Testing for Yellow Fever Vaccine Adverse Events

Key points

  • Please report suspected yellow fever vaccine adverse events to the CDC/FDA Vaccine Adverse Events Reporting System (VAERS).
  • CDC can perform testing to assess whether a patient's illness is potentially related to yellow fever vaccination.
  • Contact your state or local health department for assistance with arranging testing if you suspect your patient has a yellow fever vaccine adverse event.
Man holding his head while sitting on the edge of a bed.

Reporting

Healthcare providers are encouraged to report cases of adverse events potentially caused by vaccination to CDC/FDA VAERS by one of the following methods:

  1. Submit a report online
  2. Print a VAERS form and upload as instructed.
  3. Call 1-800-822-7967

There have been previous reports of rare but serious adverse events following yellow fever vaccination, including anaphylaxis, yellow fever vaccine-associated neurologic disease (YEL-AND), and yellow fever vaccine-associated viscerotropic disease (YEL-AVD). For suspect cases of YEL-AND and YEL-AVD, CDC can perform special testing on specimens collected from patients to determine if their illness is potentially due to their recent yellow fever vaccination. The following tests can be performed at CDC:

  • Quantification of yellow fever virus antibody titers in acute- and convalescent-phase specimens or cerebrospinal fluid (CSF);
  • Polymerase chain reaction (PCR) analysis and viral culture of acute-phase sera, CSF, and fresh-frozen tissue samples;
  • Immunohistochemical analysis of fixed tissue; and
  • Molecular analysis of vaccine virus from the same lot as that administered to the patient.

Storage and shipment of specimens

Please refer to the following for details on storage and shipment of specimens:

Table 1. Storage and Shipment of Sera, Cerebrospinal Fluid, Peritoneal Fluid, Pleural Fluid
Type Test Preferred Amount Storage Shipping Other
Serum or CSF Serologic testing 1 mL 4°C Wet ice Multiple, serial samples may be tested.
Serum, CSF, peritoneal, or pleural fluid Viral isolation and PCR 1 mL -70°C Dry ice Promptly freeze at -70°C. Repeated freeze/thaw cycles are deleterious to virus. Multiple, serial samples may be tested.
Table 2. Storage and Shipment of Vaccine Vials (from same lot as that administered to patient)
Vaccine Preferred Amount Storage Shipping Other
Lyophilized form (preferred) Vial 4°C Wet ice Lyophilized form preferred over rehydrated form.
Rehydrated form 1 mL -70°C Dry ice Promptly freeze at -70°C.
Table 3. Storage and Shipment of Biopsy, Surgical, or Autopsy Specimens
Tissue Preferred Amount Storage Shipping Other
Solid organ (brain, liver, spleen, pancreas, heart, kidney, etc.) – fresh frozen 1 g -70°C Dry ice Promptly freeze at -70°C. NO formalin or other preservatives.
Solid organ – fixed (formalin or similar preservatives) Representative samples Ambient Ambient Do NOT freeze.
Solid organ – in paraffin Representative tissue blocks Ambient Ambient Do NOT freeze.
Skin (rash) – fixed (formalin or similar preservatives) Representative samples Ambient Ambient Do NOT freeze.
Postmortem heart serum 1 mL -70°C Dry ice Promptly freeze at -70°C.

WARNING: Although not documented in recipients of yellow fever vaccine, persons with naturally acquired yellow fever and associated bleeding diathesis have died of bleeding complications after liver biopsy. Liver biopsy should be performed only with extreme caution in recent recipients of yellow fever vaccine who develop hepatitis or serious systemic illness.

Requesting testing

To submit specimens for testing, please contact your state or local health department. They can assist you with determining if samples should be sent to the CDC Arbovirus Diagnostic Laboratory for further testing. Specimens should be submitted to CDC through state health departments. All results will be sent from CDC to the appropriate state health department.