ObjectiveTo examine predefined risk factors and outcome of seizures in community-acquired bacterial meningitis (CABM).DesignObservational cohort studiesSettingDenmarkParticipantsIn the derivation ...cohort, we retrospectively included all adults (>15 years of age) with CABM in North Denmark Region from 1998 to 2014 and at Hvidovre and Hillerød hospitals from 2003 to 2014. In the validation cohort, we prospectively included all adults (>18 years of age) with CABM treated at all departments of infectious diseases in Denmark from 2015 to 2017.Primary and secondary outcome measuresIn the derivation cohort, we used modified Poisson regression to compute adjusted relative risks (RRs) with 95% confidence intervals for predefined risk factors for seizures during CABM as well as for risks of death and unfavourable outcome assessed by the Glasgow Outcome Scale score (1-4). Next, results were validated in the validation cohort.ResultsIn the derivation cohort (n=358), risk factors for seizures at any time were pneumococcal aetiology (RR 1.69, 1.01–2.83) and abnormal cranial imaging (RR 2.27, 1.46–3.53), while the impact of age >65 years and immunocompromise was more uncertain. Examining seizures occurring after admission, risk factors were abnormal cranial imaging (RR 2.23, 1.40–3.54) and immunocompromise (RR 1.59, 1.01–2.50). Seizures at any time were associated with increased risks of in-hospital mortality (RR 1.45, 1.01–2.09) and unfavourable outcome at discharge (RR 1.27, 1.02–1.60). In the validation cohort (n=379), pneumococcal aetiology (RR 1.69, 1.10–2.59) and abnormal cranial imaging (RR 1.68, 1.09–2.59) were confirmed as risk factors for seizures at any time. For seizures occurring after admission, only pneumococcal meningitis (RR 1.92, 1.12–3.29) remained significant. Seizures at any time were also associated with in-hospital mortality (RR 3.26, 1.83–5.80) and unfavourable outcome (RR 1.23, 1.00–1.52) in this cohort.ConclusionsPneumococcal aetiology, immunocompromise and abnormal cranial imaging were risk factors for seizures in CABM. Seizures were strongly associated with mortality and unfavourable outcome.
In this review of tetanus in Denmark, it is discussed, why tetanus cases continue to occur especially in elderly people, although it is a preventable disease. The phenomenon is due to a lack of ...primary or booster vaccination and waning immunity with age, and immediate diagnosis and treatment are crucial to prevent deadly outcome. In Denmark, booster vaccination is recommended every tenth year. Estimation of immunisation status by medical interview is unreliable, and a future solution may be the use of a tetanus quick test and focus on booster vaccination in a primary care setting.
Older age and chronic disease are important risk factors for developing severe COVID-19. At population level, vaccine-induced immunity substantially reduces the risk of severe COVID-19 disease and ...hospitalization. However, the relative impact of humoral and cellular immunity on protection from breakthrough infection and severe disease is not fully understood.
In a study cohort of 655 primarily older study participants (median of 63 years (IQR: 51-72)), we determined serum levels of Spike IgG antibodies using a Multiantigen Serological Assay and quantified the frequency of SARS-CoV-2 Spike-specific CD4 + and CD8 + T cells using activation induced marker assay. This enabled characterization of suboptimal vaccine-induced cellular immunity. The risk factors of being a cellular hypo responder were assessed using logistic regression. Further follow-up of study participants allowed for an evaluation of the impact of T cell immunity on breakthrough infections.
We show reduced serological immunity and frequency of CD4 + Spike-specific T cells in the oldest age group (≥75 years) and higher Charlson Comorbidity Index (CCI) categories. Male sex, age group ≥75 years, and CCI > 0 is associated with an increased likelihood of being a cellular hypo-responder while vaccine type is a significant risk factor. Assessing breakthrough infections, no protective effect of T cell immunity is identified.
