Sex differences in hepatitis A incidence rates-a multi-year pooled-analysis based on national data from nine high-income countries.

BACKGROUND: Possible sex differences in hepatitis A virus (HAV) incidence rates in different age groups are not well documented. We aimed to obtain stable pooled estimates of such differences based on data from a number of high-income countries. METHODS: We obtained data on incident cases of HAV by sex and age group over a period of 6-25 years from nine countries: Australia, Canada, Czech Republic, Finland, Germany, Israel, Netherland, New Zealand and Spain. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to estimate the effects of age, country, and time period on the IRR. RESULTS: A male excess in incidence rates was consistently observed in all age groups, although in the youngest and oldest age groups, where the numbers tended to be lower, the lower bounds of the 95% confidence intervals for the IRRs were less than one. In the age groups <1, 1-4, 5-9, 10-14, 15-44, 45-64 and 65+, the pooled IRRs (with 95% CI) over countries and time periods were 1.18 (0.94,1.48), 1.22 (1.16,1.29), 1.07 (1.03,1.11), 1.09 (1.04,1.14), 1.46 (1.30,1.64), 1.32 (1.15,1.51) and 1.10 (0.99,1.23) respectively. CONCLUSIONS: The excess HAV incidence rates in young males, pooled over a number of countries, suggest that the sex differences are likely to be due at least in part to physiological and biological differences and not just behavioral factors. At older ages, differential exposure plays an important role. These findings, seen in the context of the excess incidence rates in young males for many other infectious diseases, can provide further keys to the mechanisms of the infection.

Non-polio enterovirus aseptic meningitis in infants up to three months of age, the bacterial mask of viral disease: A retrospective cohort study.

BACKGROUND: Non-polio enterovirus aseptic meningitis (NPE-AM) is a self-limiting illness that can mimic serious bacterial infection (SBI) in infants during their first months of life. OBJECTIVES: To compare the clinical features of febrile infants diagnosed with NPE-AM with those of infants who had SBI or non-bacterial infection (NBI). STUDY DESIGN: A systematic series of febrile infants < 3-months-old hospitalized between 2010 and 2019 with febrile illness in a tertiary hospital. Clinical and laboratory data were compared between the three groups. RESULTS: Overall 1278 infants were included; 207 (16.2%) had NPE-AM, 210 (16.4%) SBI and 861 (67.4%) NBI. The median age was 34 (IQR: 21.5-51.7) days. NPE-AM was documented in 25% of infants < 29 days and 9.9% of infants aged 29-90 days. Infants with NPE-AM or SBI had fever >39°C more frequently, 24.2% and 17.1% compared with 10% in infants with NBI (p < 0.001). Fever duration ≥ 2 days was reported in 3.4% of infants with NPE-AM vs 18.6% in SBI and 26.3% in NBI (p < 0001); rash occurred in 37.7% in NPE-AM compared to 4.6% in NBI and 5.7% in SBI (p < 0.001). The mean white blood count, C-reactive protein and absolute neutrophil count were significantly lower in infants with NPE-AM compared to infants with the SBI (p < 0.001) and similar to the means in infants with NBI (p = 0.848, 0.098 and 0.764 respectively). A high proportion of bloody tap 346/784 (53.1%) was detected. Infants with NPE-AM were more likely to be treated with antibiotics than infants with NBIs (88.9% vs 50.7%, p < 0.001), similarly to infants with SBIs (p = 0.571). CONCLUSIONS: The clinical presentation of infants with NPE-AM that could mimic bacterial infection and the high rate of bloody taps may lead to more hospital admissions and antibiotic prescriptions. Rapid molecular testing for detection of NPE may be of additional value in the evaluation of febrile infants.

Rational and irrational vaccine hesitancy.

In the paper published recently in this journal, Kumar et al. explained why the key to improved COVID-19 vaccine uptake is to understand societal reactions leading to vaccine hesitancy. They conclude that communications strategies should be tailored to the different phases of vaccine hesitancy. However, within the theoretical framework provided in their paper, vaccine hesitancy should be recognized as having both rational and irrational components. Rational vaccine hesitancy is a natural result of the inherent uncertainties in the potential impact of vaccines in controlling the pandemic. In general, irrational hesitancy is based on baseless information obtained from hearsay and deliberately false information. Risk communication should address both with transparent, evidence-based information. Rational concerns can be allayed by sharing the process in which dilemmas and uncertainties are dealt with by the health authorities. Messages on irrational concerns need to address head on the sources spreading unscientific and unsound information. In both cases, there is a need to develop risk communication that restores trust in the health authorities.

