The Certification Study Guide (6th edition) explains that the probability of infection after an exposure is influenced by several factors, including the dose of the infectious agent, the route of exposure, and host susceptibility. Among the options provided, an unknown concentration of infectious virions introduced via a needlestick injury represents the greatest increase in infection risk.

Percutaneous injuries, such as needlesticks, provide direct access to the bloodstream, bypassing natural protective barriers like intact skin. The study guide emphasizes that when the inoculum (number of organisms) is unknown, particularly in bloodborne exposures, the risk of transmission for pathogens such as hepatitis B virus, hepatitis C virus, and human immunodeficiency virus is significantly higher. This uncertainty necessitates immediate evaluation and consideration of post-exposure prophylaxis.

The other options describe situations with lower or reduced risk. Prior immunization for hepatitis B is protective and therefore decreases susceptibility. Exposure of clothing alone does not constitute a significant transmission route unless there is penetration to skin or mucous membranes. Blood splashes onto intact skin are considered low-risk because intact skin acts as an effective barrier against infection.

CIC exam questions frequently test understanding of exposure routes and inoculum size. Recognizing that percutaneous exposure with an unknown infectious dose poses the highest risk is essential for accurate risk assessment and appropriate occupational health response.