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A conference on «ARBOVIRUSES, A GLOBAL PUBLIC HEALTH THREAT» was organized on June 20-22, 2018 at the Merieux Foundation Conference Center in Veyrier du Lac, France, to review and raise awareness to the global public health threat of epidemic arboviruses, and to advance the discussion on the control and prevention of arboviral diseases. The presentations by scientists and public health officials from Asia, the Americas, Europe and Africa strengthened the notion that arboviral diseases of both humans and domestic animals are progressively becoming dominant public health problems in the world. The repeated occurrence of recent deadly epidemics strongly reinforces the call for action against these viral diseases, and the need for developing effective vaccines, drugs, vector control tools and strong prevention programs.

Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of >100 cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).

Background In 2019, the World Health Organization (WHO) flagged vaccine hesitancy as one of the top 10 threats to global health. The drivers of and barriers to under-vaccination include logistics (access to and awareness of affordable vaccines), as well as a complex mix of psychological, social, political, and cultural factors. Increasing vaccine uptake There is a need for effective strategies to increase vaccine uptake in various settings, based on the best available evidence. Fortunately, the field of vaccine acceptance research is growing rapidly with the development, implementation, and evaluation of diverse measurement tools, as well as interventions to address the challenging range of drivers of and barriers to vaccine acceptance. Annual Vaccine Acceptance Meetings Since 2011, the Merieux Foundation has hosted Annual Vaccine Acceptance Meetings in Annecy, France that have fostered an informal community of practice on vaccination confidence and vaccine uptake. Mutual learning and sharing of knowledge has resulted directly in multiple initiatives and research projects. This article reports the discussions from the 7th Annual Vaccine Acceptance Meeting held September 23–25, 2019. During this meeting, participants discussed emergent vaccine acceptance challenges and evidence-informed ways of addressing them in a programme that included sessions on vaccine mandates, vaccine acceptance and demand, training on vaccine acceptance, and frameworks for resilience of vaccination programmes.

Introduction The newly identified SARS-CoV-2 can cause serious acute respiratory infections such as pneumonia. In France, mortality rate in the general population was approximately 10% and could reach higher levels at the hospital. In the current context of high incidence rates of SARS-CoV-2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to estimate the prevalence and incidence of suspected or confirmed cases of nosocomial SARS-CoV-2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals. Methods and analysis This will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients and healthcare professionals in France and hospitals affiliated with the GABRIEL network. Demographic and clinical data will be collected using case report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV-2 by reverse-transcriptase PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV-2 infections relative to all patients with syndromes suggestive of SARS-CoV-2 infection, will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset. Ethics and dissemination This study was approved by the clinical research and committee of all participating countries. The findings will be submitted to peer-reviewed journal for publication and shared with national health authorities. Trial registration number NCT04290780.

The Middle East, Eastern Europe, Central Asia and North Africa Rabies Control Network (MERACON), is built upon the achievements of the Middle East and Eastern Europe Rabies Expert Bureau (MEEREB). MERACON aims to foster collaboration among Member States (MS) and develop shared regional objectives, building momentum towards dog-mediated rabies control and elimination. Here we assess the epidemiology of rabies and preparedness in twelve participating MS, using case and rabies capacity data for 2017, and compare our findings with previous published reports and a predictive burden model. Across MS, the number of reported cases of dog rabies per 100,000 dog population and the number of reported human deaths per 100,000 population as a result of dog-mediated rabies appeared weakly associated. Compared to 2014 there has been a decrease in the number of reported human cases in five of the twelve MS, three MS reported an increase, two MS continued to report zero cases, and the remaining two MS were not listed in the 2014 study and therefore no comparison could be drawn. Vaccination coverage in dogs has increased since 2014 in half (4/8) of the MS where data are available. Most importantly, it is evident that there is a need for improved data collection, sharing and reporting at both the national and international levels. With the formation of the MERACON network, MS will be able to align with international best practices, while also fostering international support with other MS and international organisations.