Corrigendum: Gender differences in tuberculosis incidence rates-A pooled analysis of data from seven high-income countries by age group and time period.

[This corrects the article DOI: 10.3389/fpubh.2022.997025.].

SARS-CoV-2 and seasonal influenza: similarities and disparities.

This report describes the differences in disease severity and clinical presentation between hospitalized patients with coronavirus disease 2019 (COVID-19) and others with seasonal influenza. A total of 136 influenza and 152 COVID-19 patients were included. Patients with influenza more frequently had dyspnea (p = 0.004), hypoxemia (p < 0.001), underlying diseases (p = 0.046), and elevated liver enzymes (p = 0.028). In contrast, patients with COVID-19 were overweight (p < 0.001), lymphopenic (p < 0.001), had elevated CRP (p = 0.011), and radiological abnormalities (p < 0.001). Patients with influenza were more severely ill on admission (NEWS > 5) (p < 0.001). However, length of hospital stay, ventilatory support, and 30-day-mortality were similar. Despite differences in clinical presentation and disease severity between influenza and COVID-19 patients, both groups had similar clinical outcomes.

Gender differences in measles incidence rates in a multi-year, pooled analysis, based on national data from seven high income countries.

BACKGROUND: Gender differences in a number of infectious diseases have been reported. The evidence for gender differences in clinical measles incidence rates has been variable and poorly documented over age groups, countries and time periods. METHODS: We obtained data on cases of measles by sex and age group over a period of 11-27 years from seven countries. Male to female incidence rate ratios (IRR) were computed for each year, by country and age group. For each age group, we used meta-analytic methods to combine the IRRs. Meta-regression was conducted to the estimate the effects of age, country, and time period on the IRR. RESULTS: In the age groups < 1, 1-4, 5-9, 10-14, 15-44, and 45-64 the pooled IRRs (with 95% CI) were 1.07 (1.02-1.11), 1.10 (1.07-1.14), 1.03 (1.00-1.05), 1.05 (0.99-1.11), 1.08 (0.95-1.23), and 0.82 (0.74-0.92) respectively. The excess incidence rates (IR) from measles in males up to age 45 are remarkably consistent across countries and time-periods. In the age group 45-64, there is an excess incidence in women. CONCLUSIONS: The consistency of the excess incidence rates in young males suggest that the sex differences are more likely due to physiological and biological differences and not behavioral factors. At older ages, differential exposure can play a part. These findings can provide further keys to the understanding of mechanisms of infection and tailoring vaccination schedules.

A Pooled Analysis of Sex Differences in Rotaviral Enteritis Incidence Rates in Three Countries Over Different Time Periods.

Background: Sex differences in incidence rates (IRs) of infectious diseases could provide clues to the mechanisms of infection. The results of studies on sex differences in the incidence of rotaviral enteritis have been inconsistent. Methods: We carried out a pooled analysis of sex differences in IRs for rotaviral enteritis in three countries for a period of 7-22 years. Male-to-female incidence rate ratios (IRRs) were computed by age group, country, and years of reporting. A meta-analytic methodology was used to combine IRRs. Metaregression was performed to evaluate the contribution of age group, country, and years of reporting to the IRR. Results: Significantly higher IRs in males were found in the age groups 0-4, 5-9, and 10-14 years, with pooled IRRs (with 95% confidence intervals [CIs]) of 1.12 (1.09-1.14), 1.07 (1.05-1.09), and 1.13 (1.05-1.21), respectively. In adults, the sex differences were reversed with higher rates in females. The pooled male-to-female IRRs (with 95% CIs) were 0.66 (0.64-0.68), 0.78 (0.72-0.85), and 0.78 (0.72-0.84) for the age groups 15-44, 45-64, and 65+ years, respectively. Metaregression results demonstrated that age is responsible for much of the variation in IRRs. Conclusions: The higher rotaviral enteritis IRs in males at a very early age suggest that sex-related factors unrelated to exposure may play a role. The higher IRs in adult females could result, at least partly, from behavioral and occupational factors.

