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.

[Guidelines for the Treatment and Follow-Up of Patients with Q Fever]. / Recomendações para o Tratamento e Seguimento de Doentes com Febre Q.

Q fever (or query fever) is a zoonotic infectious disease with worldwide distribution transmitted by an intracellular Gram-negative bacterium, Coxiella burnetii. The most common identified sources of human infection are farm animals, such as sheep, goats and cattle. The disease is endemic in mainland Portugal, with most cases notified in the central and southern regions. Q fever is a complex and pleomorphic disease, with those affected presenting with a wide range of manifestations from acute self-limited flu-like symptoms with good prognosis to persistent localized forms that may harbor a poor prognosis. Cases might occur in an isolated fashion or following outbreaks with great public health repercussion, as seen recently in the Netherlands from 2007 to 2010. Given the complexity of this infection, there is no universal consensus to date on the best strategy to manage Q fever patients. These guidelines provide recommendations regarding the treatment and follow-up of these patients, based on studies, on the author's experience and on the opinion of international experts. The aim is to harmonize the management of these patients taking into account not only the clinical manifestations but also the risk factors of the host in order to reduce disease-associated morbidity and mortality.

A febre Q (do inglês query fever) é uma zoonose de distribuição mundial transmitida por uma bactéria intracelular Gram negativo, Coxiella burnetii. Os ruminantes domésticos são os principais reservatórios implicados na transmissão da doença ao ser humano. Em Portugal continental, esta doença é endémica, com o maior número de casos notificados nas regiões Centro e Sul. A doença causada por C. burnetii é complexa e polimórfica, podendo manifestar-se sob uma forma aguda autolimitada do tipo gripal, com um curso ligeiro a moderado e prognóstico benigno, e/ou sob uma forma persistente, geralmente localizada e de evolução grave ou potencialmente fatal. Pode ocorrer em casos isolados ou em contexto de surtos, alguns com importantes implicações em saúde pública, como o verificado na Holanda em 2007 - 2010. Dada a complexidade e espetro clínico da febre Q, não existe um consenso universal sobre a melhor forma de tratamento, gestão e seguimento destes doentes. Este protocolo é uma sugestão de tratamento e seguimento dos doentes com febre Q, compilando a informação de estudos e opiniões de peritos internacionais e a experiência dos autores. Pretende-se assim uniformizar a gestão destes doentes tendo em conta não só o espetro das suas manifestações clínicas, mas também os fatores de risco do hospedeiro, por forma a reduzir morbimortalidade que a doença possa causar.

Vertebral Osteomyelitis or Infected Abdominal Aortic Endograft? A Rare Case of Q Fever.

Coxiella burnetii is the etiological agent of Q fever, a zoonosis. Vascular infections are associated with significant morbidity and mortality. Osteoarticular Q fever infections are rare. We describe a case of vertebral osteomyelitis with associated infection of an abdominal aortic endograft, caused by C. burnetii. Most probably, an initial pyogenic vertebral osteomyelitis extended locally to the endograft. Treatment consisted of antibiotic therapy and surgical resection of the infected aortic endograft and in situ reconstruction with autogenous superficial femoral vein grafts.

[Revision of guideline on Q fever fatigue syndrome (QFS)]. / Herziene richtlijn Q-koortsvermoeidheidssyndroom (QVS).

In 2012 the multidisciplinary guideline Q fever fatigue syndrome was developed for the Netherlands. The availability of new research data and developments and experiences from daily clinical practice made it necessary to revise this guideline. The multidisciplinary working group that has revised the guideline is composed of representatives from all medical professions involved in the care of patients with QFS and representatives of the patients' association. The revised guideline incorporates a number of changes, including refinement of the QFS diagnostic criteria and updates regarding advice on support and reintegration.

Persistent Coxiella burnetii cardiovascular infection on Bentall-De Bono prosthesis.

Coxiella burnetii cardiovascular prosthetic infections are associated with high morbidity and mortality and represent a major health problem due to the lack of standardized management. We were confronted with a C. burnetii infection on Bentall-De Bono prosthesis characterized by a history of vascular infection with relapse that prompted us to screen for cases of C. burnetii on Bentall-De Bono vascular prosthesis monitored in our center. We screened patients between 1991 and 2019, from the French national reference center for Q fever. A microbiological criterion in addition to a lesional criterion was necessary to diagnose C. burnetii persistent vascular infection. Two thousand five hundred and eighty two patient were diagnosed with Coxiella burnetii infection and 160 patients with persistent C. burnetii vascular infection prosthesis, 95 of whom had a vascular prosthesis, including 12 with Bentall-De Bono prosthesis. Among patients with persistent C. burnetii prosthetic vascular infection, patients with Bentall-De Bono prostheses were significantly more prone to develop complications such as aneurysm, fistula, and abscess (62 versus 32%, two-sided Chi-square test, p = 0.04). All but one patient were treated with doxycycline and hydroxychloroquine for a mean (± standard deviation) period of 29.4 ± 13.6 months. Among the 12 patients, 5 had cardio-vascular complications, and 5 had prolonged antibiotherapy with doxycycline and hydroxychloroquine. Patients with C. burnetii vascular infection on Bentall-De Bono tend to be at high risk of developing complications (fistula, aneurysm, abscess, death). Surgery is rarely performed. Clinical, serological, and PET scanner imaging follow-up is recommended.

