Vaccine-Preventable Diseases — Written Clinical Reasoning

SAQ 1 — Integrated Immunisation Plan Before Rituximab in a Multimorbid Patient (25 marks, 30 minutes)

Prompt: Outline your integrated immunisation plan for Mrs Chen, addressing: (a) the vaccines to give before rituximab and the timing; (b) the hepatitis B management; (c) the asplenic vaccination review; (d) the travel advice; (e) the live vaccine considerations; and (f) the plan for re-vaccination after rituximab. ^[1]

Model Answer

(a) Vaccines to give before rituximab and the timing (5 marks): ^[1]

The central principle is to vaccinate before immunosuppression begins, because rituximab depletes CD20-positive B-cells for 6 to 12 months and renders vaccines ineffective during that period — vaccines given after rituximab cannot generate an antibody response because B-cells are the effector cells for humoral immunity ^[1]. Inactivated vaccines should be given at least 2 weeks before rituximab (ideally 4), and live vaccines at least 4 weeks before.

Mrs Chen should receive, before rituximab:

• Pneumococcal conjugate vaccine (PCV13 or PCV20) — given now, followed by PPSV23 at least 8 weeks later if PCV13 is used (or PCV20 alone). The conjugate must come first because it primes the T-cell-dependent memory response ^[6].
• Recombinant zoster vaccine (Shingrix) — first dose now, second dose in 2 to 6 months. Shingrix is inactivated and safe in immunosuppression, unlike the old live zoster vaccine Zostavax ^[3].
• Influenza vaccine — annual, inactivated. Her last dose was 3 years ago, so she needs this year's dose before rituximab.
• dTpa — a booster dose if not given in the last 10 years, then dT every 10 years.
• Hepatitis B — a full 3-dose series (0, 1, and 6 months) because her anti-HBs is below 10 mIU/mL, starting now. At least the first dose should be completed before rituximab, with the series continued post-rituximab if B-cells have recovered.

The timing is critical: with 4 weeks before rituximab, I can complete the first doses of PCV, Shingrix, influenza, dTpa, and the first hepatitis B dose. The second Shingrix dose, the PPSV23 (at least 8 weeks after PCV), and the remaining hepatitis B doses will need to be timed around the rituximab course and the B-cell recovery. ^[1]

(b) Hepatitis B management (4 marks): ^[1]

Mrs Chen has resolved hepatitis B (HBsAg-negative, anti-HBc-positive), which carries a significant risk of HBV reactivation with rituximab. The seminal study by the American Society of Clinical Oncology and the IDSA guideline recommend that all patients starting rituximab should be screened with HBsAg AND anti-HBc, because resolved HBV can reactivate and cause fulminant hepatic failure. 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. ^[1]

In parallel, because her anti-HBs is below 10 mIU/mL, she has lost the protective antibody to hepatitis B and should receive the full 3-dose hepatitis B vaccine series to attempt to restore immunity — though the response may be blunted by her concurrent methotrexate and the impending rituximab. The HBV DNA should be checked at baseline and monitored during therapy. ^[1]

(c) Asplenic vaccination review (4 marks): ^[1]

Mrs Chen had a splenectomy 23 years ago, and her vaccination record shows no pneumococcal, Hib, or meningococcal vaccination — a significant gap. She 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 asplenic vaccination bundle must be completed before rituximab if possible: ^[1]

• Pneumococcal: PCV13 or 20 first, then PPSV23 at least 8 weeks later, with a repeat PPSV23 at 5 years ^[6].
• Haemophilus influenzae type b (Hib): single dose, given now.
• Meningococcal ACWY: single dose now, with a booster every 5 years for ongoing asplenic risk.
• Meningococcal B: Bexsero 2 doses 8 weeks apart (or Trumenba 3 doses), with a booster after 1 year then every 2 to 3 years.
• Annual influenza: continued as above.

