Acute Coxiella burnetii Infection: A 10-Year Clinical Experience at a Tertiary Care Center in the United States.

Background: Identifying and treating patients with acute Q fever who are at an increased risk of progressing to persistent disease is crucial for preventing future complications. In this study, we share our decade-long clinical experience with acute Q fever, highlighting the challenges that clinicians encounter from making an initial diagnosis and performing risk stratification to determining the appropriate prophylaxis regimen and duration. Methods: We retrieved records of adult Mayo Clinic patients (≥18 years) with positive Coxiella burnetii serology results between 1 January 2012 and 31 March 2022. Patients with Q fever anti-phase II immunoglobulin G ≥1:256 by indirect immunofluorescence were further analyzed. Results: Thirty-one patients were included. Their median age was 58 years (IQR, 50-64), and the majority were men (84%). Acute hepatitis (29%), flu-like illness (25.8%), and pneumonia (16%) were the most common presentations. Thirteen patients (42%) received antibiotic prophylaxis to prevent disease progression, with significant variation in the indications and duration across physicians. The combination of doxycycline and hydroxychloroquine was the preferred regimen. Prophylaxis was administered for a median 333 days (IQR, 168-414). Four patients (13%) progressed to Q fever native valve infective endocarditis, with elevated anticardiolipin immunoglobulin G levels being the sole risk factor in 2 cases. The small sample size precluded drawing conclusions on the impact of prophylaxis in preventing disease progression. Conclusions: Management of acute Q fever is complicated by the lack of comprehensive clinical guidelines leading to varied clinical practices. There is a critical need for randomized trials to establish robust evidence-based protocols for management.

The integration of Coxiella burnetii PCR testing in serum into the diagnostic algorithm of suspected acute Q fever in an endemic setting.

Serum polymerase chain reaction (PCR) for the detection of Coxiella burnetii DNA has been suggested for rapid Q fever diagnosis. We evaluated the role of PCR testing in serum in the diagnosis of acute Q fever in an endemic setting. We examined patients suspected of acute Q fever tested for C. burnetii-specific serum real-time PCR in a tertiary hospital between January 2019 toand December 2022. In the first half, PCR orders were consultation-based by infectious diseases specialists, while in the second half, they were guided by serology, positive IgM2, and negative IgG1 and IgG2, indicating early acute infection. Logistic regression analyzed independent predictors for positive PCR. PCR positivity rates were calculated using various clinical criteria in the diagnostic algorithm. Out of 272 patients, 13 (4.8%) tested positive and 130 exhibited serologically suspected early infection. Presentation during April-July and aspartate aminotransferase (AST) > 3× upper normal limit (UNL) were independently associated with positive PCR with an odds ratio (OR) = 15.03 [95% confidence interval (CI), 1.58-142.46], P = 0.018 and OR = 55.44 [95% CI, 6.16-498.69], P < 0.001, respectively. PCR positivity rate was 8.5% in serologically suspected early infection vs 1.4% in other serology, yielding OR = 6.4 [95% CI, 1.4-29.7], P = 0.009. Adding AST > 3× UNL increased OR to 49.5 [95% CI, 5.9-408.7], P ≤ 0.001 reducing required PCR tests for a single acute Q fever case from 11.8 to 3. Elevated AST in serologically suspected early Q fever is proposed to be used in a diagnostic stewardship algorithm integrating PCR in serum in an endemic setting. IMPORTANCE: Our study suggests in a diagnostic stewardship approach the integration of molecular testing (Coxiella burnetii targeted PCR) for the diagnosis of acute Q fever in a reliable time in the endemic setting. Integrating PCR detecting Coxiella burnetii in serum in routine testing of suspected early acute Q fever based on serology result increased the PCR positivity rate significantly. Adding increased transaminases optimizes PCR utility which is highly requested particularly in endemic areas.

Clinical and Epidemiological Aspects of Acute Q Fever in Reunion Island over Fourteen Years: A Retrospective Cohort Study.

