Immunisation with purified Coxiella burnetii phase I lipopolysaccharide confers partial protection in mice independently of co-administered adenovirus vectored vaccines.

Q fever is a highly infectious zoonosis caused by the Gram-negative bacterium Coxiella burnetii. The worldwide distribution of Q fever suggests a need for vaccines that are more efficacious, affordable, and does not induce severe adverse reactions in vaccine recipients with pre-existing immunity against Q fever. Potential Q fever vaccine antigens include lipopolysaccharide (LPS) and several C. burnetii surface proteins. Antibodies elicited by purified C. burnetii lipopolysaccharide (LPS) correlate with protection against Q fever, while antigens encoded by adenoviral vectored vaccines can induce cellular immune responses which aid clearing of intracellular pathogens. In the present study, the immunogenicity and the protection induced by adenoviral vectored constructs formulated with the addition of LPS were assessed. Multiple vaccine constructs encoding single or fusion antigens from C. burnetii were synthesised. The adenoviral vectored vaccine constructs alone elicited strong cellular immunity, but this response was not correlative with protection in mice. However, vaccination with LPS was significantly associated with lower weight loss post-bacterial challenge independent of co-administration with adenoviral vaccine constructs, supporting further vaccine development based on LPS.

Q Fever Severe Pericarditis With Cardiac Tamponade: A Case Report.

Q fever can present in acute or chronic form with a wide range of clinical symptoms and presentations. Here we report severe pericarditis with cardiac tamponade due to a chronic Coxiella burnetii (C. burnetii) infection. Our report emphasizes and justifies the importance of serological testing for chronic Q fever in patients with unexplained pericarditis, particularly in areas where C. burnetii is endemic.

Is there a higher risk of exposure to Coxiella burnetii for pre-clinical veterinary students?

Coxiella burnetii is globally distributed but evidence of zoonotic transmission in the Caribbean region is scarce. The bacterium presence is suspected on the Caribbean island of St. Kitts. The risk of exposure of veterinary students was reported in other regions of the world but is not documented in the Caribbean region. The present study aimed to evaluate the risk of exposure to C. burnetii for pre-clinical veterinary students (mostly coming from the U.S.) attending an island-based veterinary school. A cross-sectional study was conducted to compare incoming and outgoing veterinary students' seroprevalence. Serology was performed using indirect immunofluorescence assay to test Coxiella burnetii Phase I and Phase II immunoglobulins M and G. Background data were gathered using a standardized questionnaire. A parallel study enrolled veterinary school employees in the same university. Of the 98 participants (48 incoming and 50 outgoing students), 41 (41.8%, 95 %CI: 31.9-52.2) were seropositive to C. burnetii. There was no significant difference between the two groups (45.8% for incoming vs. 38.0% for outgoing students) (p = 0.4). No risk factors (demographic, animal handling practices or background) were significantly more reported in the seropositive group. In the employee study, the seroprevalence was high with 8/15 seropositives (53.3%, 95 %CI: 26.6-78.7). Pre-clinical veterinary students do not have a higher risk of exposure to C. burnetii by attending the veterinary school in St. Kitts, but they are highly exposed before arrival on the island (seroprevalence of 45.8%). Most of these participants had experience with animals either through farming or previous veterinary technician employment. This indicates a high exposure in the U.S. young population aiming to become veterinarians. There is an urgent need to increase C. burnetii surveillance in animals and humans to apply relevant prevention and control measures, including recommendations for vaccination of students and professionals at risk.

Prerequisites, barriers and opportunities in care for Q-fever patients: a Delphi study among healthcare workers.

