Single Infection Research Articles

Infection management in the extravascular implantable cardioverter defibrillator: experience from the EV ICD Pivotal study

Abstract Background The extravascular implantable cardioverter defibrillator (EV ICD) has recently emerged as an option for guideline indicated ICD patients. Results from the EV ICD Pilot and Pivotal studies demonstrated that the device can provide safe and effective therapy through chronic follow up. Lead placement outside the vasculature has the potential to reduce systemic infections. Infection occurrence and management details from the Pivotal are reported. Purpose To report on details of infection occurrence and management from the EV ICD Pivotal study. Methods The EV ICD Pivotal study was an international, prospective, single-arm, premarket clinical study. Patients with a class I or IIa indication for a single-chamber ICD per ESC or ACC/AHA/HRS guidelines were enrolled. Results In the EV ICD Pivotal study, 316 patients had an implant attempt, (74.7% male, age 53.8±13.1 years, 82% primary prevention, LVEF of 38.9%±15.4%, and NYHA Class I [23.7%] or II/III [65.5%]), of which 15 had a system or procedure-related infection (4.7%, 9 - 737 days post-implant) through an average 16.2 months follow-up. Of these infections, 8 were classified as major complications, 3 as minor, and 4 as observations. Most (n=9) infections were addressed through medication with or without wound care (2.8% of patients) while 6 (1.9% of patients) resulted in system removal. There was a single lead-related infection addressed through system explant. However, there were no reports of mediastinitis, sepsis, or endocarditis. No system removal resulted in sequelae. Conclusions Infection rates observed in the EV ICD Pivotal study were similar to those reported in the subcutaneous implantable cardioverter defibrillator. The results from this study support that EV ICD related infections are treatable with antibiotic therapy or system removal. No system or procedure-related systemic infections such as mediastinitis, sepsis, or endocarditis have been reported in the Pivotal study.

Prevalence of Torque Teno Virus, Hepatitis and Cytomegalovirus Infection in Iranian Patients With Different Types of leukemia

Background and Objectives: Torque teno virus (TTV) infection can be seen in different types of leukemia and may affect clinical outcomes. This study aims to investigate the prevalence of TTV, hepatitis B and C virus, and cytomegalovirus (CMV) in Iranian patients with different types of leukemia. Methods: In this descriptive cross-sectional study, 95 patients with different types of leukemia participated. The molecular prevalence of TTV infection was evaluated using the semi-nested PCR method. The prevalence of HBs-Ag and HCV-Ab viruses was measured by the ELISA method. Also, the prevalence of active CMV infection was investigated by the semi-quantitative antigenemia test. The data analysis was done in SPSS software version 12 using logistic regression analysis, chi-square test, and Fisher’s exact test. Results: The TTV infection was found in 40 out of 95 patients (42.1%). The presence of HBs-Ag was reported in 27 out of 95 patients (28.4%). HCV-Ab was found in 18 out of 69 patients (26.1%), and active CMV infection was found in 11 out of 69 (15.9%). Among 40 leukemia patients with TTV infection, 15 (37.5%) had hepatitis B, 14 (35%) had hepatitis C, and 7 (17.5%) had CMV infection. Conclusion: The high prevalence of single or comorbid TTV infection among Iranian patients with leukemia emphasizes the importance of this virus in causing or aggravating the clinical complications observed in these patients.

Epidemiological characteristics and meteorological factors of acute respiratory infections (ARIs) in hospitalized children in eastern Guangdong, China

