6.3 Immunizations in Special Populations: Pregnancy, Asplenia & Immunocompromise

Maternal Immunization: Protecting Mother and Neonate

Physiologic and Immunologic Alterations in Pregnancy

Pregnancy involves complex immunological modulation characterized by a physiological shift from cell-mediated Th1 responses toward humoral Th2 immunity to prevent maternal fetal rejection. Concurrently, progressive diaphragmatic elevation by the gravid uterus reduces functional residual capacity, while maternal oxygen consumption and cardiac output increase by 30–50%. These alterations significantly increase maternal vulnerability to severe viral respiratory illness, acute respiratory distress syndrome (ARDS), sepsis, and obstetric complications (preeclampsia, preterm labor, stillbirth).

Concurrently, neonates possess naive B cells, deficient complement levels, and delayed endogenous IgG production until 2 to 3 months of age. Neonatal survival depends on transplacental transfer of maternal IgG via the neonatal Fc receptor (FcRn), which surges exponentially during the third trimester (28 to 36 weeks).

Indicated Vaccines During Pregnancy

1. Inactivated Influenza Vaccine (IIV4 or RIV4):
   • Timing: Administered during any trimester (first, second, or third).
   • Impact: Reduces maternal cardiopulmonary hospitalization by 40–50% and reduces laboratory-confirmed influenza in infants during the first 6 months of life by >50%.
2. Tdap (Tetanus, Reduced Diphtheria, Acellular Pertussis):
   • Timing: Administered during each pregnancy between 27 and 36 weeks of gestation (optimally 27–32 weeks).
   • Impact: Maximizes transplacental transfer of anti-pertussis antibodies, preventing neonatal pertussis encephalopathy and death before the infant's 2-month DTaP series.
3. COVID-19 Updated Vaccine:
   • Timing: Safe and indicated in any trimester.
   • Impact: Prevents severe maternal illness, maternal ICU admission, mechanical ventilation, stillbirth, and neonatal hospitalization.
4. Maternal RSV Vaccine (Abrysvo ONLY):
   • Formulation & Timing: Bivalent unadjuvanted recombinant RSV prefusion F vaccine administered between 32 0/7 and 36 6/7 weeks of gestation, seasonally from September through January in most continental US regions.
   • Contraindication of Competitor: Arexvy is strictly NOT approved in pregnancy due to a safety signal of preterm delivery.

Strictly Contraindicated Live Attenuated Vaccines in Pregnancy

• Prohibited Vaccines: Measles-Mumps-Rubella (MMR), Varicella (VAR), Live Attenuated Influenza Vaccine (LAIV), Oral Typhoid (Ty21a), and Yellow Fever (unless travel to high-epidemic zone is unavoidable).
• Pathophysiologic Rationale: Live attenuated viruses cross the placenta, posing theoretical risks of fetal replication, viremia, and teratogenesis:
  • Congenital Rubella Syndrome (CRS): Sensorineural deafness, cataracts, microphthalmia, patent ductus arteriosus (PDA), pulmonary artery stenosis, microcephaly, and "blueberry muffin" skin lesions.
  • Congenital Varicella Syndrome: Cicatricial dermatomal skin scarring, limb hypoplasia, chorioretinitis, optic atrophy, and microcephaly.
• Preconception Screening & Counseling: Non-pregnant women of childbearing age should be screened for rubella and varicella IgG. If non-immune, vaccinate prior to conception and strictly counsel to avoid pregnancy for at least 4 weeks (28 days) after receiving MMR or varicella vaccine.
• Management of Inadvertent Administration: If MMR or varicella vaccine is inadvertently administered during pregnancy, or if conception occurs within 4 weeks of vaccination, the clinician must counsel the patient regarding theoretical risks but explicitly reassure that CDC pregnancy registries have documented zero cases of Congenital Rubella Syndrome or Congenital Varicella Syndrome. Inadvertent vaccination is NOT an indication for termination of pregnancy.
• Deferred Vaccines: HPV vaccination is deferred during pregnancy due to lack of safety data. If started prior to pregnancy, pause the series and administer remaining doses postpartum without restarting.

