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Infectious Complications

Gerarld & Master

Blood supply is initially screened by selecting healthy donors without high-risk lifestyles, medical conditions, or exposure to transmissible pathogens, such as intravenous drug use or visiting malaria endemic areas In theory, any pathogen (bacteria, viruses, parasites) can be transmitted via transfusion Most transmissions result in transient and selflimited illnesses without major sequalae Mitigation of transfusion transmission of infectious pathogens is mainly based on donor selection and donor testing Most transfusion transmitted infections occur in the window period between the infection and the ability to initially detect the infectious pathogen

Donor selection, screening, and donor questionnaire:
Questionnaire is based primarily on the honesty of the donors, donor education (don't donate if sick) and selection (volunteer, not paid donors) Demographic exclusions based on potential exposure Check list of prior deferred donors Examine and prepare phlebotomy site to minimize skin related microorganisms Test blood for selected known agents Discard components if post donation evidence of exposure or illness Limit unnecessary transfusions and increase autologous donations

Viral Infections

Hepatitis C virus
Hepatitis C virus is an RNA virus Transmitted parenterally, especially through blood transfusions (before testing) and intravenous drug use Blood donations are tested for antibodies to HCV and HCV RNA Occur approximately 1 in 2,000,000 units of blood

May be asymptomatic or lead to chronic active hepatitis, cirrhosis, and liver failure It is recommended to offer screening to patients (particularly children) who received blood products in 1992 (US) or previously, when blood was not screened for HCV Serologic testing and nucleic acidbased testing have reduced risk, although developing countries may not screen The implementation of nucleic acid testing of multiple minipools (donation samples/test well) from blood donations has markedly reduced transmission of HIV and hepatitis C virus during the infectious window period

Only 43% of the World Health Organization's 191 member states test blood for HIV, hepatitis C virus, and hepatitis B virus, so at least 13 million units of blood donated every year are not tested for these transmissible viruses. In the poorest countries, access to safe blood is financially prohibitive because testing costs between $40 and $50 per blood donation.

The nucleic acid test (NAT)

NAT system is using a semi-automated system and further ensures the safety of blood products by permitting earlier detection of infections in donors. The NAT system is capable of detecting a few more infectious donations than other current tests because it detects genetic material rather than antigens (proteins from the virus) or antibodies (immune response to the virus or bacteria). This technology detects very small amounts of genetic material by copying it numerous times, resulting in amplification of the targeted material. NAT is performed on individual samples directly, or by pooling together samples from a small number of donors.

If the test on a NAT pool is reactive, each donor's sample in the pool is tested again individually by NAT, before determining a donor has a reactive NAT result. The donor can be deferred from donating blood and notified. With the use of NAT for HCV, the window period is reduced approximately 50 days (from an average of 57 days to 7 days). For HIV-1, the average window period with antibody testing is 22 days. This window period is reduced approximately 12 days with NAT (from an average of 22 days to 10 days). Once a positive donor sample is identified, the second specific test is performed to determine if the positive result is due to an HIV-1, HCV, or HBV infection.

Human immunodeficiency virus type 1

HIV is a lentivirus, a subgroup of the retrovirus family HIV is transmitted through sexual contact, childbirth, breast-feeding, and parenteral exposure to blood HIV transmission by blood products is efficient: infectivity is 90-100% for contaminated blood versus 0-2% for needlestick injuries Transfusion associated HIV cases usually have an acute viral syndrome; if untreated, progress to AIDS in 10 years

Current standard is serologic antibody testing (1 per 33K positive) plus nucleic acid testing (reduces window of seronegativity between time of infection and development of antibodies) Donated blood is tested for antibodies to HIV-1, HIV-1 p24 antigen, and HIV RNA using NAT. Approximately a dozen seronegative donors have been shown to harbor HIV RNA. The risk of HIV-1 infection per transfusion episode is 1 in 2 million. Antibodies to HIV-2 are also measured in donated blood. No cases of HIV-2 infection have been reported in the United States since 1992.

Hepatitis B virus
Hepatitis B is a DNA virus, which is transmitted parenterally, sexually, perinatally Hepatitis B infection can result in acute infection with subsequent clearance of virus and immunity OR chronic infection with persistent viremia Previously, hepatitis B transmission was most serious transfusion-transmitted disease risk, but due to serologic testing, risk of transfusion transmitted HBV is lower To reduce rates even further, vigilance for errors and donor selection may be as important as further testing

Donated blood is screened for HBV using assays for hepatitis B surface antigen (HbsAg). NAT testing is not practical because of slow viral replication and lower levels of viremia. The risk of transfusion-associated HBV infection is several times greater than for HCV. Vaccination of individuals who require longterm transfusion therapy can prevent this complication.

Other hepatitis viruses

Hepatitis A virus is rarely transmitted by transfusion Infection is typically asymptomatic and does not lead to chronic disease Other transfusion-transmitted virusesTTV, SEN-V, and GBV-Cdo not cause chronic hepatitis or other disease states Routine testing does not appear to be warranted

West nile virus

West Nile virus is a flavivirus primarily transmitted through mosquitoes, with birds as immediate hosts Symptoms: headache, new rash, generalized weakness May cause meningoencephalitis Transfusion-transmitted WNV infections were documented in 2002 Detected by nucleic acid based testing, although virus adheres to human red blood cells in whole blood This RNA virus can be detected using NAT; routine screening began in 2003. WNV infections range in severity from asymptomatic to fatal, with the older population at greater risk.

CMV is almost always latent in immunocompetent adults; CMV virus is latent in leukocytes This ubiquitous virus infects 50% of the general population and is transmitted by the infected "passenger" WBCs found in transfused PRBCs or platelet components. Cellular components that are leukocyte-reduced have a decreased risk of transmitting CMV, regardless of the serologic status of the donor. CMV can cause pneumonitis, hepatitis, retinitis or organ failure in immunocompromised recipients Groups at risk for CMV infections include immunosuppressed patients, CMV-seronegative transplant recipients, and neonates
these patients should receive leukocyte-depleted components or CMV seronegative products

Human T lymphotropic virus (HTLV) type I

HTLV is transmitted by vertical transmission from mother to child, breast feeding, sexual relations, parenteral exposure HTLV1 infects mostly CD4+ lymphocytes while HTLV2 infects preferentially CD8+ lymphocytes Assays to detect HTLV-I and -II are used to screen all donated blood. HTLV-I is associated with adult T cell leukemia/lymphoma and tropical spastic paraparesis in a small percentage of infected persons. The risk of HTLV-I infection via transfusion is 1 in 641,000 transfusion episodes. HTLV-II is not clearly associated with any disease. Most positive donors are asymptomatic Leukoreduction may be effective in removing HTLV

Parvovirus B-19
Etiologic agent of erythema infectiosum, or fifth disease, in children Blood components and pooled plasma products can transmit this virus. Parvovirus B-19 shows tropism for erythroid precursors and inhibits both erythrocyte production and maturation. Mostly mild, self-limited illness Rash, vomiting, aching joints and limbs, fatigue and malaise Pure red cell aplasia, presenting either as acute aplastic crisis or chronic anemia with shortened RBC survival, may occur in individuals with an underlying hematologic disease, such as sickle cell disease or thalassemia. The fetus of a seronegative woman is at risk for developing hydrops from this virus. Immune response usually clears infection and provides lifelong protection, but virus may persist in blood or tissue