The Impact of Critical Care Quarantine on the Residual Risk of Unexpected Organ Donor Blood-borne Virus Infection

Abstract

Background: The transmission of undetected infections from organ donors to recipients is a persistent concern in transplantation medicine. Despite nucleic acid testing, some infections, especially those acquired recently, may evade detection. This study aimed to model the effects of critical care interval before screening on the residual risk of undetected infections in organ donors.

Methods: We modeled the risk of blood-borne virus acquisition in donors using a Poisson process, assuming that the critical care interval carries negligible risk. A continuous probability function was developed using estimates of HIV, hepatitis C virus, and hepatitis B virus incidence, viral doubling rates, and assay performance characteristics from a commonly used triplex nucleic acid screening test.

Results: Our quarantine-adjusted window period model showed that longer critical care intervals resulted in a decreased quarantine-adjusted residual risk of undetected infections. This relationship was linear for most assay window periods. For example, a typical critical care interval of 2.7 d reduces the residual risk by 43.5% for hepatitis C virus, 22.9% for HIV, and 7.4% for hepatitis B virus. In some clinical situations, the critical care quarantine effect may outweigh intragroup variations in risk behavior. The model also enabled comparisons of different blood collection times.

Conclusions: The quarantine-adjusted window period model indicates that the critical care interval further reduces the risk of undetected infections in deceased organ donors. This supports and quantifies the impact of screening organ donors as close to retrieval surgery as possible, rather than delaying surgery solely based on the risk of residual infection.

Graphical abstract

FIGURE 1.

Relationship between time since exposure and whole-day risk equivalents. $\underset{0}{\overset{\omega }{\int }}[1-D\left(t\right)]dt=C+A$$=C+B,asA=bbydefintionofR\left(\omega \right)$$=R\left(\omega \right)\ast 1$.

FIGURE 2.

Relationship between R and the 50% sensitivity point of the assay. Where A = B, and therefore (A + C) = (B + C).

FIGURE 3.

Relationship between whole-day risk equivalents and the critical care interval. $\mathrm{Q}\mathrm{R}\left(h\right)=R-h+\underset{0}{\overset{h}{\int }}D\left(t\right)dt$. QR is the cumulative risk of non-detection.

FIGURE 4.

Probability of false-negative assay result with time elapsed since exposure. Time 0 is the time of blood draw. The area under the curve is equal to the total whole-day equivalent of at-risk of nondetection exposure. HBV, hepatitis B virus; HCV, hepatitis C virus.

FIGURE 5.

Association between length of critical care quarantine and attenuation of residual risk. Green shaded area: residual risk acquired after unadjusted window period. Inset: relationship plotted over an extended range. HBV, hepatitis B virus; HCV, hepatitis C virus.