Virus Exposure Research Articles

#stayathome?: Increased children’s emotion regulation in covid-19 pandemic

Emotion Regulation is an important resource over children development, especially when facing adversities. The arrival of Convid-19 pandemic has resulted in procedures as quarantine and social distancing, which may cause mental health status challenges for children. The aim of this study was to compare parents’ perception on their children’s emotional regulation before and during quarantine. The results showed positive correlation between Covid’s behavioral and cognitive variables, as risk perception, virus exposure, preventive care, social distancing and Covid-19 knowledge with emotion regulation. Unexpectedly there was an increment on children’s emotion regulation during quarantine period perceived by their parents. This data can provide clues regarding the emotion development, the route of how mental health preventive measures should go, prioritizing parents support and psychoeducation.

Factors Influencing Nurses’ Decisions to Leave or Remain in the Home and Community Care Sector During the COVID-19 Pandemic

Background/Objectives: Home and community care (HCC) nurses experienced increased occupational challenges during the COVID-19 pandemic, including increased workloads, job stressors, and occupational risks, like virus exposure. The objective of this study was to elucidate what factors influenced nurses’ decisions to stay in their role, take a temporary leave, or exit HCC during the COVID-19 pandemic. Methods: A secondary analysis of data collected using a cross-sectional online open survey distributed among HCC Registered Practical Nurses across Ontario between June and September 2022 was conducted. The factors contributing to nurses’ decision to remain in HCC, temporarily leave, or exit the sector were evaluated using multinomial logistic regression (p < 0.05). Results: Of the 664 participants, 54% (n = 357) stayed in the HCC sector, 30% (n = 199) temporarily left, and 16% (n = 108) exited the sector. Nurses with greater years of experience working in HCC and those who avoided infection were more likely to stay in their role in HCC, which may reflect strong relationships with long-term clients, opportunity and accumulated experience to increase income, and maintenance of good health. Nurses with higher levels of emotional intelligence were more likely to take leaves and exit HCC, suggesting that stepping away may have been a strategy to safeguard themselves. Conclusions: HCC leadership should prioritize the development of solutions to support nurses in the HCC workforce, including those with fewer years of experience. This may promote nurses’ participation in the sector, particularly during times of heightened occupational challenges and crises, like COVID-19.

Appraising the life-course impact of Epstein-Barr virus exposure and its genetic signature on periodontitis.

Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein-Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown. Within a life-course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross-trait genetic correlations, followed by transcriptome-wide association and enrichment analysis to discern the genetic-phenotypic biological profiles. Heightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09-1.47],p=6.05×10-3) and demonstrate a significant genetic correlation (p=4.11×10-3). This pathogenesis may involve the high-confidence causal gene RNASEK located in 17p13.1. Genetically predicted early-life anti-EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82-0.97],p=1.76×10-3). The present study highlights the impact of life-course EBV exposure and its genetic hallmark on periodontitis, providing novel perspectives into the underlying pathogenesis and management strategies for EBV-related periodontitis. These findings underscore diverse clinical and public health implications, encompassing antiviral therapies, viral vaccination strategies, and tailored interventions for individualized periodontitis management. Further research is required to validate and expand upon our findings. Periodontitis is a chronic inflammatory disease driven by interactions between microbial pathogens and the host immune system. While bacteria have traditionally been the focus of research, recent studies highlight the significance of virus-bacteria interactions, particularly the role of Epstein-Barr virus (EBV)-a herpesvirus infecting over 90% of the global population-in the development of periodontitis. However, the underlying causal and genetic mechanisms remain unclear. Our study employed genome-wide multi-omics approaches to investigate the link between EBV exposure and periodontitis. We found that recent EBV infection or reactivation increases the risk of periodontitis, whereas early-life exposure, possibly enabling immune resistance, may reduce it. Essential genes were identified as potential mediators, including CRTC3-AS1, HLA-DQA1, and RNASEK. These findings provide novel insights into the EBV-periodontitis connection. For example, viral testing and control could benefit patients unresponsive to standard bacterial treatments, and early viral exposure via vaccination might reduce the risk of periodontitis. Further clinical studies are required to elucidate these underlying mechanisms and the contribution of virus-bacteria interactions.

