Q fever: a rare but potentially life-threatening zoonotic disease
- Pranav Mahajan ,
- Kailash Pant and
- Shirin Majdizadeh
- Internal Medicine, Carle Foundation Hospital, Urbana, Illinois, USA
- Correspondence to Dr Pranav Mahajan; pranav71293@gmail.com
Abstract
Q fever can present as a fever of unknown aetiology and can be challenging to diagnose because of the rare incidence. It can present as an acute illness with manifestations, including influenza-like symptoms, hepatitis, pneumonia or chronic disease involving the cardiovascular system. We present a case of a 39-year-old woman in the USA, who developed acute Q fever with associated sepsis and severe hepatitis. She received treatment with recovery from acute infection but currently has symptoms of post Q fever syndrome.
Background
Q fever is a zoonotic disease caused by the organism Coxiella burnetii, which is a potential agent of bioterrorism.1 2 It usually presents as an acute disease, causing mild influenza-like syndrome or hepatitis, but can also cause severe life-threatening illness. Rarely, it presents as a persistent infection, causing endocarditis, or osteomyelitis.3 4 It is one of the rare diseases found in the USA, and the Centers for Disease Control and Prevention(CDC) reported only 153 cases in 2017, out of which 40 cases had chronic disease.
Case presentation
A 39-year-old woman with a medical history of polycystic ovarian syndrome and migraine headaches started experiencing abdominal pain and diarrhoea along with tenesmus during her visit to Morocco. She also began experiencing fevers which would resolve after lasting for 2–3 days but recur in 2 weeks. After returning from a trip to Morocco, her diarrhoea and abdominal pain resolved, but she continued to have on and off fever for 1 month, due to which she presented to the hospital. She had exposure to animals, including sheep and camels, as well as contaminated water and food during her visit. The review of systems was positive for fatigue, myalgia, headache, photophobia, retro-orbital pain and drenching night sweats for 2 months.
Her vital signs revealed a temperature of 37.8°C, pulse rate 100 bpm, respiratory rate of 23 breaths/min, blood pressure 141/89 mm Hg and oxygen saturation 98% on room air. She did not have any other positive pertinent abnormal findings on physical examination.
Investigations
Complete blood count revealed leucopenia with a white cell count of 2.920 x 109 /L, an absolute lymphocyte count of 0.70 x 109 /L, aspartate transaminase (AST) 444 U/L, alanine transaminase (ALT) 428 U/L and increased C-reactive protein (CRP) level of 2.47 mg/dL. Her HIV test, hepatitis A antibody IgM, hepatitis B surface antigen and core antibody IgM, hepatitis C antibody, rapid plasma reagin (for syphilis), Epstein-Barr virus (EBV) antibody testing, urine culture and urine Chlamydia/Gonorrhoea testing were negative. Gastrointestinal pathogen panel (to detect multiple pathogens causing gastrointestinal disease) did not reveal any organism. Blood cultures, stool cultures and Karius digital culture (cell-free DNA-based testing for multiple pathogens) were negative. EBV, cytomegalovirus (CMV), Leptospira, Salmonella, Dengue serology and malaria smear were tested, which were also negative. Anti-nuclear antibodies, rheumatoid factor and cyclic citrullinated peptide antibody levels were within normal limits, but anti-smooth muscle antibody level was positive in the range of 1:80. Lymphoma/ leukaemia analysis was negative. Erythrocyte sedimentation rate was within the normal range, and Tuberculosis QuantiFERON test was negative. She underwent a CT chest/abdomen/pelvis, which did not show any acute pathology. Transthoracic echocardiogram to rule out endocarditis and MRI sacrum to rule out sacroiliitis due to suspicion of brucellosis did not reveal any pathology.
Laboratory workup worsened during the hospital stay showing AST 3875 U/L, ALT 4616 U/L, alkaline phosphatase 178 U/L, T. bilirubin 4.8 mg/dL, direct bilirubin 3.9 mg/dL, gamma-glutamyl transferase 954U/L, lactate dehydrogenase 1722U/L, CRP 1.6 mg/dL and ferritin 3829 ng/mL. Alpha-fetoprotein, ceruloplasmin and alpha-1 antitrypsin were ordered, which were all negative. Salmonella and Brucella serology were negative, but she was positive for phase II IgM and IgG against C. burnetii. Transesophageal echocardiogram did not reveal any evidence of endocarditis.
