A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion

We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR + Ki67 + on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67 + HLA-DR + Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67 + HLA-DR + T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ + IL2 + TNFα + CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67 + HLA-DR + ) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment

Prediction of Partition Coefficients of Organic Compounds in Ionic Liquids Using a Temperature-Dependent Linear Solvation Energy Relationship with Parameters Calculated through a Group Contribution Method

This article discusses the prediction of partition coefficients of organic compounds in ionic liquids

The use of home-based HIV testing and counseling in low-and-middle income countries: a scoping review

Abstract Background Knowledge of HIV status is crucial for both prevention and treatment of HIV infection. However, according to the Joint United Nations Programme on HIV/AIDS in low-and-middle-income countries (LMICs), only 10% of the population has access to HIV testing services. Home-based HIV testing and counseling (HTC) is one of the approaches which have been shown to be effective in improving access to HIV testing in LMICs. The objective of this review was to map evidence on the use of home-based HTC in LMICs. Methods We searched PubMed, EBSCOhost, Google Scholar, Science Direct, World Health Organization library database and UNAIDS databases from January 2013 to October 2017. Eligibility criteria included articles pertaining to the use of home-based HTC in LMICs. Two reviewers independently reviewed the articles for eligibility. The following themes were extracted from the included studies: use, feasibility and effectiveness of home-based HTC on patient-centered outcomes in LMICs. The risk of bias for the included studies was assessed using mixed methods appraisal tool -version 2011. Results A total of 855,117 articles were identified from all the databases searched. Of this, only 17 studies met the inclusion criteria after full article screening and were included for data extraction. All included studies presented evidence on the use of Home-based HTC by most age groups (18 months to 70 years) comprising of both males and females. The included studies were conducted in the following countries: Zambia, Uganda, South Africa, Kenya, Ethiopia, Malawi, Swaziland, Pakistan, and Botswana. This study demonstrated that home-based HTC was used in LMICs alongside supervised HTC intervention using different types of HTC tests kits produced by different manufacturers. This study also showed that home-based HTC was feasible, highly effective, and increased uptake of HIV testing and counseling. This study further demonstrated a highly successful usage of supervised home-based HTC by most age groups in LMICs, with majority of users being females (89.1%). Conclusion We therefore recommend primary studies in other LMICs to determine the feasibility and use of HTC to help achieve the UNAIDS 90:90:90 targets. Interventions to improve the use of home-based HTC by males are also recommended. Trial registration PROSPERO registration number: CRD42017056478

A subset of circulating blood mycobacteria-specific CD4 T cells can predict the time to Mycobacterium tuberculosis sputum culture conversion.

We investigated 18 HIV-negative patients with MDR-TB for M. tuberculosis (Mtb)- and PPD-specific CD4 T cell responses and followed them over 6 months of drug therapy. Twelve of these patients were sputum culture (SC) positive and six patients were SC negative upon enrollment. Our aim was to identify a subset of mycobacteria-specific CD4 T cells that would predict time to culture conversion. The total frequency of mycobacteria-specific CD4 T cells at baseline could not distinguish patients showing positive or negative SC. However, a greater proportion of late-differentiated (LD) Mtb- and PPD-specific memory CD4 T cells was found in SC positive patients than in those who were SC negative (p = 0.004 and p = 0.0012, respectively). Similarly, a higher co-expression of HLA-DR+ Ki67+ on Mtb- and PPD-specific CD4 T cells could also discriminate between sputum SC positive versus SC negative (p = 0.004 and p = 0.001, respectively). Receiver operating characteristic (ROC) analysis revealed that baseline levels of Ki67+ HLA-DR+ Mtb- and PPD-specific CD4 T cells were predictive of the time to sputum culture conversion, with area-under-the-curve of 0.8 (p = 0.027). Upon treatment, there was a significant decline of these Ki67+ HLA-DR+ T cell populations in the first 2 months, with a progressive increase in mycobacteria-specific polyfunctional IFNγ+ IL2+ TNFα+ CD4 T cells over 6 months. Thus, a subset of activated and proliferating mycobacterial-specific CD4 T cells (Ki67+ HLA-DR+) may provide a valuable marker in peripheral blood that predicts time to sputum culture conversion in TB patients at the start of treatment

ROC curve analysis of mycobacteria-specific Ki-67⁺HLA-DR⁺ CD4 T cells with time to sputum culture conversion.

<p>Receiver Operating Characteristic curve for the proportion of mycobacteria-specific Ki-67⁺HLA-DR⁺ CD4 T cells at baseline with the time to sputum clearance. The area under the curve (AUC), p-value and 95% confidence interval (c.i.) are shown on the graph. The dotted line represents an AUC of 0.5, which would depict a random test.</p

Comparison of memory maturation and activation profiles of antigen-specific CD4 T cells at baseline between sputum culture (SC) negative and positive individuals.

<p>(A) Representative overlay flow cytometry dot/density plots of TB-, PPD- and mitogen (mito)- specific CD4 T cell subsets (red) onto total CD4 sub-population (grey) for an individual with positive SC (top panel) and negative SC (bottom panel). Different CD4 subsets are shown as Naïve, Early Differentiated memory (ED), Late Differentiated memory (LD) and Terminally Differentiated (TD). The numbers in each quadrant represent the proportion of antigen-specific cell within each subset (red dots). (B) Proportion of naïve, ED, LD and TD subsets in Mtb (4 SC negative and 8 SC positive), PPD (6 SC negative and 12 SC positive) and mitogen (6 SC negative and 12 SC positive) responsive CD4 T cells. The open symbols represent patients who were SC negative and solid symbols represent patients who were SC positive. The horizontal line corresponds to the median. Non-Parametric Mann-Whitney <i>t</i>-test was used for statistical comparisons. (C) Representative flow cytometry dot-plots of the level of expression of Ki-67 and HLA-DR within PPD-specific CD4 T cell in a SC negative and a SC positive representative patient. The numbers represent the proportion of cells co-expressing Ki-67 and HLA-DR. (D) Proportion of activated cells (co-expressing Ki-67 and HLA-DR) in Mtb (4 SC negative and 8 SC positive), PPD (6 SC negative and 12 SC positive) and mitogen (6 SC negative and 12 SC positive) responsive CD4 T cells. Non-Parametric Mann-Whitney t-test was used for statistical comparisons.</p

Changes in the proportion of antigen-specific CD4 T cells co-expressing HLA-DR and Ki67 over time of chemotherapy in individuals with positive SC at baseline.

<p>(A) Representative flow cytometry dot-plots showing the level of Ki-67 and HLA-DR co-expression within PPD-specific CD4 T cells at baseline (BL), 2, 4 and 6 months (M) of treatment. The numbers in the quadrants represent the proportion of antigen-specific CD4 T cells co-expressing Ki-67 and HLA-DR. (B) Proportion of activated (Ki-67⁺HLA-DR⁺) cells within Mtb, PPD and mitogen responsive CD4 T cells over time (months). The statistical differences were assessed using Wilcoxon matched pairs test.</p