Eduovisual
Immune System
Vaccine schedule in immunocompromised hosts
— Immunocompromised adults have 2–10× higher risk of vaccine-preventable disease (pneumococcus, influenza, zoster, HBV, HPV-related cancers)
— Yet vaccination rates lag general population by 20–40% due to provider hesitancy, fragmented care, and confusion about live-vaccine contraindications
— Step 3 tests the ambulatory clinician's role in proactive immunization planning, ideally before immunosuppression begins
— Severely immunocompromised: hematologic malignancy, active chemotherapy, HSCT <2 years or on immunosuppression, solid organ transplant (SOT), HIV with CD4 <200, primary immunodeficiency, high-dose steroids (≥20 mg prednisone ≥14 days), biologics (anti-CD20, anti-TNF, JAK inhibitors), CAR-T
— Less severely: asplenia (functional/anatomic), chronic renal failure/dialysis, complement deficiency, cirrhosis, controlled HIV with CD4 ≥200
— Pregnancy is not immunocompromise for vaccine purposes but shares the live-vaccine restriction
— New diagnosis of cancer, autoimmune disease, IBD, transplant candidacy, HIV, asplenia (sickle cell, post-splenectomy)
— Patient about to start rituximab, anti-TNF, methotrexate, mycophenolate, calcineurin inhibitor, eculizumab
— Returning travelers, refugees, or patients with no documented records
— Inactivated vaccines = safe in all immunocompromised states (may have blunted response)
— Live vaccines = generally contraindicated in severe immunocompromise (MMR, varicella, zoster live [Zostavax—discontinued], LAIV, yellow fever, oral typhoid, BCG, rotavirus exception in infants)
— Vaccinate ≥2 weeks before inactivated, ≥4 weeks before live vaccines prior to starting immunosuppression
Step 3 management: At every new diagnosis of immunosuppressing condition, perform an immunization audit and update before therapy when feasible—this is a quality measure tracked in value-based care contracts.
— 45M newly diagnosed RA, rheumatologist plans to start adalimumab in 6 weeks → what vaccines now?
— 28F with SLE on mycophenolate and prednisone 30 mg, asks about "shingles shot"
— 62M s/p renal transplant 3 years ago on tacrolimus/MMF, due for routine vaccines
— 19F with sickle cell disease (functional asplenia) transitioning from peds to adult care
— 35M with HIV, CD4 180, VL undetectable on ART, never vaccinated as adult
— Pre-chemotherapy "tune-up" visit for newly diagnosed breast cancer
— Pre-splenectomy planning for ITP or hereditary spherocytosis
— Underlying condition: type, severity, duration, current activity
— Current immunosuppressive regimen: drug, dose, duration, planned changes
— Prior vaccination history: childhood records, prior pneumococcal/zoster/HPV, COVID series
— Serologic immunity status: HBsAb, measles/mumps/rubella/varicella IgG, especially in transplant candidates
— Exposure risks: occupation (healthcare, daycare), travel, household contacts (especially infants, other immunocompromised)
— Allergies: egg (yellow fever, some influenza), gelatin, prior anaphylaxis to vaccine component
— Pregnancy status/plans in reproductive-age women
— Live vaccines in household contacts of immunocompromised patients are generally safe and encouraged (MMR, varicella, rotavirus, LAIV)
— Exception: avoid contact with diaper changes for 4 weeks after rotavirus; avoid contact with vesicular rash after varicella/zoster vaccination
— Oral polio vaccine is contraindicated in household contacts (not used in US anyway)
— Document last dose of rituximab (responses blunted ≥6 months); ideally vaccinate before or wait 6 months after
— High-dose steroids: wait 1 month after discontinuation for live vaccines
Board pearl: A question stem mentioning "starting rituximab in 4 weeks" is a setup—give all indicated inactivated vaccines NOW; the response will be poor if given after.
— General: cachexia, frailty (predicts blunted vaccine response and higher VPD mortality)
— Skin: surgical scars (splenectomy in LUQ), port/catheter sites, herpetic lesions (defer zoster vaccine if active), psoriasis/eczema flares on biologics
— HEENT: oral candidiasis (marker of T-cell dysfunction in HIV/steroids), gingival hyperplasia (cyclosporine)
— Lymphatic: lymphadenopathy (active lymphoma, HIV), absent palpable spleen
— Abdomen: hepatosplenomegaly (cirrhosis—a vaccine indication itself), surgical scars
— MSK: active synovitis suggests poorly controlled autoimmune disease
— Sickle cell disease, celiac disease (up to 30%), advanced cirrhosis, prior splenic irradiation, lupus, GVHD
— Howell-Jolly bodies on peripheral smear = functional asplenia → treat as anatomic asplenia for vaccine purposes
— CD4 count and HIV viral load (HIV patients)
— Absolute lymphocyte count, IgG level (humoral function)
— Current steroid dose in prednisone-equivalents
— Time since HSCT/SOT, time since last B-cell-depleting agent
— Defer vaccines during moderate-severe acute illness with fever; mild URI is not a contraindication
— Document baseline before vaccines so post-vaccination fever isn't misattributed
— Avoid limbs with lymphedema (post-mastectomy, post-node dissection) when alternatives exist
— Patients on anticoagulation: use 23–25G needle, firm pressure ≥2 min, IM still preferred over SC for most vaccines
Key distinction: A 20 mg/day prednisone patient for <14 days is NOT considered immunosuppressed for live vaccine purposes; the threshold is ≥20 mg/day for ≥14 days (or equivalent). Below this, live vaccines remain permissible.