Acute respiratory infections (ARIs) are the most common issue in pediatric clinical practice. They pose a significant public threat, with high morbidity and mortality rates worldwide. Aiming at understanding the epidemiological characteristics of respiratory pathogens and their risk factors among children in eastern Guangdong, China. Samples obtained from 15,993 children hospitalized with ARIs in eastern Guangdong Province were tested for 14 pathogens via multiplex polymerase chain reaction (PCR) from May 2019 to July 2023. The number of hospitalizations for ARIs was correlated with pathogens, age, meteorological parameters, and the pandemic of COVID-19. The data were analyzed by different statistical methods. Among all the samples, the positive rate with ARIs accounted for 68.94% (11,026/15,993) in hospitalized patients. Cytomegalovirus (CMV) (24.49%), Streptococcus pneumoniae (SP) (20.54%), and Respiratory Syncytial Virus (RSV) (14.16%) were the top three pathogens with the greatest infection rates. Among hospitalized patients, there were more single infections in pediatric patients (40.91%, P < 0.001). Compared with bacterial infection and mixed infection, the detection rate of virus infection was higher in pediatric (36.04%, P < 0.001). Age-related increases in Mycoplasma pneumoniae (MP) infection (r = 0.729, P < 0.001) and decreases in RSV infection were observed (r = 0.88, P < 0.001). The virus infection peaked at six months, and the bacterial infection and mixed infection peaked at 1–3 years. Viral pathogens are on the rise in the post-pandemic era. The prevalence of SP infection was more influenced by the Air Quality Index (AQI), RSV infections were more clearly influenced by temperature, and Influenza A virus (IAV) infections were more strongly correlated with both the AQI and relative humidity (P < 0.001). This study highlights the need of keeping an eye on monitoring meteorological factors in assessing hospitalizations for pediatric ARIs in eastern Guangdong, China, especially RSV- and SP-associated hospitalizations.

Immunogenicity and Efficacy of Combined mRNA Vaccine Against Influenza and SARS-CoV-2 in Mice Animal Models

Background. The combined or multivalent vaccines are actively used in pediatric practice and offer a series of advantages, including a reduced number of injections and visits to the doctor, simplicity of the vaccination schedule and minimization of side effects, easier vaccine monitoring and storage, and lower vaccination costs. The practice of widespread use of the combined vaccines has shown the potential to increase vaccination coverage against single infections. The mRNA platform has been shown to be effective against the COVID-19 pandemic and enables the development of combined vaccines. There are currently no mRNA-based combined vaccines approved for use in humans. Some studies have shown that different mRNA components in a vaccine can interact to increase or decrease the immunogenicity and efficacy of the combined vaccine. Objectives. In the present study, we investigated the possibility of combining the mRNA vaccines, encoding seasonal influenza and SARS-CoV-2 antigens. In our previous works, both vaccine candidates have shown excellent immunogenicity and efficacy profiles in mice. Methods. The mRNA-LNPs were prepared by microfluidic mixing, immunogenicity in mice was assessed by hemagglutination inhibition assay, enzyme-linked immunoassay and virus neutralization assay. Immunological efficacy was assessed in a mouse viral challenge model. Results. In this work, we demonstrated that the individual mRNA components of the combined vaccine did not affect the immunogenicity level of each other. The combined vaccine demonstrated excellent protective efficacy, providing a 100% survival rate when mice were infected with the H1N1 influenza virus and reducing the viral load in the lungs. Four days after the challenge with SARS-CoV-2 EG.5.1.1., no viable virus and low levels of detectable viral RNA were observed in the lungs of vaccinated mice. Conclusions. The combination does not lead to mutual interference between the individual vaccines. We believe that such a combined mRNA-based vaccine could be a good alternative to separated human vaccinations for the prevention of COVID-19 and influenza.

Gonococcal infections and risk factors for reinfection: a descriptive and case-case analysis of notifications in the Australian Capital Territory, 2017-2022.

In Australia, gonococcal infection notification rates are increasing with reinfections representing a substantial proportion of infections. Understanding the local epidemiology of gonococcal infections and reinfections and the risk factors for reinfection can assist with the design of targeted interventions. This study aimed to describe the epidemiology of gonococcal infections and reinfections between 2017 and 2022 in the Australian Capital Territory (ACT), and to examine the risk factors for reinfection. Data for gonococcal infections notified in the ACT between 2017 and 2022 were described. The epidemiological characteristics of individuals with a single infection and reinfection were compared using a case-case study design. There were 1,886 gonococcal infection notifications during the study period. Of these, 20.4% were reinfections (n = 385). Of 1,501 individuals, 1,254 (83.5%) had a single infection and 247 (16.5%) had a reinfection. Between 2017 and 2022, the annual gonococcal infection notification rate per 100,000 population increased from 59.98 to 80.14 and the proportion of reinfections from 4.0% to 26.8%. Compared with those with a single infection, individuals with a reinfection had significantly greater odds of being male, of having a same-sex sexual exposure, of using HIV pre-exposure prophylaxis at diagnosis, and of having been diagnosed at a sexual health/family planning clinic. Individuals with a reinfection had significantly greater odds of being in the 25-34, 35-44 and 45-54 years age groups than in the 14-24 years age group. The odds of anatomical site of first infection being only the rectum, only the throat, or at more than one site, compared with urogenital only, were significantly greater for those with a reinfection. Gonococcal reinfections contribute substantially to gonococcal infection notifications in the ACT. Targeted interventions are needed to prevent gonococcal reinfections among at-risk groups, particularly among men who have sex with men, people who use HIV pre-exposure prophylaxis, and individuals accessing sexual health/family planning services.

