Prevalence Of Seropositivity Research Articles

P-1334. Assessment of Immunity Gaps and Determination of Optimal Age for Measles-Containing Vaccine Booster Dose in Measles-Endemic Country

Abstract Background Despite highly measles immunized countries, immunity gaps in adolescents and young adults are a key issue posing an obstacle to measles elimination. This study aims to identify the gaps by estimating the probability of age-stratified seropositivity and optimal age for measles-containing vaccine (MCV) booster administration to effectively fill the gaps in an endemic country. Posterior (blue) vs empirical (gray) age-stratified seroprevalence curves. Posterior error bars correspond to 95% credible intervals, while empirical error bars indicate 95% confidence intervals generated using bootstrap resampling over 1000 iterations. Methods We retrospectively obtained measles serological results among individuals aged 13 to 39 years from multi-centre hospital between January 2018 and December 2021 in Thailand. We developed a dynamic probability model, stratifying seropositivity due to vaccination or natural infection. We calibrated the model to age-stratified seropositivity data within a Bayesian setting using the Metropolis-Hastings algorithm. A scenario analysis to determine the most effective age for MCV booster administration was also performed. Posterior median estimates for individual serostatus in the year 2020, stratified by age. Results The overall prevalence of measles seropositivity was 65.6% (N=543). Young adults (aged 21 to 30 years) displayed the lowest seropositivity at 59.3% (N=208) while individuals aged 31 to 39 years demonstrated the highest seropositivity at 87.3% (N=158). The average duration of vaccine induced immunity was estimated to be 16.0 years (95% credible interval (CI), 11.1 to 21.0 years); while natural exposure immunity was estimated to be lifelong. Posterior curves for the age-stratified seroprevalence (Figure 1A) exhibited a decreasing trend from ages 14 to 20 years but an upward trend from 26 to 30 years. The relative contribution of vaccine or natural exposure caused seropositivity was estimated for individuals stratified by age in the year 2020 (Figure 1B). The age at which a given individual’s serostatus reached a 50% probability of negativity was found to be approximately 20 years depending on measles circulation (Figure 1C). Age at which a given seronegativity threshold is reached. Posterior medians (based on 1000 parameter combinations sampled uniformly at random without replacement) are shown with solid lines; ribbons indicate 95% credible intervals. Conclusion Our findings highlight young adults aged 21 to 30 years as significant gaps in measles immunity, posing an increased risk of transmission. A single MCV booster dose at the age of 20 years potentially closes the gap and enhances measles elimination programmes. Disclosures All Authors: No reported disclosures

P-1005. Seroepidemiology of Cytomegalovirus, Rubella and Toxoplasma in Women of Childbearing Age in Korea

Abstract Background This study aimed to assess the seroprevalence of Korean women of childbearing age to define the population susceptible to cytomegalovirus (CMV), rubella, and toxoplasmosis. Methods The results of cytomegalovirus, rubella, and toxoplasma antibody tests performed by chemiluminescent microparticle immunoassay in women 15-50 years of age at Seoul Clinical Laboratories from 2012 to 2022 were analyzed based on age, year, and region. Results The average positive seroprevalence rate was 92% (256/3,114) for CMV, 91% (405,207/442,998) for rubella, and 5% (819/15,712) for toxoplasma. In the age-group analysis, seroprevalence of CMV increased from 69% in women 15-19 years to ≥98% in 35-50 years of age, whereas seroprevalence of rubella was higher in women 15-39 years (90-93%) than in women 40-50 years (80-89%) of age. There was no change between age groups in seroprevalence of toxoplasma. Conclusion During the past 10 years, there was no significant difference of seroprevalence for CMV, rubella, and toxoplasma according to year or region age in reproductive women in Korea. To prevent and manage congenital infections, monitoring for the changes in seroprevalence of women with childbearing age should be continued. Disclosures All Authors: No reported disclosures

Binding Antibodies Responses to SARS-COV-2 Infection in Hospitalized Patients and Vaccinated Subjects: A Longitudinal Prospective Observational Study

