Prevention of Liver Fibrosis and Cancer in Africa: The PROLIFICA project – a collaborative study of hepatitis B-related liver disease in West Africa

Hepatitis B virus (HBV) infection causes a spectrum of acute and chronic liver disease ranging from inactive chronic carrier status to progressive chronic hepatitis, culminating in end-stage cirrhosis and liver cancer. In sub-Saharan Africa, HBV infection is endemic and the HBV-related disease burden is high, making HBV a signficant threat to health in the African continent. The European Union-funded Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) project was established in 2011, with the central directive to reduce the incidence of HBV-related liver cancer in West Africa. In this editorial, we outline some of the achievements and challenges of the PROLIFICA platform in West Africa, highlighting the the importance of collaborative studies in Africa

Acceptability and feasibility of a screen-and-treat programme for hepatitis B virus infection in The Gambia: the Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) study.

BACKGROUND: Despite the introduction of immunisation for hepatitis B virus (HBV) in the 1990s, HBV-related morbidity and mortality remain high in sub-Saharan Africa. Identification and treatment of asymptomatic people with chronic HBV infection should reduce the disease burden. We therefore assessed the feasibility of a screen-and-treat programme for HBV infection in The Gambia, west Africa, and estimated the proportion of HBV-infected people who had significant liver disease in need of treatment. METHODS: Between Dec 7, 2011, and Jan 24, 2014, individuals living in randomly selected communities in western Gambia were offered hepatitis B surface antigen (HBsAg) screening via a point-of-care test. The test was also offered to potential blood donors attending the central hospital in the capital, Banjul. HBsAg-positive individuals were invited for a comprehensive liver assessment and were offered treatment according to international guidelines. We defined linkage to care as visiting the liver clinic at least once. Eligibility for treatment was judged in accordance with the 2012 European Association for the Study of the Liver guidelines. FINDINGS: HBsAg screening was accepted by 5980 (weighted estimate 68·9%, 95% CI 65·0-72·4) of 8170 adults from 27 rural and 27 urban communities and 5559 (81·4%, 80·4-82·3) of 6832 blood donors. HBsAg was detected in 495 (8·8%, 7·9-9·7) individuals in communities and 721 (13·0%, 12·1-13·9) blood donors. Prevalence was higher in men (239 [10·5%, 8·9-12·1] of 2328 men vs 256 [7·6%, 6·5-8·7] of 3652 women; p=0·004) and middle-aged participants. Linkage to care was high in the communities, with 402 (81·3%) of 495 HBsAg-positive individuals attending the clinic. However, only 300 (41·6%) of 721 HBsAg-positive people screened at the blood bank linked into care. Of those who attended the clinic, 18 (4·4%, 2·5-7·7) patients from the communities and 29 (9·7%, 6·8-13·6) from the blood bank were eligible for treatment. Male sex was strongly associated with treatment eligibility (odds ratio 4·35, 1·50-12·58; p=0·007). INTERPRETATION: HBV infection remains highly prevalent in The Gambia. The high coverage of community-based screening, good linkage into care, and the small proportion of HBsAg carriers who need treatment suggest that large-scale screening and treatment programmes are feasible in sub-Saharan Africa. FUNDING: European Commission (FP7)

[Prevention of liver fibrosis and liver cancer linked to hepatitis B virus in Africa: the Prolifica study].

Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC. With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest. Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare. To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC. Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016. From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies

HBV continuum of care using community- and hospital-based screening interventions in Senegal: Results from the PROLIFICA programme

