Effectiveness of less than three doses of quadrivalent human papillomavirus vaccine against cervical intraepithelial neoplasia when administered using a standard dose spacing schedule: Observational cohort of young women in Australia

AbstractBackgroundOptimised two-dose human papillomavirus (HPV) vaccine schedules are now endorsed for young adolescents by the World Health Organization. Limited data are available about effectiveness of <3 doses using a standard dose schedule.MethodsDeterministic data linkage was undertaken between the Victorian Cervical Cytology Registry and National HPV Vaccination Program Register to determine quadrivalent HPV vaccination status and incidence of cervical pathology among vaccine eligible women (aged 26 years or younger in 2007) screened in Victoria, Australia between April 2007 and December 2011. Proportional hazards regression was used to estimate hazard ratios (HR) adjusted for age, socioeconomic status and area of residence. Women were stratified into those vaccinated before or after first screen.ResultsAny number of doses (1, 2 or 3) were associated with lower rates of high grade and low grade cytology diagnoses as long as doses were given before screening commencement (one dose HR high grade 0.44 (95% CI 0.32–0.59), one dose low grade 0.48 (95% CI 0.40–0.58); two doses HR high grade 0.63 (95% CI 0.50–0.80), HR low grade 0.52 (95% CI 0.44–0.61); three doses HR high grade 0.53 (95% CI 0.47–0.60), HR low grade 0.73 (95% CI 0.68–0.78)). Three doses of vaccine, but not fewer, were associated with reduced risk of high grade histologically confirmed abnormality in this cohort, regardless of whether vaccination occurred before or after screening (HR before 0.71 (95% CI 0.64–0.80), HR after 0.87 (95% CI 0.82–0.93)). Secondary analyses censoring end points occurring within 1, 6, 12, or 24 months of final vaccine dose suggested an increasing effect of partial vaccination courses over time.ConclusionOur data suggest that less than three doses of quadrivalent HPV vaccine provides some protection against cervical intraepithelial neoplasia, even when measured within 5 years in a population including those who were sexually active at the time of vaccination

Uptake and acceptability of human papillomavirus self-sampling in rural and remote Aboriginal communities : evaluation of a nurse-led community engagement model

Background: Aboriginal women experience disproportionately higher rates of cervical cancer mortality yet are less likely to participate in screening for early detection. This study sought to determine whether a community-based HPV self-sampling service model can effectively recruit never-screened and under-screened Aboriginal women to participate in cervical cancer screening; assess the clinical outcomes; and explore the acceptability of the model from the perspective of the participants. Methods: Aboriginal women aged 25–69 years of age were recruited from eight rural and remote communities in New South Wales, Australia to participate in HPV self-sampling via a community-based service model. Outcome measures were: number of women screened by HPV self-sampling, their prior cervical screening status (under-screened or never-screened), clinical outcomes and participation in follow-up pathways of care, and satisfaction with the service model. Results: In total, 215 women conducted a HPV self-sampling test and 200 evaluation surveys were completed. One-fifth of participants (n = 46) were never-screened and one-third (n = 69) were under-screened. Many were unsure of their screening status. Nine women were HPV 16/18 positive and eight had completed all follow up by the conclusion of the study. A further 30 women tested positive for a high risk type other than HPV 16/18 (HPV other), of which 14 had completed follow up at the conclusion of the study. Satisfaction with the HPV self-sampling kit, the process of self-sampling and the service model was high (> 92% satisfied on all items). Many women had difficulty understanding their official HPV results and placed high importance on the nurse explaining it to them. Conclusions: A community-based service model that respects Aboriginal Women’s Business can effectively recruit under-screened and never-screened Aboriginal women to complete cervical cancer screening. Furthermore, this service model supports them to complete recommended follow-up care and engage with their local existing health services

Management of Chlamydia Cases in Australia (MoCCA): protocol for a non-randomised implementation and feasibility trial

INTRODUCTION: The sexually transmitted infection chlamydia can cause significant complications, particularly among people with female reproductive organs. Optimal management includes timely and appropriate treatment, notifying and treating sexual partners, timely retesting for reinfection and detecting complications including pelvic inflammatory disease (PID). In Australia, mainstream primary care (general practice) is where most chlamydia infections are diagnosed, making it a key setting for optimising chlamydia management. High reinfection and low retesting rates suggest partner notification and retesting are not uniformly provided. The Management of Chlamydia Cases in Australia (MoCCA) study seeks to address gaps in chlamydia management in Australian general practice through implementing interventions shown to improve chlamydia management in specialist services. MoCCA will focus on improving retesting, partner management (including patient-delivered partner therapy) and PID diagnosis. METHODS AND ANALYSIS: MoCCA is a non-randomised implementation and feasibility trial aiming to determine how best to implement interventions to support general practice in delivering best practice chlamydia management. Our method is guided by the Consolidated Framework for Implementation Research and the Normalisation Process Theory. MoCCA interventions include a website, flow charts, fact sheets, mailed specimen kits and autofills to streamline chlamydia consultation documentation. We aim to recruit 20 general practices across three Australian states (Victoria, New South Wales, Queensland) through which we will implement the interventions over 12–18 months. Mixed methods involving qualitative and quantitative data collection and analyses (observation, interviews, surveys) from staff and patients will be undertaken to explore our intervention implementation, acceptability and uptake. Deidentified general practice and laboratory data will be used to measure pre-post chlamydia testing, retesting, reinfection and PID rates, and to estimate MoCCA intervention costs. Our findings will guide scale-up plans for Australian general practice. ETHICS AND DISSEMINATION: Ethics approval was obtained from The University of Melbourne Human Research Ethics Committee (Ethics ID: 22665). Findings will be disseminated via conference presentations, peer-reviewed publications and study reports