Abstract Background: Prevalence of seropositivity following SARS-CoV-2 infection is vital in evaluating herd immunity. However, depending on illness severity, it remains unclear whether the breadth and magnitude of immune response to SARS-CoV-2 infection is for short or long term. Objective: To test the persistence of humoral antibody responses after SARS-CoV-2 exposure in patients with different illness severity and among volunteers who had been vaccinated. Methods: This study was conducted in two Saudi Arabian tertiary hospitals. Participants were categorized as critically ill COVID-19 patients, non-critically ill COVID-19 patients, or vaccinated volunteers. We collected demographic data, COVID-19 exposure history, symptoms, vaccination details, and serum samples to analyze antibody persistence. We evaluated SARS-CoV-2 antibody concentrations in COVID-19 patients with varying disease severity and age groups, as well as in BNT162b2-vaccinated individuals, focusing on IgG levels against the S.FL and S1 domains of the spike protein. Results: The study included 172 adults: 92 unvaccinated hospitalized COVID-19 patients and 80 vaccinated volunteers. All vaccinated subjects demonstrated seropositivity to the SARS-CoV-2 spike protein, with nearly 80% having a median antibody titer of 13,500 AU/mL. Notably, vaccinated subjects exhibited significantly higher IgG levels than naturally infected patients (P < 0.001), including higher S.FL and S1 titers, regardless of severity. Age, comorbidities, and previous infections influenced S-specific antibody levels. Among hospitalized patients, 58% required intensive care, with 28- and 90-day mortality rates of 23% and 43%, respectively. Conclusion: These findings shed light on the immune response dynamics following SARS-CoV-2 infection compared to vaccinated individuals, where the latter showed significantly higher level of antibodies response, providing crucial insights for evaluating short-term herd immunity and the effectiveness of natural infection-induced immunity.

Unveiling immunity gaps and determining a suitable age for a third dose of the measles-containing vaccine: a strategic approach to accelerating measles elimination.

In highly measles immunized countries, immunity gaps in adolescents and young adults are a key issue posing an obstacle to measles elimination. This study aims to identify the gaps by estimating the age-stratified probability of seropositivity, and to ascertain a suitable age for the administration of a third dose of a measles-containing vaccine (MCV3) to effectively fill these gaps. We retrospectively obtained measles serological results from hospital setting among among individuals aged 13-39 years and developed a serocatalytic dynamic probability model, stratifying seropositivity due to vaccination or natural infection. We calibrated the model to age-stratified seropositivity data within a Bayesian setting using the Metropolis-Hastings algorithm. A scenario analysis to determine a suitable age for MCV3 administration was also performed. The overall prevalence of measles seropositivity was 65.6% (95% confidence interval [CI]: 61.5-69.6). Posterior predictive curves for the age-stratified seroprevalence exhibited a decreasing trend from ages 13-20 years but an upward trend from 26 to 30 years. The age at which a given individual's serostatus reached a 50% probability of seronegativity was found to be approximately 18-20 years depending on the annual measles force of infection. Our findings highlight a significant measles immunity gap in young adults aged 20-26 years, posing an increased risk of transmission. A MCV3 at the age of 18-20 years potentially closes the gap and aids measles elimination programmes. This work was supported by Faculty of Tropical Medicine (MCTM, ICTM grant), Mahidol University (to T.N.) and APC fee was supported by Mahidol University (to T.N.). S.M. and W.P. were funded in whole, or in part, by the Wellcome Trust [Grant number 220211]. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Rubella serosurvey of pregnant women in Albania: high seroprevalence and implications for prevention

