Vaccine-Preventable Diseases — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Mrs Margaret Chen, 58 years old, veterinary surgeon. [1]

Presenting complaint: Referred by her rheumatologist for pre-rituximab vaccination review. Rituximab is planned in 4 weeks for refractory rheumatoid arthritis. She is also planning a 3-week trip to Vietnam in 3 months. [1]

Past history:

• Rheumatoid arthritis (15 years) on methotrexate 20 mg weekly and hydroxychloroquine 400 mg daily. Refractory disease — rheumatologist plans rituximab 1 g IV on days 1 and 15.
• Resolved hepatitis B: HBsAg-negative, anti-HBc-positive, anti-HBs-negative (below 10 mIU/mL). HBV DNA pending.
• Immune thrombocytopenic purpura — splenectomy at age 35. No record of pneumococcal, Hib, or meningococcal vaccination since.
• Influenza vaccine 3 years ago. No record of zoster, pneumococcal, hepatitis B, Hib, meningococcal, or dTpa vaccination.
• Varicella IgG positive. MMR IgG: measles positive, rubella positive, mumps negative. Hepatitis A IgG pending. [1]

Examination findings: Comfortable, afebrile. RA deformities of the metacarpophalangeal and proximal interphalangeal joints, active synovitis in both wrists. No surgical scar from the splenectomy is visible (laparoscopic). No lymphadenopathy, no hepatosplenomegaly (no remaining spleen). No signs of chronic liver disease. [1]

Investigations:

• Full blood count: normal. Liver function tests: normal. Renal function: normal.
• Hepatitis B: HBsAg-negative, anti-HBc-positive, anti-HBs less than 10 mIU/mL. HBV DNA pending.
• HIV: negative.
• Immunoglobulins: IgG 6.2 g/L (low-normal), IgA and IgM normal.
• CD19 B-cells: 0.22 x 10^9 per litre (normal range 0.1 to 0.5). [1]

Drug chart (current): methotrexate 20 mg weekly, folic acid 5 mg daily (skip methotrexate day), hydroxychloroquine 400 mg daily. No penicillin prophylaxis (care gap). [1]

Candidate's structured presentation (model)

Opening statement (SASPOP): [1]

"Mrs Chen is a 58-year-old veterinary surgeon presenting for pre-rituximab vaccination review. She has refractory rheumatoid arthritis on methotrexate and hydroxychloroquine, and her rheumatologist plans rituximab in four weeks. Her main problems are: first, the pre-immunosuppression vaccination window — I must complete all indicated inactivated vaccines before rituximab begins, because B-cell depletion renders vaccines ineffective for 6 to 12 months; second, resolved hepatitis B with HBsAg-negative, anti-HBc-positive serology, which carries a significant risk of HBV reactivation with rituximab and requires prophylactic entecavir; third, a prior splenectomy at age 35 with a 23-year gap in asplenic vaccination coverage — she has never received pneumococcal, Hib, or meningococcal vaccination, and she is not on penicillin prophylaxis, which is a significant care gap; fourth, planned travel to Vietnam requiring additional travel vaccines; and fifth, her mumps IgG is negative, raising the question of whether to give the live MMR vaccine before rituximab or defer until B-cell recovery. [1]

My immediate priority is to use the four-week window before rituximab to deliver the full vaccination bundle — pneumococcal conjugate, recombinant zoster (Shingrix), influenza, dTpa, hepatitis B, Hib, meningococcal ACWY and B, and to start entecavir for HBV prophylaxis before the first rituximab dose. The travel vaccines (hepatitis A if non-immune, injectable typhoid, rabies pre-exposure) are integrated into the plan. The MMR decision requires shared decision-making with the rheumatologist." [1]

Management plan: [1]

