Primary Infection Research Articles

The Utility of Serologic TORCH Testing During Pregnancy for Maternal-related Versus Fetal-related Indications: A Retrospective Study.

Clear guidelines have not been established about the utility of TORCH serology testing in women for whom TORCH infection is suspected according to clinical and laboratory manifestations during pregnancy. We aimed to compare rates of TORCH infections [specifically cytomegalovirus (CMV), Toxoplasma and rubella] in women who underwent TORCH serology testing due to maternal- versus fetal-related indications. This 10-year single-center retrospective study included all the women beyond 24 weeks of gestation who underwent TORCH serology testing due to maternal- or fetal-related indications. Maternal-related indications included fever, gastroenteritis, elevated liver enzymes and thrombocytopenia. Fetal-related indications included intrauterine growth restriction, polyhydramnios and oligohydramnios. During the study period, 304 women underwent TORCH serology testing due to maternal-related indications and 771 due to fetal-related indications. For the maternal-related compared with the fetal-related indication group, maternal and congenital TORCH infections were more prevalent (P = 0.015), specifically CMV (P = 0.036). Eight (2.6%) of the women with maternal-related indications had a primary TORCH infection; 4 of them (50%) had concomitant congenital infections. Six (0.8%) of the women with fetal-related indications had a primary infection; none had a related congenital infection. Among the women with maternal-related indications, higher rates of maternal TORCH infection were found among those with thrombocytopenia (7.1%) and elevated liver enzymes (3.0%). During the study period, maternal-indicated TORCH testing detected 10.8% of neonates born with a confirmed TORCH infection. The clinical yield of TORCH serology for nonspecific sonographic fetal features was low. Nonetheless, maternal-related indications should prompt testing for CMV and Toxoplasma infection.

Antiviral Treatment and Risk of Hearing Loss in Asymptomatic and Mild Symptomatic Infants With Congenital Cytomegalovirus.

To assess hearing outcomes at 24 months of age in infants with mild congenital cytomegalovirus (cCMV) infection, depending on whether they have received antiviral treatment or not. A retrospective study within the European Registry of Children with cCMV was performed. Included children had cCMV diagnosed in utero/in the first 21 days of life, with normal physical examination, alanine aminotransferase <80 U/L and platelets >100,000 cs/mm3 and absence of hearing loss (HL) at birth. Cranial ultrasound (cUS) and/or cranial magnetic resonance imaging was normal or with minor findings (isolated lenticulostriate vasculopathy and/or germinolysis/caudothalamic or subependymal cysts, and/or focal/multifocal white matter involvement). The main outcome was the presence of HL at 24 months of age. One hundred ninety-six patients met inclusion criteria. A total of 34.7% received antiviral treatment with valganciclovir/ganciclovir. Children treated had lower gestational age, birth weight and head circumference, and maternal primary infection was less frequent. Among treated children, 21.3% presented minor findings in cUS versus 6.3% in nontreatment group (P = 0.003). Nine patients (4.6%) developed HL at 24 months. Among children with HL, 20% presented minor findings in cUS versus 11.3% in non-HL group (P = NS). HL rate was similar in treated and nontreated groups (4.6% vs. 6.3%; P = 0.6). One-third of the children were treated with antivirals and infants with minor neuroimaging findings at birth were more likely to receive antiviral. There were no differences in the prevalence of HL at 2 years of age between treated and not-treated children. Minor neuroimaging findings were not clearly associated with an increased risk of delayed onset HL.

Immune Modulation by Epstein-Barr Virus Lytic Cycle: Relevance and Implication in Oncogenesis.