IntroductionThe newly identified SARS-CoV2 can cause serious acute respiratory infections such as pneumonia with a mortality rate of approximately 2% to 4%. In the current context of high incidence rates of SARS-CoV2 in the community, a significant increase in the rate of nosocomial transmission is expected. The risk of nosocomial transmission could even be higher in low-income countries that have fragile healthcare systems. This protocol is intended to study and document suspected or confirmed cases of nosocomial SARS-CoV2 infection, the clinical spectrum and the determinants (risk factors/protective) at participating hospitals.Methods and analysisThis will be an international multicentre prospective, observational, hospital-based study in adults and children. It will include volunteer patients, care givers and healthcare professionals in France and hospitals affiliated with the GABRIEL network.Demographic and clinical data will be collected using case-report forms designed especially for the purpose of the project. A nasopharyngeal swab will be collected and tested for SARS-CoV2 by RT-PCR. Characteristics of the study participants, the proportion of confirmed nosocomial SARS-CoV2 infections relative to all patients with syndromes suggestive of 2019-nCoV infection will be analysed. Appropriate multivariate modelling will be used to identify the determinants associated with nosocomial onset.Ethics and disseminationThis study was approved by the clinical research and committee of Ile de France V on March 8, 2020.Registration detailsThe trial was registered in ClinicalTrials (NCT04290780).Strengths and limitations of the study➢This prospective study will generate and evaluate original data on nosocomial SARS-CoV2 infection in France and in the low-income countries of the GABRIEL network using the same protocol and standardised CRF.➢The results will provide the opportunity to compare the management of nosocomial Covid-19 infection in different settings for mutual exchanges and optimisation.➢The results will make it possible to refine the definition of nosocomial SARS-CoV2 infection, strengthen preventive campaigns for in-hospital transmission of SARS-CoV2 and pave the way for new recommendations in terms of preventive measures.➢Selection bias owing to access to care in different populations and bias owing to the extent of access to personal protective equipment, in particular, in low-income countries may occur.➢The non-exhaustivity of the confounders to be collected should be considered for interpretation of the results.

Background: The Middle East and North Africa (MENA) region faces a dual challenge with regard to influenza infection due to severe zoonotic influenza outbreaks episodes and the circulation of Northern Hemisphere human influenza viruses among pilgrims. Methods: The MENA Influenza Stakeholder Network (MENA-ISN) was set-up with the aim of increasing seasonal influenza vaccination coverage by (i) enhancing evidence-based exchanges, and (ii) increasing awareness on the safety and benefits of seasonal vaccination. During the 7th MENA-ISN meeting, representatives from 8 countries presented their influenza surveillance, vaccination coverage and actions achieved and provided a list of country objectives for the upcoming 3 years. Results: MENA-ISN countries share the goal to reduce influenza related morbidity and mortality. Participants admitted that lack of knowledge about influenza, its consequences in terms of morbidity, mortality and economy are the major barrier to attaining higher influenza vaccination coverage in their countries. The cost of the vaccine is another key barrier that could contribute to low vaccination coverage. Participants drew a list of strategic interventions to bridge gaps in the knowledge of influenza burden in this region. Conclusions: Participating countries concluded that despite an increase in vaccine uptake observed during the last few years, influenza vaccination coverage remains relatively low. Priority areas should be identified and action plans tailored to each country situation set-up to investigate the best way to move forward. Keywords: Influenza, Vaccination coverage, Surveillance, Middle East and North Africa

Immune evasion is critical for pathogens to maintain their presence within hosts, giving rise to chronic infections. Here, we examine the immune evasion strategies employed by three pathogens with high medical burden, namely, tuberculosis, HIV and HBV. Establishment of chronic infection by these pathogens is a multi-step process that involves an interplay between restriction factor, innate immunity and adaptive immunity. Engagement of these host defences is intimately linked with specific steps within the pathogen replication cycles. Critical host factors are increasingly recognized to regulate immune evasion and susceptibility to disease. Fuelled by innovative technology development, the understanding of these mechanisms provides critical knowledge for rational design of vaccines and therapeutic immune strategies.