BACKGROUND: Q-fever is a zoonotic disease that can lead to illness, disability and death. This study aimed to provide insight into the perspectives of healthcare workers (HCWs) on prerequisites, barriers and opportunities in care for Q-fever patients. METHODS: A two-round online Delphi study was conducted among 94 Dutch HCWs involved in care for Q-fever patients. The questionnaires contained questions on prerequisites for high quality, barriers and facilitators in care, knowledge of Q-fever, and optimization of care. For multiple choice, ranking and Likert scale questions, frequencies were reported, while for rating and numerical questions, the median and interquartile range (IQR) were reported. RESULTS: The panel rated the care for Q-fever patients at a median score of 6/10 (IQR = 2). Sufficient knowledge of Q-fever among HCWs (36%), financial compensation of care (30%) and recognition of the disease by HCWs (26%) were considered the most important prerequisites for high quality care. A lack of knowledge was identified as the most important barrier (76%) and continuing medical education as the primary method for improving HCWs' knowledge (76%). HCWs rated their own knowledge at a median score of 8/10 (IQR = 1) and the general knowledge of other HCWs at a 5/10 (IQR = 2). According to HCWs, a median of eight healthcare providers (IQR = 4) should be involved in the care for Q-fever fatigue syndrome (QFS) and a median of seven (IQR = 5) in chronic Q-fever care. CONCLUSIONS: Ten years after the Dutch Q-fever epidemic, HCWs indicate that the long-term care for Q-fever patients leaves much room for improvement. Facilitation of reported prerequisites for high quality care, improved knowledge among HCWs, clearly defined roles and responsibilities, and guidance on how to support patients could possibly improve quality of care. These prerequisites may also improve care for patients with persisting symptoms due to other infectious diseases, such as COVID-19.

FEVER OF UNKNOWN ORIGIN: ATYPICAL CLINICAL PRESENTATION OF MURINE TYPHUS

CASE: 66yo woman with a past medical history of hypertension and monoclonal gammopathy of undetermined significance was sent from clinic in winter for 4 days of worsening fevers and sinus congestion unrelieved by over-the- counter medications. COVID and flu negative. Patient has had no sick contacts or recent travel and has pet cats but no recent scratches. Initial chest x-ray showed no acute processes, but patient was continuing to have fevers up to 103 with mild dyspnea and chills so a CT chest was completed which showed ground glass opacities in the right middle lobe. Blood and sputum cultures were obtained, and patient was started on ceftriaxone and azithromycin for community acquired pneumonia. Urine strep and legionella antigens were also acquired, both negative. Over the next two days, she continued to have high fevers and chills at nights with leukocytosis, thrombocytopenia, hyponatremia, and notable worsening of mild elevation of liver enzymes on admission. Cultures were negative and patient had no other indication of an infection aside from the cyclical fevers therefore empiric doxycycline was added for coverage of atypical infections. Over the next two days, she continued to have nightly fevers up to 103 so ID was consulted for fever of unknown origin. On repeat exposure assessment, patient revealed that she lived with multiple animals including cats, dogs, parakeets, chickens, geese and a pony. Patient was continued on doxycycline while additional lab tests were sent for atypical infections including Rickettsia typhi, Coxiella brunetti (Q fever), and Brucella spp given patient's history of exposure to multiple animals at home. Patient was discharged on doxycycline after being afebrile for 48hrs with declining white count and liver enzymes. Lab results confirmed the diagnosis with high titers for Rickettsia typhi IgG and IgM. IMPACT/DISCUSSION: This case illustrates an atypical presentation of murine typhus with pneumonia in winter. There are several key teaching points in this case: 1. Ricketssia typhi infections have largely nonspecific symptoms therefore it should should be included in differential diagnoses of febrile illnesses with thrombocytopenia and elevated liver enzymes 2. Although a complete history is acquired on admission, it is important to revisit and review information again when a clinical diagnosis has not been established 3. Defeverscence after starting doxycycline can take anywhere from 4 to 66hrs so fevers during this timeframe is not an indication of failure of therapy CONCLUSION: Murine typhus presents with non-specific symptoms so it should be included in the differential diagnosis of patients with fevers of unknown origin with potential exposure to flea-bearing animals. The optimal therapy is doxycycline 100mg twice a day for seven days. Patients should also be advised to treat their animals for fleas to prevent recurrent infections.

