Vaccine-Preventable Diseases — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mrs Margaret Chen is a 58-year-old veterinary surgeon with refractory rheumatoid arthritis on methotrexate and hydroxychloroquine, whose rheumatologist plans to start rituximab in four weeks. She has three problems that intersect at the immunisation decision: first, the pre-rituximab window — I must complete all indicated vaccinations before B-cell depletion begins, because vaccines given after rituximab are ineffective for 6 to 12 months. Second, resolved hepatitis B (HBsAg-negative, anti-HBc-positive), which carries a significant risk of HBV reactivation with rituximab and requires prophylactic entecavir or tenofovir. Third, a prior splenectomy at age 35 for immune thrombocytopenia, with a significant gap in her asplenic vaccination coverage — she has never received pneumococcal, Hib, or meningococcal vaccination. [1]

My immediate priority is to use the four-week window before rituximab to deliver the inactivated vaccines that will be rendered ineffective by B-cell depletion — pneumococcal conjugate, recombinant zoster (Shingrix), influenza, dTpa, hepatitis B, Hib, meningococcal ACWY and B. I will also start entecavir for HBV prophylaxis before the first rituximab dose. The live vaccine question — her mumps IgG is negative and MMR is a live vaccine — requires shared decision-making with the rheumatologist about whether to give it now (at least 4 weeks before rituximab) or defer until B-cell recovery. Her travel to Vietnam adds hepatitis A, injectable typhoid (not the oral live form), and rabies pre-exposure prophylaxis." [1]

Examiner probing questions and model answers

Q1: "Why must you vaccinate before rituximab? What happens if you give vaccines after rituximab?" [1]

"Rituximab is an anti-CD20 monoclonal antibody that depletes B-cells for 6 to 12 months. Because B-cells are the effector cells for antibody production in response to vaccination, any vaccine given during the B-cell-depleted period cannot generate a meaningful antibody response. The IDSA 2013 guideline on vaccination of the immunocompromised host established the principle that inactivated vaccines should be given at least 2 weeks before immunosuppression — ideally 4 — so the immune response can develop before the B-cells are depleted [1]. Live vaccines need at least 4 weeks before immunosuppression because they must replicate to generate immunity, and the replication and immune response take longer. If vaccines are given after rituximab, they are essentially wasted — the patient receives the injection but develops no protective antibody. The teaching point is that the pre-immunosuppression window is a brief and closing opportunity, and the physician who does not address vaccination before the first rituximab dose has missed the optimal window."

Q2: "She has resolved hepatitis B. How does that change your management?" [1]

"Mrs Chen is HBsAg-negative but anti-HBc-positive, which indicates resolved hepatitis B. The virus persists in the liver in a dormant state, held in check by the HBsAg-neutralising antibody response. Rituximab depletes the B-cells that produce this neutralising antibody for 6 to 12 months, removing the immune control and allowing HBV to reactivate — sometimes causing fulminant hepatic failure. Every patient starting rituximab must be screened with HBsAg AND anti-HBc, not just HBsAg, because resolved HBV can reactivate. The prophylactic strategy is entecavir 0.5 mg daily or tenofovir 300 mg daily, started before rituximab and continued for at least 12 to 18 months after the last dose — longer in high-risk patients. Lamivudine is inferior because of resistance. I will also check her HBV DNA at baseline and monitor it during therapy. The teaching point is that this is a preventable complication — the screening and prophylaxis are the standard of care, and the failure to screen or to prophylax is a never-event." [1]

Q3: "She had a splenectomy 23 years ago and has never had pneumococcal or meningococcal vaccines. How do you address this?" [1]