The application value of low-risk human papillomavirus testing in cervical cancer prevention and treatment in low- and middle-resource areas

ObjectivesTo assess the application value of low-risk human papillomavirus (lrHPV) detection in the prevention and treatment of cervical cancer in low- and middle-resource areas (LMRAs). Study designA retrospective cross-sectional study. MethodsCervical HPV typing results were collected from 2019 to 2023, utilizing fluorescence PCR technology. An adjusted logistic regression model was used to assess the relative risk (OR) and 95 % confidence interval (CI) for co-infection with lrHPV and high-risk HPV (hrHPV). ResultsOut of 113,883 women included in the study, the overall lrHPV positivity rate was 1.9 %. In total, 47.7 % (1033/2167) of lrHPV positive women also had hrHPV co-infections. Multivariate analysis identified 12 hrHPV subtypes (T-hrHPV) significantly associated with co-infection risk, including HPV16, 31, 33, 39, 51, 52, 53, 56, 59, 66, 68, and 73. The risk of T-hrHPV infection was 3.77 times higher (95 % CI: 3.44-4.12) for women with a single lrHPV infection and 9.71 times higher (95 % CI: 4.72-19.99) for those with two lrHPV infections. Women screened in the gynecological outpatient clinic faced a T-hrHPV infection risk 2.64 times higher (95 % CI: 2.54-2.74) than those in the general health check department. ConclusionslrHPV positivity significantly increases the risk of T-hrHPV co-infection, particularly under multiple infections, highlighting the importance of comprehensive HPV screening in LMRAs. The notable differences in T-hrHPV infection risks across various screening settings highlight their critical role in cervical cancer prevention and offer new insights into optimizing vaccination strategies to enhance effective prevention and treatment in LMRAs.

Characteristics and outcomes of patients hospitalized for infection with Influenza A, SARS-CoV-2 or respiratory syncytial virus in the season 2023/2024 in a large German primary care centre

BackgroundIn addition to the persistence of SARS-CoV-2 infections, those with Influenza A/B and RSV have reappeared in 2022/23. To compare the development of prevalence, clinical outcomes and risk factors, we analysed data of the season 2023/24 from the same region/hospital as for 2022/23.MethodsPatients covering the whole age range with a positive polymerase chain reaction (PCR) test for SARS-CoV-2, Influenza A/B, RSV were included from the internal, neurological and paediatric units of the RoMed hospital Rosenheim, Germany/Bavaria, from August 1st 2023 to 29th February 2024.ResultsOf 932 patients included, 912 showed single infections with SARS-CoV-2, Influenza A or RSV (47.9% female, median age 68.0 years; 52.9% SARS-CoV-2, 23.2% Influenza A, 21.8% RSV). Co-infections (2.0%) and Influenza B (0.1%) were negligible. In patients of age ≥ 18 years (n = 628, 68.5% SARS-CoV-2, 26.0% Influenza A, 5.6% RSV), patients with Influenza A were younger compared to SARS-CoV-2 (p < 0.001), with RSV similar to SARS-CoV-2. Heart failure and asthma were the most prevalent comorbidities for RSV, immunosuppression for Influenza A. Admission to Intensive Care Unit (ICU) occurred in 111 patients (17.0% of SARS-CoV-2, 17.2% Influenza A, 28.6% RSV), and 59 patients died (8.8% SARS-CoV-2, 8.6% Influenza A, 20.0% RSV). Low-flow oxygen supplementation and non-invasive ventilation (NIV) were most frequent for RSV (68.6% and 20.0%, respectively), oxygen demand upon admission for Influenza A (39.3%), without differences in high-flow oxygen supply or length of hospital stay. Among patients aged < 18 years (n = 284, 21.4% SARS-CoV-2, 18.0% Influenza A, 57.1% RSV), 15 were admitted to ICU (4.8% SARS-CoV-2, 3.8% Influenza A, 6.0% RSV); none of them died. Oxygen supply via high-flow, low-flow or upon admission was highest for RSV (23.8%, 70.2%, 21.4%, respectively), as well as the length of hospital stay.ConclusionBetween 8/2023 to 2/2024, a large population of patients hospitalized due to respiratory tract infection, showed relative contributions of SARS-CoV-2, Influenza A or RSV similar to those in 2022/23. The findings underline that in both, adults and children, RSV posed a relatively higher clinical risk than Influenza A and SARS-CoV-2, though absolute numbers remained highest for SARS-CoV-2.