Gender Differences in Adverse Events Following the Pfizer-BioNTech COVID-19 Vaccine.

Background: The adverse events reported from the COVID-19 mRNA vaccines have varied from very mild, such as pain near the vaccination site, to more severe, with occasional anaphylaxis. Details of age-specific gender differences for the adverse effects are not well documented. Methods: Age and gender disaggregated data on reports of adverse events following two or three doses of the Pfizer-BioNTech COVID-19 vaccine were obtained from four cross-sectional studies. The first was from reports submitted to the Israel Ministry of Health national adverse events database (for ages 16 and above). The second was from a national cross-sectional survey based on an internet panel (for ages 30 and above), and the third and fourth were from cross-sectional surveys among employees of a large company (for ages 20-65) using links to a self-completed questionnaire. Results: In all studies, the risks of adverse events were higher following the second dose and consistently higher in females at all ages. The increased risk among females at all ages included local events such as pain at the injection site, systemic events such as fever, and sensory events such as paresthesia in the hands and face. For the combined adverse reactions, for the panel survey the female-to-male risk ratios (RRs) were 1.89 for the first vaccine dose and 1.82 for the second dose. In the cross-sectional workplace studies, the female-to-male RRs for the first, second and third doses exceeded 3.0 for adverse events, such as shivering, muscle pain, fatigue and headaches. Conclusions: The consistent excess in adverse events among females for the mRNA COVID-19 vaccine indicates the need to assess and report vaccine adverse events by gender. Gender differences in adverse events should be taken into account when determining dosing schedules.

Attitudes Toward the Use of Medical Cannabis and the Perceived Efficacy, Side-effects and Risks: A Survey of Patients, Nurses and Physicians.

Gaps between physician and patient perceptions may lead to misunderstandings and mismanage of treatment. There are sparse data about the differences in opinions toward medical cannabis (MC) between patients and health professionals. The aim of this study was to examine the attitudes toward MC, its perceived efficacy, side effects and risk of dependency, among patients, nurses and physicians. A cross-sectional study of samples of 430 patients, 65 nurses and 65 physicians in two large medical centers in Israel. Questionnaires were administered on attitudes, perceived efficacy, side-effects and perceived risks of dependency. Compared with nurses and physicians, patients who were using MC had the most positive attitudes toward MC (p < .001). Younger age, high school education, being Jewish and ever using MC, were associated with more positive attitudes toward MC among patients (p < .001). Among nurses and physicians, having an oncology specialty predicted more positive attitudes toward MC. Physicians had a less positive attitude toward MC compared to nurses (p < .01). Our study provides evidence that physicians are less positive in their views toward MC compared to nurses and patients. More information and awareness to MC may reduce the gap in perceptions between physicians and patients.

Gender differences in tuberculosis incidence rates-A pooled analysis of data from seven high-income countries by age group and time period.

Introduction: Gender differences in the incidence rates for tuberculosis are occasionally reported. However, the magnitude and consistency of the differences by age group, among different populations, and over extended periods of time are not clear. Materials and methods: We obtained national data from seven countries from open-access internet sites or personal communications with official representatives. We computed the male-to-female incidence rate ratios (IRRs) by country and year for every age group and pooled these ratios using meta-analytic methods. Meta-regression analysis was performed to estimate the contribution of age, country, and calendar years to the variation in the IRRs. Results: In the age groups of < 1, 1-4, 5-9, and 10-14, the pooled male-to-female IRRs (with 95% CI) were as follows: 1.21 (1.05, 1.40), 0.99 (0.95, 1.04), 1.01 (0.96, 1.06), and 0.83 (0.77, 0.89), respectively. In the age groups 15-44, 45-64, and 65+ years, incidence rates were significantly higher in men, with IRRs of 1.25 (1.16, 1.35), 1.79 (1.56, 2.06), and 1.81 (1.66, 1.96), respectively. Meta-regression analysis revealed that age significantly contributed to the variation in the IRRs. Conclusions: There were gender differences in the incidence rates for tuberculosis, with higher rates in boys aged less than one, no significant differences in boys of ages 1-9, and higher rates in boys/men older than 15. The only excess in female gender was in the age group 10-14 years. The age-related gender differences in tuberculosis incidence rates observed over several countries indicate the importance of including sex as a biological variable when assessing the risk factors for tuberculosis.

