Risk factors for placental human papillomavirus infection.

OBJECTIVE: Human papillomavirus (HPV) has been associated with adverse pregnancy outcomes but placental HPV infection has been rarely studied. The objective was to determine the proportion of HPV-positive placentas and the associated risk factors among HPV-positive women during pregnancy. METHODS: We analysed data from pregnant women enrolled in HERITAGE cohort study between 2010 and 2016 with positive vaginal HPV infection during the first trimester of pregnancy (n=354). Placental swabs and biopsies were collected. HPV genotyping was performed using Linear Array. The predictors of placental HPV detection were identified by generalised estimating equations models. RESULTS: HPV was detected in 78 placentas (22.0%) (one among 96 caesarean sections and 77 among 258 vaginal deliveries). Overall, 91% of HPV-positive placentas were positive for a genotype that was detected in vaginal samples during pregnancy. Among women who delivered vaginally, abnormal cytology (adjusted OR (aOR) 1.78 (95% CI 1.02 to 3.10)), other genitourinary infection (aOR 2.41 (95% CI 1.31 to 4.44)), presence of multiple HPV genotypes in the first trimester (aOR 2.69 (95% CI 1.76 to 4.12)) and persistence of high-risk HPV infections during pregnancy (HPV-16/18: aOR 3.94 (95% CI 2.06 to 7.55) and other than HPV-16/18: aOR 2.06 (95% CI 1.05 to 4.02)) were independently associated with placental HPV. CONCLUSIONS: HPV was frequently detected in the placenta of women who delivered vaginally and may be associated with host immune response characteristics.

Association between the Mode of Delivery and Vertical Transmission of Human Papillomavirus.

Human papillomavirus (HPV) can be vertically transmitted. Our objective was to measure the association between the mode of delivery and the detection of HPV in infants. We used data collected from pregnant women during the HERITAGE study. Self-collected vaginal samples from the first and third trimester were obtained for HPV testing. Specimens from oral, pharyngeal, conjunctival and anogenital mucosa were collected from infants 36-48 h after delivery and at 3 months of age. All samples were tested for HPV DNA by the Linear Array assay. Adjusted odd ratios (aOR) and 95% confidence interval (CI) were estimated using multivariate logistic regressions. From the 282 women revealed to be HPV-positive in both the first and third trimesters, 25 infants were born HPV-positive. The overall probability of transmission was 8.9% (25/282); 3.7% (3/81) in participants with a caesarean section and 10.9% (22/201) for those who delivered vaginally. Vaginal delivery increased the risk of HPV in infants compared to caesarean (aOR: 3.63, 95%CI: 1.03-12.82). Infants born after a caesarean with ruptured membranes were not at increased risk of HPV compared to infants born after an elective caesarean section with intact membranes (aOR: 1.31, 95%CI: 0.10-17.76). Our results support the hypothesis that transmission occurs mostly during the passage in the vaginal canal.

Knowledge, attitude and practice (KAP) and risk factors on dengue fever among children in Brazil, Fortaleza: A cross-sectional study.