Rubella virus (RV) represents a notable pathogen on a global scale, leading to a relatively harmless illness referred to as rubella. In Albania, rubella has been recognized as an endemic disease since the early years, largely due to inadequate vaccination efforts and the virus's ability to spread rapidly through different interactions. Pregnant women who were not immunized against the rubella virus faced dire consequences, often leading to severe outcomes for their infants, including various congenital conditions such as Congenital Rubella Syndrome. The objective of this research is to conduct a serological surveillance of rubella in Albania between December 2023 and May 2024, examining IgG levels in serum samples and evaluating the overall immunological profile related to rubella infections. The study was conducted at the Institute of Public Health, Tirana where a total of 750 pregnant women from different cities were analyzed. Antirubella IgG antibodies were found in 716 pregnant women examined. The findings indicate that the prevalence of seropositivity reaches 95.46% in instances where antibody levels are at 10 UI/ml, whereas the rate of sero-negativity for IgG is recorded at 4.53% under the same antibody concentration. Updating vaccination initiatives is crucial to ensure that campaigns fulfill their designated aims. Special attention should be given to seronegative pregnant women, who require tailored preventive measures and thorough health education concerning rubella transmission and the sequelae associated with congenital rubella syndrome. Given the public health significance of Rubella, it is imperative that our nation's public health institutions thoroughly evaluate and determine the necessity of ongoing surveillance within the Albanian population, as well as enhance vaccination initiatives and immunization programs.

Prevalence of Hepatitis E Virus Infection among Blood Donors in a Tertiary Healthcare Facility in Osun State, Nigeria

Hepatitis E virus (HEV) is currently the most common cause of viral hepatitis in developing countries. While prospective blood donors are routinely screened for HIV, Hepatitis B and C globally in endemic areas, HEV is not included in the protocol, despite the increase in global prevalence of HEV. Till date, only a handful of studies exist on the prevalence of HEV in Nigeria. The aim of this study was to fill this knowledge gap by determining the prevalence of HEV among blood donors at the LAUTECH Teaching Hospital, Osogbo, Osun State, Nigeria. A total of 102 consenting individuals were enrolled into the study between ages 20 and 55. A volume of 5ml blood sample was collected, and the serum harvested, stored at 20°C until ready for analysis. A double antibody sandwich HEV ELISA was performed to analyze the sera in duplicate for HEV antigen, using an ELISA Kit. Of the 102 samples analyzed, 15 (14.7%) tested positive for HEV antigen, confirming the presence of HEV infection among blood donors in the study population. There was significant association between HEV seropositivity and contact with animals (P=0.010) and alcohol consumption (P=0.000), which means there was a higher chance of donors who consumed alcohol or have had contact with animals to get infected with HEV. However, age, educational status, occupation and gender did not show any statistically significant association with HEV infection. The prevalence of HEV seropositivity was high (14.7%) and a cause for concern as HEV continues to be a major public health issue especially in developing countries.

Significance of serological atrophic gastritis on proton pump inhibitor prescriptions and referrals to gastroscopy in the general population.

We aimed to investigate whether individuals with low pepsinogen I levels differed from those with normal pepsinogen I levels in terms of proton pump inhibitors (PPIs) use, referral to gastroscopy, and findings on gastroscopy. Serum pepsinogen I was measured in 518 persons (mean age 51.6, SD 8.8; 49% women). A medical chart review focused on PPI prescriptions and gastroscopic findings in the follow-up period. Patients with serological atrophic gastritis (pepsinogen I < 28 μg/L) had higher body mass index (27.5 vs 26.2 kg/m2; P = 0.007), were less likely to be current smokers (8% vs 17%; P = 0.025), and had higher prevalence of Helicobacter pylori seropositivity (57% vs 36%; P < 0.001) compared with those without. During follow-up (mean 21.4 years, SD 6.5 years), the patients with serological atrophic gastritis had more often findings of atrophic gastritis or gastric polyps on gastroscopy (20% vs 8%; P < 0.001), despite no differences in the mean number of gastroscopies per 1000 person-years (33 vs 23; P = 0.19) and the mean prescribed PPI dose (omeprazole equivalents) per year (1064 mg vs 1046 mg; P = 0.95). Persons with serological atrophic gastritis had lower odds of being prescribed PPIs at least once (odds ratio [95% confidence interval]: 0.58 [0.35-0.96]), but there was no significant difference in the chance of being referred to gastroscopy at least once (1.15 [0.70-1.96]). Persons with serological atrophic gastritis were less likely to be prescribed PPIs. Persons with serological atrophic gastritis had more often gastric polyps and atrophic gastritis when referred to gastroscopy.

Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone

ObjectiveSub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA...

Trends in hepatitis C virus seroprevalence and associated risk factors among msm in Pakistan: insights from a community-based study

Pakistan bears a substantial burden of hepatitis C virus (HCV) infection, with the second-highest prevalence globally. This community-based cross-sectional study, conducted from January to December 2022 in Punjab, Pakistan, investigates the seroprevalence of HCV among the men who have sex with men (MSM) population. The study identifies demographic and behavioral risk factors associated with HCV infection within this population group. Among the 501 participants, the study found an HCV seroprevalence of 14.86%. The association between demographic characteristics and seroprevalence is assessed by calculating the percentage of positive cases, revealing notable associations with age, education level, and self-identified sexual orientation. Furthermore, the study identified several behavioral risk factors positively associated with HCV seroprevalence, including sharing personal items such as razors and toothbrushes, histories of surgery, blood transfusion, dental procedures, intravenous drug use, and therapeutic injection histories. These risk factors were identified through structured interviews, and the prevalence of HCV seropositivity among the exposed groups was calculated accordingly. Interestingly, a lower HCV positivity rate was observed among self-reported HIV-positive individuals, contradicting previous research. The findings underscore the need for comprehensive, targeted prevention strategies such as risk factor awareness campaigns and educational programs tailored for the MSM population in Pakistan. Further research is warranted to validate these findings and better understand the complex interplay of factors contributing to HCV seroprevalence in this high-risk population.

Seroprevalence and Risk Factors of Hepatitis B, C and D in Adults in Trabzon, Türkiye

Viral hepatitis are infections that can cause liver damage, become chronic, lead to cirrhosis, hepatocellular carcinoma and ultimately result in death due to their ability to spread in the community through blood and infected body fluids. The aim of this study was to determine the seroprevalence of hepatitis B (HBV), hepatitis C (HCV), and hepatitis D (HDV) transmitted through blood among individuals living in Trabzon province and to examine the factors potentially associated with seroprevalence. This cross-sectional study was conducted in Trabzon province, located in the northeast of Türkiye, including a total of 10 districts, including the central district. Since seroprevalence was calculated for HBV, HCV, and HDV in the study, the sample size was separately calculated for each, and the calculated maximum sample size of 1116 was accepted as the minimum sample size for the study. The study was completed with 1502 participants. Serological tests for HBV included HBsAg, anti-HBs, and anti-HBc IgG; for HCV, anti-HCV; and for HDV, anti-HDV were analysed. Data were evaluated for HBV risk factors using univariate analyses with Chi-square test and for multiple analyses using enter model logistic regression analysis. The mean age of the participants was 45.7 ± 16.6 years, with 767 (51.1%) being female. The prevalence of HBV seropositivity, indicating vaccination, was 23.0%, while the seroprevalence of HBV among unvaccinated adults was 27.4%. HBsAg positivity was 5.1%, and isolated anti-HBc IgG positivity was 4.2%. The proportion of individuals with HBsAg in the gray zone was 0.5%, while the positivity rates for anti-HBs and anti-HBc IgG (indicating past infection) were 17.6%. The prevalence of anti-HCV was six per thousand, while anti-HDV was not detected in the analyses. HBsAg positivity and co-infection with HCV were found in one person, and among the nine individuals positive for anti-HCV, isolated anti-HBc IgG positivity was detected in three. Increasing age, presence of a person with jaundice in the family, presence of diabetes mellitus, alcohol use and cupping therapy were identified as risk factors for HBV in the logistic regression analysis. Risk factors for HCV in univariate analyses were being over 40 years old, presence of hepatic steatosis and receiving dialysis treatment. The results of the study indicate that despite being included in our vaccination schedule and the administration of vaccines to high-risk adults, HBV still requires intensive attention as a public health problem. HCV, lacking a vaccine has been evaluated as an infectious agent that needs to be taken into consideration due to its potential risks and requires the complete implementation of individual and social precautions.

