Zoonotic and Vector-Borne Infections — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mr William Baxter, 58 years old, abattoir worker, regional New South Wales. [1]

Presenting complaint: Four weeks of intermittent fevers (up to 38.5 degrees Celsius), drenching night sweats that soak the sheets, progressive fatigue, and a 5 kg unintentional weight loss (from 85 to 80 kg). [1]

Past history: Bicuspid aortic valve disease, with bioprosthetic aortic valve replacement 4 years ago. Hypertension (on perindopril 5 mg daily). No known drug allergies. Never smoked. Drinks 10 standard drinks per week. [1]

Occupational history: Has worked in the local abattoir (sheep and cattle processing) for 22 years. Has never received the Q fever vaccine. No recent travel outside Australia. [1]

Examination findings (trainee elicits):

• Thin but comfortable. Febrile at 38.3 degrees Celsius. Pulse 88, blood pressure 128 over 72, respiratory rate 18, oxygen saturation 97 per cent on room air.
• Cardiovascular: soft early diastolic murmur at the left sternal edge, no radiation. No signs of heart failure.
• Three splinter haemorrhages in the fingernail beds. No Osler nodes, Janeway lesions or Roth spots.
• Abdomen: spleen palpable 3 cm below the costal margin. Liver not enlarged. No ascites.
• No peripheral oedema. No focal neurological deficit. [1]

Investigations (available results):

• Full blood count: Hb 105 (normocytic, normochromic), WCC 7.8, platelets 180.
• ESR 85, CRP 62.
• U and E: normal. LFTs: normal except mildly elevated globulins (42 g per litre).
• Three sets of blood cultures over 48 hours: negative.
• Transthoracic echocardiography: small (7 mm) vegetation on the prosthetic aortic valve. Left ventricular function normal. No perivalvular abscess identified on TTE (TOE requested). [1]

Drug chart (current): perindopril 5 mg daily, paracetamol as needed. [1]

Candidate's structured presentation (model)

Opening statement (SASPOP): [1]

"Mr Baxter is a 58-year-old abattoir worker presenting with a four-week history of intermittent fevers, drenching night sweats, fatigue and a 5 kg weight loss. He has a bioprosthetic aortic valve replacement performed 4 years ago for bicuspid aortic valve disease. His main problems are: first, culture-negative endocarditis on a prosthetic aortic valve — the leading diagnosis is chronic Q fever (Coxiella burnetii), given his 22-year abattoir occupation, the culture-negative blood cultures, the small prosthetic valve vegetation, and the subacute course with splenomegaly and splinter haemorrhages; second, the constitutional decline with normocytic anaemia and elevated inflammatory markers; and third, the occupational health and public health dimensions of the Q fever diagnosis. My immediate priority is the aetiological diagnosis — I would send Coxiella phase I and phase II serology, Bartonella and Brucella serology, repeat blood cultures with extended incubation, and perform a transoesophageal echocardiogram. If the diagnosis is confirmed, I would start doxycycline plus hydroxychloroquine for at least 24 months." [1]

Management plan: [1]

1. Confirm the aetiological diagnosis — Coxiella burnetii phase I and phase II serology by immunofluorescence (the phase I IgG titre above 1:800 is diagnostic of chronic Q fever and is a major Duke criterion). Send Bartonella henselae and B. quintana serology, Brucella serology, and 16S rRNA PCR on blood. Repeat blood cultures with prolonged incubation (up to 21 days). Perform transoesophageal echocardiography to characterise the prosthetic valve and exclude perivalvular complications.
2. Start treatment once the diagnosis is confirmed (or empirically if the clinical picture is highly suggestive and the patient is deteriorating) — doxycycline 100 mg twice daily plus hydroxychloroquine 200 mg three times daily for at least 24 months (the prosthetic valve duration). Monitor doxycycline plasma levels (target above 5 micrograms per mL). Baseline and annual ophthalmic review for hydroxychloroquine.
3. Monitor response — serial phase I and phase II serology every 3 to 6 months (aiming for a declining phase I IgG titre), serial echocardiography, and clinical assessment (defervescence, resolution of night sweats, weight recovery, falling inflammatory markers).
4. Assess for surgical intervention — valve surgery is required for heart failure, perivalvular abscess or prosthetic dehiscence, or failure of medical therapy. Even if surgery is required, it must be accompanied by prolonged antibiotic therapy before and after.
5. Notify public health — Q fever is a notifiable disease. The public health unit should be notified.
6. Occupational health — assess the abattoir for Q fever risk. Offer serological screening to colleagues. Recommend Q-VAX vaccination (with mandatory pre-vaccination screening) for seronegative workers.
7. Supportive care — monitor for Q fever fatigue syndrome, provide nutritional support, and arrange occupational rehabilitation. [1]

Communication and shared decision-making: Explain to Mr Baxter that the most likely diagnosis is Q fever — an infection he almost certainly acquired through his work in the abattoir, by inhaling organisms from the animals he handles. Explain that Q fever can settle on heart valves, especially prosthetic valves, and that the treatment is long (at least 2 years) but effective. Surface the occupational health implications early — the diagnosis has implications for his colleagues and his workplace. Address his likely concerns about his livelihood and whether he can continue working in the abattoir. [1]

Examiner discussion questions

Q1: "Walk me through your interpretation of the culture-negative endocarditis and how it drives the diagnostic plan." [1]