In addition, she should be on lifelong penicillin prophylaxis (penicillin V 500 mg BD, or amoxicillin), have a standby dose of amoxicillin to take at the first fever, and carry an alert card and medical bracelet. The education that any fever is a medical emergency is essential. It is concerning that these vaccinations and prophylaxis have not been addressed in the 23 years since her splenectomy — this is a care gap that must be rectified. ^[1]

(d) Travel advice (4 marks): ^[1]

Mrs Chen is planning a trip to Vietnam in 3 months. The travel consultation should ideally occur 4 to 6 weeks before departure, which aligns with her timeline. The vaccines to consider: ^[1]

• Hepatitis A — check IgG first (she may be immune from prior exposure in an endemic area or from prior vaccination); if non-immune, give 2 doses (0 and 6 to 12 months). This is important for travel to Vietnam.
• Typhoid — the injectable Vi polysaccharide (inactivated, single dose, every 2 to 3 years) is preferred over the oral Ty21a (live, contraindicated in immunosuppression). Given that she will be on rituximab, the injectable form is mandatory.
• Japanese encephalitis — if she will have prolonged rural exposure (more than 1 month), a 2-dose inactivated schedule (0 and 28 days) is recommended. For a short urban trip, it may not be necessary.
• Cholera — oral Dukoral for high-risk travel; not routinely needed for Vietnam.
• Rabies — pre-exposure prophylaxis (3 doses, days 0, 7, and 21 to 28) if she will have animal exposure as a veterinary surgeon; Vietnam is a rabies-endemic country.
• Yellow fever — not required for Vietnam (Vietnam is not in the yellow fever zone).
• Standard boosters — ensure dTpa and hepatitis B are up to date as above. ^[1]

Mosquito avoidance (dengue, Zika, Japanese encephalitis) and food and water safety (hepatitis A, typhoid, cholera, traveller's diarrhoea) counselling is essential. ^[1]

(e) Live vaccine considerations (3 marks): ^[1]

Mrs Chen's mumps IgG is negative, which means she is susceptible to mumps. The MMR vaccine is a live vaccine and is contraindicated once rituximab begins. With 4 weeks before rituximab, it would be possible to give the MMR now (at least 4 weeks before immunosuppression), but this must be weighed against the risk that the live vaccine may not be fully controlled in a patient already on methotrexate (which constitutes moderate immunosuppression). The IDSA guideline recommends that live vaccines be given at least 4 weeks before immunosuppression, and that the degree of immunosuppression be assessed — methotrexate at standard doses for RA (without high-dose steroids) is generally considered low enough to permit a live vaccine, but this decision involves shared decision-making with the rheumatologist and infectious diseases team. ^[1]

Alternatively, the MMR can be deferred until after rituximab when B-cells have recovered (6 to 12 months after the last dose) and the immunosuppression has been weaned. The risk of mumps in a 58-year-old is low in Australia, and the defer strategy is reasonable. Her varicella IgG is positive, so no varicella vaccine is needed. ^[1]

(f) Plan for re-vaccination after rituximab (5 marks): ^[1]

After rituximab, the B-cell count (CD19) should be monitored. Once B-cells have recovered — typically 6 to 12 months after the last rituximab dose — the following vaccines should be re-evaluated and re-administered as needed: ^[1]

• Influenza — annual, regardless of B-cell recovery, because some protection is better than none and the T-cell response may persist.
• Pneumococcal — a booster PCV or PPSV23 may be needed if the initial response was inadequate (check pneumococcal antibody titres if available).
• Recombinant zoster (Shingrix) — the second dose if not completed pre-rituximab.
• Hepatitis B — post-vaccination serology (anti-HBs) to confirm response; if below 10 mIU/mL, consider a repeat series or double-dose schedule.
• dTpa — a booster if not given pre-rituximab.
• MMR — if deferred, give once B-cells have recovered and immunosuppression is low. ^[1]

The principle is that rituximab creates a window of vaccine non-responsiveness, and the immunisation plan must account for this by completing what can be done before therapy, maintaining influenza during therapy (partial protection), and re-vaccinating once the immune system has recovered. The patient should be entered into a recall system (the Australian Immunisation Register) to ensure no doses are missed. ^[1]