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Anatomical and Functional Asplenia: Encapsulated Pathogen Vulnerability

Pathophysiology of the Asplenic State

• Etiologies: Surgical splenectomy (trauma, idiopathic thrombocytopenic purpura, hereditary spherocytosis, rupture), functional asplenia (sickle cell disease due to repeated microvascular vaso-occlusive splenic infarctions leading to complete autosplenectomy by age 5–6), celiac disease-associated splenic atrophy, and congenital asplenia.
• Splenic Host Defense: The spleen contains approximately 25% of the body's lymphoid tissue. The splenic red pulp filters senescent erythrocytes and un-opsonized blood-borne pathogens through endothelial slits. Marginal zone macrophages phagocytose poorly opsonized bacteria, while marginal zone B cells produce IgM antibodies (specifically against polysaccharide capsular antigens) that trigger the classical and alternative complement pathways.
• Overwhelming Post-Splenectomy Infection (OPSI):
  • Clinical Course: A catastrophic medical emergency characterized by a mild flu-like prodrome rapidly progressing within 12–24 hours to high-grade bacteremia (10⁶–10⁸ CFU/mL), fulminant septic shock, disseminated intravascular coagulation (DIC), purpura fulminans, bilateral adrenal hemorrhage (Waterhouse-Friderichsen syndrome), and death in 50–70% of cases.
  • Causative Encapsulated Organisms: Streptococcus pneumoniae (responsible for 50–70% of OPSI cases), Neisseria meningitidis, and Haemophilus influenzae type b (Hib).
  • Additional Pathogens: Capnocytophaga canimorsus (a fastidious gram-negative rod transmitted by dog or cat bites, causing overwhelming gangrenous sepsis in asplenics) and Babesia microti (an intraerythrocytic protozoan transmitted by Ixodes ticks, causing massive uncontrolled intravascular hemolysis).

Comprehensive Asplenia Immunization Protocol

[!IMPORTANT] MenACWY and MenB Are Non-Interchangeable: Serogroup B capsular polysaccharide mimics human fetal neural cell adhesion molecules (NCAM) and is non-immunogenic in standard conjugate vaccines; MenB vaccines utilize recombinant surface proteins (FHbp, NadA, NHBA). Asplenic patients REQUIRE BOTH MenACWY and MenB to ensure coverage against all five virulent meningococcal serogroups.

Splenectomy Perioperative Immunization Timing

• Elective Splenectomy (e.g., planned hematologic splenectomy):
  • Administer all indicated vaccines AT LEAST 14 DAYS PRIOR to surgery.
  • Rationale: Allows intact splenic architecture to process antigens, present to T cells, and generate high titers of protective memory B cells before splenic tissue is excised.
• Emergency Splenectomy (e.g., trauma, acute splenic rupture):
  • DELAY vaccination until AT LEAST POSTOPERATIVE DAY 14.
  • Rationale: Administering vaccines in the immediate postoperative period yields severely blunted, subtherapeutic antibody titers due to trauma-induced acute immune suppression, inflammatory catabolism, and massive surgical stress.

Outpatient Asplenia Safety & Prophylaxis Rules

1. Standby Emergency Antibiotics: Provide the patient with an outpatient prescription for broad-spectrum antibiotics (e.g., amoxicillin-clavulanate 875/125 mg BID; or levofloxacin 750 mg daily for severe penicillin allergy) to keep at home or while traveling. Instruct the patient to ingest the first dose immediately and proceed directly to an emergency department for ANY fever ≥ 38.0°C (100.4°F) or rigors.
2. Animal Bite Prophylaxis: Any dog or cat bite or scratch requires immediate medical attention, thorough wound cleansing, and prompt initiation of empiric amoxicillin-clavulanate to prevent fatal Capnocytophaga canimorsus bacteremia.
3. Tick Precautions: Counsel on avoiding tick-endemic brush to prevent Babesia microti parasitemia.
4. Medical Alert: Patients should continuously wear a medical alert bracelet indicating "Asplenic / High Sepsis Risk".