Serological evidence of tick-borne Crimean-Congo haemorrhagic fever and Dugbe orthonairovirus infections in cattle in Kwara State in northern Nigeria indicate independent endemics.

Crimean-Congo haemorrhagic fever orthonairovirus (CCHFV) and Dugbe orthonairovirus (DUGV) are zoonotic viruses transmitted by ticks. Whereas CCHFV has caused numerous human cases, DUGV, although less reported, shares ticks and ruminants as hosts. Since its first discovery in Nigeria in 1964, there has been no detailed sero-epidemiological investigation on DUGV in sub-Saharan Africa. This study is aimed at assessing the current seroprevalence and associated risk factors of CCHFV and DUGV infections in Nigerian cattle. Using a cross-sectional design with random sampling method, blood samples were collected from 877 cattle on pastoralist farms and at abattoirs in Kwara State, North-Central Nigeria. CCHFV IgG antibodies were detected in extracted sera using three panels of in-house indirect enzyme-linked immunosorbent assay (ELISA) based on bacteria-expressed recombinant nucleoprotein (rNP), the cattle-adapted VectoCrimean ELISA and the ID Screen CCHF double antigen multi-species ELISA, while DUGV IgG antibodies were detected using in-house indirect ELISA with bacteria-expressed rNP, indirect immunofluorescence assay and micro-Virus Neutralization test. Overall seroprevalence rates of 71.9% (631/877) and 52.8% (451/854) were obtained for CCHFV and DUGV, respectively. It was observed that 37.9% (314/829) of the cattle were co-exposed to both CCHFV and DUGV while 34.5% (286/829), 14.8% (123/829) and 12.8% (106/829) were exposed to single infections with CCHFV, DUGV or none of the two viruses, respectively. Multivariate analysis showed that only location, sex, age and tick infestation score were the risk factors that significantly affected CCHFV seroprevalence in cattle, while DUGV seroprevalence was significantly influenced by month of the year, location, cattle breed and sex (p<0.05). This is the first comprehensive sero-epidemiological surveillance for DUGV in sub-Saharan Africa. Our findings reveal widely distributed independent CCHFV and DUGV infections in cattle in Kwara State, Nigeria.

Infection-Related Mortality in Children Undergoing Hematopoietic Stem Cell Transplants at a Referral Center in Mexico