SARS-CoV-2 Spike-specific immune responses in both the cellular and serological compartment of the adaptive immune system increase with each vaccine dose and are progressively lower with older age and higher prevalence of comorbidities. The findings contribute to the understanding of the vaccine response in individuals with increased risk of severe COVID-19 disease and hospitalization.
Cerebral malaria continues to be a substantial cause of death and disability worldwide. Although many studies deal with cerebral malaria in children, only very few pertain to adults. Presence of ...multiorgan failure makes the prognosis poor. Various mechanisms in the pathogenesis of cerebral malaria and the role of adjuvant therapy will be discussed.
Artemisinin-based therapies have improved antiparasitic treatment, but in-hospital mortality still remains high, as do neurological sequelae. Several recent studies have given new insights in the pathophysiology of cerebral malaria particularly the role of immune mechanisms in disease progression. Recent findings have identified several potential candidates for adjuvant neuroprotective treatment. Recombinant human erythropoietin has shown beneficial effect in experimental cerebral malaria and will soon enter into large clinical trials.
Advances have been made in terms of antiparasitic treatment, but the identification of a well tolerated and effective adjuvant treatment to increase survival and reduce brain damage is still pending. The search for new approaches is a major challenge, not least of which is that mechanisms of malaria pathogenesis remain incompletely understood. The paper reviews newer information on pathogenesis and strategies in the management of cerebral malaria in adults.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with persistent symptoms ("long COVID"). We assessed the burden of long COVID among nonhospitalized adults with ...polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection.
In the fall of 2020, a cross-sectional survey was performed in the adult Danish general population. This included a self-administered point-of-care test for SARS-CoV-2 antibodies, the Short Form Health Survey (SF-12), and coronavirus disease 2019 (COVID-19)-associated symptom questions. Nonhospitalized respondents with a positive SARS-CoV-2 PCR test ≥12 weeks before the survey (cases) were matched (1:10) to seronegative controls on age, sex, and body mass index. Propensity score-weighted odds ratios (ORs) and ORs for risk factors were estimated for each health outcome.
In total, 742 cases and 7420 controls were included. The attributable risk of at least 1 long-COVID symptom was 25.0 per 100 cases (95% confidence interval CI, 22.2-27.4). Compared to controls, cases reported worse general health (OR, 5.9 95% CI, 5.0-7.0) and had higher odds for a broad range of symptoms, particularly loss of taste (OR, 11.8 95% CI, 9.5-14.6) and smell (OR, 11.2 95% CI, 9.1-13.9). Physical and Mental Component Summary scores were also significantly reduced with differences of -2.5 (95% CI, -3.1 to -1.8) and -2.0 (95% CI, -2.7 to -1.2), respectively. Female sex and severity of initial infection were major risk factors for long COVID.
Nonhospitalized SARS-CoV-2 PCR-positive individuals had significantly reduced physical and mental health, and 1 in 4 reported persistence of at least 1 long-COVID symptom.
SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron ...breakthrough infection.
The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR 95% CI for BA.2: 0.83 0.73–0.95, p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR 95% CI for BA.2 spike-specific IgG: 0.65 0.48–0.88, p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 0.30–0.69, p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.
High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.
Display omitted
•High antibody levels are associated with low odds of Omicron breakthrough infection•Vaccine-induced antibodies are an immune marker of protection against infection•Sex stratification revealed a clear association for females in particular
Immunology; Molecular medicine; Immune response
In this review, we discuss Staphylococcus aureus bac-teraemia (SAB), which is a frequent and severe condition associated with high morbidity and mortality. Despite these facts, high-quality data on ...diagnostic approach, treatment and management of SAB remain scarce. Consequently, evidence-based guidelines concerning antibiotic therapy including the optimal choice of antibiotic drug, route of administration and treatment duration are not available. Thus, controlled clinical trials are urgently needed to increase evidence and to potentially improve the outcome for patients with SAB.
PDF