BACKGROUND: Dengue fever is a mosquito-borne viral disease that is associated with four serotypes of the dengue virus. Children are vulnerable to infection with the dengue virus, particularly those who have been previously infected with a different dengue serotype. Sufficient knowledge, positive attitudes, and proper practices (KAP) are essential for dengue prevention and control. This study aims to estimate the dengue seropositivity for study participants and to examine the association between households' dengue-related knowledge, attitudes, and practices (KAP), and children's risk of dengue seropositivity, while accounting for socioeconomic and demographic differences in Brazil. METHODOLOGY/PRINCIPAL FINDINGS: This analysis was based on a cross-sectional study from Fortaleza, Brazil between November 2019, and February 2020. There were 392 households and 483 participant children who provided a sample of sufficient quality for serological analysis. The main exposure was a household's dengue-related knowledge, attitudes, and practices, assessed through a questionnaire to construct a composite KAP score categorized into three levels: low, moderate, and high. The main outcome is dengue immunoglobulin G(IgG) antibodies, collected using dried blood spots and assessed with Panbio Dengue IgG indirect ELISA (enzyme-linked immunosorbent assays) test commercial kits. The estimated crude dengue seroprevalence among participating children (n = 483) was 25%. Five percent of households (n = 20) achieved a score over 75% for KAP, sixty-nine percent of households (n = 271) scored between 50% and 75%, and twenty-six percent of households (n = 101) scored lower than 50%. Each KAP domain was significantly and positively associated with the others. The mean percentage scores for the three domains are 74%, 63%, and 39% respectively. We found high household KAP scores were associated with an increased adjusted relative risk (aRR) of seropositivity (aRR: 2.11, 95% CI: 1.11-4.01, p = 0.023). Household adult respondents' education level of elementary school or higher was negatively associated with children's risk of being seropositive (aRR: 0.65, 95% CI: 0.48-0.87, p = 0.005). The risk of seropositivity in older children (6-12 years old) was over 6 times that of younger children (2-5 years old) (aRR: 6.08, 95% CI: 3.47-10.64, p<0.001). Children living in households with sealed water tanks or no water storage had a lower risk of being seropositive (aRR: 0.73, 95% CI: 0.54-0.98, p = 0.035). CONCLUSIONS/SIGNIFICANCE: Our results provide insight into the prevalence of dengue seropositivity in Fortaleza, Brazil in children, and certain demographic and socioeconomic characteristics associated with children's risk of being seropositive. They also suggest that KAP may not identify those more at-risk for dengue, although understanding and enhancing households' KAP is crucial for effective community dengue control and prevention initiatives.

Social Media and the Influence of Fake News on Global Health Interventions: Implications for a Study on Dengue in Brazil.

Social media usage is growing globally, with an exponential increase in low- and middle-income countries. Social media changes the ways in which information-sharing occurs, intensifying the population's exposure to misinformation, including fake news. This has important repercussions for global health. The spread of fake news can undermine the implementation of evidence-based interventions and weaken the credibility of scientific expertise. This is particularly worrisome in countries, such as Brazil, in a sociopolitical context characterized by a lack of popular trust in public institutions. In this project report, we describe our experience with the spread of fake news through the social media platform WhatsApp during the implementation of a cluster randomized controlled trial aimed at reducing dengue incidence in children in Fortaleza (Brazil). During initial visits to selected clusters, the research team was met with resistance. Then, soon after data collection started, fake news began circulating about the study. As a result, the research team developed strategies to dispel suspicion and further promote the study. However, the climate of violence and mistrust, coupled with the COVID-19 pandemic, forced the interruption of the study in 2019. The lessons learned from our experience in Fortaleza can be useful to other researchers and practitioners implementing large-scale interventions in this era of health-related misinformation.

Human Papillomavirus Transmission and Persistence in Pregnant Women and Neonates.

