Hemagglutination inhibition antibody titer as a correlate of protection against influenza infection : impact and dynamics

Le titre sérique d'anticorps anti-hémagglutinine (HA) est reconnu comme corrélat de la protection à l'infection grippale. Cette thèse examine le rôle du titre d'anticorps HA comme corrélat de protection dans le contexte d'une seule infection, puis considère l'effet des expositions répétées sur la réponse immunitaire.Premièrement, l'association entre l'infection grippale par le virus A(H1N1)pdm09 et 167 variables a été explorée. Cette étude montre l'interaction complexe de facteurs qui influent sur le risque d'infection: les titres d'anticorps pré-épidémiques sont protecteurs, mais des facteurs tels que les comportements collectifs peuvent avoir un rôle important. Deux travaux réalisés dans le cadre de ce projet de thèse se basent sur les sérologies d'une cohorte française. Nous avons trouvé un association entre le titre d'anticorps dirigés contre le virus circulant 2007 A(H1N1) et le risque d'infection, la protection associée à ce titre variant avec l'âge. Une étude sur l'évolution du titre d'anticorps montre que celui-ci peut rester élevé jusqu'à deux ans après l'infection. Afin d'étudier les conséquences des expositions aux virus grippaux, nous avons modélisé les titres d'anticorps en fonction de l'âge des sujets lors de la circulation initiale de virus: la réponse immunitaire la plus importante concernant les souches A(H1N1) auxquelles les sujets ont été exposés pendant l'enfance. Ces études soutiennent l'utilisation du titre d’anticorps comme corrélat immunitaire de protection et suggèrent que d'autres facteurs peuvent influencer l'immunité anti-grippale. L'interprétation de la sérologie et les sérologiques d'homologation du vaccin devraient être indépendants de l'âge.Hemagglutination inhibition (HI) antibody titer is widely recognized as the main immune correlate of protection against influenza infection. This thesis examines the role of HI titer as a correlate of protection in the context of a single infection, and then considers the effect of repeated exposures on the immune response.HI titer was first studied among 167 covariates in an exploratory analysis to identify determinants of A(H1N1)pdm09 infection using data from a cohort of 601 households representative of the general population. This study shows the complex interaction of factors influencing risk of infection; results suggest that pre-epidemic HI titers are protective and factors such as collective behaviors may also have an important role.Two studies were based on data from a cohort investigating determinants of recurrent influenza infection. The relationship between HI titer and protection against natural seasonal 2007 A(H1N1) infection was explored; the age-adjusted model suggests differences in the HI protection curve according to age group. Longitudinal analysis suggests that recent seasonal infection may have protected against A(H1N1)pdm09 infection. We also investigated the effects of repeated influenza exposures on HI titer: our results show evidence of a strong immune response to A(H1N1) strains circulating in early childhood. These studies support the use of HI titer as the main immune correlate of protection against influenza infection and suggest that other factors may have influence on immunity to infection. Age should be considered in interpretation of serology and serological criteria for influenza vaccine licensure

Community engagement in the provision of culturally competent HIV and STI prevention services: lessons from the French experience in the era of PrEP

International audienceCommunities have been a driving force in the response to the HIV epidemic, advocating for research, the access to treatment and healthcare, and human rights for key populations (KP) and people living with HIV (PLHIV). The importance of community engagement (CE) in the development and implementation of pertinent programmes throughout the HIV care continuum has been widely recognized 1-3. In the context of increasing pre‐exposure prophylaxis (PrEP) research, interest and access (though still limited), there is an opportunity to have a fresh look at CE regarding HIV/STI research and care delivery. France, where PrEP has been authorized and fully reimbursed since 2016, may provide key lessons for CE in the provision of comprehensive, culturally adapted HIV/STI prevention and treatment services

Risk factors of pandemic influenza A/H1N1 in a prospective household cohort in the general population: results from the CoPanFlu-France cohort

