Pre-hospital symptoms associated with acute bacterial meningitis differs between children and adults.

Community acquired bacterial meningitis (CABM) is a medical emergency requiring timely appropriate action. More knowledge about pre-hospital symptoms is needed. Retrospective observational study of pre-hospital management in patients with CABM between 2016 and 2021 admitted to a hospital in the Capital Region of Denmark. Reported symptoms were extracted from archived audio files of the initial phone call to emergency medical service. The majority of the 209 patients (82%) were adults. The most common symptoms were altered mental state (58%) and fever (57%), while neck stiffness was less common (9%). Children more often presented with fever, fatigue, rashes, and neck stiffness, while adults more often presented with altered mental state, and leg pain. Most patients (85%) reported at least 1 of the 3 symptoms in the classical triad of meningitis, while 3% reported all 3. Children more often presented at least 2 of 3 symptoms in the triad. One child (3%) and 7 adults (4%) received antibiotics pre-admission. Patients with CABM reported a variety of symptoms that differed significantly in children and adults. The classic triad was rare. Very few patients received antibiotics pre-admission. We suggest that questioning relevant symptoms should be done in febrile or mentally altered patients.

Decreased Pneumococcal Carriage Among Older Adults in Denmark During the COVID-19 Lockdown.

Background: COVID-19 containment measures reduced the burden of invasive pneumococcal disease. Data on pneumococcal carriage rates among adults during the pandemic are scarce. Methods: Naso- and oropharyngeal swabs and questionnaires were collected during January 2019 to December 2021 from adults ≥64 years of age. Carriage was determined by lytA/piaB PCR. Results: A total of 1556 participants provided paired naso- and oropharyngeal swabs. Their median age was 74 years (IQR, 70-79). Streptococcus pneumoniae DNA was detected in 146 (9.4%) oropharyngeal swabs and 34 (2.2%) nasopharyngeal. The carriage rate decreased from 12.9% (95% CI, 10.1%-16.1%, n = 66/511) prelockdown (January 2019-February 2020) to 4.2% (95% CI, 2.0%-7.5%, n = 10/240) during lockdown (March 2020-February 2021) and increased to 12.1% (95% CI, 9.8%-14.7%, n = 87/719) with the reopening of society (March 2021-December 2021; P = .0009). Conclusions: Pneumococcal carriage prevalence declined significantly during pandemic mitigation measures and rebounded to prepandemic levels as measures were lifted.

Factors associated with treatment delay and outcome in community acquired bacterial meningitis.

Background: Community acquired bacterial meningitis (CABM) is a condition associated with significant morbidity and mortality. Treatment delay remains an area of concern and might be improved by awareness of meningitis among health care professionals. Methods: Retrospective observational study of patients with CABM between 2016 and 2021 in Eastern Denmark with a population of 2,700,000. Data was extracted from electronic health records. Treatment delay and mortality was analyzed using multivariate logistic regression and expressed as odds ratio (OR) with 95% confidence intervals (CI). Results: Of 369 patients 226 (61%) had treatment delayed more than 2 hours. Old age (OR 2.42, CI 1.22;4.77), comorbidity (OR 1.30, CI 1.00;1.70), suspicion of other infections than meningitis (OR 65.93, CI 20.68;210.20), stroke (OR 7.24, CI 3.11;16.86) and other diagnoses (OR 13.00, CI 5.07;33.31) were associated with delayed treatment. Treatment delay was associated with increased 30-day mortality (OR 3.07, 95% CI 1.09;8.67). Most of the treatment delay (82%) was due lack of suspicion of CABM. Conclusions: Treatment delay is a common problem associated with 30-day mortality in CABM. Awareness of CABM in undiagnosed patients is vital to achieve timely initiation of appropriate treatment. Special care should be shown for patients suspected of stroke or other infections.

A randomized placebo-controlled trial of convalescent plasma for adults hospitalized with COVID-19 pneumonia.