EBV infects more than 90% of people globally, causing lifelong infection. The phases of the EBV life cycle encompass primary infection, latency, and subsequent reactivation or lytic phase. The primary infection usually happens without noticeable symptoms, commonly in early life stages. If it manifests after childhood, it could culminate in infectious mononucleosis. Regarding potential late consequences, EBV is associated with multiple sclerosis, rheumatoid arthritis, chronic active EBV infection, lymphomas, and carcinomas. Previous reports that the lytic phase plays a negligible or merely secondary role in the oncogenesis of EBV-related tumors are steadily losing credibility. The right mechanisms through which the lytic cycle contributes to carcinogenesis are still unclear, but it is now recognized that lytic genes are expressed to some degree in different cancer-type cells, implicating their role here. The lytic infection is a persistent aspect of virus activity, continuously stimulating the immune system. EBV shows different strategies to modulate and avoid the immune system, which is thought to be a key factor in its ability to cause cancer. So, the principal goal of our review is to explore the EBV's lytic phase contribution to oncogenesis.

Manifestações dermatológicas da Monkeypox

Objective: This study aimed to identify the primary mucocutaneous manifestations secondary toMonkeypox infection and determine the prevalence of coinfection with other sexually transmittedinfections (STIs). Methods: Searches were conducted in the PubMed, LILACS, SciELO, Cochrane Library, andVirtual Health Library databases using the descriptors “monkeypox,” “dermatological,” “dermatology,”“cutaneous,” “skin,” and “mucocutaneous,” combined with the Boolean operators “and” and “or.” All articles published between January 2017 and October 2022 that addressed mucocutaneous manifestations secondary to Monkeypox infection, regardless of language, wereincluded. Technical notes from the Brazilian Ministry of Health and World Health Organization recommendations were also incorporated. The Joanna Briggs Institute (JBI) critical appraisal tool was used to assess the quality of the studies. Data were independently evaluated by three reviewers. Exclusion criteria included the absence of photographic records of the lesions, lack of laboratory confirmation of infection, “letter to the editor” publications, duplicates, and articles primarily focused on systemic manifestations without association with the integumentary system. Results: A total of 22 publications were included in this study. The most frequently affected anatomical sites were the genital and perianal regions, though lesions were also reported on the torso, face, oropharynx, limbs, palms, and soles. There is a possibility that the infection may present nonspecifically as a maculopapular rash. Lesions are typically multiple, with either localized orwidespread distribution. In the latter case, the progression is centrifugal, beginning on the face.The most prevalent characteristic of the elementary lesion is central umbilication, which eventuallydevelops a crusted appearance. Umbilicated papules are often associated with pain, which gradually transitions to varying degrees of pruritus. Coinfection with HIV and other STIs was particularly notable among men who have sex with other men and/or have multiple partners and who use condoms inconsistently.Conclusions: Monkeypox can present with various cutaneous manifestations, none of which arepathognomonic of the disease. The chronological evolution of the elementary lesions (papule, vesicle,pustule, crust) is not always precise, with multiple stages potentially coexisting in the same area of the body. The primary behavioral factor associated with infection is unprotected sexual activity, especially among men who have sex with other men. Coinfections with HIV, syphilis, gonorrhea, chlamydia, and/or herpes were observed in the majority of cases.

Fatal neonatal varicella infection despite intravenous immunoglobulin at birth.

There is a high risk of severe varicella infection in the neonate when the mother develops a rash around the time of delivery. Current guidelines recommend separation of mother-baby dyad and passive immunization to prevent severe infection in such cases. We report a case of severe varicella in a neonate whose mother developed primary varicella infection two days prior to delivery. The neonate had a fatal outcome despite physical separation from mother and passive immunization in the immediate postnatal period.

Prenatal and postnatal antiviral therapies for the prevention and treatment of congenital cytomegalovirus infections.