"This is a significant care gap that must be rectified immediately, because the asplenic patient is at lifelong risk of overwhelming post-splenectomy infection (OPSI) with encapsulated bacteria — S. pneumoniae, H. influenzae, N. meningitidis — with a mortality of 50 to 70 per cent despite treatment. The full vaccination bundle consists of pneumococcal conjugate (PCV first, then PPSV23 at least 8 weeks later), Haemophilus influenzae type b, meningococcal ACWY and B, and annual influenza [5]. Because she is about to start rituximab, I must complete these vaccinations in the pre-rituximab window — the conjugate pneumococcal, Hib, MenACWY, and MenB can all be given now, with PPSV23 8 weeks later. She also needs lifelong penicillin prophylaxis — penicillin V 500 mg BD or amoxicillin — and a standby dose of amoxicillin to take at the first fever. She should carry a medical alert bracelet and card. The teaching point is that the three pillars — vaccination, prophylaxis, and patient empowerment — must all be in place, and the omission of any one of them (as in this case, where vaccination and possibly prophylaxis were omitted) represents a failure of care that must be corrected."

Q4: "Her mumps IgG is negative. Do you give her the MMR vaccine before rituximab?" [1]

"This is a nuanced decision that requires shared decision-making with the rheumatologist and infectious diseases team. MMR is a live vaccine, and live vaccines must be given at least 4 weeks before immunosuppression so the attenuated virus can replicate and generate immunity before the immune system is suppressed. Mrs Chen is currently on methotrexate and hydroxychloroquine for her rheumatoid arthritis. Methotrexate at standard doses for RA (typically 10 to 25 mg weekly), without high-dose corticosteroids, is generally considered a level of immunosuppression that permits live vaccination — but the assessment must be individualised. The alternative is to defer the MMR until after rituximab, when B-cells have recovered (6 to 12 months) and the immunosuppression has been weaned. The risk of mumps in a 58-year-old in Australia is low, so the defer strategy is reasonable if the decision is uncertain. Her varicella IgG is positive, so no varicella vaccine is needed. The teaching point is that the live-vaccine decision in the pre-immunosuppression window depends on the degree of current immunosuppression, the urgency of the therapy, and the risk of the vaccine-preventable disease — it is a clinical judgement, not a protocol." [1]

Q5: "She is travelling to Vietnam in three months. What travel vaccines does she need?" [1]

"The travel consultation should cover the vaccines relevant to Vietnam and the broader travel risk. Hepatitis A — I would check her IgG first, because she may be immune from prior exposure; if non-immune, 2 doses (0 and 6 to 12 months). Typhoid — the injectable Vi polysaccharide (inactivated), NOT the oral Ty21a, because she will be on rituximab and the oral form is live and contraindicated. Japanese encephalitis — only if she has prolonged rural exposure (more than 1 month); for a short urban trip, it is not routinely needed. Rabies — pre-exposure prophylaxis is worth considering because she is a veterinary surgeon and Vietnam is a rabies-endemic country; 3 doses (days 0, 7, and 21 to 28). Yellow fever is not required for Vietnam. She should also receive counselling on mosquito avoidance (dengue is common in Vietnam) and food and water safety. The principle is that travel vaccination must be integrated with the immunosuppression plan — the live oral typhoid must be avoided, and the timing of the other vaccines must fit within the pre-rituximab window." [1]

Q6: "What is the single most important lesson from this case for a registrar managing immunisation before immunosuppression?" [1]

"The single most important lesson is that the pre-immunosuppression window is a brief and closing opportunity that must not be missed. Mrs Chen is about to start rituximab, and any vaccine given after the first dose will be wasted for 6 to 12 months. The registrar who sees the patient the day before rituximab and says 'we will do the vaccines later' has missed the window. The corollary is that the immunisation review must be systematic — I must address the standard age-based vaccines (influenza, pneumococcal, zoster, dTpa), the comorbidity-specific vaccines (hepatitis B for her resolved HBV and negative anti-HBs), the asplenic bundle (which was omitted for 23 years), the travel vaccines (with the live oral typhoid replaced by the injectable form), and the live vaccine considerations (MMR for her negative mumps IgG). The integrated plan — what to give, in what order, by when, and what to defer — is what makes the immunisation decision in the immunocompromised patient a clinical-reasoning task rather than a protocol." [1]