Serological Status of Vaccine and Hepatitis B Virus Exposure Among Children Under 5 and Aged 15–17 Years in Kampala, Uganda

Background: Pediatric hepatitis B virus (HBV) serostatus remains variably characterized, hardly determined at times, or documented as part of national monitoring of the Extended Programs for Immunization (EPI). Methods: We cross-sectionally characterized the seroprevalence of HBV vaccine and/or infection status among 501 and 288 children <5 and 15–17 years old, respectively, in Kawempe Division, Kampala, Uganda, between May and August 2023. These children received HBV vaccination under the Uganda National Extended Program on Immunizations (UNEPI). Samples were qualitatively screened for hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb or anti-HBs), hepatitis B e antigen (HBeAg), hepatitis B e antibody (HBeAb or anti-HBe), and for hepatitis B core antibody (HBcAb or anti-HBc) using three different HBV Combo test rapid immunochromatographic diagnostic tests: Nova, Fastep, and Beright. Results: The seroprevalence of HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc was 1.52%, 27.75%, 0.88%, 0.63%, and 0.76%, respectively, for the combined study age groups. The HBsAg seroprevalence of 2.78% was almost 3.5-fold higher among adolescents when compared to the 0.8% observed in the under-5-year-olds. The qualitative seroprevalence of anti-HBs was 33.1% and 18.4% in the under-5 and among the 15–17-year-old study groups, respectively. Conclusions: The proportion of qualitatively detectable anti-HBs in both groups of vaccinated children is low and probably indicates reduced seroprotection. Consequently, a large proportion of children who received the hepatitis B vaccine under UNEPI may be at risk of HBV infection, especially adolescents. A booster dose of the Hepatitis B Vaccine may be required for adolescents.

Risk of long COVID in migrants and the contribution of vaccinations, disease severity, social inequalities and preexisting health: A nationwide register study in Sweden

Abstract Background and aim A number of studies have found higher COVID-19 infection rates, hospitalizations and deaths in migrants and ethnic minorities throughout the Corona Pandemic. Some recent evidence also suggests higher risk of long COVID in migrants although less is known about the risk factors for long COVID in this population. The objective of our study is to examine the risk of long COVID in migrants and to examine whether preexisting health conditions, disease severity, social inequalities and vaccinations contribute to the association. Methods We used linked Swedish administrative registers to estimate the risk of a long COVID diagnosis in the population that had a confirmed COVID-19 infection. Poisson regressions were used to calculate incidence rate ratios between the Swedish born and migrant groups. Adjustments for preexisting health conditions, disease severity, vaccinations and social inequalities were separately introduced. Results Higher risks of long COVID were found among migrants from Africa, Asia, Eastern Europe, Finland, Middle-East and South America. While the contribution of vaccinations and social inequalities were modest, we found that disease severity (i.e. whether the person was hospitalized or treated in an intensive care unit) primarily contributed to the higher risk of long COVID found in migrants. Conclusions The greater exposure and impact of the COVID-19 virus among migrants during the pandemic also affected the longer-term consequences of infection in this at-risk population.

Subclinical myocardial disfunction detected by left ventricle myocardial work impairment in patients with long standing human inmmunodeficiency virus infection