1. Vaccinations to complete before rituximab (within the next 4 weeks):

   • PCV13 or PCV20 (single dose) — to be followed by PPSV23 at least 8 weeks later if PCV13 used.
   • Recombinant zoster (Shingrix) dose 1 — dose 2 in 2 to 6 months.
   • Inactivated influenza vaccine (this season's formulation).
   • dTpa booster (then dT every 10 years).
   • Hepatitis B vaccine — double-dose schedule (40 micrograms at 0, 1, and 6 months) because she is immunocompromised and her anti-HBs is below 10 mIU/mL; complete as many doses as possible before rituximab.
   • Hib vaccine — single dose.
   • MenACWY — single dose, with a booster plan (every 5 years).
   • MenB (Bexsero) — dose 1, dose 2 in 8 weeks (booster after 1 year then every 2 to 3 years). [1]

2. Hepatitis B reactivation prophylaxis: Entecavir 0.5 mg daily (or tenofovir 300 mg daily), started before the first rituximab dose and continued for at least 12 to 18 months after the last dose. Monitor HBV DNA and liver function tests during therapy. [1]

3. Asplenic management bundle: Lifelong penicillin prophylaxis (penicillin V 500 mg BD or amoxicillin); standby dose of amoxicillin for the first fever; medical alert bracelet and card; patient education that any fever is a medical emergency. [1]

4. Travel vaccines: Hepatitis A (if IgG negative) — 2 doses (0 and 6 to 12 months); injectable typhoid Vi (not oral Ty21a, which is live and contraindicated); rabies pre-exposure (3 doses: days 0, 7, and 21 to 28); Japanese encephalitis if prolonged rural exposure. No yellow fever needed for Vietnam. Mosquito avoidance and food and water safety counselling. [1]

5. MMR decision: Shared decision-making with the rheumatologist. Methotrexate 20 mg weekly without high-dose corticosteroids is generally considered a level of immunosuppression that permits live vaccination, but if there is uncertainty, defer MMR until B-cell recovery (6 to 12 months post-rituximab). [1]

6. Re-vaccination plan post-rituximab: Monitor CD19 B-cells; once recovered (6 to 12 months), complete Shingrix dose 2, hepatitis B post-vaccination serology (anti-HBs), pneumococcal PPSV23 (if not completed), and MMR if deferred. Register all vaccines on the Australian Immunisation Register (AIR). [1]

Communication and shared decision-making: Explain to Mrs Chen that rituximab works by reducing her immune system's B-cells, which means vaccines will not work properly once she starts treatment. Emphasise the importance of completing the vaccinations in the next four weeks, and explain the hepatitis B reactivation risk and the need for entecavir prophylaxis. Address the asplenic care gap honestly — explain that the spleen protects against certain bacteria and that without it she needs the vaccinations, penicillin, and a standby antibiotic plan. For travel, explain the injectable typhoid instead of the oral form and the rabies pre-exposure series. [1]

Examiner discussion questions

Q1: "Walk me through your prioritisation of the vaccinations in the four-week window before rituximab. What is non-negotiable and what can be deferred?" [1]

"The non-negotiable vaccines are those that protect against the highest-risk infections during the B-cell-depleted period: pneumococcal conjugate (PCV), influenza, and the asplenic bundle (Hib, MenACWY, MenB), because the loss of splenic function combined with B-cell depletion compounds the risk of overwhelming encapsulated bacterial sepsis. The recombinant zoster (Shingrix) dose 1 is also a priority because herpes zoster reactivation is common with immunosuppression, and the vaccine needs an intact immune system to generate the T-cell response. Hepatitis B vaccination is important but can be partially completed before rituximab and continued after B-cell recovery — I would give at least the first dose before rituximab. The travel vaccines (hepatitis A, injectable typhoid, rabies) can be given in the weeks before travel, which is 3 months away. The MMR is the deferrable one — the risk of mumps in a 58-year-old in Australia is low, and the decision can wait until B-cell recovery if there is uncertainty about the immunosuppression level. The teaching point is that the four-week window forces a prioritisation, and the registrar who tries to give everything at once without a plan will miss the key vaccines." [1]

Q2: "Why must the pneumococcal conjugate vaccine come before the polysaccharide?" [1]