Passive immunotherapy with convalescent plasma may be the only available agent during the early phases of a pandemic. Here, we report safety and efficacy of high-titer convalescent plasma for COVID-19 pneumonia. Double-blinded randomized multicenter placebo-controlled trial of adult patients hospitalized with COVID-19 pneumonia. The intervention was COVID-19 convalescent plasma and placebo was saline allocated 2:1. The primary outcome was clinical status 14 days after the intervention evaluated on a clinical ordinal scale. The trial was registered at ClinicalTrials.Gov, NCT04345289, 14/04/2020. The CCAP-2 trial was terminated prematurely due to futility. Of 147 patients randomized, we included 144 patients in the modified intention-to-treat population. The ordinal clinical status 14 days post-intervention was comparable between treatment groups (odds ratio (OR) 1.41, 95% confidence interval (CI) 0.72-2.09). Results were consistent when evaluating clinical progression on an individual level 14 days after intervention (OR 1.09; 95% CI 0.46-1.73). No significant differences in length of hospital stay, admission to ICU, frequency of severe adverse events or all-cause mortality during follow-up were found between the intervention and the placebo group. Infusion of convalescent plasma did not influence clinical progression, survival or length of hospitalization in patients with COVID-19 pneumonia.

Pneumococcal carriage among children in low and lower-middle-income countries: A systematic review.

OBJECTIVES: Streptococcus pneumoniae is one of the most important causes of diseases leading to child mortality, especially in low- and lower-middle-income countries. This review aims to describe the prevalence of carriage of S. pneumoniae and the impact of vaccination among children aged under five years in low- and lower-middle-income countries since 2012. METHOD: The study is a systematic review of the literature. Relevant publications were searched in PubMed and screened systematically for information on the prevalence of carriage of S. pneumoniae among children aged under five years. 149 publications were identified, and 20 were included in the review. RESULTS: The prevalence of S. pneumoniae ranged between 26.7% - 90.7%. The prevalence of vaccine-type carriage ranged between 4.4% - 57.6% but generally decreased in countries after the introduction of PCV, with a reduction of 15.6% - 65.7%. Half of the post- pneumococcal conjugate vaccine (PCV) studies reported a vaccine-type carriage rate below 15%. CONCLUSION: Vaccine-type-carriage has decreased in most countries with the introduction of PCV. Still, coverage is only moderate, and carriage rates of S. pneumoniae vary significantly between countries. Continuous monitoring of carriage is needed to evaluate the effect of the further introduction of PCV10 and PCV13.

Nonspecific symptoms dominate at first contact to emergency healthcare services among cases with invasive meningococcal disease.

BACKGROUND: An early appropriate response is the cornerstone of treatment for invasive meningococcal disease. Little evidence exists on how cases with invasive meningococcal disease present at first contact to emergency medical services. METHODS: Retrospective observational study of cases presenting with invasive meningococcal disease from January 1st of 2016 to December 31st of 2020 in the Capital Region of Denmark with a catchment area population of 1,800,000. A single medical emergency center provides services to the region. Data was collected from emergency medical services' call audio files, data from the call receiver registrations, registrations from ambulance personal and electronic health record data from the hospitalization. RESULTS: Of 1527 cases suspected of meningitis, 38 had invasive meningococcal disease and had been in contact with the emergency service. Most contacts were to the medical helpline rather than the emergency call center at initial contact to emergency medical services. All were hospitalized within 12 h. At initial contact, fever was present in 28 (74%) of 38 cases, while specific symptoms such as headache (n=12 (32%)), a rash or petechiae (n=9 (23%)) and stiffness of the neck (n=4 (11%)) varied and were infrequent. Cases younger than 18 years of age were more often male and more often presented with fever and rash/petechiae. Only 4 (11%) received prehospital antibiotic treatment. CONCLUSIONS: Cases with invasive meningococcal disease presented with fever and unspecific symptoms. Although few were acutely ill at their initial contact, all were admitted within 12 h. We suggest that all feverish cases should be systematically asked about specific symptoms and should be wary of symptom progression to optimize the early management if cases with invasive meningococcal disease.

Recent increased incidence of invasive serogroup W meningococcal disease: A retrospective observational study.

