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The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein–specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein–specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced T H 1 polarization of their SARS-CoV-2 spike protein–specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein–specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein–specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia. The study included one control site (three buildings) and three intervention sites which were treated as follows: targeted outdoor residual spraying only (TORS site, two buildings); deployment of autodissemination devices only (ADD site, four buildings); and the previous two treatments combined (TORS + ADD site, three buildings). The primary entomological measurement was per cent of positive ovitraps—ovitrap index (OI). The effect of each intervention on OI was analyzed by a modified ordinary least squares regression model. Relative to the control site, the TORS and ADD sites showed a reduction in the Aedes OI (−6.5%, P = 0.04 and −8.3%, P = 0.10, respectively). Analysis by species showed that, relative to control, the Ae. aegypti OI was lower in ADD (−8.9%, P = 0.03) and in TORS (−10.4%, P = 0.02). No such effect was evident in the TORS + ADD site. The present study provides insights into the methods to be used for the main trial. The combination of multiple insecticides with different modes of action in one package is innovative, although we could not demonstrate the additive effect of TORS + ADD. Further work is required to strengthen our understanding of how these interventions impact dengue vector populations and dengue transmission.

Introduction: The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). Methods: This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. Results: The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. Conclusions: Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, β-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and β-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and β-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Introduction The COVID-19 pandemic placed an unprecedented overload on healthcare system globally. With all medical resources being dedicated to contain the spread of the disease, the pandemic may have impacted the burden of other infectious diseases such as dengue, particularly in countries endemic for dengue fever. Indeed, the co‐occurrence of COVID‐19 made dengue diagnosis challenging because of some shared clinical manifestations between the two pathogens. Furthermore, the sudden emergence and novelty of this global public health crisis has forced the suspension or slow-down of several research trials due to the lack of sufficient knowledge on how to handle the continuity of research trials during the pandemic. We report on challenges we have faced during the COVID-19 pandemic and measures that were implemented to continue the iDEM project (intervention for Dengue Epidemiology in Malaysia). Methods This randomized controlled trial aims to assess the effectiveness of Integrated Vector Management (IVM) on the incidence of dengue in urban Malaysia by combining: targeted outdoor residual spraying (TORS), deployment of auto-dissemination devices (ADDs), and active community engagement (CE). Our operational activities started on February 10, 2020, a few weeks before the implementation of non-pharmaceutical interventions to contain the spread of COVID-19 in Malaysia. Results The three main issues affecting the continuity of the trial were: ensuring the safety of field workers during the interventions; ensuring the planned turnover of TORS application and ADD deployment and services; and maintaining the CE activities as far as possible. Conclusions Even though the pandemic has created monumental challenges, we ensured the safety of field workers by providing complete personal protective equipment and regular COVID-19 testing. Albeit with delay, we maintained the planned interval time between TORS application and ADDs services by overlapping the intervention cycles instead of having them in a sequential scheme. CE activities continued remotely through several channels (e.g., phone calls and text messages). Sustained efforts of the management team, significant involvement of the Malaysian Ministry of Health and a quick and smart adaptation of the trial organisation according to the pandemic situation were the main factors that allowed the successful continuation of our research. Trial registration Trial registration number: ISRCTN-81915073. Date of registration: 17/04/2020, 'Retrospectively registered'.

In the Lao People's Democratic Republic (Lao PDR), cervical cancer is the third leading cause of women cancer.The objective of this cross-sectional study was to compare the efficacy of careHPV™ test versus conventional Pap smear or Siriraj liquid-based cytology in the detection of cervical cancer in women living with human immunodeficiency virus type 1 (HIV-1).Overall, 631 women consented to participate. Four cervical specimens were taken for the purpose of conventional Pap smear, Siriraj liquid-based cytology, careHPV™ test, and HPV-16 genotyping. The exact McNemar test was used to compare the efficacy and diagnostic performance of the tests.Of the 631 women with follow-up, 331 were human papillomavirus (HPV) negative. High-grade squamous intraepithelial lesions were found in 37 women, biopsy-proven high-grade cervical intraepithelial neoplasia in 50 women, and invasive carcinoma in seven women. The proportion of women with high-grade cervical lesion or carcinoma detected after abnormal careHPV™ test was higher (6.02%; 95% confidence interval [CI]: 4.4-8.1) than that detected by conventional Pap smear (4.59%; 95% CI: 3.2-6.5). careHPV™ and HPV-16 genotyping had, respectively, the highest sensitivity (80.8%; 95% CI: 67.4-89.5) and specificity (92.2%; 95% CI: 89.8-94.2). HPV-16 was the most frequently detected genotype.careHPV™ test represents a screening option in Lao PDR, particularly in women living with HIV-1 because of higher prevalence of chronic HPV in this population.