Mobile phones are a viable option for surveying young Australian women: a comparison of two telephone survey methods

<p>Abstract</p> <p>Background</p> <p>Households with fixed-line telephones have decreased while mobile (cell) phone ownership has increased. We therefore sought to examine the feasibility of recruiting young women for a national health survey through random digit dialling mobile phones.</p> <p>Methods</p> <p>Two samples of women aged 18 to 39 years were surveyed by random digit dialling fixed and mobile numbers. We compared participation rates and responses to a questionnaire between women surveyed by each contact method.</p> <p>Results</p> <p>After dialling 5,390 fixed-lines and 3,697 mobile numbers, 140 and 128 women were recruited respectively. Among women contacted and found to be eligible, participation rates were 74% for fixed-lines and 88% for mobiles. Taking into account calls to numbers where eligibility was unknown (e.g. unanswered calls) the estimated response rates were 54% and 45% respectively. Of women contacted by fixed-line, 97% reported having a mobile while 61% of those contacted by mobile reported having a fixed-line at home. After adjusting for age, there were no significant differences between mobile-only and fixed-line responders with respect to education, residence, and various health behaviours; however compared to those with fixed-lines, mobile-only women were more likely to identify as Indigenous (OR 4.99, 95%CI 1.52-16.34) and less likely to live at home with their parents (OR 0.09, 95%CI 0.03-0.29).</p> <p>Conclusions</p> <p>Random digit dialling mobile phones to conduct a health survey in young Australian women is feasible, gives a comparable response rate and a more representative sample than dialling fixed-lines only. Telephone surveys of young women should include mobile dialling.</p

Epidemiology of Human Parvovirus 4 Infection in Sub-Saharan Africa

Human parvovirus 4 infections are primarily associated with parenteral exposure in western countries. By ELISA, we demonstrate frequent seropositivity for antibody to parvovirus 4 viral protein 2 among adult populations throughout sub-Saharan Africa (Burkina Faso, 37%; Cameroon, 25%; Democratic Republic of the Congo, 35%; South Africa, 20%), which implies existence of alternative transmission routes

High Seroprevalence of Enterovirus Infections in Apes and Old World Monkeys

To estimate population exposure of apes and Old World monkeys in Africa to enteroviruses (EVs), we conducted a seroepidemiologic study of serotype-specific neutralizing antibodies against 3 EV types. Detection of species A, B, and D EVs infecting wild chimpanzees demonstrates their potential widespread circulation in primates

Genome-wide single-cell-level screen for protein abundance and localization changes in response to DNA damage in S. cerevisiae

An effective response to DNA damaging agents involves modulating numerous facets of cellular homeostasis in addition to DNA repair and cell-cycle checkpoint pathways. Fluorescence microscopy-based imaging offers the opportunity to simultaneously interrogate changes in both protein level and subcellular localization in response to DNA damaging agents at the single-cell level. We report here results from screening the yeast Green Fluorescent Protein (GFP)-fusion library to investigate global cellular protein reorganization on exposure to the alkylating agent methyl methanesulfonate (MMS). Broad groups of induced, repressed, nucleus- and cytoplasm-enriched proteins were identified. Gene Ontology and interactome analyses revealed the underlying cellular processes. Transcription factor (TF) analysis identified principal regulators of the response, and targets of all major stress-responsive TFs were enriched amongst the induced proteins. An unexpected partitioning of biological function according to the number of TFs targeting individual genes was revealed. Finally, differential modulation of ribosomal proteins depending on methyl methanesulfonate dose was shown to correlate with cell growth and with the translocation of the Sfp1 TF. We conclude that cellular responses can navigate different routes according to the extent of damage, relying on both expression and localization changes of specific proteins.National Cancer Institute (U.S.) (R01-CA055042 (now NIEHS R01-ES022872))Massachusetts Institute of Technology. Center for Environmental Health Sciences (Grant NIEHS P30-ES002109)National Cancer Institute (U.S.) (KI Center Grant U54-CA112967)National Cancer Institute (U.S.) (Cancer Center Support Grant P30-CA14051)National Institute of Environmental Health Sciences (R01-ES022872)MIT Faculty Start-up FundMassachusetts Institute of Technology. Computational and Systems Biology Initiative (Merck & Co. Postdoctoral Fellowship

Platform adaptive trial of novel antivirals for early treatment of COVID-19 In the community (PANORAMIC): protocol for a randomised, controlled, open-label, adaptive platform trial of community novel antiviral treatment of COVID-19 in people at increased risk of more severe disease

Introduction: There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. // Methods and analysis: PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial. // Ethics and dissemination: Ethical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals. // Trial registration number: ISRCTN30448031; EudraCT number: 2021-005748-31

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data