Fatal Human Rabies Infection With Suspected Host-Mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure—Minnesota, 2021

Abstract

Background No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. Methods We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. Results Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. Conclusion This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise.

Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism

“…As a disease related to poverty, individuals, such as children, may not fundamentally understand how rabies is acquired or may not appreciate its severity (Laorujisawat et al 2022 ; Mapatse et al 2022 ; Zucca et al 2021 ). Even if a bite is reflected as a risk factor for disease acquisition, less serious or nonbite exposures may be ignored or not be recognized, such as related to bats, even in highly developed countries (Holzbauer et al 2023 ; Ma et al 2023 ). Recall bias could also be an issue if exposure occurred months to years previously (Amoako et al 2021 ).…”

Postexposure prophylaxis after bite of a broad-winged bat with evidence of European bat lyssavirus 1 (EBLV-1)

“…Im Jahr 2023 wurde aus Minnesota (USA) bei einem 84-jährigen Patienten die erste Tollwutdurchbruchsinfektion in der westlichen Hemisphäre bei Verwendung eines modernen zellkulturbasierten Tollwutimpfstoffs publiziert [ 7 ]. Die wahrscheinlichste Erklärung für diese Durchbruchsinfektion ist ein durch den Wirt vermitteltes Versagen des Primärimpfstoffs, welches von den Autoren auf das fortgeschrittene Alter und die Begleiterkrankungen (u. a. ein erst bei der Autopsie festgestelltes Prostatakarzinom) zurückgeführt wurde.…”