Zoonotic and Vector-Borne Infections — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mr William Baxter is a 58-year-old abattoir worker presenting with a four-week history of intermittent fevers, fatigue, drenching night sweats and a 5 kg weight loss. He has a bioprosthetic aortic valve replacement performed 4 years ago for bicuspid aortic valve disease. [1]

His main problems are:

1. Culture-negative endocarditis on a prosthetic aortic valve — the leading diagnosis is chronic Q fever (Coxiella burnetii), given his occupation as an abattoir worker and the characteristic features of culture-negative blood cultures, a small prosthetic valve vegetation, and a subacute course with splenomegaly and splinter haemorrhages. The differential is Bartonella endocarditis, Brucella endocarditis, and HACEK endocarditis.
2. The constitutional decline — normocytic anaemia, elevated ESR and CRP, and weight loss consistent with a chronic infective process. [1]

My immediate priority is the aetiological diagnosis — I would send Coxiella burnetii phase I and phase II serology by immunofluorescence, Bartonella serology, Brucella serology, repeat blood cultures with extended incubation, and perform a transoesophageal echocardiogram. If the phase I IgG is above 1:800, the diagnosis of chronic Q fever endocarditis is confirmed, and I would start doxycycline 100 mg twice daily plus hydroxychloroquine 200 mg three times daily for at least 24 months (the prosthetic valve duration). I would notify the public health unit, assess the workplace for Q fever risk, and recommend Q-VAX vaccination for seronegative colleagues with mandatory pre-vaccination screening." [1]

Examiner probing questions and model answers

Q1: "Why doxycycline plus hydroxychloroquine rather than doxycycline alone?" [1]

"Coxiella burnetii is an obligate intracellular pathogen that survives within the phagolysosome — the acidic, enzyme-rich compartment of the macrophage. The acidic environment protects the organism, because doxycycline is only bacteriostatic at low pH. Hydroxychloroquine is a weak base that accumulates in the phagolysosome and alkalinises it, raising the pH and restoring the bactericidal activity of doxycycline. Raoult and colleagues demonstrated that the doxycycline-hydroxychloroquine combination achieved a lower relapse rate and allowed a shorter treatment duration than the previous doxycycline-ofloxacin regimen [1]. Treating with doxycycline alone gives a high failure rate because the organism persists in the acidic phagolysosome. The duration is at least 18 months for native valve and 24 months for prosthetic valve endocarditis, guided by the declining phase I IgG titre."

Q2: "How does the Coxiella serology work, and how does it satisfy the Duke criteria?" [1]

"Coxiella burnetii undergoes antigenic phase variation of its lipopolysaccharide. Phase I is the virulent form found in nature, with a smooth LPS, and high-titre IgG against phase I antigen indicates chronic infection. Phase II is the avirulent form that arises after laboratory passage, with a rough LPS, and IgM against phase II antigen indicates acute infection. The common exam error is reversing these two — phase II IgM equals acute; phase I IgG equals chronic. In the modified Duke criteria for infective endocarditis, a phase I IgG titre above 1:800 is a MAJOR criterion. This means a patient with a prosthetic valve, clinical features of endocarditis, negative blood cultures, and a phase I IgG above 1:800 satisfies the Duke criteria for definite infective endocarditis — the serology replaces the positive blood culture as the major microbiological criterion." [1]

Q3: "He works in an abattoir. What are the public health implications?" [1]

"Q fever is a notifiable disease in Australia, and I would notify the public health unit. The abattoir is the classic setting for Q fever transmission — the organism reaches enormous concentrations in the placenta and birth fluids of infected livestock, and inhalation of aerosolised organisms is the primary route of human infection. The workplace should be assessed for Q fever risk. Colleagues who have been exposed should be offered serological screening, and seronegative workers should be offered the Q-VAX vaccine. The Q-VAX vaccine is a whole-cell formalin-inactivated vaccine, licensed only in Australia, with an efficacy of greater than 83 per cent [2]. The non-negotiable rule is that Q-VAX must NEVER be given without prior screening — both serology and skin testing — because individuals with pre-existing immunity develop severe local and systemic reactions if vaccinated. The screening identifies previously exposed individuals and excludes them from vaccination."

Q4: "What if he also has back pain and an MRI shows a paravertebral collection — does that change things?" [1]

"The paravertebral collection would indicate a second focus of chronic Q fever infection — osteomyelitis or a paravertebral abscess. This does not change the fundamental treatment (doxycycline plus hydroxychloroquine) but it does prolong the duration (at least 24 months for prosthetic valve endocarditis plus osteomyelitis) and may require surgical assessment. The differential at this point would include brucellosis, which causes spondylitis with paravertebral collections — so I would ensure Brucella serology and blood cultures are sent. If the diagnosis is brucellosis rather than Q fever, the treatment would be doxycycline plus rifampicin (or streptomycin) for at least 6 weeks, extended to 8 to 12 weeks or more for spondylitis [4]."

Q5: "What is the Q fever fatigue syndrome?" [1]

"The Q fever fatigue syndrome is a post-infective fatigue syndrome that develops in up to 20 per cent of patients after acute Q fever. It is characterised by disabling fatigue, arthralgia, myalgia, night sweats and mood disturbance, persisting for months to years. There is no evidence of active C. burnetii infection (the serological pattern is of resolved infection, not chronic infection), and prolonged antibiotics do not help. The management is supportive, with graded exercise, cognitive behavioural therapy, and symptomatic treatment. It is important to distinguish the fatigue syndrome from chronic Q fever (which has persistent active infection and requires prolonged antibiotic therapy) by the serological pattern." [1]

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

"The single most important lesson is that ANY patient with culture-negative endocarditis must have Coxiella serology sent — and the clinical exposure (occupation, animal contact, unpasteurised dairy) directs which additional serology to send (Bartonella, Brucella). The registrar who treats culture-negative endocarditis empirically with broad-spectrum antibiotics without sending the specific zoonotic serology will miss the diagnosis of chronic Q fever, which requires a unique treatment regimen (doxycycline plus hydroxychloroquine for at least 18 months), not the standard empiric endocarditis regimen. The corollary is that the phase I IgG titre above 1:800 is a major Duke criterion, which means the serology is not a supplementary test — it is the primary diagnostic test for this form of endocarditis." [1]