Abstract Heart failure is a known complication in patients living with human inmmunodeficiency virus (HVI) infection. Detection of subclinical disfunction is nowadays possible by echocardiographic strain techniques. Myocardial work is a novel technique based on global longitudinal strain (GLS) that measures global work efficiency of left ventricle (GWE) and would allow early detection of subclinical myocardial damage. Methods We performed a cross sectional echocardiographic study of patients with long standing HIV infection, and no previous cardiopathy, assessing GLS of left ventricle (LV), left atrium (LA) and free wall of right ventricle (RV-FW GLS). We identified patients with subclinical disfunction expressed by an impaired GWE , and studied its determinants by lineal regression. Results 110 patients, 78.2% male, median age 53.3 (51.2-55.4) were included. Time from diagnosis was 20.5 (18.6-22.3) years. Myocardial work strain analysis showed an impaired GWE: 91.9% (90.9-92.9);p<0.001) and a GW index of 1840.8 mmHg%(1758.7-1922.9):p<0.001. The rest of deformation parameters laid into normal range: LV GLS was -19.5% (-19.0- -20.0) GLS dispersion 55.1 (50.1-60.1), LA GLS (reservoir) 32.8% (31.2-34.5), and RV free wall GLS -22.3% (-21.4 - -23.2). By univariate analysis, determinants of impaired GWE were age, Score2 risk, time from HIV diagnosis, QRS Interval duration, long QTc Interval, LV ejection fraction (LVEF),diastolic disfunction by doppler tissue imaging, CD4 count nadir, initial and maximun viral load, and exposure to didanosine treatment. After adjustment by cardiovascular risk and diastolic function (Ea velocity by tissue Doppler) , GWE impaired depended on duration of infection (Beta 0.3;95%CI:0.04-0.56;p=0.023), initial viral load (Beta -1.1;95%CI:-2.1- -0.02;p=0.046) and exposure to stavudine (Beta -6.3;95%IC: -11.5- -1.1;p=0.019). Conclusions Subclinical myocardial disfunction is prevalent in long standing HIV infection. Global work efficiency is a very sensitive parameter for detection, even in patients with normal GLS values, and it was related to duration of infection, initial viral load, and exposure to stavudine in our patients.Determinants of Global Work Efficiency

Hepatitis B Triple Panel Testing Implementation in the Obstetric Care Setting: Unique Predictors of Hepatitis B Virus Vaccine Immunity, Exposure, and Positivity.

Hepatitis B Triple Panel Testing Implementation in the Obstetric Care Setting: Unique Predictors of Hepatitis B Virus Vaccine Immunity, Exposure, and Positivity.

Comprehensive phage display viral antibody profiling using VirScan: potential applications in chronic immune-mediated disease.

Phage immunoprecipitation sequencing (PhIP-Seq) is a high-throughput platform that uses programmable phage display for serology. VirScan, a specific PhIP-Seq library encoding viral peptides from all known human viruses, enables comprehensive quantification of past viral exposures. We review its use in immune-mediated diseases (IMDs), highlighting its utility in identifying viral exposures in the context of IMD development. Finally, we evaluate its potential for precision medicine by integrating it with other large-scale omics data sets.

Crimean Congo hemorrhagic fever virus exposure among febrile patients, cattle herders, and cattle herds in Cameroon

Problem addressedCrimean Congo hemorrhagic fever (CCHF) is a tick-borne disease with high fatality rates and an expansive geographic distribution, yet disease prevalence data in Cameroon is lacking. ObjectiveThis study aimed to determine CCHF virus (CCHFV) seroprevalence and tick distribution among cattle herders and febrile patients in West and Centre Cameroon. Methods and approachTwo cross-sectional serological studies of human and cattle were conducted from October to December 2021 and from June to July 2022, which included the collection of ticks. Enzyme-linked immunosorbent assay (ELISA) were used to detect anti-CCHFV antibodies, while a knowledge, attitudes, and practice (KAP) survey assessed tick and tickborne disease related knowledge and behaviors among herders. Tick identification used morphological keys. ResultsThe KAP survey showed adequate tick knowledge (94.5 %) among herders but poor understanding of disease transmission, with favorable attitudes towards tick control (24.7 %) but inadequate implementation. Rhipicephalus annulatus (64.1 %) predominated among the 1,296 ticks collected during each rainy season. Among cattle, 27.4 % were seropositive, and seropositivity was associated with specific villages, cattle age (>4 years), and female sex. Herders had a 17.8 % seroprevalence, while febrile patients had 8.3 %, with higher rates in those >20 years old for both groups. Self-reported tick removal by herders after contact and grazing may increase CCHFV exposure. ConclusionsThis study confirms CCHFV circulation in rural West Cameroon and unexpected exposure risk in Yaounde, highlighting the need for active entomological surveillance and preventive measures in transhumance and cattle market activities. Establishing an occupation-based surveillance system can help identify CCHFV hotspots to prevent outbreaks.

