Epidemiological characteristics of human infections with avian influenza A(H5N6) virus, China and Laos: A multiple case descriptive analysis, February 2014-June 2023.

Background: The first human infection with highly pathogenic avian influenza A(H5N6) virus was reported in 2014. From then until June 30, 2023, 85 human cases with confirmed A(H5N6) infection have been reported worldwide. Objective: To address the present gap in knowledge of the overall epidemiology of human A(H5N6) infections, the epidemiological characteristics of human infection with A(H5N6) in China from February 2014 to June 2023 are described. Methods: Considering the severity of human infections with A(H5N6) virus (case fatality rate: 39%), the increased frequency of case reports from 2021 to present day, and lack of comprehensive epidemiologic analysis of all cases, we conducted a multiple-case descriptive analysis and a literature review to create an epidemiologic profile of reported human cases. Case data was obtained via a literature search and using official intelligence sources captured by the Public Health Agency of Canada's International Monitoring and Assessment Tool (IMAT), including Event Information Site posts from the World Health Organization. Results: Most human A(H5N6) cases have been reported from China (China: 84; Laos: 1), with severe health outcomes, including hospitalization and death, reported among at-risk populations. The majority (84%) of cases reported contact with birds prior to illness onset. Cases were detected throughout the course of the year, with a slight decrease in illness incidence in the warmer months. Conclusion: As A(H5N6) continues to circulate and cause severe illness, surveillance and prompt information sharing is important for creating and implementing effective public health measures to reduce the likelihood of additional human infections.

Protection to Self and to One's Sexual Partner After Human Papillomavirus Vaccination: Preliminary Analysis From the Transmission Reduction And Prevention with HPV Vaccination Study.

BACKGROUND: It is unknown whether recently human papillomavirus (HPV)-vaccinated individuals confer protection against vaccine-preventable HPV types to their partners. METHODS: Participants 18 to 45 years old who were living in Montreal, Canada, and in a heterosexual relationship of 6 months or less were randomly assigned to receive the intervention HPV vaccine, Gardasil or Gardasil 9, or active control (AC), Avaxim, a hepatitis A vaccine. Couples attended a maximum of 6 clinic visits (baseline and at 2, 4, 6, 9, and 12 months) and provided genital samples for detection of 36 HPV genotypes. Participants were vaccinated at baseline and at 2 and 6 months. We used Cox proportional hazards regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between the administered vaccine and infections at the HPV episode level. RESULTS: We restricted analyses to 273 participants (intervention: n = 141, AC: n = 132) who had at least 2 visits with valid HPV data. The HR of becoming positive for a given vaccine-preventable HPV type in the intervention group among those who received at least 1 dose compared with AC was 0.47 (95% CI, 0.23-0.97). Comparing individuals with HPV-vaccinated versus AC-vaccinated partners, there was no difference in risk of becoming positive for a given vaccine-preventable HPV type among those whose partners received at least 1 (HR, 1.46; 95% CI, 0.73-2.94) or 2 (HR, 0.78; 95% CI, 0.31-1.96) doses. CONCLUSIONS: Our study provides inconclusive evidence that individuals whose partner recently received an HPV vaccine are protected from vaccine-preventable types but demonstrates that vaccinated individuals are at a lower risk of incident infections.Trial Registration Number: NCT01824537.

Proportion of Incident Genital Human Papillomavirus Detections not Attributable to Transmission and Potentially Attributable to Latent Infections: Implications for Cervical Cancer Screening.

BACKGROUND: Infections with human papillomaviruses (HPVs) may enter a latent state, and eventually become reactivated following loss of immune control. It is unclear what proportion of incident HPV detections are reactivations of previous latent infections vs new transmissions. METHODS: The HPV Infection and Transmission among Couples through Heterosexual activity (HITCH) cohort study prospectively followed young newly formed heterosexual partners recruited between 2005 and 2011 in Montréal, Canada. We calculated the fraction of incident HPV detections nonattributable to sexual transmission risk factors with a Bayesian Markov model. Results are the median (2.5th-97.5th percentiles) of the estimated posterior distribution. RESULTS: A total of 544 type-specific incident HPV detection events occurred in 849 participants; 33% of incident HPV detections occurred in participants whose HITCH partners were negative for that HPV type and who reported no other sex partners over follow-up. We estimate that 43% (38%-48%) of all incident HPV detections in this population were not attributable to recent sexual transmission and might be potentially reactivation of latent infections. CONCLUSIONS: A positive HPV test result in many cases may be a reactivated past infection, rather than a new infection from recent sexual behaviors or partner infidelity. The potential for reactivation of latent infections in previously HPV-negative women should be considered in the context of cervical cancer screening.

Sex- and Type-specific Genital Human Papillomavirus Transmission Rates Between Heterosexual Partners: A Bayesian Reanalysis of the HITCH Cohort.