The clinical characteristics and epidemiology of Q fever in the Tropics are poorly described. We performed a retrospective cohort study of hospitalized cases between 2004 and 2017 in Reunion Island. Acute Q fever was defined in presence of a positive serology (phase II IgG ≥ 200 and phase II IgM ≥ 50), or a seroconversion (4-fold increase in phase II IgG between paired samples), or a positive PCR (blood or serum). Forty-two cases matched the diagnostic criteria. The most common clinical manifestations were fever (85.7%) and pulmonary symptoms (61.9%), including pneumonia (45.2%). Ninety percent of the patients were living in a farming area. Cumulative incidence was estimated at 9.3 per 100,000 inhabitants (95%CI: 6.4-12.1) with cases diagnosed yearly all throughout the study period except in 2006. Together with the seroprevalence figures, these data suggest that Q fever reaches low to moderate endemic levels on Reunion Island. As previously reported, pulmonary symptoms are in the foreground.

Case Report of Acute Q Fever with Hepatitis Progressing to Chronic Q Fever with Endocarditis.

A 35-year-old male greenhouse worker presented with myalgia, fatigue, and fever. Initially, he was thought to have an unspecified viral infection and was treated with conservative therapy. However, the patient's symptoms persisted, and he reported additional symptoms of mild abdominal pain and headaches. Laboratory evaluation was significant for elevated liver enzymes. Due to concern for acute hepatitis and persistent fever the patient was hospitalized. During his hospital course, no infectious etiology was found to explain his symptoms. After discharge from the hospital, additional testing showed positive serology for Q fever IgG phase II antibody (1:8192) and phase II antibody IgM (>1:2048). He was treated with doxycycline and had a good clinical response. Upon follow-up, he had worsening Phase I IgG serologies. Transesophageal echo demonstrated vegetations consistent with endocarditis.

Delayed Diagnosis of Acute Q Fever, China.

We report a patient in China with fever of unknown origin who visited 3 hospitals in 3 weeks and was finally given a diagnosis of acute Q fever, determined by metagenomics next-generation sequencing. Our results indicate that physicians are unfamiliar with Q fever and the disease is neglected in China.

Acute multifocal retinitis in a patient with Q fever (Coxiella Burnetii infection) with endocarditis.

OBJECTIVE: To report acute multifocal retinitis in association with serologically-proven Coxiella (C) Burnetii infection (Q fever) with endocarditis. MATERIAL AND METHODS: A single case report documented with multimodal imaging. RESULTS: A 67-year-old cattle breeder presented with a 2-week history of persistent fever, headache, and floaters in both eyes. On examination, his best-corrected visual acuity was 20/20, and there was 1+ vitreous cells in both eyes. Bilateral fundus examination showed multiple small superficial white retinal lesions scattered in the posterior pole and midperiphery associated with a few retinal hemorrhages. These retinal lesions did not stain on fluorescein angiography (FA) and showed focal hyperreflectivity and thickening primarily involving the inner retinal layers on optical coherence tomography (OCT). There also was a band-like hyper-reflective area in the middle retina consistent with paramacular acute middle maculopathy. Transthoracic echocardiogram (TTE) showed a mobile echodensity on the anterior aortic leaflet consistent with a diagnosis of endocarditis. Elisa assays performed on paired serum samples collected 2 weeks apart showed increase in antibodies against C burnetii from 60 IU/ml to 255 IU/ml. The patient was treated with doxycycline 100 mg twice a day for 18 months, with subsequent resolution of the endocarditis. Sequential ocular examinations showed gradual resolution of all acute retinal findings without visible scars. CONCLUSION: Acute Q fever, caused by C burnetii infection, should be considered in the differential diagnosis of acute multifocal retinitis. A systematic cardiac assessment with echocardiography is essential for early diagnosis of associated endocarditis and for prompt administration of appropriate antibiotic treatment to improve clinical outcomes.

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.

Still New Chronic Q Fever Cases Diagnosed 8 Years After a Large Q Fever Outbreak.

