Delayed diagnosis of persistent Q fever: a case series from China.

BACKGROUND: Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. CASE PRESENTATION: We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period. CONCLUSION: Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii.

Acute Q fever pneumonia diagnosed by metagenomic next-generation sequencing.

INTRODUCTION: Q fever, a zoonotic disease caused by Coxiella burnetii (C. burnetii), presents diagnostic challenges due to its clinical and radiological nonspecificity, which often mimics community-acquired pneumonia, coupled with the limitations of traditional diagnostic methods. Metagenomic next-generation sequencing (mNGS) has become an indispensable tool in clinical diagnostics for its high-throughput pathogen identification capabilities. Herein, we detail a case of acute Q fever pneumonia diagnosed with mNGS. CASE PRESENTATION: The patient exhibited symptoms of fever, cough, expectoration, and diarrhea for three days, with the pathogen undetected in initial laboratory assessments. Bronchoscopy and bronchoalveolar lavage (BAL) were conducted, leading to the identification of C. burnetii in the lavage fluid via mNGS. Consequently, the patient was promptly initiated on a treatment regimen of 100 mg doxycycline, administered orally every 12 hours. RESULTS: Post-treatment, the patient's temperature normalized, and a full recovery was observed. The follow-up chest CT scan revealed complete resolution of the right lower lobe consolidation. CONCLUSIONS: The clinical presentation of Q fever pneumonia lacks specificity, making diagnosis based solely on symptoms and imaging challenging. mNGS offers a superior alternative for identifying elusive or rarely cultured pathogens.

Molecular and serological diagnosis of multiple bacterial zoonoses in febrile outpatients in Garissa County, north-eastern Kenya.

Bacterial zoonoses are diseases caused by bacterial pathogens that can be naturally transmitted between humans and vertebrate animals. They are important causes of non-malarial fevers in Kenya, yet their epidemiology remains unclear. We investigated brucellosis, Q-fever and leptospirosis in the venous blood of 216 malaria-negative febrile patients recruited in two health centres (98 from Ijara and 118 from Sangailu health centres) in Garissa County in north-eastern Kenya. We determined exposure to the three zoonoses using serological (Rose Bengal test for Brucella spp., ELISA for C. burnetti and microscopic agglutination test for Leptospira spp.) and real-time PCR testing and identified risk factors for exposure. We also used non-targeted metagenomic sequencing on nine selected patients to assess the presence of other possible bacterial causes of non-malarial fevers. Considerable PCR positivity was found for Brucella (19.4%, 95% confidence intervals [CI] 14.2-25.5) and Leptospira spp. (1.7%, 95% CI 0.4-4.9), and high endpoint titres were observed against leptospiral serovar Grippotyphosa from the serological testing. Patients aged 5-17 years old had 4.02 (95% CI 1.18-13.70, p-value = 0.03) and 2.42 (95% CI 1.09-5.34, p-value = 0.03) times higher odds of infection with Brucella spp. and Coxiella burnetii than those of ages 35-80. Additionally, patients who sourced water from dams/springs, and other sources (protected wells, boreholes, bottled water, and water pans) had 2.39 (95% CI 1.22-4.68, p-value = 0.01) and 2.24 (1.15-4.35, p-value = 0.02) times higher odds of exposure to C. burnetii than those who used unprotected wells. Streptococcus and Moraxella spp. were determined using metagenomic sequencing. Brucellosis, leptospirosis, Streptococcus and Moraxella infections are potentially important causes of non-malarial fevers in Garissa. This knowledge can guide routine diagnosis, thus helping lower the disease burden and ensure better health outcomes, especially in younger populations.

Acute Q fever revealed by an anti-phospholipid syndrome: A case report.