Importance: The prevalence of human papillomavirus (HPV) infection during pregnancy and its risk of transmission to newborns are not well documented. Objective: To ascertain the prevalence of HPV in pregnant women, the risk of HPV detection in the placenta and in children at birth, and the probability that HPV detected at birth may persist in newborns. Design, Setting, and Participants: The Human Papillomavirus Perinatal Transmission and Risk of HPV Persistence Among Children (HERITAGE) study was a prospective cohort study that recruited participants between November 8, 2010, and October 16, 2016. Participant follow-up visits were completed on June 15, 2017. Participants, which included pregnant women of at least 18 years of age and at 14 weeks or earlier of gestation, were recruited from 3 academic hospitals in Montreal, Québec, Canada. Laboratory and statistical analysis were completed on November 15, 2022. Exposures: HPV DNA testing on self-collected vaginal and placental samples. Among children of mothers positive for HPV, conjunctival, oral, pharyngeal, and genital samples were collected for HPV DNA testing. Main Outcomes and Measures: Vaginal HPV DNA testing was done on self-collected vaginal samples obtained among pregnant women recruited during their first trimester of pregnancy and in the third trimester for those who had HPV-positive samples in the first trimester. HPV DNA testing was also done on placental samples (swabs and biopsies) collected after birth in all participants. HPV DNA testing among children included conjunctival, oral, pharyngeal, and genital samples collected in children of HPV-positive mothers at birth, 3 months, and 6 months of age. Results: A total of 1050 pregnant women (mean [SD] age, 31.3 [4.7] years) were included in this study. Prevalence of HPV in pregnant women at recruitment was 40.3% (95% CI, 37.3%-43.3%). Among the 422 HPV-positive women, 280 (66.4%) harbored at least 1 high-risk genotype, and 190 (45.0%) were coinfected with multiple genotypes. HPV was detected in 10.7% of placentas (92 of 860; 95% CI, 8.8%-12.9%) overall, but only 3.9% of biopsies (14 of 361) on the fetal side under the amniotic membrane were positive. Neonatal HPV detection (at birth and/or at 3 months) was 7.2% (95% CI, 5.0%-10.3%) overall, with the most frequent site of infection being the conjunctiva (3.2%; 95% CI, 1.8%-5.6%), followed by the mouth (2.9%; 95% CI, 1.6%-5.2%), the genital area (2.7%; 95% CI, 1.4%-4.9%), and the pharynx (0.8%; 95% CI, 0.2%-2.5%). Importantly, all HPV detected in children at birth cleared before the age of 6 months. Conclusions and relevance: In this cohort study, vaginal HPV was frequently detected in pregnant women. Perinatal transmission was infrequent, and in this cohort, no infection detected at birth persisted at 6 months. Although HPV was detected in placentas, it remains difficult to differentiate contamination vs true infection.

Factors Associated with Post-Transplant Active Epstein-Barr Virus Infection and Lymphoproliferative Disease in Hematopoietic Stem Cell Transplant Recipients: A Systematic Review and Meta-Analysis.

This systematic review was undertaken to identify risk factors associated with post-transplant Epstein-Barr virus (EBV) active infection and post-transplant lymphoproliferative disease (PTLD) in pediatric and adult recipients of hematopoietic stem cell transplants (HSCT). A literature search was conducted in PubMed and EMBASE to identify studies published until 30 June 2020. Descriptive information was extracted for each individual study, and data were compiled for individual risk factors, including, when possible, relative risks with 95% confidence intervals and/or p-values. Meta-analyses were planned when possible. The methodological quality and potential for bias of included studies were also evaluated. Of the 3362 titles retrieved, 77 were included (62 for EBV infection and 22 for PTLD). The overall quality of the studies was strong. Several risk factors were explored in these studies, but few statistically significant associations were identified. The use of anti-thymocyte globulin (ATG) was identified as the most important risk factor positively associated with post-transplant active EBV infection and with PTLD. The pooled relative risks obtained using the random-effect model were 5.26 (95% CI: 2.92-9.45) and 4.17 (95% CI: 2.61-6.68) for the association between ATG and post-transplant EBV infection and PTLD, respectively. Other risk factors for EBV and PTLD were found in the included studies, such as graft-versus-host disease, type of conditioning regimen or type of donor, but results are conflicting. In conclusion, the results of this systematic review indicate that ATG increases the risk of EBV infection and PTLD, but the link with all other factors is either nonexistent or much less convincing.

Seroprevalence of anti-SARS-CoV-2 antibodies among school and daycare children and personnel: protocol for a cohort study in Montreal, Canada.

INTRODUCTION: Further evidence is needed to understand the contribution of schools and daycares for the spread of COVID-19 in the context of diverse transmission dynamics and continually evolving public health interventions. The Enfants et COVID-19: Étude de séroprévalence (EnCORE) study will estimate the seroprevalence and seroconversion of SARS-CoV-2 among school and daycare children and personnel. In addition, the study will examine associations between seroprevalence and sociodemographic characteristics and reported COVID-19 symptoms and tests, and investigates changes in health, lifestyle and well-being outcomes. METHODS AND ANALYSIS: This study includes children and personnel from 62 schools and daycares in four neighbourhoods in Montreal, Canada. All children aged 2-17 years attending one of the participating schools or daycares and their parents are invited to participate, as well as a sample of personnel members. Participants respond to brief questionnaires and provide blood samples, collected via dried blood spot, at baseline (October 2020-March 2021) and follow-up (May-June 2021). Questionnaires include sociodemographic and household characteristics, reported COVID-19 symptoms and tests, potential COVID-19 risk factors and prevention efforts and health and lifestyle information. Logistic regression using generalised estimating equations will be used to estimate seroprevalence and seroconversion, accounting for school-level clustering. ETHICS AND DISSEMINATION: This study was approved by the research ethics boards of the Université de Montréal (CERSES) and the Centre Hospitalier Universitaire Sainte-Justine. Results will contribute to our knowledge about SARS-CoV-2 transmission in schools and daycares and will be made available to study participants and their families, school and public health decision-makers and the research community.