Trans-chalcone ameliorates CCl4-induced acute liver injury by suppressing endoplasmic reticulum stress, oxidative stress and inflammation

BackgroundAcute liver injury serves as a crucial marker for detecting liver damage due to toxic, viral, metabolic, and autoimmune exposures. Due to the response to adverse external stimuli and various cellular homeostasis, Endoplasmic reticulum stress (ERS), Oxidative stress, and Inflammation have great potential for treating liver injury. Trans-chalcones (TC) is a polyphenolic compound derived from a natural plant with anti-oxidative and anti-inflammatory abilities. Here, TC was aimed to attenuate liver injury by triggering ER stress, oxidative stress, inflammation, and apoptosis. A single dose of carbon tetrachloride (CCl4) 1 mL/kg was administered intraperitoneally into C57BL6 mice to construct an in vivo NAFLD model, whereas AML12 cells were treated with lipopolysaccharides (LPS) to construct an in vitro NAFLD model. The mice used in the experiment were randomly assigned to two groups: a 12-hour set and a 24-hour set. Forty-nine mice were randomly divided into seven groups, the control group (Group I), TC group (Group II) 10 mg/kg TC, negative control group (Group III) CCl4, TC + CCl4 groups (Groups IV−VI), mice were subcutaneously treated with (5, 10, and 20) mg/kg of TC for three consecutive days before the CCl4 injection and the positive control group (Group VII) received 10 mg/kg Silymarin. After the experiment, serum transaminase, liver histological pathology, hepatic expression levels ERS, oxidative stress, and inflammation-related markers were assessed. TC pre-treatment significantly alleviates the expression of ER stress, oxidative stress, inflammatory cytokines, and apoptosis in both in vivo and in vitro models of liver injury. TC treatment significantly reduced serum transaminase levels (ALT and AST), and improved liver histopathological scores. TC administration also led to a reduction in MDA levels and the suppression of ROS generated by CCl4 in hepatic tissue, which contributed to an increase in GSH levels. The protective effect of TC on the liver injury mouse model was achieved by inhibiting hepatocyte apoptosis. Moreover, TC pre-treatment dramatically decreased the protein levels of ER stress indicators such as CHOP, Bip, Ero-Lα, IRE1α, PERK, Calnexin, and PDI when compared to the CCl4-only treated group. TC exerts hepatoprotective effects against CCl4-induced acute liver injuries in mice by modulating ERS, oxidative stress, and inflammation. These results suggest that TC pre-treatment at a dose of (20 mg/kg BW) was as effective as silymarin (10 mg/kg) in preventing CCl4-induced acute liver injury. Further investigations are necessary to elucidate the precise molecular mechanisms underlying the hepatoprotective effects of TC and to explore its therapeutic potential in clinical trials.

Higher Frequency of SARS-CoV-2 RNA Shedding by Cats than Dogs in Households with Owners Recently Diagnosed with COVID-19

Studies have demonstrated the susceptibility of companion animals to natural infection with SARS-CoV-2. Using quantitative reverse transcription polymerase chain reaction and sequencing analyses, this study investigated SARS-CoV-2 RNA excretion in pets in households with infected owners. Oropharyngeal and rectal swabs were collected from dogs and cats in Parana, Southern Brazil, between October 2020 and April 2021. Viral RNA was detected in 25% of cats and 0.98% of dog oropharyngeal swabs; however, systemic, respiratory, and gastrointestinal signs were absent. Complete viral genomes belonged to the Gamma lineage. Phylogenetic analyses indicated that pet samples were probably derived from human-positive cases in Parana. Viral excretion in the oropharynx was more frequent in cats than in dogs. Mutations in the S protein characteristic of Gamma strains were present in all sequenced SARS-CoV-2 strains. The receptor-binding domain of these Brazilian strains did not show any additional mutations not reported in the Gamma strains. Mutations in NSP6, NSP12, and N proteins previously mapped to strains that infect deer or minks were detected. This study highlights the importance of actively monitoring the SARS-CoV-2 strains that infect pets with continued viral exposure. Monitoring genetic changes is crucial because new variants adapted to animals may pose human health risks.