— Hepatitis B: HBsAg, anti-HBs, anti-HBc in all immunocompromised; check anti-HBs 1–2 months post-series in dialysis, HIV, transplant candidates—revaccinate if <10 mIU/mL
— Measles, mumps, rubella, varicella IgG: in transplant candidates, HIV, healthcare workers, refugees, anyone without documented 2-dose MMR/varicella
— Hepatitis A IgG: in chronic liver disease, MSM, IDU, travelers
— HIV: required before any vaccine planning if status unknown and risk factors present
— Tuberculosis: IGRA before starting biologics (anti-TNF) — not vaccine per se but bundled in pre-immunosuppression workup
— CD4 count stratifies live-vaccine eligibility in HIV:
— CD4 ≥200 (and ≥15%): MMR and varicella permitted
— CD4 <200: live vaccines contraindicated
— Quantitative immunoglobulins in suspected CVID, post-rituximab, multiple myeloma
— CBC with differential: absolute neutrophil count, lymphocyte count
— Specific antibody titers (pneumococcal, tetanus, Hib) to assess humoral function in primary immunodeficiency workup
— HBV: anti-HBs 1–2 months post-series in HIV, dialysis, transplant, healthcare workers exposed to blood—revaccinate non-responders
— Pneumococcal: routine titer checks not recommended outside research
— Measles/varicella post-vaccine titers: in HSCT recipients given inactivated MMR equivalents (live MMR given after seroconversion failure when safe—≥24 months post-HSCT, no GVHD, no immunosuppression)
— Lot number, site, route, date in EHR + state immunization registry
— Vaccine Information Statement (VIS) given (federal requirement under National Childhood Vaccine Injury Act—applies to adults too)
Step 3 management: Order HBsAg + anti-HBs + anti-HBc as a panel before HBV vaccination in any immunocompromised patient—avoids vaccinating someone with chronic infection and identifies need for treatment referral.
— Solid organ transplant candidates evaluated by transplant ID team
— Serologies obtained: HBV (3-panel), HCV Ab + RNA, HIV, HAV IgG, VZV IgG, measles/mumps/rubella IgG, EBV, CMV, syphilis, toxoplasma, strongyloides (if endemic exposure), TB (IGRA)
— Vaccines to complete pre-transplant (≥4 weeks before for live, ≥2 weeks for inactivated):
— MMR, varicella (if non-immune and CD4/immune status permits)
— HBV (double-dose series in CKD/dialysis), HAV
— Inactivated influenza, pneumococcal (PCV20 or PCV15→PPSV23), Tdap, HPV (through age 26, can extend to 45 shared decision)
— Zoster recombinant (RZV) if ≥19 with immunocompromise or ≥50
— Meningococcal ACWY + B if asplenia/complement deficiency
— COVID-19 per current ACIP guidance
— All HSCT recipients are considered immunologically naïve post-transplant—full reimmunization required
— 6–12 months post-HSCT: PCV (3 doses), Hib, inactivated influenza (start at 6 months, annually), HBV, HAV, IPV, Tdap, meningococcal
— 24 months post-HSCT (if no GVHD and off immunosuppression): live MMR and varicella vaccines
— Avoid live vaccines during active GVHD or ongoing immunosuppression regardless of time
— Similar to HSCT-lite reimmunization; inactivated vaccines starting 3–6 months post-infusion
— B-cell aplasia from anti-CD19 CAR-T may require IVIG for hypogammaglobulinemia rather than relying on vaccines
— Transplant ID, oncology, rheumatology, allergy/immunology (suspected primary immunodeficiency or vaccine allergy)
— Travel medicine for yellow fever waivers (live vaccine—often contraindicated; medical waiver letter needed)
Board pearl: HSCT patients lose prior immunity—childhood vaccines don't count. They need a complete reimmunization series starting 6 months post-transplant. This is a frequent Step 3 distractor.
