Transfusion-Related Transmission of Yellow Fever Vaccine Virus

Transfusion-Related Transmission of Yellow Fever Vaccine Virus --- California, 2009
Weekly
January 22, 2010 / 59(02);34-37


In the United States, yellow fever (YF) vaccination is recommended for travelers and active duty military members visiting endemic areas of sub-Saharan Africa and Central/South America (1,2). The American Red Cross recommends that recipients of YF vaccine defer blood product donation for 2 weeks because of the theoretical risk for transmission from a viremic donor (3). On April 10, 2009, a hospital blood bank supervisor learned that, on March 27, blood products had been collected from 89 U.S. active duty trainees who had received YF vaccine 4 days before donation. This report summarizes the subsequent investigation by the hospital and CDC to identify lapses in donor deferral and to determine whether transfusion-related transmission of YF vaccine virus occurred. The investigation found that a recent change in the timing of trainee vaccination had occurred and that vaccinees had not reported recent YF vaccination status at time of donation. Despite a prompt recall, six units of blood products were transfused into five patients. No clinical evidence or laboratory abnormalities consistent with a serious adverse reaction were identified in four recipients within the first month after transfusion; the fifth patient, who had prostate cancer and end-stage, transfusion-dependent, B-cell lymphoma, died while in hospice care. Three of the four surviving patients had evidence of serologic response to YF vaccine virus. This report provides evidence that transfusion-related transmission of YF vaccine virus can occur and underscores the need for careful screening and deferral of recently vaccinated blood donors.

On April 10, 2009, during a routine record review in connection with a subsequent blood drive, the blood bank supervisor learned of a breach in the deferral protocol for blood products collected from trainees. Further investigation revealed that the blood obtained in the previous drive was from trainees who had been vaccinated with YF vaccine 4 days before the drive. All of those blood products already had been processed and incorporated into the inventory at the hospital's blood bank. The blood bank supervisor reviewed blood bank records and identified 87 whole blood units and three apheresis platelet units obtained from the recently vaccinated trainees. Blood products that had been released for transfusion were tracked forward to identify the patients who had received the implicated blood products. Remaining unused blood products were identified and destroyed.

During April 20--30, investigators reviewed inpatient and outpatient records of patients who received the potentially infected blood products. A data collection tool was developed to capture demographic information, underlying medical conditions, blood product received, and information on previous YF vaccine doses. Because YF vaccine has been recognized to cause serious adverse events in persons who are immunocompromised or aged >60 years (1), information was collected on potential adverse events (e.g., fever, meningismus, mental status changes, elevated transaminases, or multisystem organ failure) that might have occurred during the 1 month after receipt of the blood products. All blood product recipients were notified in writing of the potential exposure to YF vaccine virus, and serum samples from the recipients were tested by enzyme-linked immunosorbent assay for immunoglobulin M (IgM) antibodies against YF virus (YFV). Samples testing positive for YFV-specific IgM antibodies were evaluated using the plaque reduction neutralization test, with a 90% cutoff value for neutralizing antibody titers against YFV (the standard evaluation at CDC for determining serologic response to YF vaccine virus). Additional testing for West Nile virus and St. Louis encephalitis virus IgM and IgG antibodies was performed using enzyme immunoassays to evaluate for possible cross-reactive flaviviral antibodies.

Blood Product Recipients

During March 31--April 9, five patients had received six blood products (three platelets, two fresh frozen plasmas, and one packed red cell unit) from six of the trainees. These six trainees had no previous history of vaccination or travel history consistent with exposure to wild-type YFV. In the month after the transfusion, one blood product recipient had died. The decedent was a man aged 82 years who was in hospice care for terminal prostate cancer and end-stage, transfusion-dependent, B-cell lymphoma. He died 20 days after receiving one of the implicated platelet units. No autopsy was performed, and no pre-mortem blood specimens were available for testing. The other four recipients of blood products had no documented laboratory abnormalities or symptoms attributable to YF vaccine (Table).

Residual blood products from the six transfusions had been discarded. Testing for pretransfusion serologic status of the blood product recipients could not be performed because banked sera were not available. However, serum samples drawn 26--37 days posttransfusion indicated that three of the four recipients had YFV-IgM antibodies confirmed by plaque reduction neutralization test. Testing for cross-reactive flaviviral infection by IgM and IgG antibodies was negative for all four recipients. Testing by reverse transcription--polymerase chain reaction or culture for the presence of YF vaccine virus in the surviving recipients was not performed because samples were obtained when viremia would no longer be expected if transfusion-related transmission had occurred. The patient without YFV-specific antibodies was a premature infant who received multiple aliquots of red blood cells from one donor. Of the three recipients demonstrating YFV-IgM antibodies, two had been previously vaccinated with YF vaccine at least 20 years earlier. A booster response was identified in these two previously vaccinated donor recipients by the presence of YFV-IgM antibodies and high neutralizing antibody titers (160 and 40,960, respectively).

Public Health Response

A review of records associated with the blood product donations confirmed that, in accordance with standard blood bank screening procedures, each trainee had been questioned regarding recent vaccinations on the day of donation. However, none reported having received YF vaccine 4 days earlier. To prevent a similar event in the future, personnel at the military training center now provides the blood bank with immunization records of all trainees at least 1 week before the blood drive, and just before donation, staff members ask each donor individually about his or her vaccination history.

Reported by
E Lederman, MD, T Warkentien, MD, M Bavaro, MD, J Arnold, MD, D DeRienzo, MD, US Navy. JE Staples, MD, M Fischer, MD, JJ Laven, OL Kosoy, RS Lanciotti, PhD, Div of Vector-Borne Infectious Diseases, National Center for Emerging and Zoonotic Infectious Diseases, CDC.

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