Age: 83.0
Sex: M
Vaccine: RAB, RAB, RAB, RAB, RAB, RAB
Symptoms: Rabies, Vaccine breakthrough infection
Clinical narrative: 84 y/o male died from rabies in January 2021 despite receiving appropriate and timely rabies post-exposure prophylaxis (PEP) after being bitten by a rabies-positive bat July 27, 2020. The bat was captured, tested, and on July 30 came back positive for rabies. The patient started rabies PEP on July 30, 2020. At the time there was no obvious bite wound; HRIG was infiltrated IM in the dorsal right hand just adjacent to MP. All four vaccines were administered per Agency. Symptoms started 1/7/21, were progressive/requiring intubation, and included fever, facial pain, nausea, vomiting, right sided facial paralysis/paresthesia, dysphagia, headache, malaise, muscle spasms, autonomic instability, right arm pain/paresthesia.  He sought care on Jan 9, Jan 13, and again Jan 14 when admitted.  Initially treated for suspect temporal arteritis but bilateral temporal artery biopsy did not show arteritis. Serum collected January 14 showed IgM monoclonal gammopathy of unknown significance (M-spike 1.86g/dL) and Myeloma/MGUS screen showed low IgA 52mg/dL (ref 85-370) and low IgG 485mg/dL (ref 661-1464) and high IgM 2699mg/dL (ref 40-275), but negative for MYD88 L265P alteration. Prior to the rabies diagnosis he was treated empirically with steroids (methylprednisolone, prednisone),  IVIG, and plasmapheresis without improvement. His illness was progressive and he died January 22. Sequencing confirmed that the patient was infected from the offending bat. Laboratory testing of HRIG and vaccine manufacturing audits were conducted.  The vials of HRIG the patient received were found to be potent, and there were no vaccine manufacturing or significant quality control deviations discovered. Additionally, serum from the patient's wife was collected February 2, 2021. She received HRIG and 4-vaccine rabies post exposure prophylaxis on the same dates and at the same healthcare facilities as her husband, the patient.  She received HRIG from a different lot, but two of the four rabies vaccines she received were from the same lot as vaccine that her husband received.  By rapid fluorescent focus inhibition test  she had presence of rabies virus neutralizing antibodies at 1:45 (0.33 IU/ml).   The patient had presence of rabies IgG antibodies in CSF (CSF collected Jan 15 and Jan 20) and serum (serum collected Jan 15), but they were non-neutralizing.  This indicates some level of host-related immune dysfunction, which presumably is why this patient developed rabies despite receiving timely post-exposure prophylaxis.  Although the patient was elderly, had several chronic conditions at the time of vaccination, and later was found to have MGUS (during hospitalization) + metastatic prostate adenocarcinoma (diagnosed during autopsy), we would not necessarily expect this type of immune dysfunction from those conditions. Given no identified issues with rabies biologics and a history of multiple comorbidities including MGUS, immune dysfunction (of unknown etiology) in the patient is the most parsimonious explanation for rabies post-exposure prophylaxis failure in this patient.     Human rabies immunoglobulin administered 30 July 2020: 1700 total units from 2 different lots of HYPERRAB in right hand around bite site and right thigh at 1446. 1500 units [5ml of (300 unit/ml)  Lot number: R2MFD00163 (Exp. 15Jun2021)]  200 units [0.667 ml of 300 units/ml. of Lot number: R2MBD00113 (Exp. 11May2021)) of HyperRab]