— Tier 1 — Always indicated (inactivated, no contraindications):
— Annual inactivated influenza (IIV or RIV—not LAIV)
— Pneumococcal: PCV20 alone OR PCV15 + PPSV23 (≥8 weeks later) for all immunocompromised ≥19
— Tdap once, then Td/Tdap every 10 years
— COVID-19 per current schedule (additional doses for immunocompromised)
— HBV (if not immune)—3-dose Engerix-B/Recombivax, 4-dose Heplisav-B, or double-dose for dialysis
— Recombinant zoster (RZV/Shingrix) ≥19 if immunocompromised, 2 doses 1–6 months apart (can be 4 weeks if urgent immunosuppression starting)
— HPV through age 26 (shared decision 27–45)
— Tier 2 — Indicated by specific condition:
— Asplenia/complement deficiency/eculizumab: meningococcal ACWY (2 doses, boost every 5 years) + MenB (2-3 doses); Hib (1 dose if not previously vaccinated)
— Chronic liver disease: HAV
— HIV: as above plus MenACWY (2 doses, boost q5y per 2024 ACIP)
— Renal failure/dialysis: high-dose HBV
— Tier 3 — Live vaccines (case-by-case, generally contraindicated):
— MMR, varicella: only if CD4 ≥200 in HIV, or pre-immunosuppression, or ≥24 months post-HSCT without GVHD
— Yellow fever: medical waiver typically
— LAIV, oral typhoid, BCG, oral polio: contraindicated
— Inactivated: ≥2 weeks before initiation; can give during therapy (lower response)
— Live: ≥4 weeks before; ≥3 months after discontinuation of most immunosuppressants; ≥6 months after rituximab
— High-dose steroids (≥20 mg/d ≥14 d): wait ≥1 month after stopping for live vaccines
Step 3 management: When asked "which vaccine first?" in a patient starting biologics in 4 weeks—RZV, PCV, HBV, influenza, Tdap now, defer any live vaccine indefinitely or give before therapy if time allows.
— All immunocompromised adults ≥19: choose either
— PCV20 (Prevnar 20) × 1 dose — preferred for simplicity, OR
— PCV15 (Vaxneuvance) × 1, then PPSV23 ≥8 weeks later (≥1 year preferred but 8 weeks acceptable in immunocompromised)
— Prior PPSV23 only: give PCV20 or PCV15 ≥1 year later
— Prior PCV13: complete with PPSV23 (≥8 weeks) or single PCV20
— ≥19 immunocompromised, ≥50 immunocompetent
— 2 doses, 2–6 months apart (can shorten to 1–2 months in immunocompromised or imminent immunosuppression)
— Adjuvanted, highly reactogenic—counsel re: arm pain, fatigue, fever 24–48 hr
— Efficacy ~68–91% in immunocompromised cohorts
— Inactivated (IIV) or recombinant (RIV), never LAIV in immunocompromised
— High-dose (HD-IIV) or adjuvanted (aIIV) preferred in ≥65 and reasonable in solid organ transplant
— Give annually, ideally Sept–Oct, but anytime during season
— Heplisav-B (2-dose, 4 weeks apart) preferred—higher seroprotection in immunocompromised
— PreHevbrio (3-dose) acceptable
— Dialysis: Engerix-B 40 mcg × 4 doses (0,1,2,6 mo) or Recombivax HB 40 mcg × 3 (0,1,6 mo)
— Check anti-HBs 1–2 months post-series; revaccinate non-responders (<10 mIU/mL) with second full series
— MenACWY: 2 doses 8 weeks apart, booster every 5 years
— MenB: Bexsero (2 doses, ≥1 month apart) or Trumenba (3-dose 0, 1–2, 6 months)
— Eculizumab/ravulizumab: vaccinate ≥2 weeks before first dose or give prophylactic penicillin if urgent
— 9-valent, 3-dose series (0, 1–2, 6 months) for all immunocompromised regardless of age at initiation through 26 (shared decision to 45)
Board pearl: RZV is the only zoster vaccine available in the US—live Zostavax is discontinued. RZV is safe and indicated in immunocompromised patients ≥19.
— Vaccinate ≥2 weeks before elective splenectomy:
— PCV20 (or PCV15→PPSV23)
— MenACWY × 2 doses 8 weeks apart + MenB series
— Hib × 1 dose
— Emergency splenectomy (trauma): vaccinate ≥14 days post-op (immune response better than immediate post-op)
— Lifelong revaccination: MenACWY boost q5y, PPSV23 once at 5 years if PCV15 pathway used
— Pre-transplant (waitlist): complete all inactivated vaccines, finish live vaccines ≥4 weeks before transplant
— Post-transplant 3–6 months: resume inactivated vaccines (influenza often given at 1 month if outbreak)
— Post-transplant lifelong: no live vaccines while on immunosuppression
— Annual influenza, COVID per ACIP, pneumococcal completion, RZV, HBV titers
— Rituximab/anti-CD20: vaccinate ≥4 weeks before dose; response blunted up to 6 months after
— Methotrexate: hold for 2 weeks after influenza vaccine (improves response, per ACR 2023)
— Abatacept: blunts response significantly—vaccinate before initiation when possible
— JAK inhibitors (tofacitinib, baricitinib, upadacitinib): increase zoster risk—RZV strongly indicated before initiation
— Anti-TNF: minimal effect on vaccine response; vaccinate without holding
— Anti-CD19 CAR-T: no live vaccines for ≥1 year; inactivated resumed at 3–6 months
— Black-box warning for meningococcal disease
— MenACWY + MenB ≥2 weeks before first dose
— Prophylactic penicillin VK 500 mg BID during therapy if vaccines not completed
— Order: "Vaccine reconciliation, immunization registry query, indicated vaccines today, schedule follow-up for series completion, document VIS provided"
CCS pearl: For a patient starting eculizumab urgently for aHUS or PNH, don't wait 2 weeks—give vaccines AND start penicillin prophylaxis concurrently with eculizumab; document the urgency.
