Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021

Stacy M Holzbauer, Caroline A Schrodt, Rajesh M Prabhu, Rebecca J Asch-Kendrick, Malia Ireland, Carrie Klumb, Melanie J Firestone, Gongping Liu, Katie Harry, Jana M Ritter, Min Z Levine, Lillian A Orciari, Kimberly Wilkins, Pamela Yager, Crystal M Gigante, James A Ellison, Hui Zhao, Michael Niezgoda, Yu Li, Robin LevisDorothy Scott, Panayampalli S Satheshkumar, Brett W Petersen, Agam K Rao, W Robert Bell, Sonja M Bjerk, Sara Forrest, Wangcai Gao, Richard Dasheiff, Kari Russell, Melissa Pappas, Jessica Kiefer, Wesley Bickler, Anthony Wiseman, Joel Jurantee, R Ross Reichard, Kirk E Smith, Ruth Lynfield, Joni Scheftel, Ryan M Wallace, Jesse Bonwitt

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Background: No human rabies post-exposure prophylaxis (PEP) failure has been documented in the United States using modern cell culture-based vaccines. In January 2021, an 84-year-old male died from rabies 6 months after being bitten by a rabid bat despite receiving timely rabies 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 patient contacts. Results: Rabies virus antibodies present in serum and cerebrospinal fluid were nonneutralizing. Antemortem blood testing revealed that 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, 3 (0.9%) warranted PEP. Conclusions: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture-based 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.

Original languageEnglish (US)
Pages (from-to)1201-1208
Number of pages8
JournalClinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume77
Issue number8
Early online dateMar 29 2023
DOIs
StatePublished - Oct 15 2023

Bibliographical note

Publisher Copyright:
© 2023 Published by Oxford University Press on behalf of Infectious Diseases Society of America.

Keywords

  • bat
  • post-exposure prophylaxis
  • rabies
  • vaccine failure
  • whole-genome sequencing

PubMed: MeSH publication types

  • Journal Article
  • Case Reports
  • Review

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