International audienceBackground : The CoPanFlu-France household cohort was set up in 2009 to identify risk factors of infection by the pandemic A/H1N1 (H1N1pdm09) virus in the general population.Objectives : To investigate the determinants of infection during the 2010–2011 season, the first complete influenza season of study follow-up for this cohort.Patients/Methods : Pre- and post-epidemic blood samples were collected for all subjects, and nasal swabs were obtained in all subjects from households where an influenza-like illness was reported. Cases were defined as either a fourfold increase in the serological titer or a laboratory-confirmed H1N1pdm09 on a nasal swab, with either RT-PCR or multiplex PCR. Risk factors for H1N1pdm09 infections were explored, without any pre-specified hypothesis, among 167 individual, collective and environmental covariates via generalized estimating equations modeling. We adopted a multimodel selection procedure to control for model selection uncertainty.Results : This analysis is based on a sample size of 1121 subjects. The final multivariable model identified one risk factor (history of asthma, OR = 2·17; 95% CI: 1·02–4·62) and three protective factors: pre-epidemic serological titer (OR = 0·51 per doubling of the titer; 95% CI: 0·39–0·67), green tea consumption a minimum of two times a week (OR = 0·39; 95% CI: 0·18–0·84), and proportion of subjects in the household always covering their mouth while coughing/sneezing (OR = 0·93 per 10% increase; 95% CI: 0·86–1·00).Conclusion : This exploratory study provides further support of previously reported risk factors and highlights the importance of collective protective behaviors in the household. Further analyses will be conducted to explore these findings

A Community-Led Research Model for Qualitative Evaluation of Access to and Quality of HCV Services in Five Middle Income Countries (2018)

Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, San Francisco, CA, NOV 09-13, 201

Antibody persistence and serological protection among seasonal 2007 influenza A(H1N1) infected subjects: Results from the FLUREC cohort study

International audienceIntroduction : Haemagglutination-inhibition (HI) antibody titer is a correlate of protection against influenza; its persistence after infection or vaccination is important to determining susceptibility to subsequent infection. Few studies, however, have reported longitudinal data regarding the magnitude and duration of HI protection following natural seasonal influenza A infection.Methods : Using French influenza cohort study data collected from 2008 to 2010, we investigated persistence of serological protection among subjects according to influenza-like illness (ILI) and laboratory-confirmed seasonal 2007 influenza A(H1N1) infection status at inclusion in 2008 (ILI-A(H1N1) positive, ILI-A(H1N1) negative, or no-ILI). Antibody titers against seasonal 2007 A(H1N1) were determined using the HI technique for sera. Regression models for interval-censored data were used to estimate geometric mean titers (GMT) for HI assays. A logistic regression model adjusted for age group (subjects 50 years old) was used to quantify the association between HI titer and protection against infection.Results : Based on 310 total subjects, influenza A(H1N1) infection was confirmed in 39 of 115 ILI subjects at inclusion. GMT associated with 50% probability of protection among ILI subjects decreased with age group (subjects 50 yo: 8.9 [95CI: 15.3%; 84.7%]). GMT declined after the first annual study visit among ILI-A(H1N1) positive subjects but remained higher compared to inclusion at the 2010 study visit (41.5 [95CI: 34.8; 49.5], p = 0.0157). GMT remained stable among ILI-A(H1N1) negative subjects (p = 0.7502), but decreased among no-ILI subjects (p < 0.0001).Conclusion : Our results confirm the positive relationship between HI titer and probability of protection among naturally infected subjects, and provides evidence that protection associated with HI titer varies with age. This longitudinal analysis suggests the rise in HI titers following seasonal 2007 influenza A(H1N1) infection may persist into subsequent influenza seasons

Fear of stigma from health professionals and family/neighbours and healthcare avoidance among PLHIV in Morocco: results from the Stigma Index survey Morocco