Transplacental SARS-CoV-2 protein ORF8 binds to complement C1q to trigger fetal inflammation.

Prenatal SARS-CoV-2 infection is associated with higher rates of pregnancy and birth complications, despite that vertical transmission rates are thought to be low. Here, multi-omics analyses of human placental tissues, cord tissues/plasma, and amniotic fluid from 23 COVID-19 mother-infant pairs revealed robust inflammatory responses in both maternal and fetal compartments. Pronounced expression of complement proteins (C1q, C3, C3b, C4, C5) and inflammatory cytokines (TNF, IL-1α, and IL-17A/E) was detected in the fetal compartment of COVID-19-affected pregnancies. While ~26% of fetal tissues were positive for SARS-CoV-2 RNA, more than 60% of fetal tissues contained SARS-CoV-2 ORF8 proteins, suggesting transplacental transfer of this viral accessory protein. ORF8-positive fetal compartments exhibited increased inflammation and complement activation compared to ORF8-negative COVID-19 pregnancies. In human placental trophoblasts in vitro, exogenous ORF8 exposure resulted in complement activation and inflammatory responses. Co-immunoprecipitation analysis demonstrated that ORF8 binds to C1q specifically by interacting with a 15-peptide region on ORF8 (C37-A51) and the globular domain of C1q subunit A. In conclusion, an ORF8-C1q-dependent complement activation pathway was identified in COVID-19-affected pregnancies, likely contributing to fetal inflammation independently of fetal virus exposure.

Analysis of Monkeypox Virus Exposures and Lesions by Anatomic Site.

We used cross-sectional data from 226 patients with monkeypox virus to investigate the association between anatomic exposure site and lesion development. Penile, anorectal, and oral exposures predicted lesion presence at correlating anatomic sites. Exposure site also predicted the first lesion site of the penis and anus.

Sequential early-life viral infections modulate the microbiota and adaptive immune responses to systemic and mucosal vaccination.

Increasing evidence points to the microbial exposome as a critical factor in maturing and shaping the host immune system, thereby influencing responses to immune challenges such as infections or vaccines. To investigate the effect of early-life viral exposures on immune development and vaccine responses, we inoculated mice with six distinct viral pathogens in sequence beginning in the neonatal period, and then evaluated their immune signatures before and after intramuscular or intranasal vaccination against SARS-CoV-2. Sequential viral infection drove profound changes in all aspects of the immune system, including increasing circulating leukocytes, altering innate and adaptive immune cell lineages in tissues, and markedly influencing serum cytokine and total antibody levels. Beyond changes in the immune responses, these exposures also modulated the composition of the endogenous intestinal microbiota. Although sequentially-infected mice exhibited increased systemic immune activation and T cell responses after intramuscular and intranasal SARS-CoV-2 immunization, we observed decreased vaccine-induced antibody responses in these animals. These results suggest that early-life viral exposures are sufficient to diminish antibody responses to vaccination in mice, and highlight the potential importance of considering prior microbial exposures when investigating vaccine responses.

Belatacept-related cytomegalovirus infection: Advocacy for tailored immunosuppression based on individual assessment of immune fitness

Belatacept, a fusion protein combining CTLA-4 and the Fc region of human IgG1, is increasingly used as a calcineurin inhibitor–sparing regimen in patients with chronic graft dysfunction. Older kidney transplant recipients, particularly from expanded criteria donors, may be switched to belatacept due to poor renal recovery. However, late-onset cytomegalovirus (CMV) reactivation is increasingly reported with this treatment, especially in older patients with graft dysfunction. This suggests a progressive loss of CMV-specific T cell response, potentially driven by T cell exhaustion. Contributing factors include preexisting T cell dysfunction, increased viral antigen exposure, and interference in the PD-L1/PD-1 pathway by belatacept. mTOR inhibitors have shown efficacy in preventing CMV reactivation by reinvigorating CMV-specific T cells. These findings support combining belatacept with mTOR inhibitors in high-risk CMV-seropositive recipients and emphasize the need for personalized immune assessments to guide immunosuppressive strategies.

Novel Mouse Model of Recurrent Sublethal Herpes Simplex Virus Infection Recapitulates Human Antibody Responses to Primary and Chronic Infection.