Hepatitis E Virus in the United States and Canada: Is It Time to Consider Blood Donation Screening?

Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis in the world and can lead to severe complications in immunocompromised individuals. HEV is primarily transmitted through eating pork, which has led to an increased in anti-HEV IgG seropositivity in the general population of Europe in particular. However, it can also be transmitted intravenously, such as through transfusions. The growing evidence of HEV contamination of blood products and documented cases of transmission have given rise to practice changes and blood product screening of HEV in many European countries. This review covers the abundant European literature and focuses on the most recent data pertaining to the prevalence of HEV RNA positivity and IgG seropositivity in the North American general population and in blood products from Canada and the United States. Currently, Health Canada and the Food and Drug Administration do not require testing of HEV in blood products. For this reason, awareness among blood product prescribers about the possibility of HEV transmission through blood products is crucial. However, we also demonstrate that the province of Quebec has a prevalence of anti-HEV and HEV RNA positivity similar to some European countries. In light of this, we believe that HEV RNA blood donation screening be reevaluated with the availability of more cost-effective assays.

Clinic-based evaluation of point-of-care dual HIV/syphilis rapid diagnostic tests at primary healthcare antenatal facilities in South Africa and Zambia

BackgroundSouthern African countries have the largest global burden of HIV and syphilis, with a high prevalence among women of reproductive age. Although antenatal screening is standard of care, syphilis screening has generally lagged behind HIV screening. We aimed to evaluate the performance and operational characteristics of two commercial dual HIV/syphilis point-of-care tests (POCTs) for simultaneous maternal HIV/syphilis screening.MethodsA clinic-based evaluation of dual HIV/syphilis POCTs (SD Bioline and Chembio) was conducted at five primary healthcare centres (PHCs) in South Africa and Zambia. POCT results using capillary fingerprick blood were compared to reference laboratory syphilis and HIV serological assays.ResultsThree thousand four hundred twelve consenting pregnant women aged ≥ 18 years were enrolled. The prevalence of treponemal antibody seropositivity and HIV infection ranged from 3.7 to 9.9% (n = 253) and 17.8 to 21.3% (n = 643), respectively. Pooled sensitivity for syphilis compared to the reference assay was 66.0% (95%CI 57.7–73.4) with SD Bioline and 67.9% (95%CI 58.2–76.3) with Chembio. Pooled specificity for syphilis was above 98% with both POCTs. The sensitivities of SD Bioline and Chembio assays were 78.0% (95%CI 68.6–85.7) and 81.0% (95%CI 71.9–88.2), respectively compared to an active syphilis case definition of treponemal test positive with a rapid plasma reagin titre of ≥ 8. The negative predictive values (NPVs) based on various prevalence estimates for syphilis with both assays ranged from 97 to 99%. The pooled sensitivity for HIV was 92.1% (95%CI 89.4–94.2) with SD Bioline; and 91.5% (95%CI 88.2–93.9) with Chembio. The pooled specificities for HIV were 97.2% (95%CI 94.8–98.5) with SD Bioline and 96.7% (95%CI 95.1–97.8) with Chembio. The NPV based on various prevalence estimates for HIV with both assays was approximately 98%. Most participating women (91%) preferred dual POCTs over two single POCTs for HIV and syphilis, and healthcare providers gave favourable feedback on the utility of both assays at PHC level.ConclusionsBased on the need to improve antenatal screening coverage for syphilis, dual HIV/syphilis POCTs could be effectively incorporated into antenatal testing algorithms to enhance efforts towards elimination of mother-to-child transmission of these infections.