BACKGROUND & AIMS: Strategies to implement HBV screening and treatment are critical to achieve HBV elimination but have been inadequately evaluated in sub-Saharan Africa (sSA). METHODS: We assessed the feasibility of screen-and-treat interventions in 3 real-world settings (community, workplace, and hospital) in Senegal. Adult participants were screened using a rapid HBsAg point-of-care test. The proportion linked to care, the proportion who had complete clinical staging (alanine transaminase [ALT], viral load, and FibroScan®), and the proportion eligible for treatment were compared among the 3 intervention groups. RESULTS: In 2013-2016, a total of 3,665 individuals were screened for HBsAg in the community (n = 2,153) and in workplaces (n = 1,512); 199/2,153 (9.2%) and 167/1,512 (11%) were HBsAg-positive in the community and workplaces, respectively. In the hospital setting (outpatient clinics), 638 HBsAg-positive participants were enrolled in the study. All infected participants were treatment naïve. Linkage to care was similar among community-based (69.9%), workplace-based (69.5%), and hospital-based interventions (72.6%, p = 0.617). Of HBV-infected participants successfully linked to care, full clinical staging was obtained in 47.5% (66/139), 59.5% (69/116), and 71.1% (329/463) from the community, workplaces, and hospitals, respectively (p <0.001). The proportion eligible for treatment (EASL criteria) differed among community- (9.1%), workplace- (30.4%), and hospital-based settings (17.6%, p = 0.007). Acceptability of antiviral therapy, adherence, and safety at 1 year were very good. CONCLUSIONS: HBV screen-and-treat interventions are feasible in non-hospital and hospital settings in Senegal. However, the continuum of care is suboptimal owing to limited access to full clinical staging. Improvement in access to diagnostic services is urgently needed in sSA. LAY SUMMARY: Hepatitis B infection is highly endemic in Senegal. Screening for infection can be done outside hospitals, in communities or workplaces. However, the hepatitis B continuum of care is suboptimal in Senegal and needs to be simplified to scale-up diagnosis and treatment coverage

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Rôle de la tranferrine dans le système nerveux central et dans la fonction testiculaire

Diplôme : Dr. d'Universit

La protéomique : identification des protéines du fluide de l'épididyme de verrat

Diplôme : Maîtris

Rôle de la transferrine dans le système nerveux central et dans la fonction testiculaire

Transferrin (Tf) is well known as an iron transport glycoprotein mainly synthesized by hepatocytes. Because of the blood barrier, Tf is also synthesized by oligodendrocytes (Ols) in the central nervous system (SNC) and by Sertoli cells in testis. In order to determinate extrahepatic Tf function, we used transgenic mice overexpressing human Tf gene. In the brain, Tf overexpression increased Ols progenitor maturation by inducing Sox10 expression. In testis, Tf overexpression decreased spermatozoids production without affecting mice fertility. Tf inhibition in Sertoli cells by siRNA increases residual bodies (RB) phagocytosis. We also show the existance of a dimeric Tf form in Sertoli cells, which inhibits ingestion of RB in an iron dependent manner. Tf dimer specifically stimulates the expression of Gas6, a powerful regulator of the phagocytosis process. In order to confirm these results, in vivo, we created a transgenic mouse model expressing Tf shRNA only in Sertoli cell or in Ols.La transferrine (Tf), glycoprotéine connue pour son rôle de transporteur de fer, est principalement synthétisée par les hépatocytes. Du fait de la présence de barrière hématique, la Tf est synthétisée localement dans le système nerveux central (SNC) par les oligodendrocytes (Ols) et dans le testicule par les cellules de Sertoli. Afin de comprendre le rôle de la Tf extra-hépatique, nous avons utilisé un modèle de souris exprimant Tf humaine. Dans le cerveau, la suxexpression de la Tf entraîne une accélératoin de la maturation des Ols via l'activation de Sox10. Au niveau testiculaire, la surexpression provoque une baisse de la réserve spermatique sans altérer la fertilité. L'inhibition de la Tf sertolienne par siRNA stimule la phagocytose des corps résiduels (CR). Nous montrons l'existence d'une forme dimérique de la Tf capable d'inhiber l'ingestion des CR par les cellules de Sertoli de façon dépendante du fer. La Tf dimérique stimule spécifiquement l'expression de Gas6, un puissant régulateur de la phagocytose. Pour valider ces résultats in vivo, nous avons créé un modèle de souris exprimant le shRNA de la Tf uniquement dans les cellules de Sertoli ou dans les Ols.TOURS-BU Sciences Pharmacie (372612104) / SudocSudocFranceF

Une nouvelle fonction pour la transferrine exprimée par le testicule

National audienc

The transferrin expression by Sertoli cell was critical to the early morphological events of testis cord formation

National audienc