Ability of epidemiological studies to monitor HPV post-vaccination dynamics: a simulation study

Genital human papillomavirus (HPV) infections are caused by a broad diversity of genotypes. As available vaccines target a subgroup of these genotypes, monitoring transmission dynamics of nonvaccine genotypes is essential. After reviewing the epidemiological literature on study designs aiming to monitor those dynamics, we evaluated their abilities to detect HPV-prevalence changes following vaccine introduction. We developed an agent-based model to simulate HPV transmission in a heterosexual population under various scenarios of vaccine coverage and genotypic interaction, and reproduced two study designs: post-vs-prevaccine and vaccinated-vs-unvaccinated comparisons. We calculated the total sample size required to detect statistically significant prevalence differences at the 5% significance level and 80% power. Although a decrease in vaccine-genotype prevalence was detectable as early as 1 year after vaccine introduction, simulations indicated that the indirect impact on nonvaccine-genotype prevalence (a decrease under synergistic interaction or an increase under competitive interaction) would only be measurable after >10 years whatever the vaccine coverage. Sample sizes required for nonvaccine genotypes were >5 times greater than for vaccine genotypes and tended to be smaller in the post-vs-prevaccine than in the vaccinated-vs-unvaccinated design. These results highlight that previously published epidemiological studies were not powerful enough to efficiently detect changes in nonvaccine-genotype prevalence

Detailed Contact Data and the Dissemination of Staphylococcus aureus in Hospitals

on behalf of the I-Bird study GroupInternational audienceClose proximity interactions (CPIs) measured by wireless electronic devices are increasingly used in epidemiological models. However, no evidence supports that electronically collected CPIs inform on the contacts leading to transmission. Here, we analyzed Staphylococcus aureus carriage and CPIs recorded simultaneously in a long-term care facility for 4 months in 329 patients and 261 healthcare workers to test this hypothesis. In the broad diversity of isolated S. aureus strains, 173 transmission events were observed between participants. The joint analysis of carriage and CPIs showed that CPI paths linking incident cases to other individuals carrying the same strain (i.e. possible infectors) had fewer intermediaries than predicted by chance (P < 0.001), a feature that simulations showed to be the signature of transmission along CPIs. Additional analyses revealed a higher dissemination risk between patients via healthcare workers than via other patients. In conclusion, S. aureus transmission was consistent with contacts defined by electronically collected CPIs, illustrating their potential as a tool to control hospital-acquired infections and help direct surveillance

Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial

International audienceBackground.Genital infection with Chlamydia trachomatis (Ct) is the most common bacterial sexually transmitted infection, especially among young women. Mostly asymptomatic, it can lead, if untreated, to pelvic inflammatory disease (PID), tubal factor infertility and ectopic pregnancy. Recent data suggest that Ct infections are not controlled in France and in Europe. The effectiveness of a systematic strategy for Ct screening in under-25 women remains controversial. The main objective of the i-Predict trial (Prevention of Diseases Induced by Chlamydia trachomatis) is to determine whether early screening and treatment of 18- to-24-year-old women for genital Ct infection reduces the incidence of PID over 24 months.Methods/design.This is a randomised prevention trial including 4000 eighteen- to twenty-four-year-old sexually active female students enrolled at five universities. The participants will provide a self-collected vaginal swab sample and fill in an electronic questionnaire at baseline and at 6, 12 and 18 months after recruitment. Vaginal swabs in the intervention arm will be analysed immediately for Ct positivity, and participants will be referred for treatment if they have a positive test result. Vaginal swabs from the control arm will be analysed at the end of the study. All visits to general practitioners, gynaecologists or gynaecology emergency departments for pelvic pain or other gynaecological symptoms will be recorded to evaluate the incidence of PID, and all participants will attend a final visit in a hospital gynaecology department. The primary endpoint measure will be the incidence of PID over 24 months. The outcome status (confirmed, probable or no PID) will be assessed by two independent experts blinded to group assignment and Ct status.Discussion.This trial is expected to largely contribute to the development of recommendations for Ct screening in young women in France to prevent PID and related complications. It is part of a comprehensive approach to gathering data to facilitate decision-making regarding optimal strategies for Ct infection control. The control group of this randomised trial, following current recommendations, will allow better documentation of the natural history of Ct infection, a prerequisite to evaluating the impact of Ct screening. Characterisation of host immunogenetics will also allow identification of women at risk for complications.Trial registration.ClinicalTrials.gov, NCT02904811. Registered on September 14, 2016.World Health Organisation International Clinical Trials Registry, NCT02904811.AOM, 15-0063 and P150950. Registered on September 26, 2016. A completed Standard Protocol Items : Recommendations for International Trials (SPIRIT) Checklist is available in additional file 1

CPI-based network and <i>S</i>. <i>aureus</i> carriage in the hospital.

<p>The network shown corresponds to interactions occurring during 1 d. Patients are shown as triangles and HCWs as diamonds. Color-coding corresponds to the <i>spa</i> type of the last known colonization status (i.e. the preceding week). Because of the large <i>S</i>. <i>aureus spa</i> types diversity, only the 3 most common are reported in the legend. We used Fruchterman-Reingold force-directed algorithm for the layout (individuals in the network are closer together as the density of links among them increases). Force-directed edge bundling was used to accommodate their high density.</p

CPI supported transmitters.

<p><b>(Top)</b> CPI-supported transmitters were selected among carriers of the same strain (green) as the incident case (yellow) who were the closest in the CPI network. Here, P1 and H1 are two CPI-supported transmitters in the incident case’s 2-hop neighborhood, but not P2 who is further away (3-hop neighborhood). Patients are shown as triangles and HCWs as diamonds. <b>(Bottom left)</b> Comparison of the distance distribution between CPI-supported transmitters and incident cases in the data (black) and with random permutations of carriage data (white) in the simulation study. <b>(Bottom right)</b> Comparison of the distance between CPI-supported transmitters and incident cases in the original data.</p

Incident-colonization episodes, candidate transmitters and CPI support.

<p>Incident-colonization episodes were investigated when the incident strain had been isolated from at least one another participant (candidate transmitter). When a CPI path existed between a candidate transmitter and the incident case, the episode was considered as CPI-supported.</p><p>* Episodes where CPI were not recorded for the incident case were discarded</p><p>† Among those with available CPI network</p><p>Incident-colonization episodes, candidate transmitters and CPI support.</p

Statistical power computed for the three proposed test statistics.

<p>Power was determined for an increasing set of incident colonization episodes, with 500 replicates each time.</p><p>Statistical power computed for the three proposed test statistics.</p