Background The recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics. Objectives The objective of this field study was to assess the clinical performance of the FilmArray® BioThreat-E test for the detection of Ebola Zaire virus in whole blood in symptomatic patients suspected of Ebola Virus Disease in Conakry (Guinea) from March to July 2015. Study design The BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStar® Filovirus RT-PCR Kit 1.0 (Altona-Diagnostics). We also assessed the performance of this assay in noninvasive specimens (urine and saliva) to detect infected patients. Results Of 135 patients enrolled and eligible for performance assessment on whole blood, the sensitivity was 95.7% [95% CI: 85.5–99.5] and specificity 100% [95% CI: 95.9–100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive with the BioThreat-E test. Conclusions This study showed that the FilmArray BioThreat-E test performs comparably to conventional molecular tests under field conditions, providing results and interpretation in approximately 1 h. Due to its operational characteristics, it can be easily deployed in the field during an epidemic and could also be a useful tool for post-outbreak surveillance.

International audience; Pneumonia is the leading cause of death in children. The objectives were to evaluate the microbiological agents linked with hypoxemia in hospitalized children with pneumonia from developing countries, to identify predictors of hypoxemia, and to characterize factors associated with in-hospital mortality. A multicenter, observational study was conducted in five hospitals, from India (Lucknow, Vadu), Madagascar (Antananarivo), Mali (Bamako), and Paraguay (San Lorenzo). Children aged 2-60 months with radiologically confirmed pneumonia were enrolled prospectively. Respiratory and whole blood specimens were collected, identifying viruses and bacteria by real-time multiplex polymerase chain reaction (PCR). Microbiological agents linked with hypoxemia at admission (oxygen saturation \textless 90%) were analyzed by multivariate logistic regression, and factors associated with 14-day in-hospital mortality were assessed by bivariate Cox regression. Overall, 405 pneumonia cases (3,338 hospitalization days) were analyzed; 13 patients died within 14 days of hospitalization. Hypoxemia prevalence was 17.3%. Detection of human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) in respiratory samples was independently associated with increased risk of hypoxemia (adjusted odds ratio [aOR] = 2.4, 95% confidence interval [95% CI] = 1.0-5.8 and aOR = 2.5, 95% CI = 1.1-5.3, respectively). Lower chest indrawing and cyanosis were predictive of hypoxemia (positive likelihood ratios = 2.3 and 2.4, respectively). Predictors of death were Streptococcus pneumoniae detection by blood PCR (crude hazard ratio [cHR] = 4.6, 95% CI = 1.5-14.0), procalcitonin >= 50 ng/mL (cHR = 22.4, 95% CI = 7.3-68.5) and hypoxemia (cHR = 4.8, 95% CI = 1.6-14.4). These findings were consistent on bivariate analysis. hMPV and RSV in respiratory samples were linked with hypoxemia, and S. pneumoniae in blood was associated with increased risk of death among hospitalized children with pneumonia in developing countries.

Despite long-standing vaccination programs, substantial increases in reported cases of pertussis have been described in several countries during the last 5years. Cases among very young infants who are at greatest risk of pertussis-related hospitalizations and mortality are the most alarming. Multiple hypotheses including but not limited to the availability of more sensitive diagnostic tests, greater awareness, and waning vaccine-induced immunity over time have been posited for the current challenges with pertussis. The conference "Pertussis: biology, epidemiology and prevention" held in Annecy-France (November 11-13, 2015) brought together experts and interested individuals to examine these issues and to formulate recommendations for optimal use of current vaccines, with a particular focus on strategies to minimize severe morbidity and mortality among infants during the first months of life. The expert panel concluded that improving vaccination strategies with current vaccines and development of new highly immunogenic and efficacious pertussis vaccines that have acceptable adverse event profiles are currently the two main areas of investigation for the control of pertussis. Some possible pathways forward to address these main challenges are discussed in this report.

