Clinical efficacy, safety, and immunogenicity of a live attenuated tetravalent dengue vaccine (CYD-TDV) in Children: a systematic review with meta-analysis

BACKGROUND Dengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children. METHODS This is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 - RR)*100], safety (RR), and immunogenicity (weighted mean difference) in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies. RESULTS The overall efficacy of CYD-TDV vaccine was 54% (40-64), while serotype-specific efficacy was 77% (66-85) for DENV4, 75% (65-82) for DENV3, 50% (36-61) for DENV1, and 34% (14-49) for DENV2. 15% (-174-74) vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months) revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04-1.17; p-value = 0.001). Immunogenicity (expressed as geometric mean titers) in descending order was 439.7 (331.7-547.7), 323 (247 - 398.7), 144.1 (117.9-170.2), and 105 (88.7-122.8) for DENV3, DENV2, DENV1, and DENV4, respectively. CONCLUSION CYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months) from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine safety in children. However, CYD-TDV vaccine should be considered for use in regions where DENV2 is not endemic as currently there is no specific treatment for dengue infection

Elimination of Falciparum Malaria and Emergence of Severe Dengue:An Independent or Interdependent Phenomenon?

The global malaria burden, including falciparum malaria, has been reduced by 50% since 2000, though less so in Sub-Saharan Africa. Regional malaria elimination campaigns beginning in the 1940s, up-scaled in the 1950s, succeeded in the 1970s in eliminating malaria from Europe, North America, the Caribbean (except Haiti), and parts of Asia and South- and Central America. Dengue has grown dramatically throughout the pantropical regions since the 1950s, first in Southeast Asia in the form of large-scale epidemics including severe dengue, though mostly sparing Sub-Saharan Africa. Globally, the WHO estimates 50 million dengue infections every year, while others estimate almost 400 million infections, including 100 million clinical cases. Curiously, despite wide geographic overlap between malaria and dengue-endemic areas, published reports of co-infections have been scarce until recently. Superimposed acute dengue infection might be expected to result in more severe combined disease because both pathogens can induce shock and hemorrhage. However, a recent review found no reports on more severe morbidity or higher mortality associated with co-infections. Cases of severe dual infections have almost exclusively been reported from South America, and predominantly in persons infected by Plasmodium vivax. We hypothesize that malaria infection may partially protect against dengue – in particular falciparum malaria against severe dengue – and that this inter-species cross-protection may explain the near absence of severe dengue from the Sub-Saharan region and parts of South Asia until recently. We speculate that malaria infection elicits cross-reactive antibodies or other immune responses that infer cross-protection, or at least partial cross-protection, against symptomatic and severe dengue. Plasmodia have been shown to give rise to polyclonal B-cell activation and to heterophilic antibodies, while some anti-dengue IgM tests have high degree of cross-reactivity with sera from malaria patients. In the following, the historical evolution of falciparum malaria and dengue is briefly reviewed, and we explore early evidence of subclinical dengue in high-transmission malaria areas as well as conflicting reports on severity of co-morbidity. We also discuss examples of other interspecies interactions

Isolement d’amibes libres à partir de la muqueuse nasale de l’homme

De mars 1976 à décembre 1978, nous avons analysé 1039 écouvillons nasaux dans le but de dépister les porteurs sains d’amibes libres. Nous avons ainsi isolé 9 souches amibiennes dont une Hartmannelia vermiformis. Des 8 Acanthamibes restantes, une seule, O.R.L. 561 (Acanthamoeba hatchetti) est pathogène pour la souris, au même titre que les 2 souches identiques connues et A. culbertsoni

Changing sero-epidemiology of hepatitis A in Asia Pacific countries: A systematic review

Objectives: Hepatitis A is a viral liver disease whose prevalence is associated with low socio-economic and hygiene levels due to its faecal–oral transmission. Severity increases with age, and immunity is life-long. Decreased endemicity could result in increased age and severity of cases. A literature review was conducted to describe changes in age-stratified hepatitis A seroprevalence in Asia Pacific countries from 1980 to 2016, and to identify gaps in the literature. The PRISMA guidelines were followed. Methods: The PubMed database was searched for studies on age-specific hepatitis A seroprevalence in 17 Asia Pacific countries. All studies published in the English language, reporting human hepatitis A seroprevalence levels in any age group, were included. Results: Seventy-three publications from 11 countries were identified. A trend of increasing age at first exposure over time was observed, particularly in developed countries such as Japan, Taiwan, Thailand, and Korea, suggesting a transition in terms of endemicity. Conclusions: Extensive gaps in the literature were identified between countries and year of publication, indicating the need for further research. Decreasing hepatitis A exposure and thus immunity conferred during childhood, may render older populations susceptible to infection. The public health and economic value of vaccination against hepatitis A should be assessed within this changing epidemiological context. Keywords: Hepatitis A, Seroprevalence, Asia Pacific, Epidemiolog