"The conjugate vaccine (PCV) links the pneumococcal polysaccharide to a protein carrier — typically diphtheria or tetanus toxoid — which converts the immune response from a T-cell-independent response to a T-cell-dependent response. The T-cell-dependent response generates immunological memory and a robust booster response on subsequent vaccination. If the polysaccharide vaccine (PPSV23) is given first, the T-cell-independent response it generates does not create memory, and it actually blunts the subsequent response to the conjugate vaccine — the immunological term is 'hyporesponsiveness.' This is why the ACIP 2012 recommendation established the sequence: conjugate first, then polysaccharide at least 8 weeks later to broaden the serotype coverage (PPSV23 covers 23 serotypes versus 13 in PCV13 or 20 in PCV20). Alternatively, PCV20 alone covers 20 serotypes with the conjugate platform and eliminates the need for PPSV23 entirely — this is the simplification that the 2024 ACIP guidance has moved toward." [1]

Q3: "She is not on penicillin prophylaxis despite her splenectomy 23 years ago. How do you address this?" [1]

"This is a significant care gap that I must address immediately. The asplenic patient is at lifelong risk of overwhelming post-splenectomy infection, and the risk is highest in the first two years after splenectomy, in children and older adults, and in patients with inadequate vaccination — which Mrs Chen is. The penicillin prophylaxis is penicillin V 500 mg twice daily (or amoxicillin), and it is recommended lifelong in high-risk groups. I would start it immediately, along with a standby dose of amoxicillin that she carries at all times to take at the first fever, a medical alert bracelet and card, and thorough patient education. I would also acknowledge the care gap honestly with the patient and the team — the failure to vaccinate and to provide prophylaxis for 23 years after a splenectomy is a quality-of-care issue that should be reviewed. The teaching point is that the three pillars of asplenic management — vaccination, prophylactic antibiotics, and patient empowerment — must all be in place, and the omission of any one is a preventable failure." [1]

Q4: "What is the significance of her resolved hepatitis B for the rituximab plan?" [1]

"Resolved hepatitis B — HBsAg-negative, anti-HBc-positive — means the virus persists in the liver in a dormant state, held in check by the HBsAg-neutralising antibody produced by B-cells. Rituximab depletes the B-cells for 6 to 12 months, removing the immune control and allowing HBV to reactivate. The reactivation can cause acute hepatitis, fulminant hepatic failure (which can be fatal), and acceleration of any underlying cirrhosis. This is why 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. I will also check her HBV DNA at baseline and monitor it during therapy. The teaching point is that this is a preventable complication, and the failure to screen or to prophylax is a never-event." [1]

Q5: "She is travelling to Vietnam. How do you adapt the travel vaccination for a patient about to start rituximab?" [1]

"The key adaptation is that the live oral typhoid vaccine (Ty21a) is contraindicated because she will be on rituximab — I use the injectable Vi polysaccharide typhoid instead, which is inactivated and safe. The other travel vaccines (hepatitis A, rabies pre-exposure, Japanese encephalitis if indicated) are all inactivated and can be given safely. The timing must be integrated with the pre-rituximab window — ideally the travel vaccines are given before rituximab if the response needs to develop, or after B-cell recovery if the travel is more than 6 months away. In Mrs Chen's case, the travel is 3 months away, which coincides with the period after the first rituximab dose, so I would give the travel vaccines before rituximab if possible. Yellow fever is not required for Vietnam, which is fortunate because yellow fever is live and would be contraindicated. The teaching point is that travel vaccination in the immunocompromised traveller requires identifying the live vaccines and substituting the inactivated alternatives." [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, and the immunisation review must be systematic. Mrs Chen has five intersecting problems — the pre-rituximab window, the resolved hepatitis B, the asplenic care gap, the travel plans, and the live vaccine question — and each requires a specific decision within the four-week window. The registrar who sees the patient the day before rituximab and says 'we will do the vaccines later' has missed the window, because any vaccine given after rituximab is wasted for 6 to 12 months. The corollary is that the systematic immunisation review must address the standard age-based vaccines, the comorbidity-specific vaccines, the asplenic bundle, the travel vaccines, and the live vaccine considerations — and the integrated plan is what makes the immunisation decision in the immunocompromised patient a clinical-reasoning task rather than a protocol." [1]

DCE Short Case — The Patient with a Suspected Vaccine Adverse Reaction

Instruction

"You are the medical registrar assessing a 55-year-old nurse who 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. You have 5 minutes to outline your approach and 5 minutes for discussion." [1]

