Prostate malignant tumor and benign prostatic hyperplasia microenvironments in black African men: Limited infiltration of CD8+ T lymphocytes, NK‐cells, and high frequency of CD73+ stromal cells

Abstract Background Anti‐cancerous immunology has yet to be investigated in the African black population, despite being the dawn of precision medicine. Aim Here we investigated the tumor microenvironment of prostate cancer and benign prostatic hyperplasia (BPH) in black Africans. Methods Through immunohistochemistry analysis of prostate cancer and BPH patients' biopsies, we investigated the expression and distribution of CD73, CCD8 T‐lymphocytes, and natural killer cells. In addition, we looked at tumor‐infiltrating features CD8 T‐lymphocytes and natural killer cells. Results We show for the first time in black Africans a high expression of CD73 in epithelial‐stromal cells and virtually no infiltration of CD8 T lymphocytes and natural killer cells in the tumoral area. In addition, CD73 was seven (7) times more likely to be expressed in prostate cancer stromal tissues than in benign prostatic hyperplasia tissues (odds ratio = 7.2; χ2 = 21; p < .0001). In addition, PSA concentration was significantly higher in prostate cancer patients than in BPH patients (p < .001). Also, the PSA‐based ROC. analysis showed an area under the curve of 0.87 (p < .0001). Conclusion CD73 expression is more likely expressed in prostate cancer stromal tissues than in benign prostatic hyperplasia tissues. The features of prostate cancer in Black Africans suggest CD73 expression as a possible target for immunotherapy in this population

Relationship between Antibody Levels, IgG Binding to Plasmodium falciparum-Infected Erythrocytes, and Disease Outcome in Hospitalized Urban Malaria Patients from Dakar, Sénégal

Background. Management of clinical malaria requires the development of reliable diagnostic methods and efficient biomarkers for follow-up of patients. Protection is partly based on IgG responses to parasite antigens exposed at the surface of infected erythrocytes (iRBCs). These IgG responses appeared low during clinical infection, particularly in severe disease. Methods. We analyzed the IgG binding capacity to the surface of live erythrocytes infected by knob positive FCR3 strain. Sera from 69 cerebral malaria (CM) and 72 mild malaria (MM) cases were analyzed by ELISA for IgG responses to five antigens from iRBC and by flow cytometry for IgG binding as expressed in labeling index ratio (LIR). The relationship between IgG levels, LIR, parasitemia, age, and the clinical outcomes was evaluated. Results. We found a significant decrease of LIR in adult CM fatal cases compared to surviving patients (p=0.019). In MM, LIRs were correlated to IgG anti-iRBC and anti-PfEMP3/5 levels. In CM, no correlation was found between LIR, IgG levels, and parasitemia. Conclusion. The IgG binding assay was able to discriminate outcome of cerebral malaria cases and it deserves further development as a potential functional-associated assay for symptomatic malaria analysis

Hepatitis B virus (HBV) infection amongst children in Senegal: current prevalence and seroprotection level

Introduction:&nbsp;hepatitis B virus (HBV) infection is highly endemic in Senegal. HBV vaccine of all children has been introduced in 1999 and included in the Expanded Programme on Immunization in 2004. The aim of this study was to assess the HBV prevalence and immunity status against HBV amongst children in Senegal. Methods:&nbsp;between March and August 2016, consecutive children aged from 6 months to 16 years old were recruited in outpatient department of three main children hospitals in Senegal. Serum samples were analyzed for HBV serology (HBsAg, HBcAb, HBsAb) using ARCHITECT analyzer. Children with HBsAb levels ≥ 10 IU/l) were considered as seroprotected against HBV. Results:&nbsp;during the study period, 295 children fulfilled the criteria for the study and were further analyzed. Three children were HBsAg positive giving a seroprevalence at 1.1% (95% CI: 0.2-3.3), 12/267 (4.5%, 95% CI=2.3-7.7) had positive HBcAb and 226/295 (76.6%, 71.4-81.3) had positive HBsAb including 191 (77.3%, 71.6-82.4) with isolated HBsAb related to previous active immunization. However only 165 children (56%, CI 50-62) had seroprotective HBsAb levels (HBsAb ≥ 10 UI/L) and 63 (21.4, 16.8-26) had a strong seroprotectiondefined by HBsAb ≥ 100 IU/L. Conclusion:&nbsp;our results suggest that although HBV prevalence has significantly decreased in children in Senegal following a better HBV vaccine coverage, the number of children correctly seroprotected is insufficient (56%). Assessing the levels of&nbsp

Evaluation of the LumiraDx SARS-CoV-2 antigen assay for large-scale population testing in Senegal