IntroductionDelay between symptom onset and access to care is essential to prevent clinical worsening for different infectious diseases. For COVID-19, this delay might be associated with the clinical prognosis, but also with the different characteristics of patients. The objective was to describe characteristics and symptoms of community-acquired (CA) COVID-19 patients at hospital admission according to the delay between symptom onset and hospital admission, and to identify determinants associated with delay of admission.MethodsThe present work was based on prospective NOSO-COR cohort data, and restricted to patients with laboratory confirmed CA SARS-CoV-2 infection admitted to Lyon hospitals between February 8 and June 30, 2020. Long delay of hospital admission was defined as ≥6 days between symptom onset and hospital admission. Determinants of the delay between symptom onset and hospital admission were identified by univariate and multiple logistic regression analysis.ResultsData from 827 patients were analysed. Patients with a long delay between symptom onset and hospital admission were younger (pversus27.6%), p100 mg/L at admission was associated with a long delay (aOR: 1.84 95% CI (1.32–2.55)).DiscussionDelay between symptom onset and hospital admission is a major issue regarding prognosis of COVID-19 but can be related to multiple factors such as individual characteristics, organization of care and severe pathogenic processes. Age seems to play a key role in the delay of access to care and the disease prognosis.

Information gathered so far from published studies attest the existence of a complex relationship between tobacco smoking and the severity of COVID‐19. We investigated the association between smoking habits and the severity of COVID‐19 in patients hospitalized in university‐affiliated hospitals in Lyon, France. Baseline sociodemographic, clinical and biological characteristics of adult COVID‐19 hospitalized patients presenting from the community were prospectively collected and analyzed. Tobacco exposure was documented at admission. Characteristics of patients hospitalized in medical wards to those admitted or transferred to intensive care units (ICUs) were compared using Mann–Whitney and Χ 2 or Fisher's exact test. A composite endpoint including admission or transfer to ICU or death was created as a proxy for severe outcome. Adjusted odds ratio (aOR) and 95% confidence interval (95% CI) were calculated to identify variables independently associated with a severe outcome. Of the 645 patients with documented information on smoking habits, 62.6% were never‐smokers, 32.1% ex‐smokers, and 5.3% active smokers. Past tobacco use was independently associated with an increased risk of severe outcome (aOR: 1.71; 95% CI: 1.12–2.63), whereas a nonsignificant protective trend was found for active smoking. The results suggest that past smoking is associated with enhanced risk of progressing toward severe COVID‐19 disease in hospitalized patients.

The incidence of dengue in Malaysia has shown an increasing trend since the year 2000. Vector control is the primary approach for dengue control in Malaysia. There is an urgent need for new or modified approaches such as the residual spraying on the outer walls that can potentially last long enough to control the Aedes population, particularly in the outbreak-prone areas. In this field study, we conducted outdoor residual spraying (ORS) using a newly formulated polymer-enhanced suspension concentrate (SC-PE) of deltamethrin. The objectives of this study were to evaluate the efficacy of ORS using deltamethrin SC-PE and its effect on wild Aedes populations and to assess its residual bio-efficacy on painted cement walls against the pyrethroid-susceptible strains of laboratory-reared Aedes mosquitoes. Three rounds of spraying in a four-month cycle were conducted between 2014 and 2015 in four residential areas (low-rise and high-rise housing types) in Hulu Langat, Selangor. The bio-efficacy of the insecticide was evaluated by assessing its impact on vector population using ovitrap surveillance. Standard WHO wall deposit bioassay was adapted to determine bio-efficacy of deltamethrin, i.e. post 30 min knockdown and post 24 h mortality after exposure. During the treatment period, we observed significant reductions in the population of Ae. albopictus in the sprayed low-rise housing in both semi-indoor and outdoor environments, while in the high-rise housing, there was also a significant decline in Ae. aegypti population in the semi-indoor environment. The evaluation of the residual bio-efficacy of deltamethrin SC-PE against laboratory-reared Aedes mosquitoes showed that the insecticide lasted longer in the high-rise housing compared to the low-rise housing with >80% mortality achieved continuously for 16 weeks. We provide initial evidence on residual efficacy of deltamethrin SC-PE in reducing Aedes population size in the low-rise and high-rise housing. Our results showed that ORS is a promising tool in the dengue vector control and like IRS in malaria control; it is a powerful and effective method if conducted correctly. However, large scale and well-designed studies with entomological and epidemiological endpoints are still warranted before its routine use in dengue control.

