Does exposure to different menstrual products affect the vaginal environment?

The vaginal ecosystem is a key component of women's health. It also represents an ideal system for ecologists to investigate the consequence of perturbations on species diversity and emerging properties between organizational levels. Here, we study how exposure to different types of menstrual products is linked to microbial, immunological, demographic, and behavioural measurements in a cohort of young adult women who reported using more often tampons (n = 107) or menstrual cups (n = 31). We first found that cup users were older and smoked less than tampon users. When analysing health indicators, we detected potential associations between cups use reporting and fungal genital infection. A multivariate analysis confirmed that in our cohort, reporting using cups over tampons was associated with the higher odds ratio to report a fungal genital infection diagnosis by a medical doctor within the last 3 months. We did not detect significant differences between groups in terms of their bacterial vaginal microbiota composition and found marginal differences in the level of expression of 20 cytokines. However, a multivariate analysis of these biological data identified some level of clustering based on the menstrual product type preferred (cups or tampons). These results suggest that exposure to different types of menstrual products could influence menstrual health. Larger studies and studies with a more powered setting are needed to assess the robustness of these associations and identify causal mechanisms.

Receptor binding domain-IgG levels correlate with protection in residents facing SARS-CoV-2 B.1.1.7 outbreaks.

BACKGROUND: Limited information exists on nursing home (NH) residents regarding BNT162b2 vaccine efficacy in preventing SARS-CoV-2 and severe COVID-19, and its association with post-vaccine humoral response. METHODS: 396 residents from seven NHs suffering a SARS-CoV-2 B.1.1.7 (VOC-α) outbreak at least 14 days after a vaccine campaign were repeatedly tested using SARS-CoV-2 real-time reverse-transcriptase polymerase chain reaction on nasopharyngeal swab test (RT-qPCR). SARS-CoV-2 receptor-binding domain (RBD) of the S1 subunit (RBD-IgG) was measured in all residents. Nucleocapsid antigenemia (N-Ag) was measured in RT-qPCR-positive residents and serum neutralizing antibodies in vaccinated residents from one NH. RESULTS: The incidence of positive RT-qPCR was lower in residents vaccinated by two doses (72/317; 22.7%) vs one dose (10/31; 32.3%) or non-vaccinated residents (21/48; 43.7%; p < .01). COVID-19-induced deaths were observed in 5 of the 48 non-vaccinated residents (10.4%), in 2 of the 31 who had received one dose (6.4%), and in 3 of the 317 (0.9%) who had received two doses (p = .0007). Severe symptoms were more common in infected non-vaccinated residents (10/21; 47.6%) than in infected vaccinated residents (15/72; 21.0%; p = .002). Higher levels of RBD-IgG (n = 325) were associated with a lower SARS-CoV-2 incidence. No in vitro serum neutralization activity was found for RBD-IgG levels below 1050 AU/ml. RBD-IgG levels were inversely associated with N-Ag levels, found as a risk factor of severe COVID-19. CONCLUSIONS: Two BNT162b2 doses are associated with a 48% reduction of SARS-CoV-2 incidence and a 91.3% reduction of death risk in residents from NHs facing a VOC-α outbreak. Post-vaccine RBD-IgG levels correlate with BNT162b2 protection against SARS-CoV-2 B.1.1.7.

High prevalence and diversity of hepatitis B and hepatitis delta virus in Gabon.

Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country-wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg-positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north-south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country.

Addressing pandemic-wide systematic errors in the SARS-CoV-2 phylogeny.

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 3,960,704 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of March 2023, viewable at https://viridian.taxonium.org. Each genome was constructed using a novel assembly tool called Viridian (https://github.com/iqbal-lab-org/viridian), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. Phase 2 of our project will address the fact that the data in the public archives is heavily geographically biased towards the Global North. We therefore have contributed new raw data to ENA/SRA from many countries including Ghana, Thailand, Laos, Sri Lanka, India, Argentina and Singapore. We will incorporate these, along with all public raw data submitted between March 2023 and the current day, into an updated set of assemblies, and phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

Concomitant and productive genital infections by HSV-2 and HPV in two young women: A case report.