Éthique de la recherche : réglementations françaises et applications en oncologie radiothérapie

International audienc

A comparative study on active and passive epidemiological surveillance for dengue in five countries of Latin America

Background: Dengue is a notifiable infectious disease in many countries, but under-reporting of cases to National Epidemiological Surveillance Systems (NESSs) conceals the true extent of the disease burden. The incidence of dengue identified in a cohort study was compared with those reported to NESSs. Methods: A randomized, placebo-controlled study was undertaken in Brazil, Colombia, Honduras, Mexico, and Puerto Rico to assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in children aged 9–16 years. The incidence of dengue in the placebo group was compared with that reported to NESSs in a similar age group (10–19 years) from June 2011 to April 2014. Results: Three thousand six hundred and fifteen suspected dengue cases were identified in the study over 13 527 person-years of observation. The overall incidence of confirmed dengue was 2.9 per 100 person-years (range 1.5 to 4.1 per 100 person-years). In the NESSs combined, over 3.2 million suspected dengue cases were reported during the same period, corresponding to over 1 billion person-years of observation. The incidence of confirmed dengue reported by the NESSs in the same locality where the study took place was 0.286 per 100 person-years across Brazil, Colombia, and Mexico (range 0.180 to 0.734 per 100 person-years). The incidence of confirmed dengue was 10.0-fold higher in the study than that reported to NESSs in the same localities (range 3.5- to 19.4-fold higher). Conclusions: There is a substantial under-reporting of dengue in the NESSs. Understanding the level of under-reporting would allow more accurate estimates of the dengue burden in Latin America

Cell and tissue responses at the interface with a chitosan hydrogel intended for vascular applications: in vitro and in vivo exploration

Aims: The need for small caliber vessels to treat cardiovascular diseases has grown. However, synthetic polymers perform poorly in small-diameter applications. Chitosan hydrogels can provide a novel biological scaffold for vascular engineering. The goal of this study was to explore host cell and tissue behavior at the interface with chitosan-based scaffolds in vitro and in vivo.Methods and results: in vitro, we assessed the ability of endothelial cells lining chitosan hydrogels to produce tissue factor (TF), thrombomodulin (TM) and nitric oxide. We showed that endothelial cells behave as a native endothelium since under stimulation, TF and TM expression increased and decreased, respectively. Endothelial cells seeded on chitosan produced nitric oxide, but no change was observed under stimulation. After in vivo subcutaneous implantation of chitosan hydrogels in rats, macrophage activation phenotypes, playing a crucial role in biomaterial/tissue, were explored by immunohistochemistry. Our results suggested a balance between pro- and anti-inflammatory signals since we observed an inflammatory response in favor of macrophage M2 phenotype.Conclusion: in vitro exploration of endothelial cell response at the interface with chitosan hydrogel showed a functional endothelium and in vivo exploration of tissue response revealed a biointegration of chitosan hydrogels

A recombinant live attenuated tetravalent vaccine for the prevention of dengue

Introduction: Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in ‘real-life’ following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed

Towards an in vitro model of glomerular barrier unit with an innovative bioassembly method

Background: The development of an artificial glomerular unit may be pivotal for renal pathophysiology studies at a multicellular scale. Using a tissue engineering approach, we aimed to reproduce in part the specific glomerular barrier architecture by manufacturing a glomerular microfibre (Mf).Methods: Immortalized human glomerular cell lines of endothelial cells (GEnCs) and podocytes were used. Cells and a three-dimensional (3D) matrix were characterized by immunofluorescence with confocal analysis, Western blot and polymerase chain reaction. Optical and electron microscopy were used to study Mf and cell shapes. We also analysed cell viability and cell metabolism within the 3D construct at 14 days.Results: Using the Mf manufacturing method, we repeatedly obtained a cellularized Mf sorting human glomerular cells in 3D. Around a central structure made of collagen I, we obtained an internal layer composed of GEnC, a newly formed glomerular basement membrane rich in α5 collagen IV and an external layer of podocytes. The cell concentration, optimal seeding time and role of physical stresses were modulated to obtain the Mf. Cell viability and expression of specific proteins (nephrin, synaptopodin, vascular endothelial growth factor receptor 2 (VEGFR2) and von Willebrandt factor (vWF)) were maintained for 19 days in the Mf system. Mf ultrastructure, observed with EM, had similarities with the human glomerular barrier.Conclusion: In summary, with our 3D bio-engineered glomerular fibre, GEnC and podocytes produced a glomerular basement membrane. In the future, this glomerular Mf will allow us to stu