Abstract Background Infections constitute a major cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, infection-associated mortality rate ranging from 7% to 17% has been reported, depending on the type of HSCT, being lower in autologous transplants and higher in cases involving unrelated donors. Other factors related to HSCT that influence the clinical outcomes of these patients include the intensity of the conditioning regimen, the development of graft-versus-host disease (GVHD), cytotoxic and immunosuppressive effects of the medications used, the presence of disease activity prior to HSCT, length of hospital stay, and the use of intravascular devices, among many others. Methods All pediatric patients (under 16 years old) undergoing HSCT at the ‘Dr. José Eleuterio González’ University Hospital over a 55-month period (March 2019 – October 2023) were included. Clinical and epidemiological characteristics of the patients, mortality rate, and risk factors related to transplantation and infectious events (IEs) in these patients were recorded. Results A total of 75 patients who received HSCT were included, among them, 52 patients (69%) presented IEs. The mortality associated with IEs among these patients was 6% at day 30 and 12% at day 100, compared to 0% and 1.3% respectively in the non-IEs related deaths. The epidemiological characteristics, baseline diagnosis, donors and graft source are described in table 1. The average number of IEs in the associated mortality cases was 2.8 compared to 1.6 in the survival group. Among the mortality group (8 cases), 67% presented multiple infections and 33% single infections, with a 75% of them caused by viral infections. Regarding HSCT characteristics, in the group with IE-associated mortality, a higher proportion of haploidentical transplants, myeloablative conditioning regimens, lower use of total body irradiation, and a higher proportion of patients with detectable disease by flow cytometry prior to HSCT were observed compared to the survival group. Among non-infectious complications related to HSCT a lower frequency of acute GVHD grade I-II, a higher frequency of acute GVHD grade III-IV in the IE-associated mortality group was identified. Among the risk factors associated with hospital care, the IE-associated mortality group showed a higher use of central venous catheters, mucositis, systemic steroids, and pediatric intensive care unit stay compared to the survival group. Conclusion Pediatric patients undergoing HSCT present multiple risk factors that increase the incidence of infectious events and contribute to higher mortality rates. It is crucial to identify those factors related to adverse events and death to implement strategies that reduce exposure to these factors and improve the clinical outcomes.

Microbiological Profile of the Upper and Lower Respiratory Tract of Suckling and Weaned Dairy Calves with Acute Respiratory Disease

Bovine respiratory disease (BRD) is a significant global health issue in cattle farming, leading to substantial economic losses. This study analyzed the microbiological profiles of BRD outbreaks in nine dairy cattle herds in southern Brazil. We examined 36 biological samples, including 24 deep nasopharyngeal swabs (NS) and 12 lung tissue, from 29 suckling and 7 weaned heifer calves with acute BRD. PCR and RT-PCR techniques were used to partially amplify the genes of five viruses and four respiratory bacteria. A total of 8 different microorganisms, 4 viruses (bovine viral diarrhea virus, n = 5; bovine coronavirus, n = 3; bovine alphaherpesvirus 1, n = 3; and bovine parainfluenza virus 3, n = 2), and 4 bacteria (Pasteurella multocida, n = 16; Mycoplasma bovis, n = 8; Histophilus somni, n = 7; and Mannheimia haemolytica, n = 4) were identified in 29 (80.5%) samples. Seven samples (four lung tissue and three NS) were negative for all the microorganisms. Mixed infections were more common (62.1%) than single infections (37.9%). Bacterial nucleic acids were more commonly co-detected in NS than in lung tissue. Nucleic acids from a single pathogen were more frequently detected in lung tissues than in NS. M. bovis was the only bacterium detected in the lower respiratory tract. Understanding the microbiological profiles of the respiratory tracts of dairy calves with clinical signs of BRD is crucial for implementing effective biosecurity measures to prevent BRD in suckling and weaned dairy heifer calves.

Comparative study on the epidemiological characteristics and hazards of respiratory syncytial virus and influenza virus infections among elderly people

ObjectiveTo investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections.MethodsIn this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted.ResultsAmong 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection.ConclusionsDuring the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients.

The underlying mechanism of single and co-infection of DIV1 and WSSV in Litopenaeus vannamei