INTRODUCTION: Q fever is a zoonosis caused by Coxiella burnetii. Acute infection is mainly asymptomatic. In other cases it mainly causes a flu-like illness, a pneumonia, or an hepatitis. We present an atypical case of an acute Q fever revealed by a massive pleural effusion. CASE REPORT: We report the case of a 43-year-old man referred to our hospital for an acute respiratory distress. Further analyses showed an exudative eosinophilic pleural effusion, associated with a pulmonary embolism and a deep femoral vein thrombosis. Aetiologic explorations revealed an acute Q fever (IgM and IgG against C. burnetii phase II antigens) associated with anti-phospholipids. The outcome was favorable with vitamin K antagonists, doxycycline, and hydroxychloroquine, till the negativation of the anti-phospholipid antibodies. DISCUSSION AND CONCLUSION: During acute C. burnetii infections, anti-phospholipid antibodies are highly prevalent but thrombotic complications are rare. The 2023 ACR/EULAR APS criteria restricts the diagnosis of APS, as in our case of acute severe infection. In front of an atypical pneumonia and/or thrombotic events, screening of C. burnetii and anti-phospholipid antibodies could be useful. Given its low level of evidence, prolongated treatment by doxycycline, hydroxychloroquine ± anticoagulant for C. burnetii's associated anti-phospholipid syndrome is discussed, but succeeded in our case.

Southern Queensland general practitioners' knowledge and attitudes towards Q fever and behaviours in the management of the disease.

BACKGROUND AND OBJECTIVES: Q fever (QF) is a zoonotic disease caused by Coxiella burnetii, often associated with abattoir workers and farmers. Recent analysis suggests that QF might occur more frequently in urban areas. This study ascertains the knowledge of, and attitudes towards, QF and behaviours in the management of QF among general practitioners (GPs) across rural and urban areas. METHOD: This cross-sectional survey study targeted GPs working in regional Queensland. GPs were asked to complete a 59-item questionnaire. Logistic regression was used to compare respondent demographics with attitude ratings and knowledge scores. RESULTS: Diagnosing a patient with QF was significantly related to practitioner age, years in practice and practising in a rural area. DISCUSSION: This study shows gaps in GP QF knowledge, particularly around QF management. With increased urbanisation of rural areas potentially leading to increases in acute QF cases, GPs need to improve their knowledge of this disease.

A case report of Vancomycin in the treatment of Q fever endocarditis.

The patient, a 43-year-old male, was admitted to the hospital with gradually aggravated exertional palpitations and chest tightness over a 2-day period. Upon hospital admission, a cardiac ultrasound revealed aortic valve redundancy, however multiple blood culture investigations came back negative. Blood mNGS was perfected, revealing Coxiella burnetii, and the diagnosis of Q fever (query fever) was established. The temperature and inflammatory indices of the patient were all normal with the treatment of vancomycin before cardiac surgery. But for the potential liver damage of and the Coxiella burnetii was still positive in the anti-phase II IgG titer, the doxycycline and hydroxychloroquine instead of vancomycin were applied for the patient. Despite receiving standardized anti-infective therapy of doxycycline combined with hydroxychloroquine, this patient had fever and increased leukocytes following surgery. After the addition of vancomycin as an anti-infective treatment, the temperature and leukocytes improved quickly. During the treatment of vancomycin, a discovery of liver injury may have resulted. These findings provide new therapy options for future professionals.

Q Fever-Associated Chorioretinitis.

Coxiella burnetii is the causative agent in Q fever, a zoonotic disease. Ocular manifestations of this disease are extremely rare and have been infrequently reported. In this report, we describe a rare case of chorioretinitis in a patient incompletely treated for Q fever. We highlight the unique ocular manifestation with multimodal imaging, and the importance of a thorough history and prompt and correct treatment of the disease with systemic therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:412-414.].

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.

The Prognostic Value of Serology in Persistent Q Fever Infection.