— Immunosenescence + iatrogenic immunosuppression = highest VPD mortality
— High-dose influenza (Fluzone HD), adjuvanted (Fluad), or recombinant (Flublok) preferred ≥65
— RZV: indicated regardless of immune status ≥50; reactogenicity high but tolerable
— PCV20 simplifies; consider for any ≥65 not previously vaccinated
— RSV vaccine (Abrysvo, Arexvy, mResvia): shared clinical decision-making ≥60, recommended ≥75 — safe in immunocompromised (recombinant/protein subunit, not live)
— Polypharmacy review—prednisone tapering may unmask vaccine candidacy
— Cognitive impairment: ensure consent capacity or surrogate decision-maker documented
— Higher infection risk; antibody responses blunted ~50% vs general population
— HBV: high-priority vaccine; use Heplisav-B (2-dose) or double-dose 3-dose Engerix-B; check anti-HBs 1–2 months post, revaccinate if <10 mIU/mL
— Influenza, pneumococcal, RZV, Tdap, COVID: all indicated
— Live vaccines: not contraindicated by CKD alone, but contraindicated by concurrent immunosuppression (e.g., transplant, lupus nephritis on cyclophosphamide)
— Dose timing around dialysis: give after hemodialysis to allow rest; IM in deltoid (avoid AV fistula arm)
— HAV and HBV strongly indicated (decompensation risk with hepatitis superinfection)
— PCV20 or PCV15→PPSV23 (cirrhosis is an immunocompromising condition)
— Influenza annually
— RZV ≥50 (cirrhosis increases zoster risk)
— Avoid live vaccines in decompensated cirrhosis or post-liver-transplant
— Vaccines still indicated in frail elders unless life expectancy <6 months and goals shift to comfort
— Shared decision-making document in chart
Key distinction: RSV vaccines are recombinant protein subunit, not live—safe in immunocompromised. Don't confuse with the live nasal influenza or live attenuated rotavirus.
— Indicated in every pregnancy (regardless of immune status):
— Tdap at 27–36 weeks each pregnancy (neonatal pertussis protection)
— Inactivated influenza any trimester
— RSV (Abrysvo) at 32–36 weeks Sept–Jan (or maternal vaccine OR nirsevimab to infant)
— COVID-19 per current ACIP
— Contraindicated in pregnancy: MMR, varicella, LAIV, HPV (deferred, not teratogenic—resume postpartum)
— HBV, HAV, pneumococcal, meningococcal: safe if indicated
— Immunosuppressed pregnant patients (e.g., transplant, lupus, HIV): same schedule; coordinate with high-risk OB
— Live vaccines (MMR, varicella, rotavirus, LAIV): contraindicated in severe primary/secondary immunodeficiency, active chemotherapy, HSCT, SOT on immunosuppression
— Rotavirus exception: severe combined immunodeficiency (SCID) is absolute contraindication; HIV-exposed infants can receive if CD4 adequate
— Catch-up schedules per CDC for children with cancer post-chemo (resume 3 months after completion, 6 months after rituximab/anti-CD20)
— Pediatric HSCT: full reimmunization series at 6–12 months post-transplant
— HPV through age 26 (3-dose series for immunocompromised regardless of initiation age)
— MenACWY at 11–12 and 16; MenB shared decision 16–23 or required if asplenia/complement deficiency
— Transitioning chronic illness (sickle cell, congenital heart, IBD) to adult care: vaccine reconciliation is a quality metric
— Encouraged to receive all age-appropriate vaccines including MMR, varicella, rotavirus, LAIV (no risk of transmission for most)
— Caveats: avoid contact with vesicular rash post-varicella/zoster, careful diaper hygiene 4 weeks post-rotavirus
Step 3 management: A pregnant SLE patient on hydroxychloroquine + low-dose prednisone should receive Tdap, flu, RSV, and COVID per ACIP—pregnancy alone is not immunocompromise, and her medications don't preclude inactivated vaccines.
