Clinical management and humoral immune responses to rabies post-exposure prophylaxis among three patients who received solid organs from a donor with rabies

Abstract

Background: The rabies virus causes a fatal encephalitis and can be transmitted through organ transplantation. In 2013, a man developed rabies 18 months after receiving a kidney from a donor with rabies, who was not known to have been infected when the organs were procured. Three additional persons who received organs from the same donor (liver, kidney, heart), all of whom were not vaccinated for rabies before transplantation, received rabies post-exposure prophylaxis (PEP) with rabies immune globulin and 5 doses of rabies vaccine as soon as the diagnosis of rabies was made in the donor (18 months after their transplant surgeries). We describe their clinical management.

Methods: As the 3 recipients were all on immunosuppressive medications, post-vaccination serologic testing was performed using the rapid fluorescent focus inhibition test to measure rabies virus neutralizing antibodies (RVNAs). An acceptable antibody response to administration of rabies vaccine was defined as detection of RVNAs at a concentration ≥0.1 IU/mL from a serum specimen collected ≥7 days after the fifth vaccine dose.

Results: All 3 recipients demonstrated an acceptable antibody response despite their immunosuppressed states. More than 36 months have passed since their transplant surgeries, and all 3 recipients have no evidence of rabies.

Conclusions: The survival of 3 previously unvaccinated recipients of solid organs from a donor with rabies is unexpected. Although the precise factors that led to their survival remain unclear, our data suggest that PEP can possibly enhance transplant safety in settings in which donors are retrospectively diagnosed with rabies.

Keywords: post-exposure prophylaxis; rabies; solid organ transplantation.

Fig. 1

Antibody responses to rabies post-exposure prophylaxis (PEP) among 3 patients who received solid organs procured from a donor with rabies. The graph shows the concentration of rabies virus neutralizing antibodies (RVNAs) (Y-axis, logarithmic scale) at various time points after initiation of rabies PEP (X-axis) for 3 solid organ recipients who had received organs procured from a donor with rabies. The lower limit of detection for RVNAs by the laboratory assay we used is 0.04 IU/mL but, for simplicity, 0.05 IU/mL is indicated on this graph. The cutoff defined by the Advisory Committee on Immunization Practices for an acceptable antibody response to administration of rabies vaccine corresponds to an RVNA concentration of approximately 0.1 IU/mL; in contrast, the World Health Organization cutoff is 0.5 IU/mL.