Purpose: Real-time reverse-transcription polymerase chain reaction (RT-PCR)-based testing remains the gold standard for the diagnosis of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to the high diagnosis demand of SARS-CoV-2 and the limited resources for RT-PCR testing, especially in Low-Income Countries (LICs), antigen-based methods are being considered as an option. The aim of this study was to assess the performance of LumiraDx SARS-CoV-2 antigen assay for large population screening compared to RT-PCR.Methods: This evaluation was conducted on 4146 participants including travelers and participants under household survey and vaccine evaluation studies before injection of the first dose. Oropharyngeal and nasopharyngeal swaps were collected from each participant into 2 mL of viral transport medium (VTM) and 400 &mu;l of VTM were used to assess the performance of LumiraDx SARS-CoV-2 antigen assay, compared to RT-PCR.&nbsp;Results: The prevalence of SARS-CoV-2 of the cohort was 4.5% with RT-PCR and 4.1% with LumiraDx antigen test. Compared to the RT-PCR, the sensitivity and specificity of the LumiraDx antigen SARS-CoV-2 test were 82,7% [95% CI 74.1-89,7] and 99.9% [95% CI 99.6-99.9] respectively. Given the RT-PCR threshold cycle (Ct) range, the sensitivity was 92.1% [95% CI 84.6-96.3] when the Ct value was below or equal 33 cycles, and 38.1% [95% CI 18.9-61.3] when it was above 33 cycles. The inter-rater reliability showed a kappa coefficient of 0.88 when considering all the patients and 0.94 for Ct values below 33 cycles.&nbsp;Conclusion: Our data have shown that the LumiraDx platform can be considered for large-scale testing of SARS-CoV-2

Bland-Altman plot of the whole data.

<p>The x-axis represents the average of CD4 count between the PIMA and the BD FACSCount^TM, and the y-axis represents the bias (difference) between the PIMA^TM Alere and the BD FACSCount^TM. The solid blue line represents the mean of the difference between the two measurements, and the light black lines represent the upper and lower limits of agreement (ULA: mean differences plus and 1,96 x standard deviation of the mean difference; LLA: mean differences minus and 1,96 x standard deviation of the mean difference). Legend for CD4 categories: 1: CD4 T-cells < 200/mm³; 2: CD4 T-cells between 200 and 350/mm³; 3: CD4 T-cells between 351 and 500/mm³; 4: CD4 T-cells above 500/mm³.</p

Bland-Altman analysis.

<p>Bland-Altman plots of <b>(A)</b> CD4 T-cells < 200/mm³, <b>(B)</b> between 200 and 350/mm³, <b>(C)</b> between 350 and 500/mm³, and <b>(D)</b> above 500/mm³ according the CD4 cell count levels. For each plot, the x-axis represents the average of CD4 count between the PIMA and the BD FACSCount^TM, and the y-axis represents the bias (difference) between the PIMA^TM Alere and the BD FACSCount^TM. The solid red line represents the mean of the difference between the two measurements, and the light black lines represent the upper and lower limits of agreement (ULA: mean differences plus and 1,96 x standard deviation of the mean difference; LLA: mean differences minus and 1,96 x standard deviation of the mean difference)</p

Passing-Bablok regression between PIMA^TM Alere CD4 and BD FACSCount^TM.

<p>The x-axis represents CD4 counts provided by the BD FACSCount^TM reference and the y-axis represents the CD4 counts provided by the PIMA^TM CD4. The solid line represents the regression line, and the dashed line represents the line y = x. The linear equation of the regression is y = 0.9347 x + 11.</p

Comparison of the mean difference between the CD4 PIMA^TM Alere and BD FACSCount^TM CD4 measurements.

<p>Comparison of the mean difference between the CD4 PIMA^TM Alere and BD FACSCount^TM CD4 measurements.</p

Analysis of the median CD4 counts between the PIMA and the FACSCount.

<p>Categories of absolute CD4+ T-cells counts (< 200/mm³, [200-350/mm³], [351-500/mm³], and > 500/mm³, in before-after scatter plots comparing the PIMA^TM Alere and the BD FACSCount^TM are shown. Data are shown as median values. P-values were calculated in SPSS 20 using nonparametric Mann-Whitney U test and the graphing was performed using GraphPad Prism software version 5.00.</p

Evaluation of PIMA^TM CD4 System for Decentralization of Immunological Monitoring of HIV-Infected Patients in Senegal

<div><p>Background</p><p>HIV infection is a concern in the army troupes because of the risk behaviour of the military population. In order to allow regular access to CD4⁺ T cell enumeration of military personnel as well as their dependents and civilians living with HIV, the Senegalese Army AIDS program is implementing PIMA^TM Alere technology in urban and semi-urban military medical centres. Validation such device is therefore required prior their wide implementation. The purpose of this study was to compare CD4⁺ T cell count measurements between the PIMA^TM Alere to the BD FACSCount^TM.</p><p>Methodology</p><p>We selected a total of 200 subjects including 50 patients with CD4⁺ T-cells below 200/mm³, 50 between 200 and 350/mm³, 50 between 351 and 500/mm³, and 50 above 500/mm³. CD4⁺ T-cell count was performed on venous blood using the BD FASCount^TM as reference method and the PIMA^TM Point of Care technology. The mean biases and limits of agreement between the PIMA^TM Alere and BD FACSCount^TM were assessed with the Bland-Altman analysis, the linear regression performed using the Passing-Bablok regression analysis, and the percent similarity calculated using the Scott method.</p><p>Results</p><p>Our data have shown a mean difference of 22.3 cells/mm³ [95%CI:9.1–35.5] between the BD FACSCount^TM and PIMA^TM Alere CD4 measurements. However, the mean differences of the two methods was not significantly different to zero when CD4⁺ T-cell count was below 350/mm³ (P = 0.76). The Passing-Bablok regression in categorized CD4 counts has also showed concordance correlation coefficient of 0.89 for CD4⁺ T cell counts below 350/mm³ whilst it was 0.5 when CD4 was above 350/mm³.</p><p>Conclusion</p><p>Overall, our data have shown that for low CD4 counts, the results from the PIMA^TM Alere provided accurate CD4⁺ T cell counts with a good agreement compared to the FACSCount^TM.</p></div