Background Improving knowledge regarding Streptococcus pneumoniae distribution in pneumonia cases is important to better target preventive and curative measures. The objective was to describe S. pneumoniae serotypes in children with or without pneumonia Methods It was a case-control study carried out in 8 developing and emerging countries between 2010 and 2014. Cases were children aged Results In nasopharyngeal samples, S. pneumoniae were detected in 68.2% of the cases and 47.5% of the controls (P < .001). Nasopharyngeal carriage was associated with a higher risk of being a case in 6/8 study sites (adjusted odds ratio ranged from 0.71 [95% confidence interval [CI], .39–1.29; P = .26] in India [Pune/Vadu] to 11.86 [95% CI, 5.77–24.41; P < .001] in Mongolia). The 13-valent pneumococcal conjugate vaccine (PCV13) serotypes were more frequently detected in cases with nasopharyngeal carriage (67.1%) than in controls with nasopharyngeal carriage (54.6%), P < .001. Streptococcus pneumoniae was detected in blood by polymerase chain reaction in 8.3% of the cases. Of 34 cases with an S. pneumoniae serotype detected in blood, 27 (79%) had the same serotype in the nasopharyngeal sample. Conclusions The results confirm the assumption that the isolate carrying or causing disease in an individual is of the same serotype. Most serotypes independently associated with nasopharyngeal carriage or pneumonia are covered by PCV13, suggesting that increased PCV coverage would reduce the burden of S. pneumoniae–related pneumonia.

Respiratory diseases are a major contributor to morbidity and mortality in many tropical countries, including Lao PDR. However, little has been published regarding viral or bacterial pathogens that can contribute to influenza-like illness (ILI) in a community setting. We report on the results of a community-based surveillance that prospectively monitored the incidence of ILI and its causative pathogens in Vientiane capital in Lao PDR. A cohort of 995 households, including 4885 study participants, were followed-up between May 2015 and May 2016. Nasopharyngeal swabs, throat swabs, and sputum specimens were collected from ILI cases identified through active case-finding. Real-Time PCR was used to test nasopharyngeal swabs for 21 respiratory pathogens, while throat and sputum samples were subjected to bacterial culture. Generalized linear mixed models were used to assess potential risk factors for associations with ILI. In total, 548 episodes of ILI were reported among 476 (9.7%) of the study participants and 330 (33.2%) of the study households. The adjusted estimated incidence of ILI within the study area was 10.7 (95%CI: 9.4-11.9) episodes per 100 person-years. ILI was significantly associated with age group (p

Item does not contain fulltext The heterologous or non-specific effects (NSEs) of vaccines, at times defined as "off-target effects" suggest that they can affect the immune response to organisms other than their pathogen-specific intended purpose. These NSEs have been the subject of clinical, immunological and epidemiological studies and are increasingly recognized as an important biological process by a growing group of immunologists and epidemiologists. Much remain to be learned about the extent and underlying mechanisms for these effects. The conference "Off-target effects of vaccination" held in Annecy-France (June 8-10 2015) intended to take a holistic approach drawing from the fields of immunology, systems biology, epidemiology, bioinformatics, public health and regulatory science to address fundamental questions of immunological mechanisms, as well as translational questions about vaccines NSEs. NSE observations were examined using case-studies on live attenuated vaccines and non-live vaccines followed by discussion of studies of possible biological mechanisms. Some possible pathways forward in the study of vaccines NSE were identified and discussed by the expert group.

The 2015 Cent Gardes Conference on HIV vaccines took place on October 25-27 at the Merieux Foundation Conference Center in Veyrier du Lac, near Annecy, France. The meeting reviewed progress in the development of HIV vaccines and identified new directions of future research. The field has advanced incrementally over the past year but major progress will require additional information from new clinical trials. In this article, we review the presentations on humoral immune responses to HIV, and highlight the difficulty of eliciting broadly neutralizing antibodies by vaccination. Advances in cellular immunity for HIV prevention will be reviewed separately, in a following article.