IgG seroprevalence of Toxoplasma gondii and Leishmania infantum in leprosy patients: Implications for screening and management of co-infections

Parasitic co-infections are common in developing countries and can interfere with leprosy treatment, leading to an increased risk of inflammatory leprosy reactions. This study assessed serum immunoglobulin G (IgG) levels against Toxoplasma gondii and Visceral Leishmaniasis (VL) antigens in 270 leprosy patients from Brazilian states. Regarding the respective cut-offs, the prevalence of IgG seropositivity for T. gondii and VL were 21.05 % and 47.36 % in the leprosy-negative group, and 77.7 % and 52.6 % in the leprosy-positive group. Of the 270 leprosy patients, 158 (58.5 %) presented with inflammatory leprosy reactions. Of those, 72 (59.5 %) had neuritis, 35 (48.6 %) had reverse reactions, and 28 (38.9 %) had ENL in both Brazilian states. Leprosy patients with anti-Leishmania IgG seropositivity were 3.25 times more likely to develop neuritis (95 % C.I.: 1.187 - 9.154; p = 0.019). These findings are particularly relevant for clinical settings where both leprosy and parasitic diseases are prevalent and could provide essential guidance for detecting and addressing complications arising from parasitic co-infections in leprosy patients, thereby improving clinical management strategies.

Prevalence and risk factors for HPV seropositivity and anogenital DNA positivity among men who have sex with men: a repeated cross-sectional study

ObjectivesThis study aimed to assess associations of potential risk factors with human papillomavirus (HPV) seropositivity among men who have sex with men (MSM) and compare these to risk factors for anal and penile (HPV) deoxyribonucleic acid (DNA)-positivity in the same study population. MethodsSeropositivity and anal and penile HPV DNA-positivity were determined for seven high-risk HPV genotypes for MSM aged 16-24 years participating in Papillomavirus Surveillance among STI clinic Youngsters in the Netherlands (PASSYON) 2009-2021. Logistic regression models were conducted to assess risk factors for seropositivity, anal and penile HPV DNA-positivity. ResultsOverall, 1019 MSM were included. HPV-16 and -18 were most common for serology, and anal and penile HPV DNA-positivity. Although no clear similarities were observed for most risk factors for HPV seropositivity and anal or penile DNA positivity, receptive anal intercourse (RAI) was the strongest associated risk factor for both seropositivity (‘RAI ever’ adjusted odds ratio [aOR] 3.50, 95% confidence interval [CI] 1.56-7.88; ‘RAI previous 6 months’ aOR 2.17, 95% CI 1.44-3.26) and anal DNA-positivity (‘RAI previous 6 months’ aOR 1.67, 95% CI 1.09-2.56). ConclusionsOur study is suggestive of site-specific immune response after HPV infection; RAI might lead to anal HPV infections and consequently to seroconversion. Finally, as the two genotypes that are most oncogenic and preventable by all HPV vaccines were most common, our results underline the importance of gender-neutral vaccination.

Prevalence and risk factors for Anaplasma marginale seropositivity in cattle in California

Bovine anaplasmosis, a tick-borne disease caused by Anaplasma marginale, imposes considerable economic bur­den on cattle industries throughout the world. Clinical signs of bovine anaplasmosis include fever, weight loss, lethargy, jaundice, abortion and death. The severity of the disease in­creases with age, and calves under 1 year of age generally do not progress to clinical disease or develop mild disease. Once infected, cattle remain persistently infected carriers for life. Climate change and drought conditions may affect the distri­bution and prevalence of tick populations and tick-borne dis­eases and re-evaluating the seroprevalence of Anaplasma would provide a better understanding of the disease dynamics in California. To our knowledge, there has been no updated study regarding the distribution of Anaplasma infection status in California since 2008, and the information on weather factors related to the disease is also limited. There is an urgent need to evaluate the prevalence of Anaplasma infection in different regions of California. The goal of this study is to estimate the seroprevalence of Anaplasma infection in California cattle over time, and the specific goal is to identify potential risk factors for infection including animal demographics, region, Anaplasma seroprevalence of wild ruminants, Dermacentor tick species presence, and weather effects.