Incidence and severity of SARS-CoV-2 infection in former Q fever patients as compared to the Dutch population, 2020-2021.

Surveillance data shows a geographical overlap between the early coronavirus disease 2019 (COVID-19) pandemic and the past Q fever epidemic (2007-2010) in the Netherlands. We investigated the relationship between past Q fever and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 2020/2021, using a retrospective matched cohort study.In January 2021, former Q fever patients received a questionnaire on demographics, SARS-CoV-2 test results and related hospital/intensive care unit (ICU) admissions. SARS-CoV-2 incidence with 95% confidence intervals (CI) in former Q fever patients and standardised incidence ratios (SIR) to compare to the age-standardised SARS-CoV-2 incidence in the general regional population were calculated.Among 890 former Q fever patients (response rate: 68%), 66 had a PCR-confirmed SARS-CoV-2 infection. Of these, nine (14%) were hospitalised and two (3%) were admitted to ICU. From February to June 2020 the SARS-CoV-2 incidence was 1573/100 000 (95% CI 749-2397) in former Q fever patients and 695/100 000 in the general population (SIR 2.26; 95% CI 1.24-3.80). The incidence was not significantly higher from September 2020 to February 2021.We found no sufficient evidence for a difference in SARS-CoV-2 incidence or an increased severity in former Q fever patients vs. the general population during the period with widespread SARS-CoV-2 testing availability (September 2020-February 2021). This indicates that former Q fever patients do not have a higher risk of SARS-CoV-2 infection.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion of the corpus callosum in childhood: a single-center experience

Background/aim: Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a rare clinicoradiological syndrome that typically presents with central nervous system symptoms such as loss of consciousness, seizure, headache, and ophthalmoparesis. Materials and methods: Here, we highlight the characteristics of this syndrome together with the clinical and MRI findings of 6 pediatric patients with MERS. Results: Between January 2017 and October 2020, 6 patients with MERS (3 boys and 3 girls) presented to our center. The mean age was 122 ± 54.6 (min-max: 44-180) months. None of the patients had a chronic disease. In our study, infectious agents were detected in 4 patients (66.6%), while noninfectious causes (one seizure and the other hyponatremia) were detected in two patients. All of our cases were discharged without any sequelae after an average of 12.1 ± 7 (min–max: 4–20) days of hospitalization. In 1 patient (case 6), control MRI could not be performed, and the radiological recovery of our other patients was shown to be between 14 days and 2 months. Conclusion: MERS is an acute encephalopathy with good prognosis and should be considered by neurologists in differential diagnosis due to its variable clinical presentation and specific MRI findings.

Sensitivity of the EQ-5D-5L for fatigue and cognitive problems and their added value in Q-fever patients.

PURPOSE: Measuring health-related quality of life (HRQoL) with the EQ-5D-5L might lack sensitivity for disease-specific health complaints. This cross-sectional study analyzed whether fatigue and cognitive problems are captured by the EQ-5D-5L in a Q-fever patient population with persistent fatigue/cognitive problems, and whether addition of fatigue/cognition improved the explained variance for HRQoL. METHODS: A Dutch sample of Q-fever patients filled out the EQ-5D-5L and EQ VAS, the fatigue subscale of the Checklist Individual Strength, and a cognition dimension in the EQ-5D-5L format. The extent to which fatigue and cognition were captured by the EQ-5D-5L was determined based on distributional effects, head-to-head comparisons, Spearman rank correlation coefficients, and regression analyses. Explanatory power was determined of the EQ-5D-5L for the EQ VAS with and without a fatigue and cognition dimension. RESULTS: Out of 432 respondents, 373(86%) reported severe fatigue, 387(90%) cognitive problems. EQ-5D-5L utility and EQ VAS scores of respondents reporting severe fatigue/cognitive problems were significantly lower. Fatigue was strongly correlated with EQ-5D-5L dimensions usual activities and pain/discomfort (r = 0.602 and r = 0.510) and moderately with other EQ-5D-5L dimensions (r = 0.305-0.476). Cognition was strongly correlated with usual activities (r = 0.554) and moderately with other dimensions (r = 0.291-0.451). Adding fatigue to the EQ-5D-5L increased explanatory power for the EQ VAS with 6%. CONCLUSION: Fatigue and cognitive problems in Q-fever patients were partially captured by the EQ-5D-5L dimensions. The addition of fatigue to the EQ-5D-5L slightly improved explained variance for the EQ VAS. This potentially also accounts for patients who experience sequelae of other infectious diseases, such as COVID-19.