Q fever endocarditis: is it always subacute or chronic?

Q fever is a zoonotic disease caused by Coxiella burnetii, an obligate intracellular bacterium, which cannot be grown using routine blood culture methods. Although C. burnetii is reported to be the causative agent in approximately 50% of blood culture-negative infective endocarditis cases in developed countries, the incidence in Turkey is yet to be defined. The clinical course of Q fever endocarditis is generally subacute and chronic; the disease may be present for years with only subtle symptoms and no vegetation visible on echocardiography while the bacteria gradually destroy the heart valves. This is the case of the successful treatment of a young man with Q fever endocarditis that had an acute clinical course. In 1 month, he developed New York Heart Association class IV heart failure and a large, 3-cm vegetation was observed on an echocardiogram.

New insights in Coxiella burnetii infection: diagnosis and therapeutic update.

Introduction: Coxiella burnetii infection is still challenging physicians, mainly because no international coordination has been stated to standardize the therapeutic strategy and improve the clinical outcomes.Areas covered: Based on the recent knowledge on Q fever, we review here the clinical practices from Q fever diagnosis to therapy. We searched PubMed and Google Scholar to perform the qualitative synthesis.Expert opinion: Four major critical points are highlighted in this review. The first point is that Q fever diagnosis has been reviewed in the light of the new diagnosis tools, including molecular biology, transthoracic echocardiography, and 18F-FDG-PET/CT-scan imaging. Q fever diagnosis results from the presence of a microbiological criterion in addition to a lesional criterion. Second, the identification of the anticardiolipin antibodies as a novel biological predictive marker for acute Q fever complications (hemophagocytic syndrome, acute Q fever endocarditis, alithiasic cholecystitis, hepatitis, and meningitis). Third, the observation of a coincidence between Q fever and non-Hodgkin lymphoma that has made persistent C. burnetii infection a risk of non-Hodgkin lymphoma. Finally, we expose here the close follow-up we proposed from the French National Reference Center for patients with Q fever infection to detect relapse and complications.

Epidemiological scenario of Q fever hospitalized patients in the Spanish Health System: What's new.

OBJECTIVES: The objective of this study was to assess the epidemiology and burden of Q fever (QF) in Spain. METHODS: We designed a retrospective descriptive study using the minimum basic data set in patients admitted to hospitals of the National Health System between 1998 and 2015 with a diagnosis of Q fever (ICD-9: 083.0.). RESULTS: We found 4214 hospitalized patients with a mean age (±SD) of 50.9±19.3 years. The male/female ratio was 3:1. The incidence rate was between 0.41 and 0.65 cases per 100,000 person-years over the 18-year period. The highest incidence of cases was from March to August (p=0.024). 21.1% patients had pneumonia, 17.5% had liver disease, and only 3.2% had endocarditis. The average hospital stay was 13.8 days (±12.8). A total of 117 (2.8%) patients died. The total mean cost of QF is approximately €154,232,779 (€36,600±139,422 per patient). CONCLUSIONS: QF is an important zoonosis in Spain with a stable incidence rate and high cost for hospitalization. Older patients have a more severe clinical picture and higher mortality, which can be decreased with early clinical suspicion.

[CHRONIC Q FEVER IN PATIENTS AT THE HILLEL YAFFE MEDICAL CENTER - THREE YEARS OF FOLLOW UP].

INTRODUCTION: Q fever is an acute zoonotic infection, which in some cases is complicated by a chronic disease. Diagnosis is based on serology, and in patients with a chronic disease, the source of infection must be investigated. AIMS: To describe patients with chronic Q fever, who were treated at the Hillel Yaffe Medical Center: risk factors, course of the disease, and serological findings. METHODS: This was an observational study; patients with chronic Q fever who were treated in the Infectious Diseases Clinic during the period 5/2015 - 1/2018 were included. The diagnosis was based on clinical findings and results of phase 1 IgG ≥ 800. Clinical, laboratory and imaging data from diagnosis to the end of treatment were collected. RESULTS: Sixteen patients were included in the study; all these patients were treated with antibiotics, and three also underwent operations. Risk factors for a chronic infection were a significant valvular disease in 11 patients (69%) and vascular diseases in five (31%). Trans-esophageal echocardiogram (TEE) was performed in 13 patients (81%), and a 18F-FDG/PET-CT was performed in eight patients (50%). The source of infection was found in seven patients, four with endocarditis and three with vascular infection. CONCLUSIONS: Endocarditis was more common than vascular infection. In 56% of the patients, the source of the infection was not found. DISCUSSION: We presented patients with chronic Q fever who were treated in a unique clinic in Israel. Diagnosing the source of the infection is challenging; the increasing use of 18F-FDG/PET-CT allowed accurate diagnosis in some patients in which TEE results were negative.

Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study.

BACKGROUND: Previously, we reported a randomized placebo-controlled trial, the Qure study, showing that cognitive behavioural therapy (CBT), and not doxycycline, was significantly more effective than placebo in reducing fatigue severity in Q fever fatigue syndrome (QFS) patients. This follow-up study evaluates the long-term effect of these treatment regimens, 1 year after completion of the original trial. METHODS: All patients who completed the Qure study, CBT (n = 50), doxycycline (n = 52), and placebo (n = 52), were included in this follow-up study. Between twelve and fifteen months after end of treatment (EOT), patients filled out web-based questionnaires including the main outcome measure fatigue severity, assessed with the Checklist Individual Strength (CIS), subscale fatigue severity. RESULTS: Fatigue severity in the CBT, but not doxycycline or placebo, group was significantly increased at follow-up compared to EOT (respective means 39.5 [95% CI, 36.2-42.9] and 31.3 [95% CI, 27.5-35.1], mean difference 8.2 [95% CI, 4.9-11.6]; P < .001). Fatigue severity scores of CBT (adjusted mean 39.8 [95% CI, 36.1-43.4]) and doxycycline (adjusted mean 41.0 [95% CI, 37.5-44.6]) groups did not significantly differ from the placebo group (adjusted mean 37.1 [95% CI, 33.6-40.7]; P = .92 and P = .38, respectively). CONCLUSION: The beneficial effect of CBT on fatigue severity at EOT was not maintained 1 year thereafter. Due to its initial beneficial effect and side effects of long-term doxycycline use, we still recommend CBT as treatment for QFS. We suggest further investigation on tailoring CBT more to QFS, possibly followed by booster sessions.

Q fever: A rural disease with potential urban consequences

BACKGROUND: Q fever often presents as an undifferentiated febrile illness. Cases occur throughout Australia, with higher rates occurring in northern New South Wales and southern Queensland. OBJECTIVE: This article aims to provide clinicians with an overview of Q fever, and covers epidemiology, clinical features, laboratory diagnosis, sequelae, management and prevention. DISCUSSION: In Australia, Q fever is the most commonly reported zoonotic disease. Presentation includes fever, rigors, chills, headache, extreme fatigue, drenching sweats, weight loss, arthralgia and myalgia, often in conjunction with abnormal liver function tests. These features make it indistinguishable from many other febrile illnesses. Exposure occurs through contact with livestock and other animals. Coxiella bacteria can survive in dust, where infection may result from inhalation. Laboratory diagnosis is made by serology or polymerase chain reaction. An effective vaccine is available for adults (aged >15 years), but can only be administered after a rigorous pre-vaccination assessment to exclude prior exposure to Coxiella burnetii, requiring a detailed medical history, skin test and serology.

Coxiella burnetii endocarditis on bioprosthetic aortic valve, with peripheral arterial embolism.

Acute limb ischemia related to Coxiella burnetii endocarditis is rare. We report an original case of a 68-year-old man hospitalized for recurrent acute left limb ischemia in a context of atrial flutter, which revealed C. burnetii endocarditis. This case illustrates that even if embolic events are uncommon, septic embolisms must be systematically searched for in case of C. burnetii endocarditis. Conversely, extensive etiologic explorations must be performed in case of systemic embolism. New molecular techniques represent a major step forward in infective endocarditis diagnosis. Finally, diagnosis must be suspected in case of unexplained fever, inflammatory syndrome, or embolic event, especially in patients at risk. Conversely, in case of chronic Q fever, an immunodeficiency cause must be researched.

A case of giant cell arteritis associated with culture-proven Coxiella burnetii aortitis.

A case of proven Coxiella burnetii aortitis, possibly associated with giant cell arteritis (GCA), is reported. A 72-year-old man, who is a hunter, presented with weight loss, fever, jaw claudication, and hardened temporal arteries associated with a persistent inflammatory syndrome and arteritis of the whole aorta, including the brachiocephalic arteries, as seen on 18F-fluorodeoxyglucose positron emission tomography/computed tomography. The diagnosis of GCA was retained, and treatment with prednisolone was started. Given the aneurysm of the abdominal aorta, the patient underwent replacement of the abdominal aorta with an allograft. Histology showed intense chronic arteritis attributed to atherosclerosis with dissection. However, Coxiella burnetii infection was confirmed by serology and then by culture and molecular biology on the surgical specimen. A combination of hydroxychloroquine and doxycycline was added to tapered prednisolone and the outcome was favourable.