Exploring the relationship between HCMV serostatus and outcomes in COVID-19 sepsis.

Sepsis, a life-threatening condition caused by the dysregulated host response to infection, is a major global health concern. Understanding the impact of viral or bacterial pathogens in sepsis is crucial for improving patient outcomes. This study aimed to investigate the human cytomegalovirus (HCMV) seropositivity as a risk factor for development of sepsis in patients with COVID-19. A multicenter observational study enrolled 95 intensive care patients with COVID-19-induced sepsis and 80 post-surgery individuals as controls. HCMV serostatus was determined using an ELISA test. Comprehensive clinical data, including demographics, comorbidities, and 30-day mortality, were collected. Statistical analyses evaluated the association between HCMV seropositivity and COVID-19 induced sepsis. The prevalence of HCMV seropositivity did not significantly differ between COVID-19-induced sepsis patients (78%) and controls (71%, p = 0.382) in the entire cohort. However, among patients aged ≤60 years, HCMV seropositivity was significantly higher in COVID-19 sepsis patients compared to controls (86% vs 61%, respectively; p = 0.030). Nevertheless, HCMV serostatus did not affect 30-day survival. These findings confirm the association between HCMV seropositivity and COVID-19 sepsis in non-geriatric patients. However, the lack of an independent effect on 30-day survival can be explained by the cross-reactivity of HCMV specific CD8+ T-cells towards SARS-CoV-2 peptides, which might confer some protection to HCMV seropositive patients. The inclusion of a post-surgery control group strengthens the generalizability of the findings. Further research is needed to elucidate the underlying mechanisms of this association, explore different patient populations, and identify interventions for optimizing patient management. This study validates the association between HCMV seropositivity and severe COVID-19-induced sepsis in non-geriatric patients, contributing to the growing body of evidence on viral pathogens in sepsis. Although HCMV serostatus did not independently influence 30-day survival, future investigations should focus on unraveling the intricate interplay between HCMV, immune responses, and COVID-19. These insights will aid in risk stratification and the development of targeted interventions for viral sepsis.

Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study

A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×101 50% tissue culture infectious dose (TCID50) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals. Healthy, UK volunteers aged 18-30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×101, 1×102, 1×10³, 1×104, or 1×105 TCID50 SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal-nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (NCT04864548); enrolment and follow-up to 12 months post-enrolment are complete. Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×101 to 1×105 TCID50 SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×105 TCID50, we were unable to induce sustained infection in any volunteers. Five (14%) of 36volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8+ T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events. Our study demonstrates potent protective immunity induced by homologous vaccination and homologous or heterologous previous SARS-CoV-2 infection. The community breakthrough infections seen with the omicron variant supports the use of newer variants to establish a model with sufficient rate of infection for use in vaccine and therapeutic development. Wellcome Trust and Department for Health and Social Care.

Global and regional seroprevalence of coxiellosis in small ruminants: A systematic review and meta-analysis.

Coxiellosis is a neglected zoonosis for occupationally exposed people in many parts of the world. Sheep and goats are two important small ruminants that act as reservoirs for human contamination; however, there is a lack of comprehensive data on the epidemiological aspects of coxiellosis in sheep and goats at regional and global levels. The aim of this study was to systematically review the available articles on seroprevalence of coxiellosis in sheep and goats and estimate the overall seroprevalence in different regions. A systematic search strategy was performed in five electronic repositories for articles published until December 2021. Relevant data were extracted from the selected articles based on the inclusion criteria. A random effect meta-analysis model was used to analyse the data. Results are presented as the prevalence of seropositivity as a percentage and 95% confidence intervals. The global pooled seroprevalence of coxiellosis in sheep was 17.38% (95% confidence interval [CI]: 15.59%-19.17%). Overall, the regional level pooled prevalence estimates in sheep ranged from 15.04% (95% CI: 7.68%-22.40%) to 19.14% (95% CI: 15.51%-22.77%), depending on region. The global pooled seroprevalence of coxiellosis in goats was 22.60% (95% CI: 19.54%-25.66%). Overall, the regional level pooled prevalence estimates in goats ranged from 6.33% (95% CI: 2.96%-9.71%) to 55.13% (95% CI: 49.61%-60.65%), depending on the region. The prevalence estimates also varied significantly in both sheep and goats depending on age, sex, and rearing systems of the animals (p<0.001). Seroprevalence of coxiellosis in both sheep and goats is considerable. Routine monitoring of the sheep and goat populations is needed to prevent spillover infection in other livestock and humans.