Congenital cytomegalovirus infection (cCMV) is the leading infectious cause of sensorineural hearing loss and lifelong neurodevelopmental disabilities. Studies suggest antiviral therapy can prevent fetal infection after maternal primary infection, as well as halt the progression of hearing loss and neurodevelopmental disabilities in newborns with symptomatic cCMV. With growing worldwide momentum on early detection and diagnosis of cCMV, this review describes the exciting recent advances in antiviral therapies in CMV infected pregnant mothers and babies, as well as emerging evidence on anti-CMV vaccines. New opportunities for prenatal and neonatal interventions have driven a rising interest in screening and identification of asymptomatic CMV infection. Routine screening of pregnant women to identify primary infection in first trimester is now advocated in Western Europe but has yet to be examined from a public health perspective in other regions. Evidence is emerging for maternal valaciclovir therapy to prevent fetal infection after a maternal primary CMV infection in the first trimester of pregnancy. For those infants who are born with symptomatic cCMV, a 6-month course of valganciclovir, started within the first 4 weeks of life, and possibly up to 13 weeks of life, is the current recommended therapy. However, there is unclear evidence for the benefit of treatment for asymptomatic cCMV and cCMV with isolated hearing loss. Research to identify more effective antivirals and an effective CMV vaccine continues. More research is needed to determine the region-specific applicability of the new European recommendations for routine CMV screening in pregnancy. Areas of uncertainty in postnatal management include timing of initiation, duration of treatment and identifying pediatric subgroups that benefit from modification of the standard treatment recommendations.

TianTan vaccinia virus-based EBV vaccines targeting both latent and lytic antigens elicits potent immunity against lethal EBV challenge in humanized mice

ABSTRACT Epstein–Barr virus (EBV) infection has been related to multiple epithelial cancers and lymphomas. Current efforts in developing a prophylactic EBV vaccine have focused on inducing neutralizing antibodies. However, given the lifelong and persistent nature of EBV infection following primary infection, it is rationalized that an ideal vaccine should elicit both humoral and cellular immune responses targeting multiple stages of the EBV lifecycle. This study used a DNA vector and a TianTan vaccinia virus to express key EBV antigens, including BZLF1, EBNA1, EBNA3B, and gH/gL, to generate multi-antigen vaccines. The multi-antigen vaccine expressing all four antigens and the multi-antigen vaccine expressing BZLF1, EBNA1, and EBNA3B showed comparable protection effects and prevented 100% and 80% of humanized mice, respectively, from EBV-induced fatal B cell lymphoma by activating BZLF1, EBNA1, and EBNA3B specific T cell. The vaccine expressing lytic protein BZLF1 elicited stronger T cell responses and conferred superior protection compared to vaccines targeting single latent EBNA1 or EBNA3B. The vaccine solely expressing gH/gL exhibited no T cell protective effects in our humanized mice model. Our study implicates the potential of EBV vaccines that induce potent cellular responses targeting both latent and lytic phases of the EBV life cycle in the prevention of EBV-induced B cell lymphoma.

A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection.

Clostridioides difficile infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccine targeting C. difficile toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic C. difficile from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel C. difficile therapeutics with potential for limiting acute disease and promoting bacterial decolonization.

Ad5-nCoV boosted vaccine and reinfection-induced memory T/B cell responses and humoral immunity to SARS-CoV-2: based on two prospective cohorts

Here, we regularly followed SARS-CoV-2 infected cohorts to investigate the combined effects of neutralizing antibodies (NAbs) and B and T cell profiles during the convalescent period. Ten participants infected with SARS-CoV-2 in December 2022 were selected to assess the effects of an inhaled adenovirus type 5 vectored COVID-19 vaccine (Ad5-nCoV) booster on B cells and humoral immunity. To evaluate T cell responses, eight primary and 20 reinfection participants were included. Blood samples from all 38 participants were collected at 1-, 2-, and 6-months post-infection. The assays included single B cell technology, activation-induced marker (AIM) assays, and pseudovirus neutralization. In the first cohort, eighteen monoclonal antibodies (mAbs) with neutralizing activity from memory B cells (MBC) against SARS-CoV-2 mutants were obtained by high throughput single-B-cell cloning method, which lasted from 1- month to 6- month post infection. The overall number of mAbs from MBC in the inhaled Ad5-nCoV-boosted immunization group was higher than that in the non-boosted immunization group at 2-, and 6-months post-infection. In the second cohort, circulating T follicular helper cells (cTfh) and AIM + CD4 + T cells increased over time in the reinfection group (P < 0.05). The serum NAb levels against XBB.1.22, EG.5.1, and JN.1 in the primary infection group tended to increase from the post 1-month to 2-month infection (P < 0.05). In both cohorts, serum NAb titers showed significant immune escape, while cTfh and AIM + CD4 + T cells in the second cohort essentially showed no immune escape to new strains (including XBB, EG.5) during the six-month follow-up period. AIM + CD4 + T cells against BA.5 and EG.5 were strongly negatively correlated with the time to viral clearance in the reinfected group after months of 6M infection. The broader significance of this study was to comprehensively assess the ability of the SARS-CoV-2 boosted immunization and reinfection-induced generation of T/B cell immune memories in preventing reinfection.