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Immunocompromised Adults: Stratification, Contraindications & Pre-Treatment Optimization

Categorization of Immune Suppression

• Severe / High-Level Immunocompromise:
  • Hematologic malignancies (leukemia, lymphoma, multiple myeloma)
  • Cancer chemotherapy or radiation therapy
  • Solid organ transplant recipients on maintenance immunosuppression (calcineurin inhibitors [tacrolimus, cyclosporine], antimetabolites [mycophenolate mofetil], mTOR inhibitors)
  • Hematopoietic stem cell transplant (HSCT) recipients within 2 years
  • Advanced or untreated HIV infection (CD4 count < 200 cells/μL or CD4 percentage < 14%)
  • Biologic immunomodulators: TNF-alpha inhibitors (infliximab, adalimumab, certolizumab, etanercept), B-cell depleting therapies (rituximab, ocrelizumab), IL-6 inhibitors (tocilizumab), JAK inhibitors (tofacitinib, baricitinib)
  • Systemic high-dose corticosteroids: Defined as ≥ 20 mg of prednisone equivalent daily for ≥ 14 consecutive days (or ≥ 2 mg/kg/day)
• Low-Level Immunocompromise: Prednisone < 20 mg/day, alternate-day corticosteroids, low-dose methotrexate (≤ 0.4 mg/kg/week), azathioprine (≤ 3 mg/kg/day), HIV infection with CD4 ≥ 200 cells/μL.

Absolute Contraindication: Live Attenuated Vaccines

Live attenuated vaccines (MMR, Varicella, LAIV, Yellow Fever, Oral Typhoid Ty21a, BCG) are STRICTLY CONTRAINDICATED in severely immunocompromised hosts due to the risk of uncontrolled vaccine-strain viral or bacterial replication, tissue dissemination, and fatal disease.

• The HIV Exception for MMR and Varicella: MMR and varicella vaccines are indicated in HIV-infected patients ONLY IF their CD4 count has been documented ≥ 200 cells/μL (and ≥ 15%) for at least 6 consecutive months. If CD4 < 200, live vaccines are strictly prohibited.

Pre-Immunosuppression Optimization Window

When elective biologic therapy, chemotherapy, or immunosuppression is planned:

• Live Attenuated Vaccines: Must be administered AT LEAST 4 WEEKS PRIOR to initiating immunosuppressive therapy.
• Inactivated Vaccines: Should be administered AT LEAST 2 WEEKS PRIOR to initiating immunosuppressive therapy to optimize immunologic priming and antibody generation.

Priority Inactivated Vaccines for Immunocompromised Hosts

• Pneumococcal: Single-dose PCV20 alone, single-dose PCV21 alone, or PCV15 followed by PPSV23 ≥ 8 weeks later.
• Recombinant Zoster Vaccine (Shingrix): Recommended for all immunocompromised adults aged ≥ 19 years; 2 doses administered at 0 and 1–2 months. Because Shingrix is a non-live recombinant sub-unit vaccine, it carries zero risk of viral replication.
• Hepatitis B: High risk of reactivation during immunosuppression (especially with anti-CD20 rituximab or anti-TNF therapy). Universal adult recommendation; non-responders require repeat series (prefer Heplisav-B) and post-vaccination serologic monitoring.
• COVID-19: Updated annual vaccine, with additional doses permitted ≥ 2 months apart.

Household Contacts of Immunocompromised Patients

• Household members should receive annual inactivated influenza vaccine, COVID-19, MMR, and Varicella vaccines to establish a protective "cocoon".
• If a household contact develops a vesicular rash after receiving the varicella vaccine, they should avoid direct contact with the immunocompromised patient until the lesions have completely crusted.
• Avoid LAIV: Household contacts should avoid LAIV if the patient is severely immunocompromised and residing in a protective environment (e.g., bone marrow transplant unit); if LAIV is administered, contact must be avoided for 7 days.