Short Case Discussion

The patient with a suspected vaccine adverse reaction

Examiner instruction: "A 55-year-old nurse developed generalised urticaria, facial swelling, and wheeze 10 minutes after receiving the seasonal influenza vaccine in the staff immunisation clinic. She is now in the emergency department. Outline your assessment and management, and discuss the implications for her future influenza vaccination." [1]

Candidate's model answer: [1]

*"This is a presentation of suspected anaphylaxis to the influenza vaccine, and the onset within 10 minutes is consistent with an IgE-mediated reaction. My immediate priority is the ABC assessment: airway (is there stridor, facial or tongue swelling?), breathing (wheeze, respiratory distress, hypoxia), circulation (hypotension, tachycardia, signs of shock). I give intramuscular adrenaline 0.5 mg (0.5 mL of 1:1000) into the anterolateral thigh immediately, repeat every 5 minutes as needed, establish intravenous access, give fluids, and call for senior emergency and anaesthetic support. I add oxygen, nebulised salbutamol for bronchospasm, and an antihistamine and corticosteroid as adjuncts. The patient is admitted for observation for at least 6 to 12 hours because of the risk of a biphasic reaction. [1]

For the investigation: I send a serum tryptase within 1 to 2 hours of the reaction (an elevated tryptase supports mast-cell degranulation and confirms anaphylaxis rather than a vasovagal episode or a non-allergic reaction). I review the vaccine product information to identify the potential allergen — the most common culprits in influenza vaccine are trace ovalbumin (egg protein), gelatin, and latex (in the vial stopper). I report the adverse event to the national pharmacovigilance system (AEFAMS in Australia, VAERS in the US). [1]

For future influenza vaccination: this patient should NOT receive the same influenza vaccine without further evaluation. I would refer her to an allergist or clinical immunology service for investigation, which may include skin-prick testing with the influenza vaccine and its components. If the reaction is confirmed as anaphylaxis to a specific component, she may need to avoid that vaccine product, or if the allergen is identified and an alternative product is available (for example, an egg-free formulation), she may be able to receive it under specialist supervision. If she cannot receive any influenza vaccine, I would ensure that her household contacts are vaccinated (cocooning) and counsel on non-pharmacological infection prevention."* [1]

Examiner: "How common is anaphylaxis after influenza vaccination, and what is the role of egg allergy?" [1]

"Anaphylaxis after influenza vaccination is extremely rare — estimated at approximately 1 to 10 per million doses. The egg allergy question is important because influenza vaccines are produced in embryonated chicken eggs and contain trace ovalbumin. However, the ovalbumin content of modern influenza vaccines is very low (typically less than 1 microgram per dose), and multiple large studies have confirmed that influenza vaccine is safe in patients with egg allergy, including severe egg allergy — reactions are exceptionally rare. In Australia and the US, the influenza vaccine can be given in the standard setting to egg-allergic patients with the standard 15-minute observation, without additional precautions. The true cause of vaccine-associated anaphylaxis is more often gelatin, latex, or another component rather than egg. The teaching point is that egg allergy is not a contraindication to influenza vaccination, and the over-cautious deferral of influenza vaccination in egg-allergic patients represents a missed opportunity for prevention." [1]

Examiner: "What is the single most important lesson from this case for a registrar managing vaccine adverse events?" [1]

"The single most important lesson is that true vaccine contraindications are narrow, and the registrar must distinguish the true contraindication (anaphylaxis to a vaccine component) from the many conditions that are NOT contraindications (mild illness, antibiotic therapy, family history, stable neurological conditions). Anaphylaxis within 30 minutes of a vaccine is a true adverse event that requires adrenaline, specialist referral, and a plan for future vaccination that may involve alternative products or desensitisation. The corollary is that common reactions — local pain, low-grade fever, malaise — are expected and self-limiting, and the registrar who defers the next dose because of a local reaction has converted a minor side effect into a missed vaccination. The registrar should also report all significant adverse events to the national surveillance system, because pharmacovigilance depends on clinician reporting." [1]