Human and hamster sera correlate well in identifying antigenic drift among SARS-CoV-2 variants, including JN.1.

Antigenic assessments of SARS-CoV-2 variants inform decisions to update COVID-19 vaccines. Primary infection sera are often used for assessments, but such sera are rare due to population immunity from SARS-CoV-2 infections and COVID-19 vaccinations. Here, we show that neutralization titers and breadth of matched human and hamster pre-Omicron variant primary infection sera correlate well and generate similar antigenic maps. The hamster antigenic map shows modest antigenic drift among XBB sub-lineage variants, with JN.1 and BA.4/BA.5 variants within the XBB cluster, but with fivefold to sixfold antigenic differences between these variants and XBB.1.5. Compared to sera following only ancestral or bivalent COVID-19 vaccinations, or with post-vaccination infections, XBB.1.5 booster sera had the broadest neutralization against XBB sub-lineage variants, although a fivefold titer difference was still observed between JN.1 and XBB.1.5 variants. These findings suggest that antibody coverage of antigenically divergent JN.1 could be improved with a matched vaccine antigen.IMPORTANCEUpdates to COVID-19 vaccine antigens depend on assessing how much vaccine antigens differ antigenically from newer SARS-CoV-2 variants. Human sera from single variant infections are ideal for discriminating antigenic differences among variants, but such primary infection sera are now rare due to high population immunity. It remains unclear whether sera from experimentally infected animals could substitute for human sera for antigenic assessments. This report shows that neutralization titers of variant-matched human and hamster primary infection sera correlate well and recognize variants similarly, indicating that hamster sera can be a proxy for human sera for antigenic assessments. We further show that human sera following an XBB.1.5 booster vaccine broadly neutralized XBB sub-lineage variants but titers were fivefold lower against the more recent JN.1 variant. These findings support updating the current COVID-19 vaccine variant composition and developing a framework for assessing antigenic differences in future variants using hamster primary infection sera.

Exploring pathogen population density as a metric for understanding post-COVID infectious disease surges.

After the easing of COVID-19 restrictions, peaks of common infectious diseases surpassed pre-pandemic levels, raising questions about causes and ways to monitor these changes. A proposed measure, the Pathogen Population Density (PPD) score, could help track these shifts. PPD refers to the concentration of infectious agents within a population at a given time and location, serving as a potential indicator of infection levels in susceptible individuals at the population level. It is likely that PPD remains relatively stable within a specific community, as an equilibrium forms between infections and susceptibility. During the pandemic, nonpharmaceutical interventions (NPIs) led to a reduction in infectious diseases, possibly lowering population immunity and decreasing the PPD score. Once NPIs were lifted, the PPD score likely increased sharply due to a larger pool of susceptible individuals, causing more primary infections and stronger recurrent infections, faster transmission, and more severe pathogenic outcomes at the individual level. Monitoring the PPD score over time could help predict when infection peaks will occur. PPD is influenced by factors such as public health strategies, vaccination programs, and the behavior of high-risk individuals. As a quantitative measure, PPD has the potential to serve as a valuable predictive and monitoring tool, helping public health officials anticipate and track changes in infectious disease dynamics. It could be an effective tool for managing future outbreaks or pandemics and serve as a communication tool between scientists and the public to understand the emergence of new disease peaks.

