Testing of Selected Patients with Serious Adverse Events Potentially Related to Yellow Fever Vaccination

Healthcare providers are encouraged to report cases of adverse events potentially caused by vaccination to the CDC/FDA Vaccine Adverse Events Reporting System (VAERS) by one of the following methods:

1. Submit a report online
2. Print a VAERS Form [PDF – 2 pages] and fax or mail it using information at: http://vaers.hhs.gov/contact.
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.

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 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.
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.

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General sample shipping information

After the patient has been reported and specimen submission has been discussed with VAERS and CDC medical officers, samples may be shipped to the CDC Division of Vector-Borne Diseases.

A CDC Submission Form (CDC 50.34) must accompany each specimen. Please fill out the form as completely as possible and include the following:

• Date of yellow fever vaccination
• Date of onset of symptoms
• Date of collection of specimen
• Travel history for the 3 months before onset of symptoms
• Also indicate that the patient is being evaluated for adverse events potentially related to yellow fever vaccination and include the VAERS identification number (if one is available)

Using precautions and packaging required for shipping of potentially infected materials, samples should be sent by overnight shipping to:

Arbovirus Diseases Branch
Division of Vector-Borne Diseases
Immediate attention: Arboviral Diagnostic Reference Laboratory
3156 Rampart Road
Fort Collins, Colorado 80521
Phone number: 970.221.6400

To ensure that these samples arrive during the week, shipments should be scheduled to arrive on Monday through Thursday (unless previous arrangements have been made with the lab).

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