Provided data: The patient is a 55-year-old nurse, previously well, who received the seasonal inactivated influenza vaccine 20 minutes ago. She developed generalised urticaria, lip and tongue swelling, and audible wheeze within 10 minutes. Her observations: heart rate 110, blood pressure 92/58, respiratory rate 24, oxygen saturation 94 per cent on room air. She has a history of seasonal allergic rhinitis but no known drug or food allergy. [1]

Presentation template

"This patient has suspected anaphylaxis to the influenza vaccine, with the classic triad of skin (urticaria and angioedema), respiratory (wheeze), and cardiovascular (hypotension and tachycardia) involvement. The onset within 10 minutes is consistent with an IgE-mediated reaction. My immediate priority is the ABC: intramuscular adrenaline 0.5 mg (0.5 mL of 1:1000) into the anterolateral thigh, high-flow oxygen, nebulised salbutamol for bronchospasm, intravenous access with fluid resuscitation, and senior support. I would repeat the adrenaline every 5 minutes as needed. Once stabilised, I would send a serum tryptase within 1 to 2 hours, admit for 6 to 12 hours of observation for a biphasic reaction, and report the adverse event to the national surveillance system. For future influenza vaccination, I would refer to an allergist for component testing and plan alternative products or specialist-supervised desensitisation. The teaching point is that true vaccine anaphylaxis is extremely rare — approximately 1 to 10 per million doses — and the most common allergen is gelatin or latex rather than the trace ovalbumin that is often blamed." [1]

Discussion

Examiner: "What are the common conditions that are NOT contraindications to vaccination?" [1]

"The common conditions that are NOT contraindications include: mild illness (upper respiratory infection, low-grade fever below 38.5 degrees), antibiotic therapy, breastfeeding, premature birth, a stable neurological condition (including well-controlled epilepsy, cerebral palsy, and a family history of seizures), and a personal or family history of allergies that are not to a vaccine component. The registrar who defers vaccination because the patient has a mild cold or is on antibiotics has created a missed opportunity, and these patients may not return. The true contraindications are narrow: anaphylaxis to a vaccine component or a previous dose, severe immunosuppression for live vaccines, and pregnancy for live vaccines. Everything else is either a precaution (which requires individualised risk-benefit assessment) or not a concern at all." [1]

Examiner: "What is the role of egg allergy in vaccine decisions?" [1]

"Egg allergy is a common source of confusion. The key points are: first, MMR is safe in egg allergy because the measles and mumps components are grown in chick fibroblast cell culture, not in egg, and the trace protein is negligible. Second, inactivated influenza vaccines contain only trace ovalbumin and are safe in all but the most severe egg allergy; they can be given in the standard setting with 15-minute observation. Third, the live attenuated influenza vaccine (LAIV, intranasal) also contains trace egg protein and the same precautions apply. Fourth, the one vaccine that genuinely requires caution in egg allergy is yellow fever, which is grown in embryonated chicken eggs and contains significant egg protein — in a patient with egg anaphylaxis, yellow fever vaccination requires specialist evaluation, skin testing, or a medical waiver. The teaching point is that the over-cautious deferral of influenza or MMR vaccination in egg-allergic patients is a common and avoidable error that leaves patients unprotected." [1]

Examiner: "What is the lesson about the distinction between an expected vaccine reaction and a true contraindication?" [1]

"The lesson is that the registrar must distinguish the expected, self-limiting vaccine reaction (local pain, erythema, low-grade fever, malaise — which occur in 10 to 60 per cent of recipients and resolve in 1 to 3 days) from the rare true adverse event (anaphylaxis, GBS, VAPP) that warrants specialist referral and a modified vaccination plan. The expected reaction is NOT a contraindication to the next dose, and the registrar who defers the next dose because of a local reaction has converted a minor side effect into a missed vaccination. The rare adverse event IS a reason to seek specialist advice, report to the surveillance system, and plan an alternative strategy. The communication with the patient is key: counsel the patient about the expected reactions so they are not alarmed, and have a clear plan for what to do if a significant reaction occurs." [1]