Abstract
Background
Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in ...which otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection.
Methods
We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were evaluated. Data were analyzed by Mann-Whitney U test.
Results
We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients.
Conclusions
This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.
This study identifies genetic variants of pathogenic potential and explores innate interferon and cytokine responses to VZV infection in VZV encephalitis patients. These data suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.
This nationwide registry-based cohort study aimed to compare the risk of psychiatric diagnoses among HIV-exposed uninfected (HEU) children with a matched comparison group of HIV-unexposed uninfected ...(HUU) children, born in Denmark. We hypothesized that HEU children had an increased risk of psychiatric diagnoses and that this increased risk may differ by sex and age. All HEU children born in Denmark between year 2000 and 2020 were included. Each HEU child was matched by year of birth, maternal age at birth, and maternal immigration status to 10 HUU children. The primary outcome was risk of any psychiatric diagnosis (International Classification of Diseases, 10th Revision F00-F99). Incidence rate ratios (IRRs) were estimated using Poisson regression. Analyses stratifying by sex and age were also conducted. In total, 550 HEU children and 5500 HUU children were included. HEU children had an increased risk of any psychiatric disorder IRR 1.45; 95% confidence interval (CI): 1.04-2.04 in the unadjusted analysis, but in the adjusted analysis, the risk was only significant for children aged 6-11 years adjusted incidence rate ratio (aIRR) 1.93; 95% CI: 1.14-3.28. Stratifying by sex, girls aged 6-11 years had an increased risk of any psychiatric disorder (aIRR 3.04; 95% CI: 1.27-7.28), while boys had an increased risk at age 12-20 years (aIRR 2.47; 95% CI: 1.18-5.17). In conclusion, HEU girls aged 6-11 years and HEU boys aged 12-20 years had an increased risk of any psychiatric disorder compared with HUU girls and boys, respectively. These findings highlight the importance of addressing the mental health needs of HEU children/adolescents.
Abstract
People with HIV are at increased risk of pneumococcal disease. We investigate oral and anal carriage rates of Streptococcus pneumoniae by molecular methods among 82 men with HIV who have sex ...with men (MSM). A questionnaire, oral wash, and anal swab samples were obtained at baseline and 12 months. Oral carriage rates were 32.9% (27/82) at baseline and 41.7% (30/72) at follow-up. Anal carriage rates were 2.4% (2/82) at baseline and 2.9% (2/70) at follow-up. Genogroup 24 was predominant. Results suggest high oral carriage rates of S. pneumoniae among MSM living with HIV. A minority were anal carriers.
Data on the clinical presentation are scarce and prognostic factors of herpes simplex virus type 2 (HSV-2) meningitis remain unknown.
Prospective, nationwide, population-based database identifying ...all adults treated for HSV-2 meningitis at departments of infectious diseases in Denmark from 2015 to 2020. Unfavorable outcome was defined as Glasgow Outcome Scale (GOS) scores of 1-4 and Extended GOS scores of 1-6. Modified Poisson regression was used to compute relative risks with 95% confidence intervals for unfavorable outcome.
HSV-2 meningitis was diagnosed in 205 patients (76% female; median age interquartile range (IQR), 35 27-49 years) yielding an incidence of 0.7/100 000 population/y. Common symptoms were headache (195 of 204 patients 95%), photophobia or phonophobia (143 of 188 76%), and neck stiffness (106 of 196 54%). The median (IQR) time to lumbar puncture was 2.0 (1-4.8) hours, and the median cerebrospinal fluid (CSF) leukocyte count was 360 (166-670) × 10 × 6/L, with a mononuclear predominance of 97% (91%-99%). Lumbar puncture was preceded by brain imaging in 61 of 205 patients (30%). Acyclovir or valacyclovir was administered in 197 of 205 patients (96%) for a median (IQR) of 10 (7-14) days. Unfavorable outcome was observed in 64 of 205 patients (31%) at discharge and 19 of 181 (11%) after 6 months and was not associated with female sex (relative risk 95% confidence interval, 1.08 .65-1.79), age ≥35 years (1.28 .83-1.97), immunocompromise (1.07 .57-2.03), or CSF leukocyte count >1000 × 10 × 6/L (0.78 .33-1.84).
HSV-2 meningitis often presented as meningeal symptoms in younger women. Unfavorable outcome at discharge was common and was not associated with sex, age, immunocompromise, or CSF leukocyte count. Sequelae persisted beyond 6 months in one-tenth of patients.