BACKGROUND: It is unclear whether sexual transmission rates of human papillomaviruses (HPV) differ between sexes and HPV types. We estimate updated transmission rates from the final HITCH cohort study and propose an estimation method that accounts for interval-censored data and infection clearance. METHODS: We enrolled young women 18-24 years old and their male sex partners ≥18 years old in Montréal, Canada, between 2005 and 2011. We followed women over 24 months and men over 4 months. We tested genital samples with Linear Array for HPV DNA detection and genotyping. We calculated infection transmission rates between partners using a multistate Markov model via a Bayesian approach. We report the posterior median and 2.5%-97.5% percentile intervals (95% PI). RESULTS: We observed 166 type-specific incident HPV transmission events in 447 women and 402 men. The estimated median transmission rate from an HPV-positive to a negative partner was 4.2 (95% PI = 3.1 to 5.3) per 100 person-months. The transmission rate from men-to-women was 3.5 (95% PI = 2.5 to 4.7) and from women-to-men was 5.6 (95% PI = 3.8 to 7.0) per 100 person-months, corresponding to a rate ratio of 1.6 (95% PI = 1.0 to 2.5). Partners reporting always using condoms had a 0.22 (95% PI = 0.05 to 0.61) times lower HPV transmission rate than those reporting never using condoms. HPV16/18 did not have particularly high transmission rates relative to other HPV types. CONCLUSION: Our updated analysis supports previous research suggesting higher women-to-men than men-to-women HPV transmission rates and a protective effect of condoms in heterosexual partnerships. Our results also suggest that crude incidence rates underestimate HPV transmission rates due to interval-censoring. See video abstract at http://links.lww.com/EDE/B794.

Transmission reduction and prevention with HPV vaccination (TRAP-HPV) study protocol: a randomised controlled trial of the efficacy of HPV vaccination in preventing transmission of HPV infection in heterosexual couples.

INTRODUCTION: Human papillomavirus (HPV) is a causal agent of malignancies including cervical, vulvar, vaginal, penile, anal and oropharyngeal cancer, as well as benign conditions such as anogenital warts. HPV vaccination protects individuals against infections with the target HPV types and their clinical outcomes. However, little is known about the protection an immunised individual confers to their sexual partner or its impact on HPV transmission dynamics. In this context, the Transmission Reduction and Prevention with HPV vaccination (TRAP-HPV) study was designed to determine the efficacy of an HPV vaccine in reducing transmission of genital and oral HPV infection in sexual partners of vaccinated individuals. METHODS AND ANALYSIS: The TRAP-HPV study is an ongoing randomised controlled trial among heterosexual couples living in Montreal, Canada. Sexually active couples, aged between 18 and 45 years, who have been in a relationship no longer than 6 months are considered eligible. Participants are independently randomised to receive either the intervention HPV vaccine, Gardasil 9, or a placebo hepatitis A vaccine, Avaxim, creating four vaccination groups among couples: intervention-intervention, intervention-placebo, placebo-intervention and the placebo-placebo. Participants provide genital (vaginal/penile) and oral samples at baseline and five follow-up visits over a 1-year duration. Linear Array HPV genotyping is used to detect 36 HPV types. Cox proportional hazard regression models will be used to estimate the effect of vaccination on HPV transmission. ETHICS AND DISSEMINATION: The TRAP-HPV study received ethical approval by institutional review boards McGill University, Concordia University and Centre Hospitalier de l'Université de Montréal. Before enrolment, all participants provide informed written consent. Results will be published in peer-reviewed journals and presented at national and international conferences. The generated empirical evidence could be used in mathematical models of vaccination to inform policymakers in Canada and elsewhere. TRIAL REGISTRATION NUMBER: NCT01824537.

Directionality of Genital Human Papillomavirus Infection Transmission Within Heterosexual Couples: A Systematic Review and Meta-analysis.

BACKGROUND: Limited evidence indicates greater female-to-male (F-M) transmission of genital infection with human papillomavirus (HPV) relative to male-to-female (M-F). We verified the hypothesis of a differential transmission rate in couple-based studies by conducting a systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, Scopus, and Cochrane Library databases for studies published until December 2019. We calculated pooled estimates of F-M and M-F transmission rates and their rate differences per 100 person-months, with 95% confidence intervals (CI), using a random-effects model. We counted occurrences of directionality preponderance for each HPV type. RESULTS: We identified 7 eligible studies published between 2008 and 2019, providing data for 752 couples. Pooled estimates for F-M and M-F transmission rates were 3.01 (95% CI, 1.19-7.64; I2 = 97%) and 1.60 (95% CI, 0.86-2.98; I2 = 89%), respectively. The overall rate difference was 0.61 (95% CI, -0.27 to 1.49; I2 = 75%). Three studies provided rates by sex and HPV genotype; 2 favored a preponderance of F-M and 1 favored M-F transmission. CONCLUSIONS: There was slight evidence for a differential transmission rate favoring higher F-M than M-F transmission with substantial statistical heterogeneity across studies.

Mind the Gap: Genetic Variation and Personalized Therapies for Cardiomyopathies.

Inherited cardiomyopathies are cardiovascular disorders that are one of the leading causes of death and are strongly associated with genetic mutations. These include hypertrophic, dilated, restrictive, as well as arrhythmogenic right ventricular cardiomyopathies. Among the patients presenting with these specific forms of cardiomyopathies, there is significant phenotypic, genotypic, and environmental heterogeneity. Over the years, the identification of the underlying mutations common to specific forms of cardiomyopathies have facilitated clinic diagnosis. However, the variation between patient genetics and phenotypes highlights the need for improved understanding of these diseases and the development of innovative treatments. To better understand the diseases, researchers are capitalizing on two innovative technologies: cardiac reprogramming and gene editing using CRISPR-Cas9. Deriving cardiomyocytes from patient blood samples and gene editing allows for the efficient generation of cellular and animal models that allow researchers to model the disease more accurately. In addition, the recent advances in high throughput drug screening allows for the efficient testing of patient-derived cardiomyocytes for patient-specific susceptibility to various drugs that are currently approved. In addition, this technology can facilitate the development of new pharmacological compounds for the treatment of specific cardiomyopathies. Overall, the recent technological advances in molecular medicine now presents an opportunity to gain unprecedented insight into solving the complex issue of inherited cardiomyopathies. These techniques pave the way for the new generation of personalized medicine in treating cardiovascular diseases.