BACKGROUND: Chronic Q fever usually develops within 2 years after primary infection with Coxiella burnetii. We determined the interval between acute Q fever and diagnosis of chronic infection, assessed what factors contribute to a longer interval, and evaluated the long-term follow-up. METHODS: From 2007 to 2018, patients with chronic Q fever were included from 45 participating hospitals. The interval between acute and chronic infection was calculated in patients with a known day of first symptoms and/or serological confirmation of acute Q fever. Chronic Q fever-related complications and mortality were assessed by 2 investigators based on predefined criteria. RESULTS: In total, 313 (60.3%) proven, 81 (15.6%) probable, and 125 (24.1%) possible chronic Q fever patients were identified. The date of acute Q fever was known in 200 patients: in 45 (22.5%), the interval was longer than 2 years, with the longest observed interval being 9.2 years. Patients in whom serological follow-up was performed after acute Q fever were diagnosed less often after this 2-year interval (odds ratio, 0.26; 95% confidence interval, 0.12-0.54). Chronic Q fever-related complications occurred in 216 patients (41.6%). Chronic Q fever-related mortality occurred in 83 (26.5%) of proven and 3 (3.7%) of probable chronic Q fever patients. CONCLUSIONS: Chronic Q fever is still being diagnosed and mortality keeps occurring 8 years after a large outbreak. Intervals between acute Q fever and diagnosis of chronic infection can reach more than 9 years. We urge physicians to perform microbiological testing for chronic Q fever even many years after an outbreak or acute Q fever disease.

Q Fever Endocarditis and a New Genotype of Coxiella burnetii, Greece.

Underdiagnosis of Coxiella burnetii infections in Greece is possible because of lack of awareness by physicians, and most suspected cases are in patients with no bovine contact. We found serologic evidence of C. burnetii infection throughout Greece and identified a new C. burnetii genotype in the aortic valve of a patient with Q fever endocarditis.

Clinical characteristics of acute Q fever patients in South Korea and time from symptom onset to serologic diagnosis.

BACKGROUND: Acute Q fever usually presents as a nonspecific febrile illness, and its occurrence is rapidly increasing in South Korea. This study investigated the clinical characteristics of acute Q fever patients in South Korea and the time from symptom onset to serologic diagnosis. The clinical courses were examined according to antibiotic treatment. METHODS: Data of patients diagnosed with acute Q fever at Chungbuk National University Hospital between January 2015 and February 2018 were retrospectively collected. Demographic and epidemiologic data were reviewed. The time from symptom onset to serologic diagnosis by an immunofluorescence assay (IFA) was analyzed. Clinical courses and the percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) were compared between patients administered antibiotics with anti-Coxiella burnetii activity and patients not administered such antibiotics. RESULTS: Forty-eight patients (median age: 51.5 years) were included. Most were male (95.8%) and had no history of animal contact (91.7%). The median time from illness onset to serologic diagnosis was 21 days. Thirty-nine patients received antibiotics with anti-C. burnetii activity. The length of hospital stay and fever duration did not significantly differ between patients who received antibiotics with anti-C. burnetii activity (7 and 15 days) and those who did not (5 and 8 days) (P = 0.110 and P = 0.137, respectively). The percentage of patients with a high phase I immunoglobulin G titer (≥ 1:1024) did not significantly differ between patients who received antibiotics with anti-C. burnetii activity and those who did not (P = 0.340). CONCLUSIONS: Most acute Q fever patients had a nonspecific febrile illness with mild elevation of transaminases and no history of animal contact or occupational risk. The time from symptom onset to a positive IFA test was longer than the fever duration in most acute Q fever patients. Consequently, it may be difficult for clinicians to serologically diagnose acute Q fever. However, inappropriate antibiotic treatment was not associated with prolongation of symptoms or progression to chronic Q fever.

Acute kidney injury in acute Q fever.

Coxiella burnetii infection is not known to involve directly the kidneys. Kidney injury associated with Q fever usually manifests in the setting of chronic infection or endocarditis with development of immune complex deposition. Acute kidney injury (AKI) in the context of acute Q fever infection may be more pathologically heterogeneous. We describe two cases of severe AKI secondary to acute Q fever infection, each with marked differences in pathological characteristics, and clinical course.

Notification data and criteria during a large Q-fever epidemic reassessed.