Background: Herpes simplex virus (HSV) vaccine development has been impeded by the absence of predictive preclinical models and defined correlates of immune protection. Prior candidates elicited neutralizing responses greater than natural infection but no antibody-dependent cellular cytotoxicity (ADCC) and failed to protect in clinical trials. Primary HSV infection also elicits only neutralizing responses, but ADCC and an expanded antigenic repertoire emerge over time. This evolution may contribute to the decreased frequency and severity of recurrences. To test this notion, we developed a recurrent HSV infection mouse model and evaluated changes in humoral immunity with repeated challenges. Methods: Mice were repeatedly infected intranasally with clinical isolates of HSV-1 or HSV-2 for four months. HSV binding IgG, neutralizing (with or without complement) and ADCC-mediating antibodies were quantified prior to each round of infection. Viral targets were assessed by western blotting. Pooled immune serum (750 μg IgG per mouse) was passively transferred into naïve wild-type or Hvem knockout mice 24 h prior to lethal skin challenge. Results: Repeated exposure to HSV-1 or HSV-2 induced an increase in total HSV-binding IgG but did not boost neutralizing titers. In contrast, ADCC-mediating responses increased significantly from the first to the fourth viral exposure (p < 0.01). The increase was associated with an expanded antigenic repertoire. Passive transfer of fourth round immune serum provided significant protection whereas first round serum failed to protect (p < 0.01). However, protection was lost when serum was transferred into Hvem knockout mice, which are impaired in mediating ADCC killing. Conclusion: This novel model recapitulates clinical responses, highlights the importance of ADCC in protecting against recurrent infection, and provides a strategy for evaluating therapeutic vaccines.

Highly pathogenic avian influenza (HPAI) H5 virus exposure in domestic cats and rural stray cats, the Netherlands, October 2020 to June 2023.

BackgroundHighly pathogenic avian influenza (HPAI) H5Nx and human H1N1pdm2009 influenza viruses can infect cats. Infections in cats may result in viral adaptations or recombinant viruses, which may facilitate zoonotic transfer.AimWe aimed to investigate the presence of HPAI H5 clade 2.3.4.4 and H1 influenza viruses and antibodies to these viruses in domestic and rural stray cats in the Netherlands and factors associated with exposure.MethodsSera from stray and domestic cats, sampled 2020-2023, were analysed by ELISA and confirmed by hemagglutination inhibition assay (HAI) and pharyngeal swabs and lung tissue for influenza A virus by RT-qPCR.ResultsIn 701 stray cats, 83 (11.8%; 95% confidence interval (CI): 9.5-14.5) sera were positive for HPAI H5 and 65 findings were confirmed. In HAI, two sera were positive for both HPAI H5 and H1. In 871 domestic cats, four (0.46%; 95% CI: 0.13-1.2) sera were HPAI H5 positive and none were confirmed but 40 (4.6%; 95% CI: 3.3-6.2) sera were seropositive for H1 and 26 were confirmed. Stray cats living in nature reserves (odds ratio (OR) = 5.4; 95% CI: 1.5-20.1) and older cats (OR = 3.8; 95% CI: 2.7-7.1) were more likely to be HPAI H5 seropositive. No influenza A virus was detected in 230 cats.ConclusionThe higher HPAI H5 seroprevalence in stray cats compared with domestic cats suggests more frequent viral exposure, most likely due to foraging on wild birds. In contrast, exposure to H1 was more common in domestic cats compared with stray cats.

Goat seropositivity as an indicator of Rift Valley fever (RVF) infection in human populations: A case-control study of the 2018 Rift Valley fever outbreak in Wajir County, Kenya