Association Between Human Papillomavirus Infection Among Pregnant Women and Preterm Birth.

Importance: Preterm birth remains a leading cause of perinatal mortality and lifelong morbidity worldwide. The cause of most preterm births is unknown, although several infectious processes have been implicated. Objective: To assess whether human papillomavirus (HPV) infection, a frequent infection among women of childbearing age, is associated with preterm birth. Design, Setting, and Participants: The prospective HERITAGE cohort study was conducted at 3 academic hospitals in Montreal, Québec, Canada, among 899 pregnant women recruited between November 8, 2010, and October 16, 2016. Follow-up was completed on June 15, 2017. Statistical analysis was conducted from February 6, 2020, to January 21, 2021. Exposures: Vaginal HPV DNA detection in the first and third trimesters of pregnancy and placental HPV infection. Main Outcomes and Measures: The main outcome was preterm birth (defined as a live birth or stillbirth between 20 weeks and 0 days and 36 weeks and 6 days of gestation). The association between HPV DNA detection and preterm birth was measured using logistic regression. Odds ratios (ORs) and 95% CIs were adjusted by inverse probability of treatment weights of the propensity score. Results: The study included 899 women (mean [SD] age, 31.3 [4.6] years [range, 19-47 years]) with singleton pregnancies. A total of 378 women (42.0%) had HPV DNA detected in vaginal samples collected during the first trimester, and it was detected in 91 of 819 placentas (11.1%) at delivery. Fifty-five participants experienced preterm birth (38 spontaneous and 17 medically indicated). Persistent vaginal HPV-16/18 detection was significantly associated with all preterm births (adjusted OR [aOR], 3.72; 95% CI, 1.47-9.39) and spontaneous preterm births (aOR, 3.32; 95% CI, 1.13-9.80), as was placental HPV infection (all preterm births: aOR, 2.53; 95% CI, 1.06-6.03; spontaneous preterm births: aOR, 2.92; 95% CI, 1.09-7.81). Results were similar when restricting the analysis to participants without a history of cervical intraepithelial neoplasia treatment. Conclusions and Relevance: The study's results suggest that persistent HPV-16/18 infection is associated with an increased risk of preterm birth, independent of cervical treatment. Future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

Seroprevalence of SARS-CoV-2 Antibodies Among Children in School and Day Care in Montreal, Canada.

