Transmission of Yellow Fever Vaccine Virus: Blood Products and Breast-feeding

Abstract & Commentary

By Mary-Louise Scully, MD

Dr. Scully is Director, Travel and Tropical Medicine Center, Sansum Clinic, Santa Barbara, CA.

Dr. Scully reports no financial relationships relevant to this field of study.

Synopsis: Two recent reports highlight the potential risk of transmission of yellow fever vaccine virus through blood products and breast-feeding.

Sources: Centers for Disease Control. Transfusion-related transmission of yellow fever vaccine virus — California, 2009. MMWR 2010:59;34-37.

Centers for Disease Control. Transmission of yellow fever vaccine virus through breast-feeding — Brazil, 2009. MMWR 2010:59;130-132.

In March 2009, 89 active-duty U.S. trainees received yellow fever (YF) vaccination as part of standard preparation for potential travel to sub-Saharan Africa and Central and South America. All the trainees were first-time recipients of YF vaccine. Four days later, these trainees took part in a blood drive. Standard blood bank screening procedures were followed, including questioning about recent vaccinations; however, none of the 89 trainees reported having received YF vaccine four days earlier. On April 10, 2009, a blood bank supervisor discovered the error during a routine record review in preparation for a subsequent blood drive. Despite a prompt recall, six units of blood products were transfused into five patients.

No clinical illness occurred in four blood recipients within a month of transfusion. The fifth patient was an 82-year-old male who was in hospice care for terminal prostate cancer and end-stage, transfusion-dependant, B-cell lymphoma. He died 20 days after receiving a platelet transfusion derived from one of the implicated lots. No pre-mortem blood specimens were available for testing in this patient, and no autopsy was performed. In three of the remaining four recipients, YF virus IgM antibodies were detected by plaque neutralization in serum samples taken between 26 and 37 days post-transfusion. No evidence of potential cross-reactive flavivirus infections, such as West Nile virus or St. Louis encephalitis virus antibodies, was detected. The one surviving patient who did not have serologic evidence of exposure to the YF virus was a pre-term infant who received 4 aliquots of irradiated red blood cells (30 cc in total). Two possible reasons for the lack of immune response in this case might be the immaturity of the pre-term infant's immune system and lower levels of YF vaccine virus in red blood cells as opposed to the other serum-containing products.

In April 2009, during epidemic YF activity in Rio Grande do Sul, Brazil, a 22-year-old mother was vaccinated for YF during a routine postpartum visit. Her infant was 15 days old, and she was exclusively breast-feeding. Eight days later, her infant was hospitalized with seizures and meningoencephalitis. Yellow fever-specific IgM was detected in the infant's serum and CSF, thus confirming yellow fever vaccine-associated neurologic disease. Other causes of meningoencephalitis (dengue, herpes simplex, cytomegalovirus, varicella, and enteroviruses) were ruled out by testing of serum and CSF. The infant did recover and at 6 months was without neurologic sequelae. This is the first laboratory-confirmed case of YF vaccine-associated neurologic disease (YEL-AND) in an infant as a result of transmission of YF vaccine virus through breast milk.

Commentary

These reports confirm what has always been suspected on theoretical grounds but never documented: first, that transfusion-related transmission of YF vaccine virus can occur and, second, that YF vaccine virus can be transmitted through breast milk and cause YEL-AND in infants. The infant recovered without sequelae, and in the transfusion cases, no clinical illness was noted in the four recipients who could be followed. The outcomes might have been very different if the affected blood lots had not been promptly recalled and instead transfused into many more immunocompromised or older patients. Despite its excellent track record for prevention of YF, we are increasingly aware of the potential complications including both YEL-AND and YF Vaccine-Associated Viscerotropic Disease (YEL-AVD) with the various strains of the 17D YF virus lineage. Both of these adverse events occur almost exclusively in first-time recipients of yellow fever vaccine.1

The documentation of YF vaccine virus transmission through breast milk has repercussions in parts of the world where epidemic YF activity occurs and breast-feeding is the predominant mode of infant feeding. The actual risk for 17 DD virus transmission through breast milk is difficult to estimate without knowing the numbers of breast-feeding women who are vaccinated without any adverse consequences for their infants. Nonetheless, it is recommended to avoid YF vaccination of nursing mothers unless travel into high-risk yellow fever-endemic areas simply cannot be avoided or postponed.2 Breast-feeding mothers who need YF vaccination should be made aware of the potential transmission issue so that an alternative mode of infant feeding could be considered during time of expected YF viremia.

Eligibility requirements for blood donation are in place to prevent inadvertent acceptance of donors with the possibility of illness or latent infections. With regard to immunizations, the American Red Cross specifically advises people to defer blood donation for two weeks after receiving either YF vaccine or oral polio vaccine, which is no longer available in the United States, and for four weeks after MMR (measles, mumps, rubella), varicella (chickenpox), and herpes zoster (shingles) vaccination. The complexities of smallpox vaccination require special considerations, but generally a minimum eight-week interval is recommended, assuming no vaccine complications have occurred. There is no deferral period after receipt of influenza, pneumococcal, tetanus (including Td or Tdap), meningitis, hepatitis A, injectable typhoid, injectable polio, or human papillomavirus (HPV) vaccination as long as the donor is in good health without any symptoms. Of note, the American Red Cross suggests a 21-day deferral after routine hepatitis B vaccination (i.e., not given for an exposure) to avoid any potential for a false-positive testing for hepatitis B carrier status.3

Although blood bank screening techniques are in place for prevention of transfusion-related illnesses, travel medicine physicians can help reinforce these recommendations at the time pre-travel vaccinations are given. Patients often ask about blood donation deferral policies after travel to malaria-endemic areas (generally one year after travel to a malaria risk area, 3 years if the person lived in a malaria area or had disease). The pre-travel visit, during which live virus vaccines such as yellow fever vaccine are administered, gives us an excellent opportunity to review with our patients the policies on blood donation deferral after immunizations.

Full eligibility requirements for blood donation are available at www.redcrossblood.org.

References

  1. CDC. Yellow fever. In: CDC Health Information for the International Traveler 2010. Atlanta, Georgia: US Department of Health and Human Services. Public Health Service;2009.
  2. CDC. Yellow fever vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR 2002;51 (No.RR-17).
  3. American Red Cross. Donating blood: Eligibility requirements. Available at http://www.redcrossblood.org/donating-blood Accessed May 1, 2010.