Sex Differences in Salmonellosis Incidence Rates-An Eight-Country National Data-Pooled Analysis.

BACKGROUND: There are few studies on sex differences in the incidence rates (IR) for salmonellosis over several countries by age and time period. The purpose of this study was to explore the extent and consistency of the sex and age-specific differences. METHODS: We analyzed national data from eight countries between 1994 and 2016. We computed country-specific male to female incidence rate ratios (IRRs) for each age group and pooled the data using meta-analytic methods. Variations of the IRRs by age, country and time period were evaluated using meta-regression. RESULTS: The pooled male to female incidence RRs for ages 0-1, 1-4, 5-9 and 10-14, were 1.04 (1.02-1.06), 1.02 (1.01-1.03), 1.07 (1.05-1.08) and 1.28 (1.23-1.33), respectively. For the ages 15-44 and 45-64, the incidence rates were significantly higher in females. Meta-regression analyses indicate that age groups contributed most of the variation in the male to female IRRs. CONCLUSIONS: We suggest that genetic and hormonal factors and interactions between hormones and gut microbiota could contribute to the sex differences observed in young children. These findings should provide clues about the mechanisms of the infection, and should be useful in targeting treatments and development of vaccines. HIGHLIGHTS: (1) This manuscript provides consistent estimates of the excess salmonellosis incidence rates in male children up to age 15, which suggests an impact of sex hormones or genetic differences. (2) Our findings should promote the further investigations on sex-related determinants of infectious diseases.

Myocarditis after BNT162b2 mRNA Vaccine against Covid-19 in Israel.

BACKGROUND: Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021. After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance. METHODS: We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition. We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons. RESULTS: Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis. Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable. The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal. The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46). As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20). The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637. CONCLUSIONS: The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients. The clinical presentation of myocarditis after vaccination was usually mild.

Antibody Response to Pertussis Vaccination in Pregnant and Non-Pregnant Women-The Role of Sex Hormones.

Pertussis containing vaccine is recommended for pregnant women to protect neonates prior to being fully immunized against the disease. The immune response during pregnancy may be impacted by changes in the hormonal status. The aim of this study was to evaluate the immune response to pertussis immunization in pregnancy and to assess the role of sex hormones. In a cross-sectional study, blood samples were drawn from 174 pregnant and 74 non-pregnant women 45-60 days following immunization. Anti-pertussis toxin (Anti-PT) IgG antibody levels, estrogen, and progestogen concentrations were compared between the two groups. Multiple logistic regression analysis was used to examine the association between serum antibody and sex hormone concentrations in each group, controlling for age, body mass index (BMI), and smoking status. The geometric mean concentration (GMC) of anti-PT IgG antibody was significantly higher in non-pregnant women compared with pregnant women (median of 2.09 and 1.86, interquartile range = 2.36-1.8 and 2.11-1.16 respectively, p < 0.0001). Among pregnant women, the anti-PT IgG antibody GMC was negatively associated with both progesterone (odds ratio = 0.300, 95% CI = 0.116, 0.772, p = 0.013) and estrogen (odds ratio = 0.071, 95% CI = 0.017, 0.292, p < 0.0001), after controlling for age, BMI, and smoking. Pregnancy was associated with lower anti-PT IgG antibody levels (odds ratio = 0.413, 95% CI = -0.190, 0.899, p = 0.026). This appears to be at least partially explained by the higher levels of hormones during pregnancy. These findings demonstrate the important role of sex hormones in the response to pertussis vaccine during pregnancy and can help to evaluate the optimum vaccination schedule.

A nationwide analysis of population group differences in the COVID-19 epidemic in Israel, February 2020-February 2021.

