Single and Combined Serum Proteins Expressed in TB Infection are Candidates for Point-of-care Diagnostic Testing of Active TB Patients in Lambaréné, Gabon.

Background and Objectives: Point-of-care testing using nonsputum samples like serum or plasma proteins can improve tuberculosis (TB) patients access to a definitive diagnosis, especially in resource-constrained and remote areas. Recently, approximately 400 proteins were identified as playing a role in the pathogenesis of TB, offering a translational clinical research repository for TB. In a previous manuscript, we proved the potential use of these proteins for point-of-care testing for active TB diagnosis. The present work aims to confirm the performance of single and combination proteins to select the best candidate biomarkers for further development as a diagnostic testing tool for active TB. Methods: Seventy-four participants were assessed on the diagnostic performance of 17 single proteins and combinations of 2 to 4 proteins to diagnose active TB. The selection criteria included differential expression of the proteins between active TB and community-acquired pneumonia (CAP) and a performance rate ≥70% for active TB. Results: SULT4A1, WASPF3, SPTLC1, FAM107B, SORCS2, and CYTOb561 were differentially expressed in TB compared to CAP patients. Two single proteins, SULT4A1 and WASPF3, performed ≥70% to discriminate active TB from CAP patients. The diagnostic performance of 3 protein-based combinations of active TB was 81% after leave-one-out cross-validation. Conclusion: Single proteins and 3 protein-based combinations are candidate biomarkers for diagnosing active TB disease. A large and prospective study will confirm their performance as complementary diagnostic tools to rapid diagnostic methods for detecting active TB.

Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-ß, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.

Mother-to-child HIV-transmission prevention programs in a sub-Saharan African setting: The Gabonese experience.

In many developing countries, mothers' awareness remains a challenge despite the scaling up of antenatal care and programs preventing mother-to-child (MTC) HIV transmission. The present study was done in Libreville, Gabon where all antenatal care (delivery included) is free of charge. Here we assessed the timing of antenatal antiretroviral (ARV) prophylaxis initiation, HIV-exposed infants' age at their first postnatal HIV check visit and investigated the association between mothers' awareness or knowledge on their ARV therapy and infants' HIV infection. We interviewed HIV-positive mothers on their first and subsequent laboratory visits to investigate infants' HIV status and tested infants for HIV RNA and antibody between 2012 and 2014. We established that (1) of 718 HIV-positive mothers, only 6% were fully aware and knew what ARV treatment they were on during pregnancy; (2) half of the women (54%) start their antenatal ARV prophylaxis initiation during the second trimester of pregnancy; (3) 64% of HIV-exposed infants had their first HIV infection screening between birth and three months of age; (4) the overall prevalence of HIV infection in infants born from infected mothers was 8.9%; and (5) infants born from mothers uncertain about taking prophylactic ARV therapy were 13.3 times more likely to be infected by HIV than infants born from mothers certain about taking prophylactic ARV therapy. In conclusion, the study showed that despite free antenatal care, early access and adherence to components of MTC, HIV transmission preventive care remains unsatisfactory.

The risk of transfusion-transmitted viral infections at the Gabonese National Blood Transfusion Centre.

BACKGROUND: Blood transfusions carry the risk of transmitting blood-borne infections. In contrast to the situation in the developed world, there is a limited number of studies examining this problem in sub-Saharan Africa. In this study we aimed to calculate the risks of acquiring human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection from units of blood issued by the Gabonese Blood Transfusion Centre between 2009 and 2011. MATERIALS AND METHODS: All the donations were tested for infectious diseases and the seroconversion incidence rates of HIV, HBV and HCV were calculated. The residual risk of transfusion-associated transmission for each virus was calculated by multiplying the seroconversion rates by the window period expressed in fractions of a year. RESULTS: The risks of becoming infected with HIV, HCV, and HBV in subjects receiving units of blood from the Gabonese Blood Transfusion Centre were 64.7, 207.94 and 534.53 per million donations, respectively. CONCLUSIONS: This study, which is the first to quantify the true risks of transfusion-transmitted infections in Gabon, reveals and confirms the need to reinforce preventative and screening strategies to improve transfusion safety in sub-Saharan Africa.

Plasma cytokine levels during acute HIV-1 infection predict HIV disease progression.

BACKGROUND: Both T-cell activation during early HIV-1 infection and soluble markers of immune activation during chronic infection are predictive of HIV disease progression. Although the acute phase of HIV infection is associated with increased pro-inflammatory cytokine production, the relationship between cytokine concentrations and HIV pathogenesis is unknown. OBJECTIVES: To identify cytokine biomarkers measurable in plasma during acute HIV-1 infection that predict HIV disease progression. DESIGN: Study including 40 South African women who became infected with HIV-1 and were followed longitudinally from the time of infection. METHODS: The concentrations of 30 cytokines in plasma from women with acute HIV-1 infection were measured and associations between cytokine levels and both viral load set point 12 months postinfection and time taken for CD4 cell counts to fall below 350 cells/microl were determined using multivariate and Cox proportional hazards regression. RESULTS: We found that the concentrations of five plasma cytokines, IL-12p40, IL-12p70, IFN-gamma, IL-7 and IL-15 in women with acute infection predicted 66% of the variation in viral load set point 12 months postinfection. IL-12p40, IL-12p70 and IFN-gamma were significantly associated with lower viral load, whereas IL-7 and IL-15 were associated with higher viral load. Plasma concentrations of IL-12p40 and granulocyte-macrophage colony-stimulating factor during acute infection were associated with maintenance of CD4 cell counts above 350 cells/microl, whereas IL-1alpha, eotaxin and IL-7 were associated with more rapid CD4 loss. CONCLUSION: A small panel of plasma cytokines during acute HIV-1 infection was predictive of long-term HIV disease prognosis in this group of South African women.