of ≥100 isolates per setting and year. The notable inter-study variability and frequently small sample sizes make appropriate inter-study and inter-country comparisons of AMR data difficult. In conclusion, it is imperative to establish an enhanced, standardized and quality-assured NG AMR surveillance, ideally including patient metadata and genome sequencing as in WHO EGASP, in Africa, the region with the highest gonorrhea incidence globally. This will enable the monitoring of AMR trends, detection of emerging AMR, and timely refinements of national and international gonorrhea treatment guidelines. To achieve this aim, national and international leadership, political and financial commitments are imperative.