OBJECTIVES: Neisseria meningitidis serogroup W incidence has increased. Mortality associated with serogroup W has been higher than for other serogroups. Here we report epidemiological characteristics and risks of poor outcomes associated with invasive meningococcal disease in Denmark since 1980. METHODS: All cases of invasive meningococcal disease reported from 1980-2018 were analyzed. Incidence rates by age, sex, manifestation, and serogroup were calculated. Poisson regression was used to analyze the rise in serogroup W, and multivariate logistic analysis was used to analyze risk factors for mortality. RESULTS: A total of 5825 cases were analyzed. Risk of serogroup W infection increased after 2015 compared with all previous periods. Younger (<20 years) and older age (≥60 years) was associated with an increased risk of serogroup W infection compared with being aged 20-39. Crude case fatality was 12.0%, 11.9%, 9.2%, and 7.9% for serogroups W, Y, C, and B, respectively. After adjustment for age, sex, and manifestation, 30-day mortality was comparable for serogroups. Older age and manifestation with sepsis independently predicted risk of death. CONCLUSIONS: Invasive meningococcal disease caused by serogroup W has increased, but serogroup per se was not associated with an increased risk of 30-day mortality.

Necrotizing fasciitis and meningitis due to Streptococcus pneumoniae serotype 9 N: a case report.

BACKGROUND: Necrotizing fasciitis is a deep infection of the fascia and subcutaneous tissue with a high mortality rate. Meningitis is an infection of the membranes surrounding the brain with a likewise high mortality rate. Streptococcus pneumoniae is the most frequent cause of bacterial meningitis and it is an extremely rare cause of necrotizing fasciitis. Different subcapsular serotypes of S. pneumoniae are known to have diverse virulence. The serotype 9 N is associated with a high risk of death. CASE PRESENTATION: We report a case of a previously healthy 68-year-old female who presented at our clinic with complaints of pain in her left calf since having experienced a very painful leg cramp 3 weeks prior. Within a few hours after admission, she developed fever, neck stiffness and an altered mental state. Concurrently, the pain in her leg worsened. Upon further examination it was found that she suffered from both meningitis and necrotizing fasciitis due to S. pneumoniae, serotype 9 N. The patient survived and avoided leg amputation. CONCLUSIONS: The patient suffered from two very lethal infections simultaneously. Both of them were caused by S. pneumoniae. We believe that her favorable outcome was, a result of prompt surgical intervention and appropriate antibiotic treatment. Our case underlines the importance of continuous reevaluation of the symptoms and clinical findings in patients with unclear causes of severe illness, especially if the patient's condition changes.

Functional brown adipose tissue and sympathetic activity after cold exposure in humans with type 1 narcolepsy.

Study Objectives: To investigate the activity of brown adipose tissue (BAT) in patients with type 1 narcolepsy during cold exposure using two separate scans of sympathetic and metabolic activity of BAT to evaluate whether orexin deficiency leads to altered nonshivering thermoregulation in narcolepsy. Methods: Seven patients with type 1 narcolepsy and seven healthy controls underwent two consecutive scans after 2 hr cold exposure: 123I-meta-iodo-benzyl-guanidine (123I-MIBG) single photon emission computed tomography and18F-2-deoxy-glucose (18F-FDG) positron emission tomography and computed tomography to visualize sympathetic innervation and metabolic activity of BAT, respectively. Plasma levels of eight hormones regulating BAT activity were measured before and after 2 hr in the cold. Results: 18F-FDG-uptake and uptake of 123I-MIBG in BAT after 2 hr cold exposure were observed in all individuals, but the activity of BAT was not significantly different between patients with type 1 narcolepsy and healthy controls (p > 0.05). Plasma levels of GLP-1 were higher in patients with type 1 narcolepsy compared with controls (p < 0.05), but not altered by cold adaptation in patients and controls (p > 0.05). FGF21 concentrations decreased after 2 hr cold exposure in both patients with type 1 narcolepsy and healthy participants (p < 0.05). Conclusions: Sympathetic and metabolic activity of BAT was observed after cold exposure in patients with type 1 narcolepsy. Increased GLP-1 in narcolepsy may suggest autonomic dysfunction with metabolic changes. We conclude that BAT is functional after cold exposure in spite of the loss of orexinergic neurons in narcolepsy.