Sex: M
Vaccine: RAB, RAB, RAB, RAB, RAB, RAB
Symptoms: Monoclonal gammopathy, Monoclonal immunoglobulin present, Musculoskeletal discomfort, Nausea, Night sweats
Clinical narrative: Rabies; Case reference number US-BN-2021-000045 is a spontaneous case report initially received on 02-Feb-2021, and concerns a *84-year-old* male patient.  *The patient's medical history included s/p ICD (internal cardiac defibrillator) procedure, s/p coronary artery bypass graft (CABG) x 3, hypertension associated with diabetes, hyperlipidemia associated with type 2 diabetes mellitus, benign prostatic hyperplasia with lower urinary tract symptoms, unspecified morphology, coronary artery disease due to lipid rich plaque, controlled type 2 diabetes mellitus with stage 2 chronic kidney disease, without long-term current use of insulin, chronic kidney disease (CKD) stage 2,*(grade 2/3)* GFR 60-89 ml/min, rhinitis, nonallergic, chronic.*  *Family history included unspecified cardiovascular disease (father and sister), unspecified cancer (brother), colon cancer (sister), No family history of bleeding disorder/clotting disorder or anesthesia problems  and no family history of any neurological disease, had heart attacks in both his mother and father.*  *The patient's concomitant medication details included metoprolol tartrate, Aspirin (acetylsalicylic acid), Glucosamine-Chondroit-Biofl-Mn (glucosamine sulfate/ chondroitin sulfate), sotalol, losartan, atorvastatin and metformin.*  *On 26-Jul-2020*, the patient was bitten by a bat that was confirmed to be infected with rabies virus by the Direct Fluorescent Antibody test. Unknown if any wound care performed or other medications/vaccines given.*   On 30-Jul-2020, four days after exposure, the patient received the first dose of *RabaVert* (Inactivated Rabies Virus Vaccine, Batch no. ARBA651B) at dose of 2.5 units in right deltoid for a bat bite from a known rabid bat. On the same day, the patient received *Hyperrab S/D (Immunoglobulin human anti-rabies) 1700 units in right hand around bite site and remaining in right thigh, then 1500 units (5ml of (300 unit/ml) Lot number: R2MFD00163 (Exp. 15Jun2021)) and 200 units (0.667 ml of (300 units/ml) Lot number: R2MBD00113 (Exp. 11May2021)).*  On 02-Aug-2020, the patient received the second dose of *RabaVert* (Inactivated Rabies Virus Vaccine, Batch no. ARBA651B) at dose of 2.5 units in left deltoid for a bat bite from a known rabid bat.  On 06-Aug-2020, the patient received the third dose of *RabaVert* (Inactivated Rabies Virus Vaccine, Batch no. ARBA651B) at dose of 2.5 units in right deltoid for a bat bite from a known rabid bat.  On 13-Aug-2020, the patient received the fourth dose of *RabaVert* (Inactivated Rabies Virus Vaccine, Batch no. ARBA651A) at dose of 2.5 units in right deltoid for a bat bite from a known rabid bat.  *Since the patient was not known to have an immunocompromising condition at the time of vaccination, in accordance with ACIP guidance, the patient did not receive a 5th vaccine dose and was not advised to undergo antibody titer evaluation.*  On an unknown date, *either 06-Jan-2021 or possibly earlier 31-Dec-2020, approximately five months after bat bite, the patient developed symptoms of rabies that progressed over the course of 17 days, until the patient passed away. Signs and symptoms included right sided facial pain, nausea, vomiting, difficulty swallowing, bilateral shoulder discomfort, numbness of right arm and shoulders, ear pain, decreased appetite, slurred speech and night sweats.*  *On 23-Jan-2021*, the patient passed away due to *laboratory-confirmed* rabies infection.   *The clinicians did not consider the patient immunocompromised when PEP was administered. Laboratory results at the time of hospitalization indicate the patient might have had an undiagnosed underlying immunocompromising condition, however, during life the patient was not known to have an underlying immunocompromising condition. Laboratory findings include increased gamma monoclonal protein (m-spike), elevated IgM, decreased IgA, decreased IgG, no detectable anti-rabies virus IgM by IFA, and no detectable rabies virus neutralizing antibody titers by RFFIT.*  *At the time of this report it was known that the formal report of autopsy was still pending.*  The reporter assessed the event of 'rabies' as serious due to fatal outcome and did not provide causality assessment.   Additional information was received from Agency on 03-Feb-2021 included confirmation that the country of occurrence.  All follow-up information is blended into the case narrative above, with the latest information presented between asterisks (*).   Follow up information was received from Agency on 08-Feb-2021: Information included patient's age.  Additional information received from Agency on 08-Feb-2021 included updated batch numbers.  Additional information received from Agency on 09-Feb-2021 included updated medical history, concomitant medication details, information about autopsy, date of death, confirmation of country of origin, clinical course of events, details of administered RIG (rabies immunoglobulin), bite details and reason for delay vaccination.  Additional information received from Agency on 09-Feb-2021 included informations about family medical history.  Additional information received from Agency on 11-Feb-2021 included informations about batch number (administered to patient's wife).  As per call with reporter dated 12-feb-2021, further tests will be conducted and provided upon consolidation as per reporter information disclosed.  Additional information received from Agency on 22-Feb-2021 included brand name of the suspect product and updated narrative.; Reporter's Comments: In this case report, an 84-year-old male patient had a fatal outcome due to Rabies breakthrough infection, 186 days after a confirmed rabid bat bite. Four days following the bite post exposure prophylaxis was initiated, including4 doses of RabAvert along with RIG. Patients' laboratory reports for serum proteins revealed M-spike with increase in gamma monoclonal protein and his relevant concurrent conditions included diabetes and chronic renal failure. Considering presence of comorbidities in this elderly patient and laboratory reports which are suggestive of a previously unrecognized immunocompromising condition as contributory factors, as per current information available, the Agency assesses the case as not related to product. further post-mortem histopathologic tests are pending to confirm underlying immunosuppression.; Sender's Comments: In this case report, an 84-year-old male patient had a fatal outcome due to Rabies breakthrough infection, 186 days after a confirmed rabid bat bite. Four days following the bite post exposure prophylaxis was initiated, including4 doses of RabAvert along with RIG. Patients' laboratory reports for serum proteins revealed M-spike with increase in gamma monoclonal protein and his relevant concurrent conditions included diabetes and chronic renal failure. Considering presence of comorbidities in this elderly patient and laboratory reports which are suggestive of a previously unrecognized immunocompromising condition as contributory factors, as per current information available, the Agency assesses the case as not related to product. further post-mortem histopathologic tests are pending to confirm underlying immunosuppression.; Reported Cause(s) of Death: Rabies