Background: Q fever has significant consequences for patients with persistent localized infection. A combination of doxycycline with hydroxychloroquine, for at least 18-24 months, is the first-line therapy. The use of serology as a prognostic marker during therapy is controversial. Methods: A retrospective, observational cohort study in two outpatient clinics in northern Israel. All adults with persistent Q fever (2015-2021) were included in the study. Clinical failure was defined as relapse or death related to Q fever after end of treatment (EOT). Serological cure was defined as phase 1 IgG ≤800 or a four-fold decrease at EOT. Results: Twenty-two patients were included in the study, with a median follow up of 40 months (IQR = 28.5-63.5), and median treatment duration of 28.5 months (IQR = 21.8-50.5). Clinical cure occurred in 18 patients (82%), serological cure in 10 (45%). Phase 1 IgG at presentation was significantly higher in the clinical failure group (median 9600 vs. 3200 in the clinical cure group, p = 0.019), and at 6-12 months after EOT (median 6400 vs. 800 respectively, p = 0.03). Phase 1 IgG levels at 1 year and EOT were similar in both groups. Positive phase 2 IgM after one year of therapy correlated with clinical failure (p = 0.038), but not at EOT or after EOT. Conclusion: Phase 1 IgG levels at presentation, phase 2 IgM at 1 year, and Phase 1 IgG 6-12 months after EOT were associated with clinical failure in patients with persistent Q fever.

Increased recognition of Q fever aortitis as a chronic manifestation of Q fever in tropical North Queensland, Australia.

Aortitis is a life-threatening, manifestation of chronic Q fever. We report a series of 5 patients with Q fever aortitis who have presented to our hospital in tropical Australia since 2019. All diagnoses were confirmed with polymerase chain reaction (PCR) testing of aortic tissue. Only one had a previous diagnosis of acute Q fever, and none had classical high-risk exposures that might increase clinical suspicion for the infection. All patients underwent surgery: one died and 3 had significant complications. Q fever aortitis may be underdiagnosed; clinicians should consider testing for Coxiella burnetii in people with aortic pathology in endemic areas.

Detection of Coxiella antibodies in ruminants using a SucB recombinant antigen.

The detection of Coxiella burnetii in ruminants remains challenging despite the use of new technology and the accumulation of novel knowledge. Serology tools, the primary methods of infection surveillance in veterinary medicine, have limitations. We used recombinant antigen production to develop an ELISA based on the SucB protein, one of the major immunodominant antigens described in humans and laboratory animals. We produced the antigen successfully in an Escherichia coli heterologous system, confirmed by sequencing and mass spectrometry, and seen as a band of ~50 kDa in SDS-PAGE and on western blot analysis. We compared the performance of the recombinant ELISA with a commercial ELISA. We observed agreement of 83.5% and a substantial Cohen κ value of 0.67 in our pilot study.

Coxiella burnetii infection in a patient with tick bite.

INTRODUCTION: We report the case of a 60-year-old male who was hospitalized with fever, headache, fatigue, nausea, and myalgia for six days. METHODOLOGY: Polymerase chain reactions (PCR) were performed on patient blood samples, and four ticks were collected from the area the patient mowed. Indirect immunofluorescence assays (IFAs) were performed on serum samples to detect specific antibodies. RESULTS: The collected ticks were identified as Haemaphysalis longicornis. Coxiella species-specific nested PCR (N-PCR) and sequencing confirmed the presence of Coxiella burnetii in the patient, and Coxiella-like bacteria were identified in three of the four ticks. IFA results showed ≥ 4-fold increases in both IgM and IgG antibody titers against Q fever. CONCLUSIONS: Despite positive PCR results for Coxiella species in both the patient and the ticks, different bacterial species were isolated, suggesting that the patient was not infected with C. burnetii through tick bites. Further investigation is required to identify the carriers or transmitters of the infection.

Pediatric Acute Q Fever in Rural Wisconsin: A Case Report.

INTRODUCTION: Q fever is a zoonotic disease with a variable clinical presentation and potentially fatal complications. While rare, it is more common in rural areas due to its transmission from animals, including cattle. CASE PRESENTATION: A 3-year-old boy presented in December 2020 with intermittent fevers, headache, rash, and lymphadenopathy. After several months of symptoms, he was diagnosed with acute Q fever. DISCUSSION: This case demonstrates the importance of considering Q fever in the differential diagnosis when a patient presents with nonspecific infectious symptoms and an epidemiological link that places them at risk. CONCLUSIONS: While rare, Q fever is a potentially serious infection that can affect people living in Wisconsin's rural farming communities.