There is an active discussion in the public health community on how to assess and incorporate, in addition to safety and measures of protective efficacy, the full public health value of preventive vaccines into the evidence-based decision-making process of vaccine licensure and recommendations for public health use. The conference "Beyond efficacy: the full public health impact of vaccines in addition to efficacy measures in trials" held in Annecy, France (June 22-24, 2015) has addressed this issue and provided recommendations on how to better capture the whole public health impact of vaccines. Using key examples, the expert group stressed that we are in the midst of a new paradigm in vaccine evaluation, where all aspects of public health value of vaccines beyond efficacy should be evaluated. To yield a wider scope of vaccine benefits, additional measures such as vaccine preventable disease incidence, overall efficacy and other outcomes such as under-five mortality or non-etiologically confirmed clinical syndromes should be assessed in addition to traditional efficacy or effectiveness measurements. Dynamic modelling and the use of probe studies should also be considered to provide additional insight to the full public health value of a vaccine. The use of burden reduction and conditional licensure of vaccines based on collection of outcome results should be considered by regulatory agencies.

Background Sickle cell disease (SCD) accounts for 5% of mortality in African children aged

BackgroundInfluenza-like illness occurs annually worldwide, with peak timing and severity varying seasonally, resulting in significant annual mortality.ObjectivesThere were three objectives: (1) to describe the epidemiological and clinical features of hospitalised patients with severe acute respiratory infection caused by influenza and other respiratory viruses (ORVs); (2) to report the influenza seasonality in the region and (3) to correlate findings of influenza circulation and immunisation time in Brazil.Patients/methodsThis study took place in three Brazilian hospitals located in cities with different climatic conditions (Curitiba (south), Rio de Janeiro (south-east) and Fortaleza (north-east)). Patients presenting with an acute process with indication for admission consisting of a predefined set of conditions potentially associated with recent influenza infection were enrolled.ResultsWe screened 1666 patients, with 595 meeting the inclusion criteria. Influenza viruses and ORVs were detected in 6.5% and 59% of patients, respectively. Influenza-positive cases fell into the severe spectrum as compared with those with ORVs (30% vs 11%), but without any difference in mortality rates. Epidemiological results revealed variations in the peak time of influenza infections between north-east (Fortaleza) and south (Curitiba) Brazil, basically following the rain period of each region. In north-east Brazil, viral circulation was prevalent in the first 4 months of the year, indicating that the vaccination campaign occurred in a postseasonal period, possibly explaining the low effectiveness.ConclusionsThe active-surveillance model is a valuable tool for investigating respiratory virus impact on hospitalised patients, with influenza-infection monitoring enabling implementation of adequate preventive measures.

The 2014 Cent Gardes Conference took place on October 5–7, 2014, at the Fondation Merieux Conference Center, on the shores of the Annecy Lake and aimed to review the progress and promise of HIV vaccines. The elicitation of broadly neutralizing antibodies (bNAbs), their use in passive immunization, as well as their genetic delivery (vector immunoprophylaxis) by a recombinant Adenovirus-associated virus (AAV) vector were reviewed in a preceding article [1]. Approaches to the elicitation of long-lasting T cell or mucosal immunity were also discussed and are now reviewed here. The possibility of eliciting mucosal IgAs was discussed, since it was demonstrated that transcytosis-blocking IgAs can protect monkeys against repeated vaginal challenge with a pathogenic chimeric simian and human immunodeficiency virus (SHIV). The possibility of purging the HIV reservoirs from HIV-infected persons and developing a cure of the disease was also discussed.