Background: In common with many South East Asian countries, Malaysia is endemic for dengue. Dengue control in Malaysia is currently based on reactive vector management within 24 hours of a dengue case being reported. Preventive rather than reactive vector control approaches, with combined interventions, are expected to improve the cost-effectiveness of dengue control programs. The principal objective of this cluster randomized controlled trial is to quantify the effectiveness of a preventive integrated vector management (IVM) strategy on the incidence of dengue as compared to routine vector control efforts. Methods: The trial is conducted in randomly allocated low and medium cost clusters located in the Federal Territory of Kuala Lumpur and Putrajaya. The IVM approach combines: targeted outdoor residual spraying with K-Othrine Polyzone, deployment of mosquito traps as auto-dissemination devices, and community engagement activities. The trial includes 280 clusters randomly allocated in a 1:1 ratio. The clusters receive either the preventive IVM in addition to the routine vector control activities, or the routine vector control activities only. Epidemiological data from monthly confirmed dengue cases during the study period will be obtained from the Vector Borne Disease Sector, Malaysian Ministry of Health e-Dengue surveillance system. Entomological surveillance data will be collected in 12 clusters randomly selected from each arm. To measure the effectiveness of the IVM approach on dengue incidence, a negative binomial regression model will be used to compare the incidence between control and intervention clusters. To quantify the effect of the interventions on the main entomological outcome, ovitrap index, a modified ordinary least squares regression model using a robust standard error estimator will be used. Discussion: Considering the ongoing expansion of dengue burden in Malaysia, setting up proactive control strategies is critical. Despite some limitations of the trial such as the use of passive surveillance to identify cases the results will be informative for a better understanding of effectiveness of proactive IVM approach in the control of dengue. Evidence from this trial may help justify investment in preventive IVM approaches as preferred to reactive case management strategies. Trial registration: ISRCTN, ISRCTN81915073, retrospectively registered on 17 April 2020 (https://doi.org/10.1186/ISRCTN81915073)

PurposeStaphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotising pneumonia in older patients. Methicillin resistance and the Panton–Valentine leukocidin (PVL) toxin, as well as less specific factors, have been associated with poor outcome in severe CAP, but their roles are unclear.MethodsA prospective multicentre cohort study of severe staphylococcal CAP was conducted in 77 paediatric and adult intensive care units in France between January 2011 and December 2016. After age-clustering, risk factors for mortality, including pre-existing conditions, clinical presentation, laboratory features, strain genetic lineage, PVL, other virulence factors and methicillin resistance were assessed using univariate and multivariable Cox and LASSO (least absolute shrinkage and selection operator) regressions.ResultsOut of 163 included patients, aged 1 month to 87 years, 85 (52.1%) had PVL-positive CAP; there were 20 (12.3%) patients aged S. aureus lineages and the presence of other determinants of virulence.ConclusionPVL was associated with staphylococcal pleuropneumonia in toddlers and was a risk factor for mortality in older patients with severe CAP, independently of methicillin resistance, S. aureus genetic background and other virulence factors.

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.