— Local: injection-site pain (RZV >90%), erythema, swelling—reassure, NSAIDs
— Systemic: low-grade fever, myalgia, fatigue 24–72 hr (especially RZV, adjuvanted flu, COVID); pre-medicate acetaminophen if anticipated
— Anaphylaxis: rare (~1 per million); manage with IM epinephrine 0.3–0.5 mg, observation, refer to allergy for skin testing/desensitization
— Guillain-Barré syndrome: rare association with influenza (~1 per million); not absolute contraindication to future vaccines unless within 6 weeks of prior dose
— Live vaccine in immunocompromised host: disseminated vaccine-strain disease (vaccine-strain measles, varicella, yellow fever encephalitis, BCG-osis)—catastrophic in severely immunocompromised
— Higher in immunocompromised (blunted humoral and cellular response)
— Manage breakthrough disease aggressively: e.g., post-vaccine herpes zoster still warrants valacyclovir if within 72 hours
— Monitor anti-HBs in dialysis/transplant—boost annually if titer wanes
— Invasive pneumococcal disease in asplenia: mortality up to 50% in overwhelming post-splenectomy infection (OPSI)
— Meningococcal sepsis on eculizumab without vaccination/prophylaxis: case fatality ~20%
— Disseminated zoster with visceral involvement in HSCT/transplant
— HBV reactivation during rituximab (test HBsAg + anti-HBc before; entecavir/tenofovir prophylaxis if positive)
— Live vaccine inadvertently given to immunocompromised host: monitor closely, ID consult, consider IVIG (for measles exposure) or specific antivirals (acyclovir for varicella-strain disease)
— Federally mandated for: anaphylaxis, encephalopathy within 7 days, GBS, intussusception post-rotavirus, any event in Vaccine Injury Table
Board pearl: A patient on rituximab who develops herpes zoster despite RZV vaccination—the vaccine still works partially; outcomes (PHN, dissemination) are reduced even if breakthrough occurs.
— Allergy/Immunology:
— Prior anaphylaxis to vaccine or vaccine component (egg-severe, gelatin, latex, polyethylene glycol)
— Suspected primary immunodeficiency (recurrent sinopulmonary infections, hypogammaglobulinemia)
— Need for desensitization protocol
— Infectious Disease:
— Inadvertent live vaccine in severely immunocompromised host
— Pre-transplant complex vaccine planning
— Post-exposure prophylaxis (measles, varicella, HBV, rabies) in immunocompromised
— Travel vaccination with live vaccine requirements (yellow fever waiver)
— Transplant team: pre- and post-transplant vaccine coordination
— Oncology: timing vaccines with chemotherapy cycles
— Rheumatology: coordinating biologic timing with vaccine administration
— Vaccine-strain disseminated disease: hospitalization, IV antivirals (acyclovir for varicella-strain, ribavirin for measles considered), supportive care
— Anaphylaxis: ED observation ≥4–6 hours, longer if delayed reactions, epinephrine auto-injector at discharge
— Post-vaccine GBS: admission for IVIG or plasma exchange, neurology consult
— Invasive pneumococcal disease, meningococcemia, OPSI: ICU admission, broad-spectrum antibiotics (ceftriaxone + vancomycin), source control
— Measles exposure: IVIG 400 mg/kg within 6 days (live MMR contraindicated)
— Varicella exposure: VariZIG within 10 days; acyclovir alternative if VariZIG unavailable
— Hepatitis B exposure (occupational): HBIG + initiate/complete HBV series
— Rabies: full series + HRIG regardless of immune status
— "Pre-splenectomy vaccine bundle: PCV20, MenACWY, MenB, Hib, schedule surgery ≥14 days later"
Step 3 management: A leukemia patient on chemo exposed to measles in a clinic waiting room—order IVIG 400 mg/kg IV within 6 days, do NOT give MMR. Document exposure, notify public health.
— Anaphylaxis to prior dose or vaccine component
— Live vaccines in:
— Severe immunocompromise (active chemo, HSCT on immunosuppression, SOT, HIV with CD4 <200, primary T-cell deficiencies)
— Pregnancy
— High-dose steroids (≥20 mg/d ≥14 days)—wait 1 month after stopping
— Recent IVIG / blood products (MMR, varicella—defer 3–11 months depending on product)
— Pertussis vaccine: encephalopathy within 7 days of prior dose (Tdap then deferred; Td used instead)
— Rotavirus: history of intussusception, SCID
— Moderate-severe acute illness with fever: defer until improved
— GBS within 6 weeks of prior tetanus/influenza: weigh risk
— Recent antibody-containing product: timing adjustment for MMR/varicella
— Bleeding disorders / anticoagulation: IM still given with 23G needle and prolonged pressure
— Latex allergy: avoid vaccines in latex-containing vials/stoppers
— Mild URI without fever
— Breastfeeding (live vaccines OK in mother except smallpox, yellow fever in some cases)
— Recent exposure to infectious disease
— Premature birth (vaccinate per chronologic age)
— Family history of adverse events
— Antibiotic use
— Egg allergy (modern influenza vaccines—any severity OK with standard observation per 2023 ACIP)
— Low-dose steroids (<20 mg/d or <14 days), inhaled, intra-articular, topical
— CD4 ≥200: MMR and varicella permitted
— CD4 <200: live vaccines contraindicated; once on ART with CD4 recovery ≥200 for ≥6 months, can give live vaccines
Key distinction: Egg allergy is no longer a contraindication or precaution for influenza vaccines (2023 ACIP)—any patient with egg allergy can receive any age-appropriate flu vaccine with standard observation.