The 2014 Cent Gardes Conference took place on October 5–7 at the Fondation Merieux Conference Center, on the shores of the Annecy Lake. The aim of the meeting was to review progress in the field of HIV vaccines during the last two years and to explore the promising avenues of future research. The identification of broadly neutralizing antibodies (bNAbs) able to neutralize a majority of circulating HIV strains has encouraged hopes for a highly effective “universal” HIV vaccine. Analysis of B-cell maturation that leads to the production of bNAbs, however, appears extremely complex, and not easily reproduced by classical active immunization. The use of bNAbs for passive immunization is thus being explored as an alternative, either for immunotherapy or prophylaxis. Their delivery by a recombinant adenovirus-associated virus (AAV), also known as vector immunoprophylaxis, has demonstrated proof-of-concept in animal models and is now in early stage clinical trials. Other approaches were discussed at the meeting, such as eliciting long-lasting T cell or mucosal immunity. In spite of remarkable progress, the quest for an efficacious HIV vaccine remains a daunting challenge.

There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes. Following an initial conference at the Fondation Merieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016. The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines.

An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be more affordable. CoPs are lacking today for most existing and investigational enteric vaccines. In order to share the latest information on CoPs for enteric vaccines and to discuss novel approaches to correlate mucosal immune responses in humans with protection, the Foundation Merieux organized an international conference of experts where potential CoPs for vaccines were examined using case-studies for both bacterial and viral enteric pathogens. Experts on the panel concluded that to date, all established enteric vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines, are based on serological immune responses even though these may poorly reflect the relevant gut immune responses or predict protective efficacy. Known CoPs for cholera, norovirus and rotavirus could be considered as acceptable for comparisons of similarly composed vaccines while more work is still needed to establish CoPs for the remaining enteric pathogens and their candidate vaccines. Novel approaches to correlate human mucosal immune responses with protection include the investigation of gut-originating antibody-secreting cells (ASCs), B memory cells and follicular helper T cells from samples of peripheral blood during their recirculation.

Background Vaccination is a complex ecosystem with several components that interact with one another and with the environment. Today’s vaccine ecosystem is defined by the pursuit of polio eradication, the drive to get as many of the new vaccines to as many people as possible and the research and development against immunologically challenging diseases. Despite these successes, vaccine ecosystem is facing keys issues with regard to supply/distribution and cost/profitability asymmetry that risk slowing its global growth. The conference “Vaccination ecosystem health check: achieving impact today and sustainability for tomorrow” held in Annecy-France (January 19–21, 2015) took stock of the health of today’s vaccination ecosystem and its ability to reliably and sustainably supply high-quality vaccines while investing in tomorrow’s needed innovation. Main findings Small and decreasing numbers of suppliers/manufacturing facilities; paucity of research-driven companies; regulatory pressures; market uncertainties; political prioritization; anti-vaccine movements/complacency; and technological and programmatic issues were acknowledged as the major challenges that could weaken today’s vaccination ecosystem. The expert panel discussed also drivers and barriers to a sustainable vaccination ecosystem; the metrics of a vaccination ecosystem; and what should be added, removed, increased, or reduced to maintain the health of the vaccination ecosystem. Electronic supplementary material The online version of this article (doi:10.1186/s12919-016-0069-y) contains supplementary material, which is available to authorized users.

Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions. We demonstrated that endogenous miRNA-200a-3p, whose expression was synergistically induced following co-infection, indirectly regulates CXCL10 expression by targeting suppressor of cytokine signaling-6 (SOCS-6), a well-known regulator of the JAK-STAT signaling pathway. Additionally, in a subsequent clinical pilot study, immunomodulators levels were evaluated in samples from 74 children (≤5 years-old) hospitalized with viral and/or bacterial community-acquired pneumonia. Clinically, among the 74 cases of pneumonia, patients with identified mixed-detection had significantly higher (3.6-fold) serum IP-10 levels than those with a single detection (P = 0.03), and were significantly associated with severe pneumonia (P

The recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics.The objective of this field study was to assess the clinical performance of the FilmArrayThe BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStarOf 135 patients enrolled and eligible for performance assessment on whole blood, the sensitivity was 95.7% [95% CI: 85.5-99.5] and specificity 100% [95% CI: 95.9-100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive with the BioThreat-E test.This study showed that the FilmArray BioThreat-E test performs comparably to conventional molecular tests under field conditions, providing results and interpretation in approximately 1h. Due to its operational characteristics, it can be easily deployed in the field during an epidemic and could also be a useful tool for post-outbreak surveillance.

