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Transfusion Transmitted Viruses

Transfusion transmitted infectious diseases usually share the following properties;

• Long period of subclinical infection
• Lengthy viremic phase or carrier state
• Survivability in stored blood components

The following viruses are known to be transmitted by transfusion.

Viruses Transmitted by Transfusion

Hepatitis

Before the late 1970’s, the risk of transmitting hepatitis by transfusion was very high because of blood collection from prisoners and paid donors and the lack of sensitive serological tests. Between 1965 and 1972, approximately 1 in 60 units of blood transmitted hepatitis. The change to an all-volunteer blood supply and the introduction of a third generation test for HBsAg in the mid 1970’s led to a marked reduction in transfusion transmitted hepatitis B infection. The risk decreased even further with the implementation of ALT and anti-HBc tests in 1987 and 1988 as surrogate markers for hepatitis C. Nucleic acid testing for Hepatitis B virus was introduced in 2009. Today the risk of transmitting hepatitis B is estimated to be 1 case per 352,000 units and the window period has been reduced to 5-8 days.

In the late 1970’s, approximately 10% of patients who were transfused with multiple units of red cells became infected with hepatitis C. The introduction of more stringent donor eligibility criteria and both serological and nucleic acid tests hepatitis C virus antibody and RNA has reduced the risk of transmission to about 1 infection per 2,000,000 units transfused.

The natural history of transfusion acquired HCV is similar to that of HCV acquired through other modes of transmission. Approximately 50% of patients will develop chronic elevations of liver enzymes and 10% of these will develop cirrhosis.

HIV-1

The risk of transmitting HIV-1 by transfusion has almost been completely eliminated over the past 25 years. The risk has decreased from 1 case per 100 transfused units in 1983 to 1 case per 2 million today. The risk declined dramatically with the identification and deferral of donors with high-risk behavior in 1983 and the introduction of HIV-1 antibody testing in 1985. In late 1995, blood banks began to test donors for p24 antigen to identify donors in the window period of an early infection who did not have detectable antibody. P24 antigen testing decreased the window period from 22 to 16 days. In late 1999, blood banks introduced nucleic acid testing for HIV-1 RNA to further reduce the possibility that a unit collected during the window period might be transfused. The window period is now estimated to be 11 days.

HIV-2

HIV-2 also causes AIDS and can be transmitted by blood. The FDA licensed the first combination test kit for detecting antibodies to HIV-1 and HIV-2 on September 25, 1992. All blood centers were required to implement this combination test by June 1993. Very few cases of HIV-2 have been detected in the United States. The risk of transmitting HIV-2 by blood transfusion is very small.

HTLV

In 1988, the first generation HTLV-1 antibody test was licensed in the U.S. to screen blood donors for human T cell lymphotropic virus type 1 (HTLV-1), which is a retrovirus that has been associated with adult T cell leukemia (ATCL) and a neurological syndrome, HTLV-I associated myelopathy (HAM). Cellular blood products including red blood cells, platelets and granulocytes can transmit HTLV-1. Plasma components such as FFP and cryoprecipitate do not. Storage of cellular components for more than 14 days appears to decrease infectivity. Between 20 and 60% of recipients who received HTLV-1 positive units prior to the introduction of testing, have seroconverted.

Another related virus, HTLV-2, was originally isolated from patients with hairy cell leukemia. It is transmitted by blood and sexual intercourse. Most males in the United States with HTLV-2 infection have a history of drug abuse, while most infected females have a history of sexual contact with a known IV drug user. Because this virus is closely related to HTLV-1, the HTLV-1 antibody test detects the majority of HTLV-2 positive blood donors. A separate test that could specifically identify HTLV-2 antibody was implemented in 1992.

Disease associations arising from HTLV-I or HTLV-II infection are much less frequent than HIV. It has been estimated that 4% of individuals infected with HTLV-I at birth may progress to ATCL during their lifetime, usually after an incubation period of at least 20 to 30 years. HAM has been estimated to occur in 0.25% of persons infected with HTLV-1 after an incubation period of months to years. A similar neurological syndrome has been documented as a result of HTLV-II infection. However, there is no evidence linking HTLV-II infection with ATCL.

CMV

Cytomegalovirus (CMV) is present within the leukocytes of at least 60% of adult blood donors. However, only 1% of seropositive units is infectious. Only cellular blood components transmit CMV infection. Clinical disease is rare in immunocompetent recipients presumably because they have protective CMV antibody levels. Adverse effects are usually limited to heterophile negative mononucleosis syndromes or mild hepatitis. Transfusion transmitted CMV infections can cause serious illness in CMV negative patients who are immunocompromised, such as premature infants (<1250 g), bone marrow and solid organ transplant recipients and CMV negative AIDS patients. Clinical manifestations include hepatitis, retinitis, pneumonitis, encephalitis and GI tract disease. Intrauterine infection may cause jaundice, thrombocytopenia, cerebral infarction and mental retardation.

The risk of transfusion associated CMV infection may be essentially eliminated by transfusing blood components that are leukocyte reduced (<5 x 10⁶ WBCs) or are CMV seronegative.

West Nile Virus

WNV is a mosquito-borne virus that is associated with meningitis and encephalitis. It was first recognized as a transfusion transmitted agent in 2002. Red blood cells, platelets, and fresh frozen plasma have been implicated in transfusion-transmitted disease.

A potential donor with a medical diagnosis of West Nile virus or suspected of having a WNV infection is deferred for 120 days after diagnosis or onset of illnees, whichever occurred later. Nucleic acid tests (NAT) for WNV in donated blood were implemented on July 1, 2003.