Viral diseases are one of the important factors restricting the shrimp industry. Decapod iridescent virus 1 (DIV1) and White spot syndrome virus (WSSV) are the two most harmful viruses to shrimp. DIV1 and WSSV were found to be carried and infected simultaneously in several samples of cultured and wild shrimps. In this study, the co-infection model of DIV1 and WSSV in Litopenaeus vannamei was constructed by TaqMan probe quantitative detection (qPCR), intestinal section, and transcriptome analysis. Our study also evaluated the virulence of the virus by calculating LC50 and detected the replication rates of DIV1 and WSSV at 7-time points and 2 tissues in L. vannamei by qPCR. As a result, DIV1 and WSSV could infect L. vannamei singly or co-infect L. vannamei. DIV1 replicated the fastest, at 12–16 h post-injection (hpi). The WSSV virus replicates the fastest 20–24 hpi. In different tissues, the amount of DIV1 carried by blood cells is higher than that in muscle, while WSSV is the opposite. In addition, the intestinal responses of DIV1 and WSSV single and co-infection of L. vannamei were explored using the RNA-Seq platform and bioinformatics analysis, and the differential expressed genes (DEGs) screened by comparison were as follows: there were significant differences in DEGs between the PBS group and the three virus infection groups, and there were differences in DEGs between the PBS group and single virus infection groups (the DIV1 group and the WSSV group), but there was no significant difference in the DEGs between the 2 single virus infection groups, and the Combine-infected group, especially, the DEGs between the WSSV group and the Combine-infected group were only 39. According to the above conclusions, it can be inferred that WSSV plays a major role in co-infection. In addition, pathways related to vitamin metabolism were significantly enriched in the viral infection group compared to the PBS group. Glycolysis/Gluconeogenesis, a hallmark of the Warburg effect, is also significantly enriched after viral infection. In this study, the co-infection phenomenon of DIV1 and WSSV was found for the first time in L. vannamei, which provided a new idea for developing and screening molecular markers for new strains resistant to complex viruses in L. vannamei.

Epidemiological study of human papillomavirus infection in 105,679 women in Wuhan, China

BackgroundQuality assessment of the prevalence and distribution of human papillomavirus (HPV) genotypes could support additional targeted HPV vaccinations. However, the characteristics of HPV infection in Wuhan city are limited in the past decade. We aimed to assess the epidemiology of HPV infection among women and provide a reference for the prevention and treatment of cervical cancer in this region.MethodsA retrospective study employing 105,679 women attending Wuhan Medical and Health Center for Women and Children for cervical cancer screening from January 2015 to December 2022 was conducted. The HPV genotype was detected by polymerase chain reaction (PCR) and diversion hybridization. The overall incidence and age-specific type distribution of HPV infection and the relationship between HPV infection and cervical cytology were analyzed.ResultsThe overall HPV infection rate was 16.87% in Wuhan city, and the prevalence rates of high-risk, low-risk and mixed high- and low-risk HPV infections were 13.64%, 1.77% and 1.46%, respectively. The five most prevalent genotypes were HPV52 (4.24%), HPV58 (2.42%), HPV16 (2.34%), HPV53 (1.87%), and HPV39 (1.66%). The prevalence of HPV in women exhibited a “two-peak” pattern, the peaks of which were observed in the < 21 years group (37.4%) and the 61–65 years group (41.72%). Logistic regression analysis revealed no significant difference in the rate of high-grade lesion positivity between single and multiple high-risk HPV infections. Among patients with a high-grade squamous intraepithelial lesion+ (HSIL+) ThinPrep cytologic test (TCT) diagnosis, HPV58 was the most common type, followed by HPV52, HPV16, HPV39 and HPV53.ConclusionsHPV types 52, 58, 16, 53, and 39 were the most common types in the general female population in Wuhan, and the prevalence of HPV infection varied among different age groups. This study provides a comprehensive overview of the epidemiological characteristics of HPV infection in women, which could support the development of targeted prevention and control strategies for cervical cancer in the region.

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.

APOE4 and Infectious Diseases Jointly Contribute to Brain Glucose Hypometabolism, a Biomarker of Alzheimer's Pathology: New Findings from the ADNI.