The Cent Gardes Conference on HIV Vaccines took place on November 5–7, 2012 at the Fondation Merieux Conference Center, Annecy, France. The aim of the meeting was to review the B cell response to human immunodeficiency virus-1 (HIV-1) infection and immunization, from broadly neutralizing antibodies (bnAbs) to non-neutralizing antibodies (n-nAbs). This paper, Part 2 of the report, focuses on potentially protective n-nAbs. Evidence was presented that n-nAbs may effectively contribute to protection against HIV, as illustrated by the recent RV144 efficacy trial. They can either act as IgGs by mediating antibody-dependent cellular cytotoxicity (ADCC) involving Fc effector functions, or as IgAs, particularly dimeric IgA1s, which can inhibit virus transcytosis through monocellular epithelia and could play an important role in mucosal immunity.

The Cent Gardes Conference on HIV Vaccines took place on November 5–7, 2012 at the Fondation Merieux Conference Center, Annecy, France. The aim of the meeting was to review the B cell response to human immunodeficiency virus-1 (HIV-1) infection and immunization, from broadly neutralizing antibodies (bnAbs) to non-neutralizing antibodies (n-nAbs). The production of cross-reactive bnAbs is one of the greatest challenges in HIV-1 vaccine development. In natural HIV infection, bnAbs are observed in only a minority of infected individuals and take a few years to develop. This report presents a comprehensive review of how these Abs arise, the possible role of viral evolution, and the activation and maturation requirements of B cell lines that lead to their production. Passive immunization with bnAbs provides efficient, cross-clade protection against simian/human immunodeficiency chimeric virus (SHIV) challenges in nonhuman primates. Despite many efforts to design immunogens that elicit them by active immunization, no immunogen other than HIV itself has yet been able to elicit a bnAb response. For this reason, innovative approaches are under investigation, including their production in the body through a gene delivery approach, vector immunoprophylaxis.

Background: Community-acquired pneumonia (CAP), a leading cause of mortality, mainly affects children in developing countries. The harsh circumstances experienced by refugees include various factors associated with respiratory pathogen transmission, and clinical progression of CAP. Consequently, the etiology of CAP in humanitarian crisis situations may differ to that of settled populations, which would impact appropriate case management. Therefore, the Pneumonia Etiology Among Refugees and the Lebanese population (PEARL) study was initiated with the objective of identifying the causal pathogenic microorganisms in the respiratory tract of children and adults from both the refugee and host country population presenting with signs of CAP during a humanitarian crisis. Methods: PEARL, a prospective, multicentric, case-control study, will be conducted at four primary healthcare facilities in Tripoli and the Bekaa valley over 15 months (including two high-transmission seasons/winters). Sociodemographic and medical data, and biological samples will be collected from at least 600 CAP cases and 600 controls. Nasopharyngeal swabs, sputum, urine and blood samples will be analyzed at five clinical pathology laboratories in Lebanon to identify the bacterial and viral etiological agents of CAP. Transcriptomic profiling of host leukocytes will be performed. Conclusions: PEARL is an original observational study that will provide important new information on the etiology of pneumonia among refugees, which may improve case management, help design antimicrobial stewardship interventions, and reduce morbidity and mortality due to CAP in a humanitarian crisis.

