Epidemiology of Syphilis in regional blood transfusion centres in Burkina Faso, West Africa

Introduction: Syphilis remains a major public health problem in  sub-Saharan Africa, including Burkina Faso. However, few published data are available on the prevalence of syphilis in the population. This study had two main objectives: to determine the seroprevalence of syphilis in acohort of 37,210 first time blood donors and to study socio-demographic factors associated with the risk of infection by Treponema pallidum.Methods: Antibodies to Treponema pallidum were screened by using  Reagin Rapid Test (RPR) and confirmed by treponema pallidum  haemagglutination test (TPHA). Results: The overall seroprevalence of syphilis was 1.5% among first time blood donors and was significantly different between centers (p <0.001). The infection was significantly higher in men than women among blood  donors in Ouagadougou and Fada N´gourma (P = 0.001 and P = 0.034). The overall seroprevalence of syphilis among blood donors was not  associated with either age group or HIV status. In contrast, a significantly high seroprevalence of syphilis was observed in blood donors with HBsAg (P = 0.014) and anti-HCV (P = 0.007) positive.Conclusion: Our report shows a low seroprevalence of syphilis in the  representative sample of the population of Burkina Faso. The  seroprevalence of syphilis remains unequally distributed between urban and rural areas and was not associated with HIV infection

Hemogram abnormalities in apparently healthy first-time blood donors in Libreville, Gabon.

Background: The objective of this study was to determine complete blood count (CBC) abnormalities in Libreville blood donors to advocate for hemoglobin pre-donation implementation and to take into account CBC results in blood donation qualification. Methods: This retrospective study was conducted with 4573 blood donors in March 2016 and from January to April 2017. CBC was performed using SysmexXP-300TM hematology analyzer (SYSMEX Corporation, Kobe, Japan). Results: Blood donors were predominantly males (83.7%) with an age ranging from 18 to 59 years. The abnormalities of leukocyte, platelet and erythrocyte counts were determined in blood donors. Leukopenia and thrombocytopenia were significantly more common in men than women (29.02% vs 24.4%, p = 0.011 and 16.2% vs 7.5%, p <0.001). Only 1.0% of women and 0.84% of men have leukocytosis, and 0.7% of women and 0.2% of men have thrombocytosis. Anemia was significantly more common in women compared to men (69.4% vs. 45.0%, P <0.001). Normocytic normochromic and normocytic hypochromic anemia were most common among Libreville blood donors with 39.4% and 23.6%; followed by microcytic normochromic (18.7%) and microcytic hypochromic (13.2%) anemia. Normocytic normochromic and normocytic hypochromic anemia were significantly more common in men than in women, whereas microcytic normochromic anemia was more prevalent among women compared to men (34.6% vs. 13.9%, p <0.001). Conclusions: The results of this study clearly show the need to perform a pre-donation hemoglobin test in blood donors and to take into account their hemogram in the blood donation selection process at the Libreville National Blood Transfusion Center. Keywords: Hemogram, Anemia, Blood Donors, Libreville, Gabon

Ostéogenèse imparfaite: à propos de quatre cas à Ouagadougou (Burkina Faso)

L'ostéogenèse imparfaite (OI) regroupe un ensemble d'affections constitutionnelles de gravité variable dû à une anomalie de la production du collagène et de la matrice de l'os entraînant une fragilité osseuse. La  présente étude rapporte quatre cas d'ostéogenèse imparfaite suivis aux Centres Hospitaliers Universitaires Charles de Gaulle et Yalgado Ouédraogo. Le but de ce travail était d'analyser les aspects cliniques, thérapeutiques et évolutifs de la maladie. Cette étude souligne la nécessité d'améliorer la prise en charge de cette maladie rare mais non exceptionnelle et handicapante.Key words: Ostéogenèse imparfaite, anomalies osseuses, Burkina-Fas

Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation

Psoriasis is a chronic autoimmune inflammatory skin disorder characterized by epidermal hyperplasia and aberrant immune response. In addition to aberrant cytokine production, psoriasis is associated with activation of the Akt/mTOR pathway. mTOR/S6K1 regulates T-lymphocyte activation and migration, keratinocytes proliferation and is upregulated in psoriatic lesions. Several drugs that target Th1/Th17 cytokines or their receptors have been approved for treating psoriasis in humans with variable results necessitating improved therapies. Fisetin, a natural dietary polyphenol with anti-oxidant and anti-proliferative properties, covalently binds mTOR/S6K1. The effects of fisetin on psoriasis and its underlying mechanisms have not been clearly defined. Here, we evaluated the immunomodulatory effects of fisetin on Th1/Th17-cytokine-activated adult human epidermal keratinocytes (HEKa) and anti-CD3/CD28-stimulated inflammatory CD4+ T cells and compared these activities with those of rapamycin (an mTOR inhibitor). Transcriptomic analysis of HEKa revealed 12,713 differentially expressed genes (DEGs) in the fisetin-treated group compared to 7,374 DEGs in the rapamycin-treated group, both individually compared to a cytokine treated group. Gene ontology analysis revealed enriched functional groups related to PI3K/Akt/mTOR signaling pathways, psoriasis, and epidermal development. Using in silico molecular modeling, we observed a high binding affinity of fisetin to IL-17A. In vitro, fisetin significantly inhibited mTOR activity, increased the expression of autophagy markers LC3A/B and Atg5 in HEKa cells and suppressed the secretion of IL-17A by activated CD4+ T lymphocytes or T lymphocytes co-cultured with HEKa. Topical administration of fisetin in an imiquimod (IMQ)-induced mouse psoriasis model exhibited a better effect than rapamycin in reducing psoriasis-like inflammation and Akt/mTOR phosphorylation and promoting keratinocyte differentiation and autophagy in mice skin lesions. Fisetin also significantly inhibited T-lymphocytes and F4/80+ macrophage infiltration into skin. We conclude that fisetin potently inhibits IL-17A and the Akt/mTOR pathway and promotes keratinocyte differentiation and autophagy to alleviate IMQ-induced psoriasis-like disease in mice. Altogether, our findings suggest fisetin as a potential treatment for psoriasis and possibly other inflammatory skin diseases

Decline in the seroprevalence of syphilis markers among first-time blood donors in Libreville (Gabon) between 2004 and 2016.

