15.3 Transfusion-Transmitted Diseases

15.3 Transfusion-Transmitted Diseases

Every unit of blood carries a small, but never entirely eliminated, residual risk of transmitting an infectious agent. This section covers the concept of residual risk, the pathogens of greatest concern, and how donor screening, laboratory testing, and pathogen reduction technology mitigate — without completely removing — that risk.

The Window Period and Residual Risk

Donor screening for transfusion-transmissible infections combines a health history questionnaire, serologic (antibody/antigen) testing, and nucleic acid testing (NAT). Even a technically negative donor can transmit infection during the window period — the interval after infection but before the marker being tested for becomes detectable. NAT, which detects viral genetic material directly rather than waiting for an antibody response, has shortened window periods dramatically compared with serology alone; for HIV, NAT narrows the window from roughly three to four weeks with antibody testing to about a week to ten days. Because a window period can never be reduced to zero, transfusion medicine describes residual risk — the very small, ongoing probability that a unit tests negative on all required assays yet is still infectious. Current estimated per-unit residual risks for HIV, HCV, and HBV in the United States are each on the order of one in several hundred thousand to roughly one in a million or better, reflecting the layered effect of questionnaire deferral, serology, and NAT; the exact order of magnitude shifts as testing technology improves, so SBB-level understanding should focus on the concept and the relative ranking of risk rather than a single fixed number.

Bacterial Contamination

Bacterial contamination is the most common infectious cause of transfusion-transmitted fatality because, unlike most viruses, bacteria can actively multiply in a stored blood component. Platelets carry the highest risk because they are stored at room temperature (20 to 24°C), an ideal growth temperature for many organisms, typically introduced from skin flora at the venipuncture site despite use of a diversion pouch to divert the first, most heavily skin-flora-contaminated milliliters away from the collection bag. Red blood cells are refrigerated and therefore lower risk overall, but psychrotrophic (cold-growing) organisms — classically Yersinia enterocolitica — can proliferate slowly during standard RBC storage; Yersinia is notable because it can enter a donor's bloodstream transiently via asymptomatic gastrointestinal translocation.

Detection and mitigation strategies include:

• Culture-based testing — automated systems sampling the platelet unit approximately 24 hours after collection, sometimes paired with a later secondary rapid test, to detect and remove contaminated units before or during the storage period.
• Pathogen reduction technology — treatments such as amotosalen/UV-A or riboflavin/UV light applied to platelets and plasma, which inactivate a broad range of bacteria, many viruses, and parasites, and in some jurisdictions serve as an alternative to gamma irradiation for preventing TA-GVHD.
• Visual inspection of a unit before issue for clots, abnormal color, or hemolysis, which can suggest contamination.

A septic transfusion reaction from a contaminated unit presents with high fever, rigors, and rapid-onset hypotension or shock — gram-negative organisms are especially dangerous because of endotoxin release — and can be difficult to distinguish clinically from AHTR. The workup overlaps significantly: stop the transfusion, culture both the residual unit and the patient's blood, Gram stain the unit, and begin empiric broad-spectrum antibiotics while providing hemodynamic support.

Viral Agents

Parasitic and Prion Agents

• Babesia microti (babesiosis) — a tick-borne intraerythrocytic parasite; donors can be asymptomatically parasitemic. FDA-licensed antibody/NAT screening is used in recognized endemic regions because Babesia survives standard refrigerated RBC storage.
• Trypanosoma cruzi (Chagas disease) — U.S. donors are screened with a one-time antibody test at first donation, since past infection confers lifelong risk of transmission through chronic parasitemia.
• Malaria (Plasmodium species) — no licensed screening test is used for U.S. blood donations; risk is instead managed entirely through travel- and residence-based donor deferral for defined periods after living in or visiting endemic areas.
• Variant Creutzfeldt-Jakob disease (vCJD, a prion disease) — no validated blood screening test exists; risk is managed through geographic and time-based donor deferral, such as deferring donors with cumulative residence or travel history in regions with recognized bovine spongiform encephalopathy exposure.

Why No Single Strategy Is Sufficient

Each transfusion-transmitted disease is controlled by whichever combination of strategies fits its biology: testing (serology/NAT) works well for agents with a reliably detectable marker (HIV, HBV, HCV, WNV, Babesia); donor deferral is used when no practical test exists or when a test would be too insensitive (malaria, vCJD); and pathogen reduction/inactivation provides a pathogen-agnostic backstop for platelets and plasma. Recognizing which category a given agent falls into — tested, deferred, or inactivated — is a frequently tested SBB concept, since the choice not to simply test for an agent like malaria hinges on test sensitivity, specificity, and cost, rather than a lack of concern for the pathogen.