— B-cell defects (CVID, XLA, hyper-IgM): inactivated vaccines OK (response variable, often poor); avoid live oral polio, BCG, yellow fever; IVIG provides passive protection
— T-cell or combined defects (SCID, DiGeorge complete, Wiskott-Aldrich): all live vaccines contraindicated
— Complement deficiencies (C5-C9, properdin, factor H/I): inactivated vaccines safe; meningococcal ACWY + MenB essential; live vaccines generally permitted
— Phagocyte defects (CGD): avoid live bacterial vaccines (BCG, oral typhoid Ty21a); other live OK
— Innate immunity defects (IRAK4, MyD88): inactivated vaccines OK
— HIV: CD4-stratified (see prior chunks)
— Hematologic malignancy (leukemia, lymphoma, myeloma): treat as severely immunocompromised during active disease and ≥6 months post-chemo; consider IVIG in hypogammaglobulinemia
— Solid organ transplant: lifelong avoidance of live vaccines
— Asplenia/hyposplenia: functional (sickle cell, celiac, cirrhosis, lupus) vs anatomic—both require encapsulated organism vaccines (pneumococcus, meningococcus, Hib)
— Iatrogenic: chemotherapy, steroids, biologics, radiation
— Pre-biologic vaccine bundle: PCV, HBV, HAV, RZV, HPV, influenza, Tdap, COVID
— Methotrexate alone: live vaccines generally permitted at low doses, but most experts avoid
— Combo immunosuppression (e.g., MTX + infliximab): treat as immunocompromised
— Pregnancy alone ≠ immunocompromise but shares live-vaccine prohibition; postpartum catch-up window important
Board pearl: Sickle cell disease patients have functional asplenia by age 1—they need pneumococcal, meningococcal ACWY+B, and Hib vaccines on an accelerated schedule, and lifelong penicillin prophylaxis until at least age 5.
— Annual: inactivated influenza (high-dose if ≥65 or SOT), COVID-19 per current ACIP guidance
— Every 10 years: Td/Tdap booster (one Tdap if not received as adult, then Td or Tdap)
— Every 5 years: meningococcal ACWY boost in asplenia/complement deficiency/eculizumab; MenB booster per ACIP guidance
— Once: PCV20 (or PCV15+PPSV23), RZV 2-dose series, HPV 3-dose if eligible, HBV series with anti-HBs confirmation
— As needed: HBV booster if anti-HBs <10 mIU/mL (dialysis especially)
— Travel: pre-travel consultation 4–6 weeks before; many live vaccines contraindicated—medical waivers, alternative inactivated options
— State immunization information system (IIS) registration
— Patient-held vaccine card / patient portal
— Annual reconciliation at wellness visit (Medicare AWV, commercial preventive visit)
— HEDIS measures: pneumococcal in ≥65, influenza in ≥18, Tdap in adults
— Immunocompromised-specific quality metrics emerging in ACO contracts
— Vaccine hesitancy: address concerns about live attenuated risk, autoimmune flare myths, mRNA platform safety
— Cocooning: vaccinate household contacts (especially flu, Tdap during pregnancy in family members, COVID)
— Travel and occupational exposures
— Post-exposure planning: provide written instructions for measles/varicella/HBV exposure
— Specialist (rheum, onc, transplant, ID) defines immunosuppression status
— Primary care executes routine schedule
— Pharmacy: many vaccines now administered at retail pharmacies—ensure communication back to PCP
— Public health department for outbreak response and reportable adverse events
Step 3 management: Schedule a yearly "immunization visit" or attach immunization reconciliation to the Medicare Annual Wellness Visit—this is a billable encounter and a measurable quality outcome.