Rift Valley fever (RVF) is a viral zoonosis, which is considered as a threat to food security in the Horn of Africa. In Kenya, RVF is the 5th ranked priority zoonotic disease due to its high morbidity and mortality, frequent outbreak events, and associated socioeconomic impacts during outbreak events. In 2018, an RVF outbreak was confirmed in Kenya's Siaya, Wajir, and Marsabit counties. During this outbreak, 30 people were confirmed infected with RVF through laboratory tests; 21 in Wajir, 8 in Marsabit, and 1 in Siaya Counties.Seventy-five (75) households (15 cases and 60 controls) were selected and interviewed using a case-control study design in 2021 (?). A case was a household with a member who was diagnosed with RVF in 2018. In addition, a total of 1029 animals were purposively selected within these households and serologically tested for RVF. The study aimed to estimate the contribution of various risk factors to RVF human occurrence in Kenya with a special focus on Wajir County. Wajir County was chosen due to high number of confirmed human cases reported in the 2018 outbreak. A univariable regression model revealed that owner-reported RVF virus exposure in livestock significantly increased the odds of an RVF human case in the household by 32.7 times (95 % CI 4.0–267.4). The respondent being linked to a goat flock that was IgG-positive increased the odds of an RVF human case by 3.8 times (95 % CI 1.17–12.3). In the final multivariable analysis, the respondent being linked to their own animals affected by RVF increased odds of having an RVF human case in the household by 56.9 times (95 % CI 4.6–700.4), while the respondent being linked to a neighbor household member affected decreased odds of having a RVF human case by 0.1 times (95 % CI 0.08–0.75).In summary, these results have revealed a potential link for the spread of RVF infection from animals to humans in pastoralist households, hence it is critical to carry out targeted, community education, One Health surveillance, prevention, and control measures against the disease. This will be critical to protecting humans against potential spillovers of infections during outbreak events in livestock.

Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial

rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation. In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36in participants who had received a homologous booster dose at month 18following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×107 plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18months after randomisation) for all randomly assigned participants who completed the 36months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227). Of the 248participants who enrolled and received their primary immunisation, 114proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57participants (24 [42%] of whom were female; median age was 42years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92participants (45 in the booster group and 47in the no-booster group) completed 36months of follow-up. At 18months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10ELISA units (EU)/mL (95% CI 7-14) to 1451EU/mL (1118-1882); GMTs in the booster group increased from 9EU/mL (6-16) to 1769EU/mL (1348-2321). At month 19, GMTs were 31 408EU/mL (23 181-42 554) for the booster group and 1406EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146EU/mL (7960-12 933) for the booster group and 1240EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%)of 57participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment. In addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure. The Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergyand Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.

Potentially zoonotic pathogens and parasites in opportunistically sourced urban brown rats (Rattus norvegicus) in and around Helsinki, Finland, 2018 to 2023.

BackgroundBrown rats (Rattus norvegicus) are synanthropic rodents with worldwide distribution, which are known to harbour many zoonotic pathogens and parasites. No systematic zoonotic surveys targeting multiple pathogens and parasites have previously been conducted in urban rats in Finland.AimIn Helsinki, Finland, we explored the presence and prevalence in brown rats of certain pathogens and parasites (including helminths, viruses and bacteria) across potentially zoonotic taxa.MethodsWe opportunistically received rat carcasses from pest management operators and citizens from 2018 to 2023. We searched for heart- or lungworms, performed rat diaphragm digestion to check for Trichinella and morphologically identified intestinal helminths. We assessed virus exposure by immunofluorescence assay or PCR, and detected bacteria by PCR (Leptospira) or culture (Campylobacter).ResultsAmong the rats investigated for helminths, no heart- or lungworms or Trichinella species were detected and the most common finding was the cestode Hymenolepis nana (in 9.7% of individuals sampled, 28/288). For some of the surveyed virus taxa, several rats were seropositive (orthopoxviruses, 5.2%, 11/211; arenaviruses, 2.8%, 6/211; hantaviruses 5.2%, 11/211) or tested positive by PCR (rat hepatitis E virus, 1.8%, 4/216). Campylobacter jejuni (6.6%, 17/259) and Leptospira interrogans (1.2%, 2/163) bacteria were also present in the rat population examined.ConclusionsPrevalences of potentially zoonotic pathogens and parasites in brown rats in Helsinki appeared low. This may explain low or non-existent diagnosis levels of rat-borne pathogen and parasite infections reported in people there. Nevertheless, further assessment of under-diagnosis, which cannot be excluded, would enhance understanding the risks of zoonoses.