Seroprevalence of cytomegalovirus among pregnant women in Singapore

BackgroundCytomegalovirus (CMV) is the most common congenital infection in pregnancy with potential long-term adverse effects on the fetus. There is limited data on CMV seroprevalence in pregnant women in Singapore, with last reported study dating back over two decades. We look at the latest CMV seroprevalence in antenatal population in Singapore.MethodsBetween January 2021 and August 2021, 385 pregnant women receiving antenatal care at Singapore General Hospital were randomly selected for CMV IgG test to be performed on their blood samples collected during the first trimester of their pregnancies. Positivity for CMV IgG represents past exposure prior to pregnancy.ResultsOverall CMV seroprevalence was 71.7% (276/385) (95% CI 067, 0.76, p value < 0.001). The trend of CMV IgG positivity increased with age, 68.3% (95% CI 0.60, 0.76, p value < 0.001) in those aged 20–29, 72.5% (95% CI 0.66, 0.78, p value < 0.001) in the 30–39 age group, and 79.0% (95% CI 0.67, 0.76, p value 0.012) in women over 40.ConclusionsThere is a declining trend in CMV seroprevalence among pregnant women in Singapore, which indicates that a substantial portion of this population faces the risk of primary maternal CMV infection during pregnancy. Emerging research suggests that prenatal treatment with valacyclovir effectively reduces the likelihood of vertical transmission. Considering this evidence, it is imperative to reevaluate the recommendations for universal maternal CMV screening during pregnancy.

Dynamics and backward bifurcations of SEI tuberculosis models in homogeneous and heterogeneous populations

The main difference between tuberculosis (TB) and other infectious diseases is that the transmission of the bacterium should be considered not only as the development of a primary infection, but also as exogenous reinfection or endogenous reactivation. Moreover, individuals in the population may have heterogeneous contact rates, which can be described by complex networks. To this end, we present two differential equation-based TB models in homogeneous and heterogeneous populations. The first model assumes that the number of contacts per unit time is constant for the whole population, whereas the second model considers the heterogeneous number of contacts per unit time for each individual. We derive the basic reproduction number of each model using the next-generation matrix method, and analyze the dynamical properties of each model in detail. We find that the two models undergo backward bifurcations and have the same threshold condition for backward bifurcation. From this threshold condition, we see that the reduced rate of exogenous reinfection of individuals plays an important role in causing the backward bifurcation. Interestingly, the second model allows the threshold condition for backward bifurcation to be independent of network parameters. Thus, unlike other infectious disease models on complex networks, in controlling the spread of tuberculosis among populations with different numbers of contacts, we only need to focus on disease parameters during treatment. Finally, numerical simulations more intuitively demonstrate the impact of parameter changes on the prevalence of tuberculosis and reveal the model's richer and more interesting dynamical properties, such as bistability. Sensitivity analysis indicates that the basic reproduction number is highly correlated with both the relapse rate of latent individuals progressing to active infection and the probability of healthy individuals becoming infected after contact with the pathogen. Therefore, enhancing the detection and treatment of latent cases and reducing contact between infected and uninfected individuals are the most crucial public health interventions.

Assessment of human Herpes Virus-8 infection in Iranian cirrhotic patients on the waiting list for liver transplantation: A cross-sectional analysis