BACKGROUND: Very few studies have been conducted on the seroprevalence of syphilis in Gabon. According to the World Health Organization, the average seroprevalence of syphilis has declined from 5.5 to 1.1% in Central Africa. The aim of this study was to test the hypothesis that syphilis decreased in Gabon between 2004 and 2016 and to identify factors involved in this pattern by testing a large sample of first-time blood donors in the capital Libreville. METHODS: The detection of Treponema pallidum was done using a Rapid Plasma Reagin test (RPR) and confirmed by an ELISA test using the Biorad Syphilis Total Antibody EIA II kit or BioMerieux Trepanostika TP recombinant. Assays were performed by dedicated technicians according to manufacturers' recommendations and following the laboratory standard operating procedures. Test results were manually transferred into the laboratory Excel files and hand-written in the laboratory logbook for syphilis testing. Logistic regression was used to assess the impact of sociodemographic characteristics on syphilis marker seroprevalence in both univariate and multivariable analysis. Odds ratios (OR) and 95% confidence intervals were calculated. RESULTS: The seroprevalence of syphilis markers was 8.4% (95% CI = 7.9-8.9) in 2004 and 2.4% (95% CI = 2.1-2.7) in 2016. The difference was significant [OR = 3.78; 95% CI (3.26-4.38); P < 0.001]. The decrease in syphilis seroprevalence was significant in both women and men and in each age group in univariate analysis. In multivariable analysis, controlling for all sociodemographic factors, the decrease in syphilis seroprevalence from 2004 to 2016 remained significant (OR = 3.29; 95% CI = 2.88-3.88, P < 0.001). The seroprevalence of syphilis decreased significantly in men compared to women and young donors compared to donors aged ≥36 years. CONCLUSIONS: This study shows a significant decline in syphilis seroprevalence in first-time blood donors in Libreville, Gabon. Government actions, including multiple HIV prevention activities, are a likely part of this decline

INSIGHTS INTO THE INTERPLAY BETWEEN KIR GENE FREQUENCIES AND CHRONIC HBV INFECTION IN BURKINA FASO

Background/Objective: The receptors of natural killer cells "Killer Cell Immunoglobulin-Like Receptor" (KIR) regulate the activity of Natural killer cells in the innate response against viral infections. To date there is no accurate method to identify high risk groups for cirrhosis and HCC in Sub-Saharan Africa. Therefore, this investigation was undertaken to assess the association between KIR genes frequencies and chronic infection HBV infection in Burkina Faso’s population. Methods: Chronic HBV carriers and healthy patients were selected for this study. The viral load for HBV were performed to confirm the serological status for HBV of the studied cohort. In addition, SSP-PCR was used to characterize the frequencies of KIR genes. Results: The study suggested that inhibitory genes KIR2DL2, KIR2DL3 and activator gene KIR2DS2 (p˂0.001 for all and OR = 2.82; 2.48 and 3.84 respectively) might be associated with chronic stages of HBV infection.  While inhibitory genes KIR3DL1 (p = 0.0018 OR = 0.49), KIR3DL2 (p = 0.005 OR = 0.40), the activator gene KIR2DS1 (p = 0.014 OR = 0.47) and the pseudo gene KIR2DP1 (p = 0.011 OR = 0.49) could be associated with immunity against HBV infection. Patients who carried the KIR3DL2 gene had a high HBV viral load compared to the rest of the study population. Conclusion: Our data showed an evidence of correlation between the propensity of developing chronic HBV infection and certain KIR gene frequencies and that KIR3DL1, KIR3DL2, KIR2DS1 and KIR2DP1 might confer a protective status against chronic HBV infection in Burkina Faso’s patients

ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome

Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS. Abstract INTRODUCTION RESULTS DISCUSSION MATERIALS AND METHODS Acknowledgments Supplementary Materials REFERENCES AND NOTES 0eLetters Abstract Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS

Synergistic combination of cytotoxic chemotherapy and cyclin-dependent kinase 4/6 inhibitors in biliary tract cancers

Background and aims: Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Approach and results: Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.Conclusions: As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.</p

Oncolytic Adenoviruses in Gastrointestinal Cancers

Gastrointestinal malignancies are challenging cancers with considerable economic and societal impacts on health care systems worldwide. While advances in surgical approaches have provided benefits to a proportion of patients, only modest improvements have been attained in the treatment of patients with advanced disease, resulting in limited improvement in survival rates in these patients. Oncolytic adenoviruses are being developed to address gastrointestinal malignancies. Each platform has evolved to maximize tumor-cell killing potency while minimizing toxicities. Tumor-specific bioengineered adenoviruses using chimeric promoters, prodrug convertase enzymes, lethal genes, tumor suppressor genes, and pseudo-typed capsids can provide the innovations for eventual success of oncolytic virotherapy. This article will review the developments in adenoviral platforms in the context of specific gastrointestinal cancers. From the bench to the implementation of clinical trials, this review aims to highlight advances in the field from its early days to the current state of affairs as it pertains to the application of adenoviral oncolytic therapy to gastrointestinal cancers