BACKGROUND: Social inequalities affect the COVID-19 burden and vaccine uptake. The aim of this study was to explore inequalities in the incidence and mortality rate of SARS-CoV-2 infection and vaccine uptake in various sociodemographic and population group strata in Israel. METHODS: We analysed nationwide publicly available, aggregated data on PCR-confirmed SARS-CoV-2 infections and COVID-19 deaths between March 2020 and February 2021, as well as the first three months of COVID-19 immunisation according to sociodemographics, including population group and residential socioeconomic status (SES). We computed incidence and mortality rates of COVID-19. Comparisons between towns with predominantly Arab, ultra-Orthodox Jewish (the minorities), general Jewish populations, and according to SES, were conducted using generalised linear models with negative binomial distribution. FINDINGS: Overall, 774,030 individuals had SARS-CoV-2 infection (cumulative incidence 84•5 per 1,000 persons) and 5687 COVID-19 patients had died (mortality rate 62•8 per 100,000 persons). The highest mortality rate was found amongst the elderly. Most (>75%) individuals aged 60 years or above have been vaccinated with BNT162b2 vaccine. The risk of SARS-CoV-2 infection was higher in towns with predominantly Arab and ultra-Orthodox Jewish populations than in the general Jewish population, and in low SES communities. COVID-19 mortality rate was highest amongst Arabs. Conversely, vaccine uptake was lower amongst Arab and ultra-Orthodox Jewish populations and low SES communities. INTERPRETATION: Ethnic and religious minorities and low SES communities experience substantial COVID-19 burden, and have lower vaccine uptake, even in a society with universal accessibility to healthcare. Quantifying these inequalities is fundamental towards reducing these gaps, which imposes a designated apportion of resources to adequately control the pandemic. FUNDING: No external funding was available for this study.

Sex differences in the case-fatality rates for COVID-19-A comparison of the age-related differences and consistency over seven countries.

BACKGROUND: Early in the COVID-19 pandemic, it was noted that males seemed to have higher case-fatality rates than females. We examined the magnitude and consistency of the sex differences in age-specific case-fatality rates (CFRs) in seven countries. METHODS: Data on the cases and deaths from COVID-19, by sex and age group, were extracted from the national official agencies from Denmark, England, Israel, Italy, Spain, Canada and Mexico. Age-specific CFRs were computed for males and females separately. The ratio of the male to female CFRs were computed and meta-analytic methods were used to obtained pooled estimates of the male to female ratio of the CFRs over the seven countries, for all age-groups. Meta-regression and sensitivity analysis were conducted to evaluate the age and country contribution to differences. RESULTS: The CFRs were consistently higher in males at all ages. The pooled M:F CFR ratios were 1.71, 1.88, 2.11, 2.11, 1.84, 1.78 and 1.49, for ages 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, 80+ respectively. In meta-regression, age group and country were associated with the heterogeneity in the CFR ratios. CONCLUSIONS: The sex differences in the age-specific CFRs are intriguing. Sex differences in the incidence and mortality have been found in many infectious diseases. For COVID-19, factors such as sex differences in the prevalence of underlying diseases may play a part in the CFR differences. However, the consistently greater case-fatality rates in males at all ages suggests that sex-related factors impact on the natural history of the disease. This could provide important clues as to the mechanisms underlying the severity of COVID-19 in some patients.

The Israel National Sera Bank: Methods, Representativeness, and Challenges.

The Israel National Sera Bank (INSB) was established in 1997 in the Israel Center for Disease Control. The purpose of the INSB was to provide policymakers with data on the immunity status of the Israeli population against vaccine-preventable diseases, and on the extent and characteristics of exposure to emerging and re-emerging infectious diseases. The aim of this paper is to describe the methods, representativeness, and challenges in maintaining the INSB. The INSB comprises residual sera collected in six laboratories. By the end of 2019, 138,898 samples had been deposited in the INSB. These include samples from four community laboratories: 30.7% from the National Blood Service, 22.2% from Haifa and the Western Galilee, 21.7% from Soroka, and 0.7% from Jerusalem; and from two medical center laboratories: 18.6% from Schneider and 6.1% from Mayanei Hayeshua. The demographic characteristics of the sample at the end of 2019 closely resembled those of the general population. The main challenges addressed in maintaining the INSB relate to its representativeness, the possibility of repeated donors, costs, stability of antibody levels after long-term storage, ethical aspects, and the data available for each sample. The INSB is a unique, powerful, and necessary tool for assessing population immunity levels, based on serum samples collected over a long period of time.