BackgroundHuman Herpes Virus 8 (HHV-8) is involved in autoimmunity. However, its association with advanced liver disease has not been fully explained. Herein, the prevalence of HHV-8 viremia was assessed in Iranian liver transplant candidates with a confirmed diagnosis of cirrhosis. MethodsThis cross-sectional study was conducted on 230 patients with cryptogenic cirrhosis, virus-related cirrhosis, and autoimmune hepatitis, as well as 140 healthy blood donors from April 2022 to September 2023. The HHV-8 IgG antibody concentration and viral load were evaluated via ELISA and RT‒PCR, respectively. ResultsAnti-HHV-8 IgG antibodies were detected in 25 cirrhotic patients (10.8 %) and four healthy individuals (2.6 %) (p = 0.022). The majority of the seropositive patients had cryptogenic cirrhosis (20.4 %), followed by autoimmune hepatitis (13.1 %) and virus-related cirrhosis (4.7 %). The seropositivity of HHV-8 IgG antibody was significantly different among the etiologies of liver cirrhosis (p = 0.011). However, HHV-8 genomic DNA was not detected in the sera of the patients or healthy blood donors. ConclusionThe role of HHV-8 infection in the development of posttransplant diseases, together with the higher seroprevalence of HHV-8 antibodies in cirrhotic patients than in healthy individuals, highlights the importance of both primary and latent infections in liver transplantation. Therefore, serological and molecular screening of HHV-8 is highly suggested for liver transplant candidates and organ donors. The possibility of antibody-mediated epitope mimicry in cryptogenic and autoimmune groups with moderate HHV-8 antibody positivity and negative viral loads may account for the development of advanced liver diseases.

Susceptibility to lenacapavir, fostemsavir and broadly neutralizing antibodies in French primary HIV-1 infected patients in 2020-2023.

Surveillance studies of Transmitted Drug Resistance (TDR) are crucial in tracking the evolution of HIV epidemiology. Our aim was to investigate TDR to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors (INIs), as well as to new drugs: lenacapavir, fostemsavir. Predictive sensitivity was evaluated for maraviroc and broadly neutralizing antibodies (bNAbs) (zinlirvimab and teropavimab). Between 2020 and 2023, 85 people with HIV (PWH) were diagnosed with primary HIV-1 infection (PHI). Pol and env sequences were analyzed and TDR was characterized according to the French ANRS algorithm. The genotypic-based prediction of bNAbs sensitivity was based on HIV env amino acid signatures I108, I201, F353 for teropavimab and N325, N332, H330 for zinlirvimab. TDR to NRTIs, NNRTIs, PIs and INIs was evidenced in 8.2%, 12.9%, 4.7%, and 5.9% strains, respectively. Ten viruses were CXCR4/dual mix. All viruses were susceptible to lenacapavir (100%) and 52% harbored resistance to fostemsavir. The genotypic profile was associated with a predictive positive value (PPV) > 83% of susceptibility to both teropavimab and zinlirvimab for 23 viruses (31%), while 22 (29%) had a PPV between 62% and 75%, suggesting reduced susceptibility to both bNAbs as soon as primary infection. The surveillance of TDR evidenced at the time of PHI is important with regard to new strategies for HIV patients with virological failure and global implementation of PrEP using NRTI, INI such as recently approved injectable cabotegravir, and future long-acting drugs such as lenacapavir and bNAbs.

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.

Beyond the biting - limited impact of explicit mosquito dynamics in dengue models

Mathematical models play a crucial role in assisting public health authorities in timely disease control decision-making. For vector-borne diseases, integrating host and vector dynamics into models can be highly complex, particularly due to limited data availability, making system validation challenging. In this study, two compartmental models akin to the SIR type were developed to characterize vector-borne infectious disease dynamics. Motivated by dengue fever epidemiology, the models varied in their treatment of vector dynamics, one with implicit vector dynamics and the other explicitly modeling mosquito-host contact. Both considered temporary immunity after primary infection and disease enhancement in secondary infection, analogous to the temporary cross-immunity and the Antibody-dependent enhancement biological processes observed in dengue epidemiology. Qualitative analysis using bifurcation theory and numerical experiments revealed that the immunity period and disease enhancement outweighed the impact of explicit vector dynamics. Both models demonstrated similar bifurcation structures, indicating that explicit vector dynamics are only justified when assessing the effects of vector control methods. Otherwise, the extra equations are irrelevant, as both systems display similar dynamics scenarios. The study underscores the importance of using simple models for mathematical analysis, initiating crucial discussions among the modeling community in vector-borne diseases.