— 15–30 min observation after vaccination for anaphylaxis (especially first dose or known allergy history)
— 1–2 months post-HBV series: check anti-HBs; revaccinate non-responders
— Annual: review immunization registry, document next-due vaccines
— Post-HSCT/transplant: structured 6, 12, 24-month vaccine clinic visits
— Expected reactions: arm soreness, low fever, fatigue 24–48 hr—especially RZV, adjuvanted flu, COVID; reassure these are immune response, not infection
— When to seek care: difficulty breathing, swelling of face/throat, hives, persistent high fever, severe neurologic symptoms (numbness, weakness)
— Live vaccine education: explain why deferred or avoided; discuss household contact vaccination as cocooning
— Series completion importance: emphasize all doses (especially 2-dose RZV—single dose has limited efficacy)
— Vaccine card: keep updated, photograph for digital copy
— VIS provision: required by federal law for each vaccine encounter
— Routine antibody titer testing is not recommended for most vaccines (pneumococcal, RZV, influenza)
— Exception — HBV: check anti-HBs in dialysis, HIV, healthcare workers, transplant candidates
— Exception — MMR/varicella: post-vaccine titers in HSCT recipients given live vaccine after immune recovery
— Tie vaccine status to chronic disease visits (CKD, HIV, IBD, post-transplant) to capture missed opportunities
— Standing orders in clinic for nurses to administer indicated vaccines without provider re-evaluation
— Reminder/recall systems (text, portal, postcards)—proven to increase rates 5–20%
— Discharge from hospital, transfer between facilities, change of insurance all create vaccine gaps
— Medication reconciliation should include vaccine reconciliation
CCS pearl: When advancing time after vaccination, schedule "Routine follow-up in 1 month" for HBV antibody check or second RZV dose, and "Annual exam" for influenza catch-up—these clicks score on CCS preventive care metrics.
— Federal National Childhood Vaccine Injury Act of 1986 requires VIS (Vaccine Information Statement) for covered vaccines—applies to adults too for routinely recommended vaccines
— Document: date VIS given, edition, verbal consent (or signed if institutional policy)
— Capacity assessment: in cognitively impaired or critically ill patients, identify healthcare proxy or surrogate
— Document discussion, risks of declining (specific to their condition—e.g., OPSI in asplenia, IPD in transplant)
— Use AAP-style "Refusal to Vaccinate" form for high-risk pediatric cases
— Re-address at each visit—decisions can change
— VAERS reporting: adverse events listed in Vaccine Injury Table or any serious event (death, hospitalization, life-threatening, permanent disability)
— Vaccine Injury Compensation Program (VICP): no-fault federal compensation; statute of limitations 3 years for injury, 2 years for death
— Outbreak-associated VPDs (measles, pertussis, meningococcus) → notify local health department
— Cost barriers: Vaccines for Children (VFC) program <19 if uninsured/Medicaid; Section 317 funding for adults
— Inflation Reduction Act (2023): ACIP-recommended vaccines free for Medicare Part D enrollees
— Pharmacy-based vaccination expands access but must communicate back to PCP—orphaned records are a safety risk
— Hospital discharge of immunocompromised patient: medication reconciliation must include vaccine status review and outpatient follow-up plan
— Specialty-to-PCP handoffs after transplant or oncology completion: who owns the vaccine schedule? Document explicitly
— Failure to vaccinate a splenectomy patient pre-op due to "we'll do it in clinic later" is a sentinel safety event in many systems
— Healthcare workers caring for immunocompromised patients should be fully vaccinated (annual flu, MMR, varicella, Tdap, HBV, COVID)—institutional ethics and CMS Conditions of Participation
Step 3 management: A patient declining the recombinant zoster vaccine on biologics—document the conversation, provide written information, offer revisit at next appointment; do not discharge from the practice for refusal alone.
— Asplenia → PCV20, MenACWY+MenB, Hib
— Eculizumab/ravulizumab → MenACWY+MenB (2 wks before or PCN prophylaxis)
— CKD/dialysis → high-dose or Heplisav HBV; check anti-HBs
— HIV CD4 ≥200 → live MMR/varicella permitted
— HSCT → full reimmunization at 6–24 months
— Pre-rituximab → vaccinate ≥4 weeks before; blunted for 6 months after
— Pre-anti-TNF → RZV especially, full bundle
— JAK inhibitor → RZV before (high zoster risk)
— Cirrhosis → HAV + HBV mandatory
— Pregnancy → Tdap 27–36 wk, flu anytime, RSV 32–36 wk in season, COVID
— MMR, varicella, zoster live (Zostavax—discontinued in US), LAIV (FluMist), oral typhoid (Ty21a), yellow fever, BCG, oral polio, rotavirus, smallpox/mpox (ACAM2000)
— IIV/RIV influenza, PCV15/20, PPSV23, HBV (all formulations), HAV, Tdap, IPV, HPV, MenACWY, MenB, Hib, RZV (Shingrix), RSV (Abrysvo/Arexvy/mResvia), COVID-19, injectable typhoid (Vi polysaccharide), rabies, JE
— Inactivated: ≥2 weeks pre-immunosuppression
— Live: ≥4 weeks pre-immunosuppression; ≥3 months post-most immunosuppressants; ≥6 months post-rituximab
— High-dose steroids: ≥1 month after discontinuation for live vaccines
— IVIG → MMR/varicella: defer 3–11 months
— Steroid threshold: ≥20 mg/d prednisone × ≥14 days = immunocompromised
— HIV: CD4 ≥200 = live vaccines permitted
— Anti-HBs: <10 mIU/mL = non-responder, revaccinate
Board pearl: The five "always now" vaccines for any newly diagnosed immunocompromised adult: influenza, pneumococcal, RZV, Tdap, COVID (plus HBV if non-immune).