"Mr Baxter has culture-negative endocarditis — three sets of blood cultures over 48 hours are negative in a patient with clear clinical and echocardiographic evidence of endocarditis. The classic teaching is that culture-negative endocarditis mandates consideration of the fastidious and intracellular organisms that do not grow on routine media: Coxiella burnetii, Bartonella, Brucella, and the HACEK group. The exposure history then directs the diagnostic focus. Mr Baxter's 22-year career as an abattoir worker puts him at the highest occupational risk for Q fever — C. burnetii reaches enormous concentrations in the placenta and birth fluids of sheep and cattle, and the organism is extremely stable in the environment. The prosthetic valve is the specific risk factor for chronic Q fever, which typically presents months to years after an often-unrecognised acute infection. The single most important test is Coxiella phase I and phase II serology — a phase I IgG titre above 1:800 confirms chronic Q fever and is a major Duke criterion. I would send Bartonella and Brucella serology in parallel, and I would repeat blood cultures with prolonged incubation to exclude HACEK. A transoesophageal echocardiogram would characterise the vegetation and look for perivalvular complications." [1]

Q2: "Why hydroxychloroquine? Explain the pharmacological rationale." [1]

"Coxiella burnetii is an obligate intracellular pathogen that survives within the phagolysosome — the acidic, enzyme-rich compartment of the macrophage. The acidic pH protects the organism, because doxycycline is only bacteriostatic at low pH. Hydroxychloroquine is a lysosomotropic weak base that accumulates in the phagolysosome and raises the pH, alkalinising the compartment. This restores the bactericidal activity of doxycycline, converting a bacteriostatic regimen into a bactericidal one. Raoult and colleagues demonstrated that the doxycycline-hydroxychloroquine combination achieved a lower relapse rate (less than 10 per cent versus approximately 20 per cent for doxycycline-ofloxacin) and a shorter treatment duration [1]. The practical implication is that treating chronic Q fever endocarditis with doxycycline alone gives a high failure rate — the combination is mandatory."

Q3: "He has never received the Q fever vaccine. Why not, and what does this tell us about the Australian Q fever vaccination programme?" [1]

"The Q-VAX vaccine has been available in Australia since 1989, and the National Q Fever Management Program was implemented in 2001 to vaccinate at-risk occupational groups — abattoir workers, farmers, shearers, veterinarians, veterinary students, and others. The programme was the world's first comprehensive national Q fever vaccination initiative. However, vaccine uptake has been incomplete, and many abattoir workers — like Mr Baxter — remain unvaccinated, particularly those who were already in the workforce before the programme or who change employers. The Q-VAX vaccine has a high efficacy (greater than 83 per cent) but requires mandatory pre-vaccination screening with both serology and skin testing, because individuals with pre-existing immunity develop severe reactions if vaccinated. This screening requirement adds complexity and cost, which may contribute to incomplete uptake. The lesson from Mr Baxter's case is that the Q fever vaccination programme, while a landmark in occupational health, has not eliminated Q fever in at-risk workers — and the physician must remain vigilant for Q fever in any unvaccinated or partially vaccinated worker in the meat and livestock industries [2]."

Q4: "What is the role of valve surgery in this patient?" [1]

"Valve surgery is not automatically required for Q fever endocarditis — the medical therapy (doxycycline plus hydroxychloroquine for at least 24 months) is the primary treatment. However, surgery is indicated for: heart failure from valvular dysfunction, perivalvular abscess or extension of infection beyond the valve leaflets, prosthetic valve dehiscence, persistent bacteraemia or failure of medical therapy, or embolic events with large vegetations. The challenge in Q fever endocarditis is that the medical therapy must be continued for a prolonged period even after surgery — typically at least 18 to 24 months total, with preoperative and postoperative antibiotic therapy. The decision for surgery is made jointly by the infectious diseases physician, the cardiothoracic surgeon, and the cardiologist, based on the echocardiographic findings and the clinical course. In Mr Baxter's case, the TTE shows a small vegetation without perivalvular complications on the initial study, but the TOE may reveal additional detail. If there are no surgical indications, medical therapy alone is appropriate." [1]

Q5: "What follow-up does he need after completing treatment?" [1]

"After completing at least 24 months of doxycycline plus hydroxychloroquine, Mr Baxter requires: ongoing serological monitoring (phase I IgG should be below 1:800 before treatment cessation, and should continue to decline afterwards), serial echocardiography to monitor the prosthetic valve, clinical follow-up for at least 12 months after treatment cessation to detect relapse (the relapse rate with the combination regimen is below 10 per cent, but late relapses occur), and assessment for the Q fever fatigue syndrome. He should also be advised about the occupational risk — if he returns to abattoir work, he should receive the Q-VAX vaccine (with screening) if his serology has returned to low levels, though the data on post-infection vaccination are limited. The public health follow-up of the workplace and his colleagues continues independently." [1]

Q6: "What is the single most important lesson from this case for a registrar managing a patient with culture-negative endocarditis?" [1]

"The single most important lesson is that the exposure history drives the differential in culture-negative endocarditis. The registrar who asks the occupation, the animal contact, and the dietary exposure will identify the likely pathogen — the abattoir worker has Q fever, the cat owner with homelessness has Bartonella, the unpasteurised-dairy consumer has Brucella. The corollary is that the specific zoonotic serology (Coxiella, Bartonella, Brucella) must be sent for EVERY case of culture-negative endocarditis — these are not supplementary tests, they are the primary diagnostic tests. And the treatment follows the diagnosis: chronic Q fever endocarditis requires the unique doxycycline plus hydroxychloroquine regimen for at least 18 to 24 months, not the standard empiric endocarditis antibiotics. The registrar who treats chronic Q fever with vancomycin and gentamicin will fail, because C. burnetii is an intracellular pathogen that requires the alkalinisation strategy to be eradicated." [1]