Abstract Objectives The HIV/AIDS epidemic has disproportionately affected men who have sex with men (MSM) since its onset. Despite important medical advancements in treatment, the enduring effects of ...living with HIV continue to adversely impact the health and well‐being of this population. This cross‐sectional nationwide study examined psychosocial and sexual health among MSM in Denmark, comparing those living with and without HIV. Methods Data from MSM living with HIV were collected from the SHARE study, a Danish nationwide survey that investigated psychosocial, sexual and reproductive health among people with HIV, and compared with data from MSM without HIV, retrieved from the nationally representative cohort study, Project SEXUS. Associations between HIV status and psychosocial and sexual health outcomes were examined using logistic regression models while controlling for potentially confounding variables. Results Among 369 MSM with HIV and 1002 MSM without HIV, logistic regression analyses revealed that living with HIV was significantly associated with having current symptoms of anxiety and depression and greater dissatisfaction with one's body. Additionally, MSM with HIV significantly more often than MSM without HIV reported low sexual desire, sexual inactivity, a lack of sexual needs in the last year and erectile dysfunction. Having received payment for sex was more frequently reported by MSM with HIV, as was sexualised drug use, including chemsex drugs. Conclusion Compared with MSM without HIV, MSM with HIV in Denmark report a higher burden of mental health and sex life challenges.
Background
A score to differentiate autoimmune (AE) and viral encephalitis (VE) early upon admission has recently been developed but needed external validation. The objective of this study was to ...evaluate the performance of the score in a larger and more diagnostically diverse patient cohort.
Methods
We conducted a retrospective nationwide and population-based cohort study including all adults with encephalitis of definite viral (2015–2022) or autoimmune aetiology (2009–2022) in Denmark. Variables included in the score-model were extracted from patient records and individual risk scores were assessed. The performance of the score was assessed by receiver-operating characteristics (ROC) curve analyses and calculation of the area under the curve (AUC).
Results
A total of 496 patients with encephalitis AE
n
= 90, VE
n
= 287 and presumed infectious encephalitis (PIE)
n
= 119 were included in the study. The score was highly accurate in predicting cases of AE reaching an AUC of 0.94 (95% CI 0.92–0.97). Having a score ≥ 3 predicted AE with a PPV of 87% and an NPV of 91%. The risk score was found to perform well across aetiological subgroups and applied to the PIE cohort resulted in an AUC of 0.88 (95% CI 0.84–0.93).
Conclusion
The excellent performance of the score as reported in the development study was confirmed in this significantly larger and more diverse cohort of patients with encephalitis in Denmark. These results should prompt further prospective testing with wider inclusion criteria.
Background. We compared the immunogenicity and reactogenicity of Cervarix or Gardasil human papillomavirus (HPV) vaccines in adults infected with the human immunodeficiency virus (HIV). Methods. This ...was a double-blind, controlled trial randomizing HIV-positive adults to receive 3 doses of Cervarix or Gardasil at 0, 1.5, and 6 months. Immunogenicity was evaluated for up to 12 months. Neutralizing anti-HPV-16/18 antibodies were measured by pseudovirion-based neutralization assay. Laboratory tests and diary cards were used for safety assessment. The HPV-DNA status of the participants was determined before and after immunization. Results. Ninety-two participants were included in the study. Anti-HPV-18 antibody titers were higher in the Cervarix group compared with the Gardasil group at 7 and 12 months. No significant differences in anti-HPV-16 antibody titers were found among vaccine groups. Among Cervarix vaccinees, women had higher anti-HPV-16/18 antibody titers compared to men. No sex-specific differences in antibody titers were found in the Gardasil group. Mild injection site reactions were more common in the Cervarix group than in the Gardasil group (91.1% vs 69.6%; P = .02). No serious adverse events occurred. Conclusions. Both vaccines were immunogenic and well tolerated. Compared with Gardasil, Cervarix induced superior vaccine responses among HIV-infected women, whereas in HIV-infected men the difference in immunogenicity was less pronounced.
Abstract
Background
Although persistent symptoms after coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on the diversity and duration of symptoms are ...needed.
Methods
Patients aged ≥18 years with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 who were hospitalized at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, in the period from March 11 to May 15 were offered follow-up after hospitalization. On admission, a comprehensive symptom and medical history was collected, including demographic characteristics, duration of symptoms, comorbidities, and concomitant medications. At discharge, patients were offered follow-up consultations—either by telephone or at an in-person visit—at 6 and 12 weeks at our post-COVID-19 outpatient clinic to assess whether symptoms present at admission had resolved.
Results
During the inclusion period, 71 patients were admitted with COVID-19. Of these, 10 patients died, 3 were transferred to another region, 4 declined to participate, and 5 were lost to follow-up before the 12-week evaluation. Thus, 49 patients were included. Overall, 96% reported 1 or more persisting symptoms at 12-week follow-up. The main symptoms were fatigue, dyspnea, cough, chemosensory dysfunction, and headache.
Conclusions
A wide range of persistent symptoms in patients recovering from COVID-19 were present 12 weeks after hospitalization, calling for larger descriptive studies and interdisciplinary research collaborations.
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