Prevalence of Powassan Virus Seropositivity Among People with History of Lyme Disease and Non-Lyme Community Controls in the Northeastern United States.

Introduction: Lyme disease (LD) affects ∼476,000 people each year in the United States. Symptoms are variable and include rash and flu-like symptoms. Reasons for the wide variation in disease outcomes are unknown. Powassan virus (POWV) is a tick-borne flavivirus that causes disease ranging from asymptomatic infection to encephalitis, neurologic damage, and death. POWV and LD geographic case distributions overlap, with Ixodes species ticks as the common vectors. Clinical ramifications of coinfection or sequential infection are unknown. Objectives: This study's primary objective was to determine the prevalence of POWV-reactive antibodies in sera samples collected from previously studied cohorts of individuals with self-reported LD history residing in the Northeastern United States. As a secondary objective, we studied clinical differences between people with self-reported LD history and low versus high POWV antibody levels. Methods: We used an enzyme-linked immunosorbent assay (ELISA) to quantify IgG directed at the POWV envelope (E) protein domain III in 538 samples from individuals with self-reported LD history and 16 community controls. The samples were also tested with an ELISA assay to quantify IgG directed at the POWV NS1 protein. Results: The percentage of individuals with LD history and possible evidence of POWV exposure varied depending on the assay utilized. We found no significant difference in clinical symptoms between those with low or high POWV IgG levels in the in-house assay. Congruence of the EDIII and NS1 assays was low with only 12% of those positive in the in-house EDIII ELISA testing positive in the POWV NS1 ELISA. Conclusions: The results highlight the difficulty in flavivirus diagnostic testing, particularly in the retrospective detection of flavivirus exposure. The findings suggest that a prospective study with symptomatic patients using approved clinical testing is necessary to address the incidence and clinical implications of LD and POWV co-infection or sequential infection.

Mumps vaccination and immune status among Japanese university students: A multicenter cross-sectional study.

During the mumps outbreak in Japan in 2016, 159,031 cases were reported. In a survey conducted in 2015, mumps vaccination rates for the first dose were 30%-40%. However, the rates for two or more doses were not determined. We assessed the mumps vaccination rates and mumps infection prevalence according to vaccine doses received. This was a multicenter cross-sectional study. Students from three universities participated in 2019. Informed consent was obtained from the students and their guardians. The primary outcome was the prevalence of breakthrough mumps infection according to the number of doses of vaccine received. We collected data on past illnesses of vaccine-preventable diseases and vaccination history using a questionnaire, photocopies of the Maternal and Child Health Handbook from the guardians, and virus antibody titers from the universities' health centers. This study assessed 2004 eligible students and included 593 (29.6%); of these, 250 (42.7%) had a mumps infection history. Furthermore, 264 (44.6%), 31 (5.2%), and 2 (0.3%) students received the first, second, and third doses of mumps vaccine, respectively. The mumps seropositivity prevalence was 43.2% (n = 127), 36.7% (n = 97), 26.7% (n = 8), and 100% (n = 2) for the no-, first-, second-, and third-dose groups, respectively (p for trend = 0.09). The mumps infection prevalence rates were 69.8% (n = 203), 11.3% (n = 28), 3.9% (n = 1), and 0% for the no-, first-, second-, and third-dose groups, respectively. Approximately 1 in 10 students who had received only one dose of mumps-containing vaccine had a breakthrough infection history.