Importance: Quebec prioritized in-person learning after the first wave of the COVID-19 pandemic, with school closures being implemented temporarily in selected schools or in hot-spot areas. Quebec's decision to keep most schools open was controversial, especially in Montreal, which was the epicenter of Canada's first and second waves; therefore, understanding the extent to which children were infected with SARS-CoV-2 provides important information for decisions about school closures. Objective: To estimate the seroprevalence of SARS-CoV-2 antibodies in children and teenagers in 4 neighborhoods of Montreal, Canada. Design, Setting, and Participants: This cohort study (the Enfants et COVID-19: Étude de séroprévalence [EnCORE] study) enrolled a convenience sample of children aged 2 to 17 years between October 22, 2020, and March 22, 2021, in Montreal, Canada. Exposures: Potential exposure to SARS-CoV-2. Main Outcomes and Measures: The main outcome was seroprevalence of SARS-CoV-2 antibodies, collected using dried blood spots (DBSs) and analyzed with a research-based enzyme-linked immunosorbent assay (ELISA). Parents also completed an online questionnaire that included questions on self-reported COVID-19 symptoms and tests, along with sociodemographic questions. Results: This study included 1632 participants who provided a DBS sample from 30 day cares, 22 primary schools, and 11 secondary schools. The mean (SD) age of the children who provided a DBS sample was 9.0 (4.4) years; 801 (49%) were female individuals, with 354 participants (22%) from day cares, 725 (44%) from primary schools, and 553 (34%) from secondary schools. Most parents had at least a bachelor's degree (1228 [75%]), and 210 (13%) self-identified as being a racial or ethnic minority. The mean seroprevalence was 5.8% (95% CI, 4.6%-7.0%) but increased over time from 3.2% (95% CI, 0.7%-5.8%) in October to November 2020 to 8.4% (95% CI, 4.4%-12.4%) in March to April 2021. Of the 95 children with positive SARS-CoV-2 antibody results, 78 (82%) were not tested or tested negative with reverse transcription-polymerase chain reaction (RT-PCR) testing, and all experienced mild (49 [52%]) or no clinical symptoms (46 [48%]). The children of parents who self-identified as belonging to a racial and ethnic minority group were more likely to be seropositive compared with children of White parents (adjusted seroprevalence ratio, 1.9; 95% CI, 1.1-2.6). Conclusions and Relevance: These results provide a benchmark of the seroprevalence status in Canadian children. The findings suggest that there was more transmission occurring in children compared with what was being detected by RT-PCR, although children experienced few or mild symptoms. It will be important to continue monitoring the serological status of children, particularly in the context of new COVID-19 variants of concern and in the absence of mass vaccination campaigns targeting young children.

Antibodies to human papillomavirus types 6, 11, 16 and 18: Vertical transmission and clearance in children up to two years of age.

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children. Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life. Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70-0·88), 0·68 (95% CI:0·5-0·80), 0·90 (95% CI:0·83-0·94) and 0·85 (95% CI:0·76-0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures. Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months. Funding: The Canadian Institutes of Health Research (CIHR).

Sustainable, healthy cities: protocol of a mixed methods evaluation of a cluster randomized controlled trial for Aedes control in Brazil using a community mobilization approach.

BACKGROUND: Dengue is increasing in its global presence with an estimated 4 billion people at-risk of infection in at least 128 countries. Despite the promising results of EcoHealth and community mobilization approaches to Aedes reduction, more evidence of their efficacy on reducing dengue risk is needed. The principal research question is to determine if interventions based upon community mobilization reduce the risk of dengue virus infection among children 3 to 9 years old compared to usual dengue control practice in Fortaleza, Brazil. METHODS: The present study will follow a pragmatic cluster randomized controlled trial (cRCT) design with randomization at the census tract level with equal allocation to the two arms. In each arm, there will be 34 clusters of 86 children between 3 to 9 years old for an expected total of 5848 children enrolled in the study, assuming a risk reduction of 29.5% based upon findings from a previous multi-site cRCT. The primary outcomes are rates of anti-dengue Immunoglobulin G (IgG) seroconversion and adult female Aedes density. The intervention is based upon a participatory health research approach, Socializing Evidence for Participatory Action (SEPA), where the research evidence is used to foster community engagement and ownership of the health issue and solution. Following allocation, intervention communities will develop and implement their own solutions that will likely include a wide variety of collective events and media approaches. Data collection activities over a period of 3 years include household visits for blood collection, household surveys, and entomological surveys; and qualitative activities including focus groups, in-depth interviews, and document analysis to evaluate the process, acceptability, fidelity, and sustainability of the intervention. Study participants will be aware of their assignment and all research staff will be blinded although the intervention assignment will likely be revealed to field staff through interaction with participants. DISCUSSION: The results of our study will provide evidence on community mobilization as an intervention for dengue control. We anticipate that if community mobilization is effective in Fortaleza, the results of this study will help develop evidence-based vector control programs in Brazil, and also in other countries struggling with Aedes-transmitted diseases. TRIAL REGISTRATION: ISRCTN66131315, registration date: 1 October 2018.