From Expert Protocols to Standardized Management of Infectious Diseases.

We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs. First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome. Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate. Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria. Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters. Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.

CXCL9, a promising biomarker in the diagnosis of chronic Q fever.

BACKGROUND: In the aftermath of the largest Q fever outbreak in the world, diagnosing the potentially lethal complication chronic Q fever remains challenging. PCR, Coxiella burnetii IgG phase I antibodies, CRP and 18F-FDG-PET/CT scan are used for diagnosis and monitoring in clinical practice. We aimed to identify and test biomarkers in order to improve discriminative power of the diagnostic tests and monitoring of chronic Q fever. METHODS: We performed a transcriptome analysis on C. burnetii stimulated PBMCs of 4 healthy controls and 6 chronic Q fever patients and identified genes that were most differentially expressed. The gene products were determined using Luminex technology in whole blood samples stimulated with heat-killed C. burnetii and serum samples from chronic Q fever patients and control subjects. RESULTS: Gene expression of the chemokines CXCL9, CXCL10, CXCL11 and CCL8 was strongly up-regulated in C. burnetii stimulated PBMCs of chronic Q fever patients, in contrast to healthy controls. In whole blood cultures of chronic Q fever patients, production of all four chemokines was increased upon C. burnetii stimulation, but also healthy controls and past Q fever individuals showed increased production of CXCL9, CXCL10 and CCL8. However, CXCL9 and CXCL11 production was significantly higher for chronic Q fever patients compared to past Q fever individuals. In addition, CXCL9 serum concentrations in chronic Q fever patients were higher than in past Q fever individuals. CONCLUSION: CXCL9 protein, measured in serum or as C. burnetii stimulated production, is a promising biomarker for the diagnosis of chronic Q fever.

Chronic Recurrent Multifocal Q Fever Osteomyelitis in Children: An Emerging Clinical Challenge.

BACKGROUND: Clinical disease caused by Coxiella burnetii occurs infrequently in children. Chronic Q fever is particularly uncommon and endocarditis is rarely seen. A small number of cases of Q fever osteomyelitis have been described but the pathophysiology is not well understood and optimal treatment is unknown. METHODS: We describe a series of cases of chronic recurrent multifocal Q fever osteomyelitis cases diagnosed in children from a single region in Australia. RESULTS: Between 2011 and 2014, 9 cases of chronic recurrent multifocal Q fever osteomyelitis were diagnosed based on clinical findings, suggestive serology and detection of C. burnetii DNA by polymerase chain reaction testing of biopsy samples (8/9). All required surgical management; antibiotic and adjuvant therapies did not appear to be consistently effective and 2 cases had clinical resolution in the absence of directed antimicrobial therapy. CONCLUSIONS: Chronic recurrent multifocal osteomyelitis is a rare manifestation of chronic Q fever infection in children. The pathophysiology of this condition is poorly understood, and effective treatment options have not been established.

Fatigue following Acute Q-Fever: A Systematic Literature Review.

BACKGROUND: Long-term fatigue with detrimental effects on daily functioning often occurs following acute Q-fever. Following the 2007-2010 Q-fever outbreak in the Netherlands with over 4000 notified cases, the emphasis on long-term consequences of Q-fever increased. The aim of this study was to provide an overview of all relevant available literature, and to identify knowledge gaps regarding the definition, diagnosis, background, description, aetiology, prevention, therapy, and prognosis, of fatigue following acute Q-fever. DESIGN: A systematic review was conducted through searching Pubmed, Embase, and PsycInfo for relevant literature up to 26th May 2015. References of included articles were hand searched for additional documents, and included articles were quality assessed. RESULTS: Fifty-seven articles were included and four documents classified as grey literature. The quality of most studies was low. The studies suggest that although most patients recover from fatigue within 6-12 months after acute Q-fever, approximately 20% remain chronically fatigued. Several names are used indicating fatigue following acute Q-fever, of which Q-fever fatigue syndrome (QFS) is most customary. Although QFS is described to occur frequently in many countries, a uniform definition is lacking. The studies report major health and work-related consequences, and is frequently accompanied by nonspecific complaints. There is no consensus with regard to aetiology, prevention, treatment, and prognosis. CONCLUSIONS: Long-term fatigue following acute Q-fever, generally referred to as QFS, has major health-related consequences. However, information on aetiology, prevention, treatment, and prognosis of QFS is underrepresented in the international literature. In order to facilitate comparison of findings, and as platform for future studies, a uniform definition and diagnostic work-up and uniform measurement tools for QFS are proposed.