No Influence of Previous Coxiella burnetii Infection on ICU Admission and Mortality in Emergency Department Patients Infected with SARS-CoV-2.

BACKGROUND: the geographical similarities of the Dutch 2007-2010 Q fever outbreak and the start of the 2020 coronavirus disease 19 (COVID-19) outbreak in the Netherlands raised questions and provided a unique opportunity to study an association between Coxiella burnetii infection and the outcome following SARS-CoV-2 infection. METHODS: We performed a retrospective cohort study in two Dutch hospitals. We assessed evidence of previous C. burnetii infection in COVID-19 patients diagnosed at the ED during the first COVID-19 wave and compared a combined outcome of in-hospital mortality and intensive care unit (ICU) admission using adjusted odds ratios (OR). RESULTS: In total, 629 patients were included with a mean age of 68.0 years. Evidence of previous C. burnetii infection was found in 117 patients (18.6%). The combined primary outcome occurred in 40.2% and 40.4% of patients with and without evidence of previous C. burnetii infection respectively (adjusted OR of 0.926 (95% CI 0.605-1.416)). The adjusted OR of the secondary outcomes in-hospital mortality, ICU-admission and regular ward admission did not show an association either. CONCLUSION: no influence of previous C. burnetii infection on the risk of ICU admission and/or mortality for patients with COVID-19 presenting at the ED was observed.

EFSA and ECDC publishes EU One Health 2020 zoonoses report

The European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC) have published the EU One Health 2020 Zoonoses Report. Campylobacteriosis was the most reported zoonosis in the EU in 2020, with 120,946 cases compared to more than 220,000 the previous year. This was followed by salmonellosis, which affected 52,702 people, compared to 88,000 in 2019. The number of reported foodborne outbreaks fell by 47%, with the report acknowledging the impact of the COVID-19 pandemic in the drop in reported zoonotic diseases in humans. The next most commonly reported diseases were yersiniosis, with 5,668 cases, and infections caused by Shiga toxin-producing Escherichia coli, with 4,446 cases. Listeriosis was the fifth most reported zoonosis, mainly affecting people over the age of 64. Listeriosis and West Nile virus (WNV) infections were the diseases with the highest case fatality and hospitalisation rates, with most locally acquired human infections of WNV reported in Greece, Spain and Italy. The report also monitors foodborne outbreaks in the EU, events during which at least two people contract the same illness from the same contaminated food. A total of 3,086 foodborne outbreaks were reported in 2020, with Salmonella remaining the most frequently detected agent, causing around 23% of outbreaks. The most common sources of salmonellosis outbreaks were eggs, egg products and pig meat. The report also includes data on Mycobacterium bovis, Mycobacterium caprae, Brucella, Trichinella, Echinococcus, Toxoplasma gondii, rabies, Q fever and tularaemia.

Acute Q Fever With Dermatologic Manifestations, Molecular Diagnosis, and No Seroconversion.

We herein described a case of acute infection by Coxiella burnetii (acute Q fever) that started with a short incubation period and showed prominent dermatological manifestations and unusual serological behavior. The infection was confirmed by molecular detection through real-time polymerase chain reaction using genomic DNA collected from peripheral blood.