International audience; BACKGROUND: There are very limited data on children with pneumonia in Mali. The objective was to assess the etiology and factors associated with community-acquired pneumonia in hospitalized children \textless5 years of age in Mali. METHODS: A prospective hospital-based case-control study was implemented in the Pediatric department of Gabriel Touré University Hospital at Bamako, Mali, between July 2011-December 2012. Cases were children with radiologically-confirmed pneumonia; Controls were hospitalized children without respiratory features, matched for age and period. Respiratory specimens, were collected to identify 19 viruses and 5 bacteria. Whole blood was collected from cases only. Factors associated with pneumonia were assessed by multivariate logistic regression. RESULTS: Overall, 118 cases and 98 controls were analyzed; 44.1% were female, median age was 11 months. Among pneumonia cases, 30.5% were hypoxemic at admission, mortality was 4.2%. Pneumonia cases differed from the controls regarding clinical signs and symptoms but not in terms of past medical history. Multivariate analysis of nasal swab findings disclosed that S. pneumoniae (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.6-7.0), human metapneumovirus (aOR = 17.2, 95% CI: 2.0-151.4), respiratory syncytial virus [RSV] (aOR = 7.4, 95% CI: 2.3-23.3), and influenza A virus (aOR = 10.7, 95% CI: 1.0-112.2) were associated with pneumonia, independently of patient age, gender, period, and other pathogens. Distribution of S. pneumoniae and RSV differed by season with higher rates of S. pneumoniae in January-June and of RSV in July-September. Pneumococcal serotypes 1 and 5 were more frequent in pneumonia cases than in the controls (P = 0.009, and P = 0.04, respectively). CONCLUSIONS: In this non-PCV population from Mali, pneumonia in children was mainly attributed to S. pneumoniae, RSV, human metapneumovirus, and influenza A virus. Increased pneumococcal conjugate vaccine coverage in children could significantly reduce the burden of pneumonia in sub-Saharan African countries.

Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Hospices Civils de Lyon. Edouard Herriot Hospital. Infection Control and Epidemiology Unit. Lyon, Grance / Universit of Lyon 1, Epidemiology and Public Health Unit. Lyon, France. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. University of Health Sciences. Faculty of Pharmacy. Phnom Penh, Cambodia. National Pediatric Hospital. Department of Pneumology. Phnom Penh, Cambodia. MOH Key Laboratory of Systems Biology of Pathogens. Dr. Christophe Mérieux Laboratory. Fondation Mérieux. Institute of Pathogen Biology (IPB), Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College. Beijing, China. Capital Medical University. Key Laboratory of Major Diseases in Children. National Key Discipline of Pediatrics. Ministry of Education. Beijing Pediatric Research Institute. Beijing Children’s Hospital. Capital Medical University, Beijing, China. GHESKIO (Groupe Haïtien d’Etude du Sarcome de Kaposi et des Infections Opportunistes) Centers. Port au Prince, Haiti. GHESKIO (Groupe Haïtien d’Etude du Sarcome de Kaposi et des Infections Opportunistes) Centers. Port au Prince, Haiti. Chatrapati Shahuji Maharaj University. Lucknow, India. Chatrapati Shahuji Maharaj University. Lucknow, India. KEM Hospital Research Center. Pune, India. KEM Hospital Research Center. Pune, India. Hôpital Femme-Mère-Enfant. Antananarivo, Madagascar. Fondation Mérieux. Centre d’Infectiologie Charles Mérieux (CICM); Antananarivo, Madagascar. Fondation Mérieux. Centre d’Infectiologie Charles Mérieux (CICM); Antananarivo, Madagascar. Gabriel Touré Hospital. Bamako, Mali. Centre d`Infectiologie Charles Mérieux (CICM). Bamako, Mali. Mongolian Academy of Medical Sciences. Ulaanbaatar, Mongolia. Bayanzurkh District General Hospital. Ulaanbaatar, Mongolia. Research Institute of health. Asuncion, Paraguay. Hospital Pediátrico ! Niños de Acosta ¨Nu". San Lorenzo, Paraguay. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e Sarampo. Rio de Janeiro, RJ, Brasil. Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Vírus Respiratórios e Sarampo. Rio de Janeiro, RJ, Brasil. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Hospices Civils de Lyon. Edouard Herriot Hospital. Infection Control and Epidemiology Unit. Lyon, Grance / Universit of Lyon 1, Epidemiology and Public Health Unit. Lyon, France. Fondation Mérieux. Centre Internationale Recherche en Infectiologie (CIRI). Emerging Pathogens Laboratory. Lyon, France. Background: Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of