Impaired brain glucose metabolism is a preclinical feature of neurodegenerative diseases such as Alzheimer's disease (AD). Infections may promote AD-related pathology. Therefore, we investigated the interplay between infections and APOE4, a strong genetic risk factor for AD. We analyzed data on 1,509 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database using multivariate linear regression models. The outcomes were rank-normalized hypometabolic convergence index (HCI), statistical regions of interest (SROI) for AD, and mild cognitive impairment (MCI). Marginal mean estimates for infections, stratified by APOE4 carrier status, were then computed. Prior infections were associated with greater HCI [β=0.15, 95% CI: 0.03, 0.27, p=0.01]. The combined effects of infections and APOE4 carriers on HCI levels were significantly greater than either variable alone. Among APOE4 carriers, the estimated marginal mean was 0.62, rising to 0.77, with infections (p<0.001), indicating an interaction effect. Carriers with multiple infections showed greater hypometabolism (higher HCI), with an estimate of 0.44 (p=0.01) compared to 0.11 (p=0.08) for those with a single infection, revealing a dose-response relationship. The estimates for the association of infections with SROI AD and SROI MCI were β=-0.01 (p=0.02) and β=-0.01 (p=0.04), respectively. Our findings suggest that infections and APOE4 jointly contribute to brain glucose hypometabolism and AD pathology, supporting a "multi-hit" mechanism in AD development.

Complex transmission of partiti-, ambi- and ourmiaviruses in the forest pathogen Heterobasidion parviporum

Utilizing Heterobasidion partitivirus 13 strain an1 (HetPV13-an1) and 15 strain pa1 (HetPV15-pa1) in co-infection is considered a potential biocontrol approach against Heterobasidion root and butt rot. Both partitiviruses mediate debilitating effects in most Heterobasidion host isolates and are generally transmitted efficiently between host strains. In this investigation, we conducted transmission experiments in the laboratory (in vitro) using several H. parviporum isolates to test whether using dual partitivirus infections is a more efficient way of transmitting viruses to new hosts compared to using single partitivirus infections, and whether co-occurring single-stranded RNA (ssRNA) viruses are co-transmitted during the process. The results showed that H. parviporum donors carrying both partitiviruses, HetPV13-an1 and HetPV15-pa1, transmitted HetPV15-pa1 more efficiently to recipients than the same donors infected with only HetPV15-pa1. In contrast, the transmission of HetPV13-an1 did not differ significantly between donors infected with both or only one partitivirus. Altogether, the transmission rates of HetPV13-an1 and HetPV15-pa1 were high on artificial media. Moreover, the transmission of the ssRNA viruses Heterobasidion ourmia-like virus 1(HetOlV1-pa7) and 4 (HetOlV4-an1) as well as Heterobasidion ambi-like virus 3 (HetAlV3-pa4) across different recipients were found to be variable. This study demonstrated for the first time the transmission of ambi- and ourmiaviruses between H. parviporum isolates in dual cultures and showed that H. parviporum mycelia can be cured of these ssRNA viruses using heat treatment.

Continuous Global Improvement of Human Papillomavirus (HPV) Genotyping Services: The 2022 and 2023 HPV LabNet International Proficiency Studies.

The International Human Papillomavirus (HPV) Reference Center launches annual global HPV genotyping proficiency panels to enhance the precision and international standardization of HPV genotyping services. This study aims to assess the proficiency levels achieved in the global HPV genotyping proficiency panels conducted in 2022 and 2023, and to evaluate trends in performance over time. The proficiency panels comprised 44 blinded samples each, including 40 samples containing various purified plasmids corresponding to HPV types combined with human DNA, plus four control samples (one negative control and three extraction controls). Proficiency required a sensitivity of 50 International Units (IU)/5 µL for HPV 16 and HPV 18 500 IU/5 µL for HPVs 6, 11, 31, 33, 45, 52, and 58 and 500 genome equivalents (GE)/5 µL for other HPV types in both single and multiple infections, while avoiding false positivity. In 2022, 78 laboratories submitted a total of 154 data sets, and in 2023, 81 laboratories contributed 141 data sets. Most data sets (87%, 258/295) utilized commercially available HPV assays. Proficiency was common, with 77% of data sets meeting the proficiency criteria in 2022 and 79% in 2023. False positive results significantly decreased from 22% in 2022 to 13% in 2023. The high proficiency and increasing specificity in HPV genotyping services indicates progress toward more reliable HPV testing. High accuracy is crucial for supporting global efforts in HPV and cervical cancer elimination.

The Sansure® Human Papillomavirus DNA Diagnostic Kit offers excellent reproducibility performance for the detection of high-risk HPV.