From 2007 to 2010, the largest reported Q-fever epidemic occurred in the Netherlands with 4026 notified laboratory-confirmed cases. During the course of the epidemic, health-seeking behaviour changed and awareness among health professionals increased. Changes in laboratory workflows were implemented. The aim of this study was to analyse how these changes instigated adjustments of notification criteria and how these adjustments affected the monitoring and interpretation of the epidemic. We used the articles on laboratory procedures related to the epidemic and a description of the changes that were made to the notification criteria. We compared the output of a regional laboratory with notifications to the regional Public Health Service and the national register of infectious diseases. We compared the international notification criteria for acute Q-fever. Screening with ELISA IgM phase II and PCR was added to the diagnostic workflow. In the course of the epidemic, serology often revealed a positive IgG/IgM result although cases were not infected recently. With increasing background seroprevalence, the presence of IgM antibodies can only be suggestive for acute Q-fever and has to be confirmed either by seroconversion of IgG or a positive PCR result. Differences in sero-epidemiology make it unlikely that full harmonisation of notification criteria between countries is feasible.

Detection of Coxiella burnetii Using Silicon Microring Resonator in Patient Blood Plasma.

Blood plasma from patients is a powerful resource for diagnosing infectious disease due to it having many genetic materials as well as being relatively easy to obtain. Thus, various biosensors have been investigated for diagnosing diseases in blood plasma. However, there are no optimized and validated sensors for clinical use due to the low sensitivity, complexity, and difficulties of removing the inhibitors from plasma samples. In this study, we described a silicon microring resonator sensor used to detect Coxiella burnetii from the blood plasma of Q-fever patients in a label-free, real-time manner. Q-fever is an infectious disease caused by Coxiella burnetii via direct contact or inhalation aerosols. We validated this biosensor in the blood plasma of 35 clinical samples (including 16 Q fever samples infected with Coxiella burnetii and 19 samples infected with other febrile diseases. The biosensors are capable of rapid (10 min), highly sensitive (87.5%), and specific (89.5%) detection in plasma samples compared to the use of the conventional method.

Characteristics of scrub typhus, murine typhus, and Q fever among elderly patients: Prolonged prothrombin time as a predictor for severity.

BACKGROUND/PURPOSE: The clinical manifestations of scrub typhus, murine typhus and acute Q fever in the elderly are not clear. METHODS: We conducted a retrospective study to identify the characteristics of the elderly aged ≥65 years with a comparison group aged 18-64 years among patients with scrub typhus, murine typhus, or acute Q fever who were serologically confirmed at three hospitals in Taiwan during 2002-2011. RESULTS: Among 441 cases, including 187 cases of scrub typhus, 166 acute Q fever, and 88 murine typhus, 68 (15.4%) cases were elderly patients. The elderly had a higher severe complication rate (10.3% vs. 3.5%, p = 0.022), but did not have a significantly higher mortality rate (1.47% vs. 0.54%, p = 0.396). Compared with those without severe complications, we found the elderly (p = 0.022), dyspnea (p = 0.006), less relative bradycardia (p = 0.004), less febrile illness (p = 0.004), prolonged prothrombin time (PT) (p = 0.002), higher levels of initial C-reactive protein (p = 0.039), blood leukocyte counts (p = 0.01), and lower platelet counts (p = 0.012) are significantly associated with severe complications. Only prolonged prothrombin time was associated with severe complications in multivariate analysis (p = 0.018, CI 95% 0.01-0.66). Among clinical symptoms and laboratory data, multivariate analysis revealed chills was less frequently occurred in the elderly (p = 0.012, 95% confidence interval [CI]: 1.33-9.99). CONCLUSION: The elderly cases with scrub typhus, murine typhus, or acute Q fever would be more likely to have severe complications, for which prothrombin time prolongation is an important predictor for severe complications.

Autoimmunity and B-cell dyscrasia in acute and chronic Q fever: A review of the literature.

Q fever infection can lead to chronic Q fever, a potentially lethal disease occurring in 1-5% of patients infected with Coxiella burnetii, characterized by the persistence of this intracellular bacterium. It usually presents as endocarditis, infected vascular aneurysms, or infected vascular prostheses. This systematic review of the literature discusses the various autoimmune syndromes and B-cell dyscrasias in acute and chronic Q fever patients, that may interfere with or impede recognition and diagnosis of Q fever. Reportedly, high concentrations of anti-cardiolipin antibodies may be found in acute Q fever patients, while specifically cardiac muscle antibodies have been reported during chronic Q fever. Systemic lupus erythematosus and antiphospholipid syndrome are the most frequently reported autoimmune syndromes, followed by neuromuscular disorders and vasculitis. B-cell dyscrasia, mostly cryoglobulinaemia, is predominantly described in chronic Q fever patients with endocarditis. We conclude that immunological (epi)phenomena are not rare during Q fever and may obscure the infectious etiology of the disease.