Background: Enacted or anticipated stigma among people living with HIV (PLHIV) can negatively impact healthcare engagement. We identified factors associated with having avoided HIV health services for fear of stigma among PLHIV in Morocco. Methods: The Stigma Index survey was conducted in Morocco in March-June 2016. Factors associated with avoiding HIV testing and treatment services for fear of stigma by (A) health personnel or family/neighbours and (B) health personnel and family/neighbours compared to people who did not avoid health services for fear of stigma from either of the two sources were assessed using multinomial logistic regression models. Results: Among 583 respondents, 280 (48.0%) were women and median number of years living with HIV was 5[IQR:2-7]. Half of the respondents reported avoiding health services for fear of stigma by health personnel and/or family/neighbours: (A) n = 228, 39.1% and (B) n = 68, 11.7%. After adjustment on perceived health status, not having had easy access to antiretroviral treatment ((A) aRR [95% CI] = 1.76[1.16; 2.68]; (B) 2.18[1.11; 4.27]), discrimination by PLHIV ((A) 1.87[1.12; 3.13]; (B) 3.35[1.63; 6.88]) and exclusion from social activities ((A) 1.70[1.10; 2.61]; (B) 2.63[1.39; 5.00]) were associated with having avoided health services for fear of stigma by health personnel or/and family/neighbours. Being female (2.85[1.48; 5.47]), not having been referred for an HIV test for suspected symptoms 3.47[1.67; 7.22], having discussed sexual/reproductive health with a health professional (4.56[2.38; 8.71]), and not having the feeling to influence decisions on local projects for PLHIV (3.47[1.37; 7.83], were associated with having avoided health services for fear of stigma by both sources. Conclusion: Results suggest a cumulative effect of fear of stigma and discrimination among PLHIV in Morocco. PLHIV who have experienced discrimination may seek to avoid similar situations at the expense of their health. These results should inform multi-level interventions and broader advocacy efforts to reduce stigma and discrimination

Determinants and effects or consequences of internal HIV-related stigma among people living with HIV in Morocco

International audienceBackground: HIV-related stigma and discrimination constitute a barrier to different intervention programs. Unlike external stigma, internal stigma is not well explored in in the Middle East and North African countries, while grasping this particular form of stigma is essential to limit its effects. The present study aims to measure internal stigma effects and to identify factors associated with this kind of stigma not yet documented among people living with HIV (PLHIV) in Morocco. Methods: The PLHIV Stigma Index questionnaire (adapted and translated into French and Moroccan Arabic dialect "darija") was used to collect information regarding the stigma and discrimination experienced by PLHIV across 8 cities in Morocco (September-October 2016). A randomly drawn cluster of 10 PLHIV, consisting of 5 men and 5 women, was drawn at each participating medical care center to achieve a nationally representative sample of PLHI V. Fifteen interviewers living with HIV and five supervisors were selected and trained to administer the questionnaire. An internal stigma score (range: 0-7), was calculated based on seven negative feelings/ beliefs. Negative binomial regression was used to identify characteristics associated with the internal stigma score. Results: Among 626 PLHIV, internal stigma was reported by 88.2%. The median [IQR] internal stigma score was 4 [2-5]. Regarding internal stigma, 51% avoided going to the local clinic when needed and 44% chose not to attend social gatherings. Belonging to at least one key population (aIRR [95%CI] = 1.15 [1.03; 1.28]), experiencing discriminatory reactions from family following HIV status disclosure (1.28 [1.11; 1.49]), avoiding HIV services for fear of stigmatization by staff (1.16 [1.05; 1.28]) and being denied health services because of HIV status (1.16 [1.03;1.32]), are among the factors significantly associated with an increase of the internal stigma score. Conclusions: Internal stigma is high among Moroccan PLHIV and significantly impacting their life decisions and their healthcare access. Multi-level interventions are needed to address internal stigma experienced by PLHIV in Morocco

Are PrEP services in France reaching all those exposed to HIV who want to take PrEP? MSM respondents who are eligible but not using PrEP (EMIS 2017)

International audiencePre-exposure prophylaxis (PrEP) is fully reimbursed by the French health insurance system since 2016. However, uptake of PrEP is slower than expected and little is known about men who have sex with men (MSM) who are eligible for PrEP according to French guidelines, but not using it. This study aims to (1) assess and describe MSM that are eligible to PrEP but not using it, and (2) identify potential individual and structural barriers of PrEP uptake among eligible MSM who are aware and intend to take PrEP. Data from EMIS-2017, a cross-sectional internet survey among gay, bisexual, and other MSM, were used. Among 7965 respondents without diagnosed HIV, 9.2% were PrEP users. Among 7231 non-PrEP users, 35.2% were eligible to PrEP and 15.2% were eligible, aware and intended to take PrEP. Eligible MSM who are not using PrEP are mostly younger, students, less "out", living in small cities, using condoms more frequently but still with low self-efficacy regarding safe sex and more distant from preventive health care and information than PrEP users. Despite free PrEP availability in France, results suggest that PrEP is not fully accessible and that there is a need to increase PrEP demand and decentralize PrEP delivery