BackgroundStaphylococcus aureus causes severe forms of community-acquired pneumonia (CAP), namely staphylococcal pleuropneumonia in young children and staphylococcal necrotizing pneumonia in older patients. Methicillin resistance and the Panton-Valentine leukocidin (PVL) toxin have both been associated with poor outcome in severe CAP, but their respective roles are unclear.MethodsProspective multicenter cohort study of severe staphylococcal CAP conducted in 77 pediatric and adult intensive care units in France between January 2011 and December 2016. Clinical features and outcomes were compared between toddlers (ResultsOf 163 included patients, aged one month to 87 years, 85 (52.1%) had PVL-positive CAP; there were 20 (12.3%) toddlers, among whom 19 (95%) had PVL-positive CAP. The features of PVL-positive CAP in toddlers matched with the historical description of staphylococcal pleuropneumonia, with a lower mortality (n = 3/19, 15%) compared to PVL-positive CAP in older patients (n=31/66, 47%). Mortality in older patients was independently predicted by PVL-positivity (hazard ratio 1.81, 95% CI, 1.03 to 3.17) and methicillin resistance (2.37, 95% CI 1.29 to 4.34). As genetic diversity was comparably high in PVL-positive and PVL-negative isolates, confounding by microbial population structure was unlikely.ConclusionPVL was associated with staphylococcal pleuropneumonia in toddlers and was a risk factor for mortality in older patients with severe CAP, independently of methicillin resistance. Funded by the French ministry of Health (PHRC 2010-A01132-37).

IntroductionA new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analyzing clinical presentation on admission and the determinants associated with direct admission or transfer to intensive care units (ICUs) in hospitalized COVID-19 patients.Patients and MethodsIn this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients were prospectively collected and analyzed. The outcome was admission/transfer to intensive care units compared with total hospital stay in medical wards according to patient characteristics.ResultsOf the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of admission/transfer to ICUs with male gender (OR, 1.99 [95%CI, 1.07-3.73]), temperature (OR, 1.37 [95% CI, 1.01-1.88] per degree Celsius increase), abnormal lung auscultation on admission (OR, 2.62 [95% CI, 1.40-4.90]), elevated level of CRP (OR, 6.96 [95% CI, 1.45-33.35 for CRP>100mg/L vs CRP10 days vs time ConclusionsClinical and biological features on admission and time until admission were associated with admission to ICUs. Signs to predict worsening on admission could be partially associated with the time until admission. This finding reinforces the need for appropriate guidelines to manage COVID-19 patients in this time window.

Currently, dengue control relies largely on reactive vector control programmes. Proactive vector-control using a rational, well-balanced integrated vector management approach may prove more successful for dengue control. As part of the development of a cluster randomized controlled epidemiological trial, a study was conducted in Johor Bahru, Malaysia. The study included one control site (three buildings) and three intervention sites which were treated as follows: targeted outdoor residual spraying only (TORS site, two buildings); deployment of autodissemination devices only (ADD site, four buildings); and the previous two treatments combined (TORS + ADD site, three buildings). The primary entomological measurement was per cent of positive ovitraps-ovitrap index (OI). The effect of each intervention on OI was analyzed by a modified ordinary least squares regression model. Relative to the control site, the TORS and ADD sites showed a reduction in the Aedes OI (-6.5%, P = 0.04 and -8.3%, P = 0.10, respectively). Analysis by species showed that, relative to control, the Ae. aegypti OI was lower in ADD (-8.9%, P = 0.03) and in TORS (-10.4%, P = 0.02). No such effect was evident in the TORS + ADD site. The present study provides insights into the methods to be used for the main trial. The combination of multiple insecticides with different modes of action in one package is innovative, although we could not demonstrate the additive effect of TORS + ADD. Further work is required to strengthen our understanding of how these interventions impact dengue vector populations and dengue transmission.