Analysis of the epidemiology and clinical characteristics of Epstein-Barr virus infection.

The Epstein-Barr virus (EBV) is responsible for a spectrum of human diseases and demonstrates a considerable prevalence among various populations. Advances in molecular epidemiological research have enhanced our comprehension of EBV-related pathologies. In this study, our objective was to examine the epidemiological profile and clinical features of EBV infection in Chongqing, China. We enrolled patients suspected of EBV-related diseases who were admitted to the First Affiliated Hospital of Chongqing Medical University between May 2013 and November 2022. Inclusion criteria were based on those who underwent EBV-specific immunofluorescence or plasma EBV-DNA testing. Among 13 584 inpatients, the overall seropositivity rates for EBNA-1-IgG, EBV-VCA-IgM, EBV-EA-IgG, EBV-EA-IgA, EBV-VCA-IgA, and EBV-DNA were 91.89%, 7.22%, 18.00%, 16.19%, 30.78%, and 18.00%, respectively. The seropositivity rate for EBNA-1-IgG steadily increased with age. The seropositivity rate for VCA-IgM, an indicator of acute EBV infection, was highest in patients aged 11-20 years at 26.41%, decreasing to 2%-6% in older patients. Additionally, among 205 outpatients, the EBV-DNA positivity rate was 14.15%. In 3670 individuals from health check-up centers, the seropositivity rates for EBV-EA-IgA and EBV-VCA-IgA were 11.96% and 28.09%, respectively, and the EBV-DNA positivity rate was 11.92%, all of which were lower than those in inpatients. Among the 762 EBV-DNA positive inpatients, adults aged 31-40 years were the least affected, with a seropositivity rate of 12.00%, which increased with age. The most common diseases associated with primary EBV infection were infectious mononucleosis (IM) (35.49%), followed by EBV infection (14.15%) and pneumonia (7.19%). The most common diseases associated with EBV reactivation were pneumonia (16.80%), nasopharyngeal carcinoma (NPC) (11.02%), and autoimmune diseases (7.04%). Patients with hemophagocytic lymphohistiocytosis (HLH) had the highest viral load, significantly higher than those with NPC, pneumonia, and liver cirrhosis. This large-scale retrospective study explores the epidemiological characteristics and disease spectrum of EBV infection across all age groups. The findings contribute to the improvement of diagnostic and management strategies for EBV infection.

The importance of IFNα2A (Roferon-A) in HSV-1 latency and T cell exhaustion in ocularly infected mice.

Published studies have generated compelling results indicating that type I IFN modulates function of HSV-1 latency-associated transcript (LAT). One member of type I IFN is IFNα2A also called Roferon-A). IFNα2A has been used in monotherapy or in combination therapy with other drugs to treat viral infections and different kinds of cancer in humans. The goal of this study was to determine whether the absence of IFNα2A affects primary and latent infections in ocularly infected mice. Therefore, we generated a mouse strain lacking IFNα2A expression (IFNα2A-/-). Ocular HSV-1 replication, IFN and immune cell expressions on days 3 and 5 post infection (PI), as well as eye disease, survival, latency-reactivation, and T cell exhaustion were evaluated in ocularly infected IFNα2A-/- and wild type (WT) control mice. Absence of IFNα2A did not affect other members of the IFNα family but it affected IFNβ and IFNγ expressions as well as some immune cells on day 5 PI compared to WT mice. Viral replication in the eye, eye disease, and survival amongst ocularly infected IFNα2A-/- mice were similar to that of WT infected mice. The absence of IFNα2A significantly reduced the levels of latency and T cell exhaustion but not time of reactivation compared with control mice. Our results suggest that blocking IFNα2A expression may be a useful tool in reducing latency and the subsequent side effects associated with higher levels of latency.

Percentage of patients using parenteral nutrition who have had a primary bloodstream infection – should this condition alert care teams?

Percentage of patients using parenteral nutrition who have had a primary bloodstream infection – should this condition alert care teams?