Differential diagnosis
Fever of unknown aetiology can be due to multiple diseases including infections, autoimmune diseases and malignancies. In this case, differential diagnoses included infections like acute EBV infection, acute CMV infection, acute HIV infection, acute hepatitis A/B, leptospirosis, salmonellosis, brucellosis, Q fever, dengue, malaria and acute endocarditis. Autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis, and malignancies, including acute leukaemia and acute lymphoma, were also included in the differential diagnosis.
Treatment
She was admitted to the hospital, and intravenous fluid hydration was started. Empiric antibiotic therapy was started with doxycycline and intravenous gentamicin for broad spectrum pathogen coverage as recommended by the infectious disease team based on hospital protocol. Her leucopenia and fever resolved, but AST/ALT worsened. Numerous discussions were held with the patient for a possible bone marrow biopsy due to a concern for haemophagocytic lymphohistiocytosis syndrome. On day 6 of hospital stay, Q fever phase II IgM and IgG titers were found to be elevated, in the range of 1:256 and 1:64, respectively. Q fever phase I IgM and IgG titers were not elevated (<1:16). Serum antiphospholipid IgM was also raised at a level of 46.4 MPL (IgM phospholipid units). Gentamicin was discontinued, and hydroxychloroquine was added to doxycycline for treatment of acute Q fever in the presence of elevated antiphospholipid antibody titers. She started improving, and her hepatic function improved as well. She was discharged on oral doxycycline 100 mg two times a day and hydroxychloroquine 100 mg three times a day until outpatient appointment with infectious disease specialist 3 weeks later.
Outcome and follow-up
The patient had an infectious disease outpatient visit 1 month after discharge from the hospital, when the antibiotics were discontinued. Repeat Q fever serology was negative 6 months later. Anti-smooth muscle antibody test was negative as well 8 months later. The patient recovered from acute infection but currently has symptoms related to post Q fever syndrome, including extreme fatigue, night sweats, insomnia and neuropathic pain. She is also scheduled to undergo polysomnography to evaluate for obstructive sleep apnoea as a potential cause of some of these symptoms. She was taking gabapentin, which she later discontinued due to a lack of symptom relief, and duloxetine was added later. She is also being treated for major depressive disorder with bupropion.
Discussion
Q fever is a zoonotic disease caused by the bacteria C. burnetii. It is capable of being transferred long distances by wind, and a 1–2 mile proximity to a livestock reservoir may be sufficient exposure for infection.5 6 It is resistant to heat, desiccation and disinfection. These factors raise the concern of C. burnetii being used as a potential agent of bioterrorism.2 5 6 The most commonly involved animal contacts are cattle, cats, dogs, goats and sheep, but it is also reported to occur from exposure to camel droppings.7 Q fever was included in the list of nationally notifiable infectious diseases for the USA in 1999.
The incubation period for acute infection is approximately 20 days (range 14–39). Symptomatic infection is more likely to occur in adults compared with children and in men compared with women.8–10 In the USA, acute Q fever infection most commonly presents as a influenza-like illness, and rarely as hepatitis or pneumonia, but it can be an asymptomatic infection as well.10 11 Severe manifestations include acute hepatitis, pneumonia and meningoencephalitis. Sometimes Q fever also presents as prolonged fever of unknown origin with characteristic ‘doughnut-like’ granulomas on liver biopsy. Rarely, Q fever can present as acute aseptic meningitis, encephalitis or acute acalculous cholecystitis.11–13
Up to 20% of patients develop a post Q fever fatigue syndrome after acute Q fever, presenting with severe fatigue, headache, myalgias, night sweats, lymphadenopathy, arthralgia, insomnia, depression and impaired short-term memory.14 Serologic evidence of past infection with C. burnetii, but not of chronic disease, is present in these patients. Chronic infection with Q fever in humans is rare, occurring in only 5% of patients after acute Q fever. It can occur months to years after an acute infection, which typically manifests as blood-culture negative endocarditis or infection of a vascular aneurysm or vascular prosthesis.14 15
Supportive laboratory evidence of acute Q fever requires anti-phase II IgG ≥200 for IgG and IgM ≥50 or a fourfold rise in anti-phase II IgG by indirect immunofluorescence assay between serum samples from the acute and convalescent phases taken 3–6 weeks apart. Seroconversion is usually detected 7–15 days after the onset of clinical symptoms. Approximately 90% of patients have detectable antibodies by the third week.16 PCR testing is being used to diagnose patients who are suspected of having an acute infection, but initial serologic testing reveals no or low levels of antibodies.16 The PCR generally remains positive for 7–10 days in acute infection. It is important to note that the Coxiella serology can be positive for a long period of time, including the IgM. However, our case improved with treatment of Q fever, so it is unlikely to be any other pathology.