— "45F newly diagnosed RA, rheumatologist plans to start adalimumab in 4 weeks. Which vaccines should be given today?"
— Answer logic: All inactivated indicated (RZV, PCV20, Tdap if due, HBV if non-immune, influenza/COVID seasonal); MMR/varicella only if non-immune AND can complete ≥4 weeks before therapy
— "32M with hereditary spherocytosis scheduled for elective splenectomy in 3 weeks. Which vaccines?"
— Answer: PCV20, MenACWY (start 2-dose series), MenB (start series), Hib × 1, all ≥2 weeks before surgery
— "28M with HIV, CD4 145, never vaccinated as adult. Which vaccines now?"
— Answer: Inactivated vaccines (flu, pneumococcal, HBV, Tdap, HPV, RZV ≥19); defer MMR and varicella until CD4 ≥200 sustained ≥6 months on ART
— "55F 8 months post-allogeneic HSCT, no GVHD, off immunosuppression. Which vaccines now?"
— Answer: PCV series, Hib, inactivated influenza, HBV, HAV, IPV, Tdap, meningococcal; defer MMR/varicella to 24 months post-HSCT
— "22M starting eculizumab for PNH urgently. Vaccine and prophylaxis plan?"
— Answer: MenACWY + MenB ASAP; if eculizumab cannot be delayed 2 weeks, start penicillin VK 500 mg BID prophylaxis concurrently
— "Toddler with newly diagnosed SCID inadvertently received rotavirus vaccine. Next step?"
— Answer: ID consult, monitor for vaccine-strain diarrhea, supportive care, consider IVIG; do not give additional rotavirus doses; expedite HSCT evaluation
— "30F kidney transplant 4 years ago on tacrolimus/MMF, 28 weeks pregnant (MMF was switched to azathioprine pre-pregnancy). Vaccines?"
— Answer: Tdap 27–36 wk, inactivated influenza, RSV in season, COVID per ACIP; no live vaccines
— Distractor: severe egg allergy ≠ flu contraindication anymore (2023 ACIP)
Step 3 management: When the question says "which is the most appropriate next step," scan for timing (before/after immunosuppression), CD4, steroid dose, and live vs inactivated distinction—these determine the answer 90% of the time.
Immunocompromised hosts need a proactive, tiered vaccine plan delivered ideally before immunosuppression begins—give all indicated inactivated vaccines (influenza, PCV20, RZV, Tdap, HBV, HPV, COVID, condition-specific MenACWY/MenB/Hib) at every opportunity, avoid live vaccines in severe immunocompromise, and reconcile immunization status at every clinical encounter.
— Timing rule: inactivated ≥2 weeks before immunosuppression, live ≥4 weeks before; live vaccines contraindicated during severe immunocompromise (active chemo, HSCT/SOT on immunosuppression, HIV CD4 <200, prednisone ≥20 mg/d ≥14 days, biologics)
— The "always now" bundle for any new immunocompromised diagnosis: influenza (inactivated), PCV20 (or PCV15→PPSV23), RZV ≥19, Tdap, HBV (if non-immune), COVID-19 per ACIP
— Condition-specific add-ons: asplenia/complement deficiency/eculizumab → MenACWY + MenB + Hib (plus penicillin prophylaxis if eculizumab urgent); CKD/dialysis → high-dose or Heplisav-B HBV with post-series anti-HBs check; cirrhosis → HAV + HBV; HSCT → full reimmunization starting 6 months post-transplant, live vaccines only ≥24 months if no GVHD/immunosuppression
— Transition-of-care safety: every hospital discharge, specialty handoff, and Medicare AWV is a vaccine-reconciliation opportunity—missed pre-splenectomy or pre-eculizumab vaccination is a sentinel safety event
— Pre-biologic: vaccinate now, especially RZV
— Pre-transplant: complete all live vaccines on waitlist
— Post-HSCT: reimmunize like a newborn
— Asplenia: encapsulated organism vaccines + lifelong boosters
— Eculizumab: MenACWY+MenB or penicillin prophylaxis—non-negotiable
— Pregnancy: Tdap + flu + RSV + COVID; no live vaccines
Board pearl: When in doubt on Step 3, default to: inactivated vaccines are safe and indicated; live vaccines need pre-immunosuppression timing or are contraindicated. This single principle answers the majority of vignette questions on this topic.