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 Influenza is an important cause of viral hospital-acquired infection involving patients, healthcare workers (HCW), and visitors. The frequency of asymptomatic influenza among HCW with possible subsequent transmission is poorly described. The objective is to determine the cumulative incidence of asymptomatic, paucisymptomatic, and symptomatic influenza among HCW. Method A multicenter prospective cohort study was done in 5 French university hospitals, including 289 HCW during the 2016–2017 influenza season. HCW had 3 physical examinations (time [T] 0, before epidemic onset; T.1, before epidemic peak; T.2, T.3, after epidemic peak). A blood sample was taken each time for influenza serology and a nasal swab was collected at T1 and T2 for influenza detection by polymerase chain reaction (PCR). Positive influenza was defined as either a positive influenza PCR, and/or virus-specific seroconversion against influenza A, the only circulating virus, with no vaccination record during follow-up. Symptoms were self-reported daily between T1 and T2. Cumulative incidence of influenza was stratified by clinical presentation per 100 HCW. Results Of the 289 HCW included, 278 (96%) completed the entire follow-up. Overall, 62 HCW had evidence of influenza of whom 46.8% were asymptomatic, 41.9% were paucisymptomatic, and 11.3% were symptomatic. Cumulative influenza incidence was 22.3% (95% confidence interval [CI]: 17.4%–27.2%). Cumulative incidence of asymptomatic influenza was 5.8% (95% CI: 3.3%–9.2%), 13.7% (95% CI: 9.9%–18.2%) for paucisymptomatic influenza, and 2.9% (95% CI: 1.3%–5.5%) for symptomatic influenza. Conclusions Asymptomatic and paucisymptomatic influenza were frequent among HCW, representing 47% and 42% of the influenza burden, respectively. These findings highlight the importance of systematic implementation of infection control measures among HCW regardless of respiratory symptoms from preventing nosocomial transmission of influenza. Clinical Trials Registration NCT02868658.

International audience; Aim: The objective of this review was to evaluate the role of diabetes as a risk factor for herpes zoster (HZ) and to discuss implications of prevention by vaccination with available HZ vaccines.Methods: We reviewed studies that investigated the incidence rates of HZ in patients with diabetes. Papers in English or French published between January 2000 and December 2018 have been selected from PubMed and Google Scholarship by using appropriate key words.Results: The risk of HZ was significantly higher in patients with diabetes as compared to controls in 11 studies out of 16, although the magnitude of risk associated to diabetes varied across studies from 1.06 to 2.38 (p < 0.05). The incidence of HZ in patients with diabetes increased with age and was higher in women than in men. The incidence of the most common complication of HZ, i.e. post-herpetic neuralgia was also higher in patients with diabetes.Conclusions: The presence of HZ adds supplementary complications to the pre-existing comorbidity in patients with diabetes. Investigating the impact of preventive measure by HZ vaccination is therefore of paramount importance in patients with diabetes.

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

Lyon Study Group on Covid19 infection (Geriatric section- Alphabetic order): Adrait, A, Benoist F, Castel-Kremer E, Chuzeville M, Dupin AC, Doh S, Kim B, Favrelle L, Hilliquin D, Kanafer N, Marion E, Martin-Gaujard G, Moyenin Y, Paulet-Lafuma H, Ricanet A, Saadatian-Elahi M, Vanhems P.

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

The Middle‐East and Africa Influenza Surveillance Network (MENA‐ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA‐ISN countries. Data were presented at the 8th MENA‐ISN meeting, organized by the Mérieux Foundation that was held on 10‐11 April 2018 in Cairo, Egypt. The meeting included MENA‐ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high‐risk groups (children under‐5, elderly, pregnant women and immunosuppressed individuals) in the MENA‐ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza‐related morbidity and mortality especially among the most vulnerable groups of the population.

Background: The first characterisation of Panton-Valentine Leucocidin (PVL)-associated staphylococcal necrotizing pneumonia (SNP) was published in 2002. A major controversy regarding the role played by PVL in the severity of community-acquired pneumonia (CAP) ensued. To address this issue, all French intensive care units (ICU) were asked to prospectively include their cases of staphylococcal CAP between January 2011 and December 2016. Method: Patients with CAP who fulfilled the following criteria were included: clinical and radiological signs of lung infection, at least one assessment of S. aureus involvement (positive culture from blood/pleural fluid, respiratory sample), and admission to ICU. At the time of data collection, clinicians were not aware of PVL status. Patterns in patient age distribution were detected using a clustering procedure. Risk factors for mortality were identified using multivariate Cox regression. Findings: One-hundred and sixty-three patients, aged from one month to 87 years, were included; 52.1% were PVL-positive. Unexpectedly, PVL-positive cases distributed into two independent clusters, with a cut-off of around 3 years of age, whereas PVL-negative cases were only observed in adolescents and adults. Features of the