The approach to treatment for Q fever depends on whether the patient has an acute infection or persistent, localised disease and also on the presence or absence of underlying valvulopathy or cardiomyopathy. In non-pregnant patients without valvulopathy or cardiomyopathy who have symptomatic acute Q fever, we treat with antibiotics to reduce the duration of symptoms. For adults, the first line of treatment is doxycycline 100 mg PO two times a day for 14 days. In case of doxycycline intolerance, minocycline, clarithromycin (500 mg two times a day), fluoroquinolones (ofloxacin 200 mg three times a day or pefloxacin 400 mg two times a day) and co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole two times a day) can be used.17 Pregnant women with acute Q fever should be treated even if they are asymptomatic, with co-trimoxazole two times a day, until the eighth month of pregnancy. For adults with acute Q fever and elevated antiphospholipid antibody titers, prolonged treatment with doxycycline and hydroxychloroquine is recommended to reduce the risk of future complications.18 Most individuals with acute Q fever who have valvulopathy or cardiomyopathy should be administered doxycycline and hydroxychloroquine for 1 year to reduce the risk of developing chronic endocarditis.9 11
For patients receiving treatment for acute Q fever, follow-up should be done by performing serologic testing 3 and 6 months after cessation of therapy to confirm the resolution of acute infection. Monitoring should be extended for those at high risk of developing persistent disease (eg, those with valvulopathy or a vascular graft, pregnant women, immunocompromised hosts).19
Patient’s perspective
After being cleared of an active Q fever infection and going off of the treatment medications, I continued to take the gabapentin that was prescribed in the hospital for pain per the recommendation of my primary care provider. I spoke to the infectious disease, and primary doctor at that time about continued extreme levels of exhaustion, neuropathic nerve pain in my feet, night sweats and lack of sleep, and oedema in my right ankle. These were all symptoms I reported from the summer and during my hospitalisation and they had remained consistent. The infectious disease doctor indicated that these should improve over the next 6 months.
Three months later, I weaned myself off of the gabapentin because I did not feel the medication was helping. All of the symptoms mentioned previously continued to negatively affect quality of life. While hospitalised, a doctor had encouraged me to join an international Facebook support group for people with Q fever. It was through this group that I learnt of post Q fever syndrome or Q fever fatigue syndrome. The limited literature indicated that the symptoms I continued to struggle with matched with this. Many in the support group had started to use Lyme disease protocols to treat the symptoms and I found some relief of the severity of the symptoms with these protocols, the nerve pain being the most improved. The pain and fatigue have been causing limitations that were also causing depression. I had hoped to get a prescription for bupropion to help but due to the COVID-19 closedown was unable to see a medical professional.
During my search for treatments, through the support group, I found an article about the lack of information and testing on Q fever internationally. The article quoted a study focused on the camels in Saudi Arabia and the prevalence of Q fever. Upwards of 50% of camels tested positive. While in Morocco, I went on an overnight trip in the Sahara by camel. The camels followed a specific path that was worn with dropping etc. During the first day of the trip, we were hit with a sandstorm that lasted for the duration of our 4–5 hours of travel to the camp. The wind and animal droppings created the perfect ‘storm’ for a potential infection.
Seven months later, I spoke with the infectious disease doctor about my most recent negative test and mentioned that I was continuing to suffer from symptoms. He suggested looking into the autoimmune issues and said that he would send the recommendation to the primary care provider.
Learning points
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Fever with unknown aetiology has a broad differential diagnosis, including infections like Epstein-Barr virus, Cytomegalovirus, HIV, Salmonella, Brucella, Q fever, autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and malignancies, including leukaemia, lymphoma.
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Transaminitis can occur due to zoonotic diseases like Q fever.
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Coxiella serology, including IgM, can be positive for a long period of time. Improvement with treatment of Q fever excludes other pathologies as etiologies of the disease presentation.
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Adults with acute Q fever and elevated antiphospholipid antibody titers need prolonged treatment with doxycycline and hydroxychloroquine.
Footnotes
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Contributors PM, KP and SM were equally involved in managing the patient during the hospitalisation. PM was mainly involved in acquiring data, analysis and interpretation of data, drafting the case report and revising it critically for important intellectual content. PM was helped by KP to do all the aforementioned tasks. Final approval of this version was provided by SM. PM and KP take responsibility for overall content.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Competing interests None declared.
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Patient consent for publication Obtained.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.
References
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