A case of Q fever with erythema nodosum.

BACKGROUND: Acute Q fever is asymptomatic in 60% of the patients, while the reminder may present with fever, pneumoniae, and hepatitis. Skin manifestations are uncommon including transient punctiform rashes, purpuric, or maculopapular eruptions. Erythema nodosum have seldom been reported. CASE PRESENTATION: A 37-year-old female presented with fever for 1 month and skin lesions consists of erythematous painful nodule of the legs. Serological testing for Coxiella burnetii was positive. Treatment consisted with doxycycline for 2 weeks. Evolution was favorable. The patient completely recovered and had no evidence of skin lesion 1 month later. CONCLUSION: Because of its nonspecific clinical presentation, Q fever with erythema nodosum is probably underestimated. Q fever should be evocated when facing unexplained erythema nodosum even if there is not other typical clinical manifestation of Q fever.

Pulmonary manifestations of Q fever: analysis of 38 patients.

BACKGROUND: Lung involvement in both acute and chronic Q fever is not well described with only a few reported cases of pseudotumor or pulmonary fibrosis in chronic Q fever. The aim of this study was to better understand the pulmonary manifestations of Q fever. METHODS: We conducted a retrospective cohort study of patients with diagnosis of Q fever at Mayo Clinic Rochester. A total of 69 patients were initially identified between 2001 and 2014. Thirty-eight patients were included in this study as 3 were pediatric patients, 20 did not meet serologic criteria for Q fever, and 8 did not have imaging available at time of initial diagnosis. Descriptive analysis was conducted using JMP software. RESULTS: The median age was 57 years [interquartile range (IQR) 43, 62], 84% from the Midwest, and 13% worked in an occupation involving animals. The most common presentation was fevers (61%). Respiratory symptoms, such as cough, were noted in only 4 patients (11%). Twelve patients (29%) had abnormal imaging studies attributed to Q fever. Three patients (25%) with acute Q fever had findings of consolidation, lymphadenopathy, pleural effusions, and nonspecific pulmonary nodules. Radiographic findings of chronic Q fever were seen in 9 patients (75%) and included consolidation, ground-glass opacities, pleural effusions, lymphadenopathy, pulmonary edema, and lung pseudotumor. CONCLUSIONS: Our results demonstrate that pulmonary manifestations are uncommon in Q fever but include cough and consolidation for acute Q fever and radiographic findings of pulmonary edema with pleural effusions, consolidation, and pseudotumor in those with chronic Q fever.

Presentation and diagnosis of acute Q fever in Portugal - A case series.

Q fever is a worldwide zoonotic infection caused by the obligate intracellular bacterium Coxiella burnetii that can course with acute or chronic disease. This series describes 7 cases of acute Q fever admitted in a Portuguese University Hospital between 2014 and 2015. All cases presented with hepatitis and had epidemiological history. Diagnosis was done by PCR on majority (5) and by serology and PCR in only 2. Serological tests can be negative in the initial period of the disease. Molecular biology methods by polymerase chain-reaction are extremely important in acute disease, allowing timely diagnosis and treatment.

Differentiation of Acute Q Fever from Other Infections in Patients Presenting to Hospitals, the Netherlands

Differentiating acute Q fever from infections caused by other pathogens is essential. We conducted a retrospective case-control study to evaluate differences in clinical signs, symptoms, and outcomes for 82 patients with acute Q fever and 52 control patients who had pneumonia, fever and lower respiratory tract symptoms, or fever and hepatitis, but had negative serologic results for Q fever. Patients with acute Q fever were younger and had higher C-reactive protein levels but lower leukocyte counts. However, a large overlap was found. In patients with an indication for prophylaxis, chronic Q fever did not develop after patients received prophylaxis but did develop in 50% of patients who did not receive prophylaxis. Differentiating acute Q fever from other respiratory infections, fever, or hepatitis is not possible without serologic testing or PCR. If risk factors for chronic Q fever are present, prophylactic treatment is advised.