Objectives: Thirty percent of the general population are Staphylococcus aureus nasal carriers. It has been shown that this increases with repeated contact with patients, but it is not known whether all categories of healthcare workers are at equal risk of carriage. We aimed to explore S. aureus nasal carriage among healthcare professionals.Methods: Prospective study conducted in two French university hospitals in 2014 and 2016. Volunteers were screened for S. aureus nasal carriage. Profession and hygiene habits were collected. Based on the results of this initial study, a second study focused on semi-skilled workers and biomedical equipment technicians (BETs) only; participants were given education on the basic rules of hygiene, then re-screened three months later.Results: In the initial study, 38.8% of the 436 participants were detected as nasal carriers. There was a significant difference in nasal carriage according to professional category (p

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.

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.

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.

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.

Elaidic acid is the main unnatural trans fatty acid isomer occurring during partial hydrogenation of vegetable oils used as ingredients for the formulation of processed foods. The main objective is to assess associations between processed food intakes and plasma phospholipid elaidic acid concentrations within the European Prospective Investigation into Cancer and Nutrition study. A cross-sectional study was used to determine fatty acid profiles in 3,003 subjects from 16 centers. Single 24-h dietary recalls (24-HDR) were collected using a standardized computerized interview program. Food intakes were computed according to their degree of processing (moderately/nonprocessed foods, processed staple foods, highly processed foods). Adjusted ecological and individual correlations were calculated between processed food intakes and plasma elaidic acid levels. At the population level, mean intakes of highly processed foods were strongly correlated with mean levels of plasma elaidic acid in men (P = 0.0016) and in women (P = 0.0012). At the individual level, these associations remained but at a much lower level in men (r = 0.08, P = 0.006) and in women (r = 0.09, P = 0.0001). The use of an averaged 24-HDR measure of highly processed food intakes is adequate for predicting mean levels of plasma elaidic acid among European populations.

Due to the increasing number of orthopaedic and cardiac procedures, these units are considered as high-risk areas because of the potentially serious consequences of surgical site infections (SSI), primarily caused by Staphylococcus aureus. The goal of this review was to evaluate the impact of S. aureus on the incidence of SSI in these high risk wards. Studies were identified by a search on the MEDLINE literature using the following mesh terms: S. aureus, cardiac, orthopaedic, surgery, SSI. Beside, data from different surveillance systems were also included. Overall, biological investigation was performed only on a small proportion of identified SSIs. Of those identified, S. aureus represented the most common pathogen accounting for approximately 20% of all SSIs. Of the 59,274 hip prostheses reported from the HELICS surveillance network, S. aureus formed 48.6% of the pathogens (416 bacteria isolated). Similarly, it represented 43.7% of pathogens after coronary artery bypass grafting. Although S. aureus turned out to be the major pathogen, this work identifies the relative lack of knowledge on the overall incidence of S. aureus infections and on the impact of this pathogenic agent when taking into consideration the degree of wound contamination and category of SSI. There is a need for more detailed information on the role of S. aureus in the burden of surgical site infections and consequently how to establish multiple approach prevention programs.

Vaccine-preventable diseases are a significant cause of morbidity and mortality. As new vaccines are proving to be effective and as the incidence of some infections decreases, vaccination practices are changing. Healthcare workers (HCWs) are particularly exposed to and play a role in nosocomial transmission, which makes them an important target group for vaccination. Most vaccine-preventable diseases still carry a significant risk of resurgence and have caused outbreaks in recent years. While many professional societies favor vaccination of HCWs as well as the general population, recommendations differ from country to country. In turn, vaccination coverage varies widely for each microorganism and for each country, making hospitals and clinics vulnerable to outbreaks. Vaccine mandates and non-mandatory strategies are the subject of ongoing research and controversies. Optimal approaches to increase coverage and turn the healthcare workforce into an efficient barrier against infectious diseases are still being debated.