Human papillomaviruses (HPVs), the most oncogenic virus known to humans, are often associated with Herpes Simplex Virus-2 (HSV-2) infections. The involvement of the latter in cervical cancer is controversial but its long-term infections might modulate the mucosal microenvironment in a way that favors carcinogenesis. We know little about coinfections between HSV-2 and HPVs, and studying the immunological and microbiological dynamics in the early stages of these infections may help identify or rule out potential interactions. We report two cases of concomitant productive, although asymptomatic, HSV-2 and HPV infections in young women (aged 20 and 25). The women were followed up for approximately a year, with clinical visits every two months and weekly self-samples. We performed quantitative analyses of their HSV-2 and HPV viral loads, immunological responses (IgG and IgM antibodies and local cytokines expression profiles), vaginal microbiota composition, as well as demographic and behavior data. We detect interactions between virus loads, immune response, and the vaginal microbiota, which improve our understanding of HSV-2 and HPVs' coinfections and calls for further investigation with larger cohorts.

Cytokine response following perturbation of the cervicovaginal milieu during HPV genital infection.

Human papillomaviruses (HPVs) are oncogenic viruses causing most cervical cancers. Highly prevalent in young, sexually active women, only a minority of HPV infections persist. To better characterize the immuno-modulatory impact of early HPV infections, we measured changes in a panel of 20 cytokines in cervicovaginal samples collected from young women who were tested for HPV and self-reported for genital inflammation and infection symptoms. Multi-factor statistical analyses revealed that increased IL-1Alpha and IL-12/IL-23p40 concentrations were associated with HPV infection and that macrophage inflammatory proteins were associated in particular with high-risk HPV infections. ClinicalTrials.gov identifier NCT02946346.

HPV cervical infections and serological status in vaccinated and unvaccinated women.

Understanding genital infections by Human papillomaviruses (HPVs) remains a major public health issue, especially in countries where vaccine uptake is low. We investigate HPV prevalence and antibody status in 150 women (ages 18 to 25) in Montpellier, France. At inclusion and one month later, cervical swabs, blood samples and questionnaires (for demographics and behavioural variables) were collected. Oncogenic, non-vaccine genotypes HPV51, HPV66, HPV53, and HPV52 were the most frequently detected viral genotypes overall. Vaccination status, which was well-balanced in the cohort, showed the strongest (protective) effect against HPV infections, with an associated odds ratio for alphapapillomavirus detection of 0.45 (95% confidence interval: [0.22;0.58]). We also identified significant effects of age, number of partners, body mass index, and contraception status on HPV detection and on coinfections. Type-specific IgG serological status was also largely explained by the vaccination status. IgM seropositivity was best explained by HPV detection at inclusion only. Finally, we identify a strong significant effect of vaccination on genotype prevalence, with a striking under-representation of HPV51 in vaccinated women. Variations in HPV prevalence correlate with key demographic and behavioural variables. The cross-protective effect of the vaccine against HPV51 merits further investigation.

Natural history, dynamics, and ecology of human papillomaviruses in genital infections of young women: protocol of the PAPCLEAR cohort study.

INTRODUCTION: Human papillomaviruses (HPVs) are responsible for one-third of all cancers caused by infections. Most HPV studies focus on chronic infections and cancers, and we know little about the early stages of the infection. Our main objective is to better understand the course and natural history of cervical HPV infections in healthy, unvaccinated and vaccinated, young women, by characterising the dynamics of various infection-related populations (virus, epithelial cells, vaginal microbiota and immune effectors). Another objective is to analyse HPV diversity within hosts, and in the study population, in relation to co-factors (lifestyle characteristics, vaccination status, vaginal microbiota, human genetics). METHODS AND ANALYSIS: The PAPCLEAR study is a single center longitudinal study following 150 women, aged 18-25 years, for up to 2 years. Visits occur every 2 or 4 months (depending on HPV status) during which several variables are measured, such as behaviours (via questionnaires), vaginal pH, HPV presence and viral load (via qPCR), local concentrations of cytokines (via MesoScale Discovery technology) and immune cells (via flow cytometry). Additional analyses are outsourced, such as titration of circulating anti-HPV antibodies, vaginal microbiota sequencing (16S and ITS1 loci) and human genotyping. To increase the statistical power of the epidemiological arm of the study, an additional 150 women are screened cross-sectionally. Finally, to maximise the resolution of the time series, participants are asked to perform weekly self-samples at home. Statistical analyses will involve classical tools in epidemiology, genomics and virus kinetics, and will be performed or coordinated by the Centre National de la Recherche Scientifique (CNRS) in Montpellier. ETHICS AND DISSEMINATION: This study has been approved by the Comité de Protection des Personnes Sud Méditerranée I (reference number 2016-A00712-49); by the Comité Consultatif sur le Traitement de l'Information en matière de Recherche dans le domaine de la Santé (reference number 16.504); by the Commission Nationale Informatique et Libertés (reference number MMS/ABD/AR1612278, decision number DR-2016-488) and by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (reference 20160072000007). Results will be published in preprint servers, peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT02946346; Pre-results.