Cervical cancer screening is a cornerstone of cervical cancer elimination. Detection of high-risk human papillomavirus (hrHPV) is recommended as the first step in screening provided that the assay used has been adequately validated. The Sansure® Human Papillomavirus DNA Diagnostic Kit is a new assay designed to detect HPV16, HPV18 and 13 other HPV in aggregate. The study aimed to evaluate the intra- and interlaboratory reproducibility of the assay according to international guidelines. Five hundred and fifty cervical residual cell samples from women attending cervical cancer screening were selected from the biobank of the HPV National Reference Centre in Belgium and used in this study. After DNA extraction, HPV was tested using the Sansure® Human Papillomavirus DNA Diagnostic Kit. The lower 95% confidence limit around the general reproducibility of this assay should be greater than or equal to 87%, with κ ≥ 0.50. Five hundred and thirty-three samples had valid results. The Sansure® Human Papillomavirus DNA Diagnostic Kit demonstrated an excellent intra-laboratory reproducibility of 93.8% (95% confidence interval [CI]: 91.4-95.7, κ = 0.85). The interlaboratory reproducibility was 93.4 (95% CI: 91.0-95.4, κ = 0.84). Intra and interlaboratory reproducibility were also excellent at the genotype level. Excluding HPV53 single infection samples from the analyses also resulted in excellent agreement. These data show that the Sansure® Human Papillomavirus DNA Diagnostic Kit is highly reproducible.

Developing a Coccidioides posadasii and SARS-CoV-2 Co-infection Model in the K18-hACE2 Transgenic Mouse.

Early reports showed that patients with COVID-19 had recrudescence of previously resolved coccidioidomycosis (Valley fever, VF), and there were indications that coinfection had more severe outcomes. We therefore investigated serial infection of Coccidioides posadasii and SARS-CoV-2 in a K18-hACE2 mouse model to assess disease outcomes. In our model, we challenged K18-hACE2 mice sequentially with a sub-lethal dose of SARS-CoV-2 and 24 hours later with low virulence strain of Coccidioides posadasii, and vice versa, compared to mice that only received a single infection challenge. We performed survival and pathogenesis mouse studies as well as looked at the systemic immune response differences between treatment groups. Here we show that co-infected groups have a more severe disease progression as well as a decrease in survival. Importantly, results differ depending on the SARS-CoV-2 variant (WA-1, Delta, or Omicron) and infection timing (SARS-CoV-2 first, C. posadasii second or vice versa). We find that groups that are infected with the virus first had a decrease in survival, increased morbidity and weight loss, increased fungal and viral burdens, differences in immune responses, and the amount and size of fungal spherules. We also find that groups coinfected with C. posadasii first have a decrease fungal burden and inflammatory responses. This is the first in vivo model investigation of a coinfection of SARS-CoV-2 and Coccidioides. Because of the potential for increased severity of disease in a coinfection, we suggest populations that live in areas of high coccidioidomycosis endemicity may experience higher incidence of complicated disease progression with COVID-19.

Asymptomatic Plasmodium falciparum and HBV coinfections among inmates at Owo Correctional Facility, Nigeria

BackgroundMalaria and hepatitis B are significant public health infections in Nigeria. Coinfection with both pathogens is common where both diseases are endemic. Epidemiological surveys are essential for determining the burden of diseases and possible coinfection with multiple pathogens in vulnerable populations. There has been a lack of reports on HBV/malaria coinfection, particularly among marginalized groups in Ondo State. Thus, we used malaria microscopy and the HBsAg serological test to examine the prevalence of asymptomatic malaria parasitemia and HBV infections respectively among inmates at the Nigerian Correctional Center in Owo, Ondo State, Nigeria.ResultsOut of the 126 prisoners and staff members who were evaluated, 20.6% and 7.9% tested positive for malaria and HBV infections, respectively. It was discovered that 1.6% of the individuals were coinfected with malaria and HBV. Plasmodium falciparum was the only malaria species recovered in malaria-infected individuals. Except for HBV, where gender was found to differ considerably with the proportion of HBV infection, variations in single infections with either pathogen did not vary with demographic characteristics.ConclusionWe suggest that the prison system should be considered in healthcare programs to improve the health of inmates.