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International Travel Vaccines: Yellow Fever, Typhoid, Japanese Encephalitis & Rabies

1. Yellow Fever Vaccine (YF-VAX)

• Microbiology: Mosquito-borne flavivirus (Aedes and Haemagogus mosquitoes) endemic to tropical sub-Saharan Africa and South America. Clinical manifestations include biphasic illness with fever, severe bradycardia relative to fever (Faget's sign), jaundice, black vomitus (hematemesis), acute kidney injury, shock, and DIC (mortality 20–50%).
• Vaccine Characteristics: Live attenuated viral vaccine (17D strain) administered as a single subcutaneous dose. Documented on the International Certificate of Vaccination or Prophylaxis (ICVP, "yellow card"), which becomes legally valid 10 days after administration and confers lifelong immunity for most travelers.
• Severe Adverse Reactions & Age ≥ 60 Precaution:
  • Age ≥ 60 years is a major ACIP precaution. Older primary vaccinees experience significantly elevated risks of two life-threatening adverse reactions:
    1. Yellow Fever Vaccine-Associated Neurotropic Disease (YEL-AND): Meningoencephalitis, Guillain-Barré syndrome, autoimmune demyelinating disease; onset 3–28 days post-vaccination (incidence ~1–2 per 100,000 in age ≥ 60).
    2. Yellow Fever Vaccine-Associated Viscerotropic Disease (YEL-AVD): Severe systemic illness mimicking wild-type yellow fever with fulminant hepatic necrosis, shock, DIC, and multi-organ failure; onset 2–8 days post-vaccination; mortality >60% (incidence ~1–3 per 100,000 in age ≥ 60).
  • Absolute Contraindications: Severe allergy to eggs/gelatin; severe immunosuppression (HIV with CD4 < 200, solid organ transplant, biologic therapy); thymus disorders (thymoma, myasthenia gravis, history of thymectomy); infants < 6 months.
  • Clinical Management: In travelers aged ≥ 60 with low exposure risk traveling to countries requiring yellow fever proof for entry, issue an official Medical Waiver Certificate of Exemption.

2. Typhoid Fever Vaccines

• Pathogen: Salmonella enterica serotype Typhi (fecal-oral ingestion of contaminated food/water in South Asia, Africa, and Latin America). Causes enteric fever with step-ladder fever, abdominal pain, hepatosplenomegaly, "rose spots", and intestinal perforation.
• Oral Live Attenuated Ty21a (Vivotif): 4 enteric-coated capsules taken on alternate days (days 1, 3, 5, 7) with cool liquid 1 hour before meals. Must be kept refrigerated (2°C–8°C). Must be completed ≥ 1 week prior to travel. Booster every 5 years. Strictly contraindicated in immunocompromised patients, pregnancy, and patients taking systemic antibiotics.
• Injectable Vi Polysaccharide (Typhim Vi): Single intramuscular injection administered ≥ 2 weeks prior to travel. Booster every 2 years. Inactivated sub-unit polysaccharide vaccine; safe in immunocompromised hosts and pregnancy.

3. Japanese Encephalitis Vaccine (IXIARO)

• Pathogen: Mosquito-borne flavivirus (Culex mosquitoes) endemic to rural agricultural areas of Asia (associated with rice paddies and domestic swine).
• Vaccine: Inactivated, Vero cell culture-derived vaccine (IXIARO). Administered as a 2-dose intramuscular series at days 0 and 28 (accelerated 7-day schedule available for adults 18–65); completed ≥ 1 week before travel.
• Indications: Travelers spending ≥ 1 month in endemic rural areas during transmission season, or short-term travelers with substantial outdoor rural exposure.

4. Rabies Pre-Exposure Prophylaxis (PrEP)

• Target Travelers: Individuals traveling to rabies-endemic regions (Asia, Africa, Central/South America) with high animal exposure risk or delayed access to local medical facilities, spelunkers (bat contact), veterinarians, and wildlife biologists.
• Updated ACIP 2-Dose Regimen (2022): Administer 2 doses intramuscularly on days 0 and 7 (replacing the historical 3-dose regimen).
• High-Yield Board Concept on Post-Exposure Prophylaxis (PEP):
  • Pre-exposure prophylaxis does NOT eliminate the need for post-exposure evaluation following an animal bite.
  • However, it ELIMINATES THE REQUIREMENT FOR RABIES IMMUNE GLOBULIN (RIG) and REDUCES the post-exposure vaccine regimen from 4 doses to 2 doses (administered on days 0 and 3).