A retrospective analysis of Q fever osteomyelitis in children, with recommendations.

Osteomyelitis in children due to Q fever is a rare occurrence. In this study, we review 25 pediatric cases of this disease entity. The mean age of these 25 patients was 3.7years (range, 2-7 years). The risk factor for infection was history of contact with animals, such as cattle and sheep (23/25, 92.0%). The most common sites of infection were foot and ankle (12/25, 48.0%). The diagnosis of Q fever was confirmed by serologic testing in 25 children. On PCR, Coxiella burnetii was detected in 17 cases and it was not detected in the remaining five cases. A total of 22 children were treated with antibiotics, of which 15 received surgical treatment. The composition and duration of treatment varied greatly. Only 18 patients achieved significant recovery of joint mobility after drug and/or surgical treatment. Our current literature review show that the clinical manifestations of Q fever osteomyelitis in children are atypical. In the absence of serological test results, mNGS identification may be a good option. Compared with the guidelines that recommend doxycycline combined with hydroxychloroquine, we recommend that ciprofloxacin-based treatment combined with rifampicin or sulfamethoxazole/trimethoprim should be preferred in children under the age of 8 years, and the need for performing combined surgical debridement and determining the treatment duration should be evaluated according to their actual clinical situation.

Q fever represented as multiple pulmonary nodules: a case report.

Q fever is an important zoonotic disease caused by the pathogen Coxiella burnetii, which is inhaled into the body through the respiratory tract leading to acute symptoms. Severe acute Q fever may result in complications, such as pneumonia, hepatitis, or myocarditis, and some patients may develop chronic Q fever after incomplete treatment. Local persistent C. burnetii infection may lead to chronic Q fever that often requires surgery and anti-infection treatment for several years, seriously endangering patient health and increasing the economic burden for families. The clinicians' lack of awareness of the disease may be one reason leading to a delay in treatment. Here, a case of Q fever in a 53-year-old male patient, which was diagnosed by next generation sequencing and exhibited a distinct computed tomographic feature, is reported, with the aim of improving clinical knowledge of this disease. Following diagnosis, the patient was treated with 0.1 g doxycycline, orally, twice daily, and 0.5 g chloramphenicol, orally, three times daily, leading to improvement of symptoms and discharge from hospital.

Overview of Q fever in Brazil: an underestimated zoonosis.

This review aims to provide current information about Q fever, elucidating the etiological, epidemiological, pathogenic, clinical, diagnostic, therapeutic, and prophylactic aspects of the disease for the medical community. We discuss the main forms of presentation of the agent, its ability to persist in the body, the infinite possibilities of susceptible hosts, the main known forms of transmission, its importance in populations at occupational risk, and the role of arthropods in the natural history of the disease. Focusing on Brazil, we present the cases already described and studies developed since its first report, and how there is still much to unravel. We are aware of the possibilities of the persistence of the agent and the development of severe clinical pictures and the specific treatments currently instituted. We also wish to raise awareness about the future, the new genotypes that are emerging, the need to study the effects of vaccines, and the impact of Q fever on the population. Q fever is a poorly understood disease in Latin America, and recent studies, especially in Brazil, have revealed the importance of developing new studies.

Erythema exudativum multiforme-like exanthema in a patient with Q fever: a case report and literature review.

Q fever is a rare worldwide zoonosis, caused by the rickettsial bacteria Coxiella burnetii. There are many clinical manifestations of infection, but the most common ones are fever, atypical pneumonia, and/or liver disease. Cutaneous involvement, however, is not a typical feature of Q fever, but it is nevertheless present in up to 20% of cases. We present a 42-year-old male patient with Q fever and erythema exudativum multiforme (EEM)-like parainfectious exanthema, which to the best of our knowledge has not been described before. We recommend considering Coxiella burnetii infection in the differential diagnosis of an EEM-like rash in a patient with an unexplained or "query" fever.