Age: 54.0
Sex: M
Vaccine: FLUX
Symptoms: Essential tremor, Gastrointestinal sounds abnormal, Glucose urine present, Headache, Hyperlipidaemia
Clinical narrative: This clinical study case (initial receipt 19-Feb-2015) concerns a 54 year old male subject enrolled in a study to evaluate the immunogenicity and safety of a quadrivalent influenza vaccine (CSL QIV) in comparison with a trivalent influenza vaccine (CSL TIV-1), and a trivalent influenza vaccine containing the alternate B strain (CSL TIV-2), in adults aged 18 years and above. The subject had a medical history of a left knee meniscus tear repair in 1998, cholecystectomy in 2004 and a tonsillectomy in 1972. At the time of the event, the subject concomitantly suffered from benign familial hand tremor since 2005, type 2 diabetes mellitus since 2000, hyperlipidaemia since 2005 and testicular failure/low testosterone since 2010. The subject never drank alcohol and was never a smoker. He had no previous history of renal failure of chronic kidney disease. Concomitant medications included oral atorvastatin (20mg daily) for hyperlipidaemia since 2005, oral ASA (acetylsalicylic acid) (81mg daily or 325mg daily) for prophylaxis since 2003, oral losartan (50mg daily) for renal protection since 2005, oral metformin (1000mg daily) for T2 DM (type 2 diabetes mellitus) since 2010, oral pioglitazone (30mg daily) for T2 DM (type 2 diabetes mellitus) since Jan-2014, oral propranolol (60mg daily) for benign familial hand tremor since 2005, intramuscular testosterone (200mg/ml, 1 mL every two weeks) for low testosterone since 15-Jul-2014, oral multivitamin 1 tablet as a supplement since 2004, oral fish oil (1200mg daily) as a supplement since 2004, oral canagliflozin (100mg daily) for T2DM (type 2 diabetes mellitus) since 28-Aug-2014 and oral promethazine (25mg one tablet every six hours as needed) since 23-Mar-2007. The subject had no documented history of respiratory illness prior to the event. The subject had last received influenza vaccine in Sep-2013. On 19-Aug-2014 at 16:38, the subject received the study vaccine 0.5 mL via the intramuscular route in the left deltoid. On 29-Aug-2014, 31-Aug-2014 and on 06-Sep-2014, the subject took paracetamol 1000mg as needed for the treatment of the adverse event of headache. On 31-Jan-2015, the subject had flu symptoms which included chills, malaise, myalgias, weakness, headache, nasal congestion, rhinorrhoea, sore throat, cough, SOB (shortness of breath) but no fever. Associated symptoms were lightheadedness, dry mouth and decreased urination but no chest pain, no neck stiffness and no diarrhoea. A week prior to 06-Feb-2015, the subject had a low grade fever of about 100.2 associated with nausea and vomiting. He declined over 24-48 hours although he was able to take some p.o. intake on Monday (02-Feb-2015). On 02-Feb-2015, the subject developed moderate influenza. Medical advice was sought and concomitant medication was taken. He went to his Primary Care Physician (PCP) who diagnosed him with influenza and on 02-Feb-2015, the subject was commenced on oral promethazine-codeine (1 tablet as needed) as needed for influenza, and oral oseltamivir phosphate (75mg tablet twice daily) for influenza. He had a decreased solid intake but continued to take sips of water. He was very somnolent and was sleeping for long periods of time. He had a productive cough of some yellow sputum. The fever did dissipate. On 02-Feb-2015, the subject was tested for influenza with a positive influenza result (flu A/B screen test). On 06-Feb-2015, the subject developed severe acute renal failure and severe acute bronchitis. Medical advice was sought and concomitant medications were taken. On 06-Feb-2015, the subject followed up with the PCP and he was found to be hypotensive (blood pressure was occasionally in the 70's). In the routine clinic, the subject was found to be not hydrated, could not urinate and would not eat as his stomach was hurting. The subject did not have chest pain, no neck stiffness and no diarrhoea. The subject's glycaemic control had been good with no symptoms and was adherent with his medication regimen and denied any side effects. The subject was sent to the ER (emergency room) due to dehydration and increased congestion. At the emergency department, his workup showed evidence of acute kidney injury with creatinine in the 6 range (6.2mg/dl). He felt weak. His cough had subsided but was slightly nauseated with no vomiting, no chest pain, no significant abdominal pain, no suprapubic tenderness and no dysuria. A review of the body systems found that he had fever and chills which had resolved, no headache, no stiff neck, no sore throat, no bruising/ecchymosis, no rash, no joint pains or swelling. He was constipated but the rest of the systems were negative. Upon physical examination, he was weak but alert and orientated, blood pressure was low (80/43, but was 91/52 at the time of examination), temperature was 97.3 and pulse was 73. His mucous membranes were very dry. His lung fields had diminished breath sounds but were clear and he had diminished bowel sounds. On 06-Feb-2015 at 14:14, the subject or guardian reported cough with productive sputum that was purulent. The symptoms/episode began/occurred 1 week ago and became worse today. In the emergency department the symptoms were actually worse. The symptoms were alleviated by nothing. The subject had nausea, felt weak and was not urinating a lot. The subject was concerned that he felt dehydrated and may have pneumonia. The subject was hospitalised for dehydration, acute renal failure and acute bronchitis. Diagnostically, his white count was normal, lactate was normal, BUN (Blood Urea Nitrogen) was 61mg/dl, creatinine was 6.2mg/dl, CO2 (carbon dioxide) was 21 mmol/L. Urine osmolarity was 234 mosm/kg. The impression from CT (Computed Tomography) scan of the abdomen was suspect constipation and nephrolithiasis (non-obstructing). He had some mild non-specific perinephric stranding of uncertain chronicity. There were no acute findings in the chest X-ray. The primary assessment showed acute kidney injury, likely to be secondary to decreased oral intake (in a patient on an angiotensin receptor blocker and metformin), hypotension (improved with fluids), nausea and vomiting (now improved), type 2 diabetes mellitus, metabolic acidosis, hyperlipidaemia and essential tremor. Differential diagnosis included bronchitis influenza upper respiratory infection asthma exacerbation pneumonia. Antibiotic administration was not indicated as the subject did not have an appreciated infiltrate and the subject had a suspected viral illness. Dispensed medications included inhaled albuterol 2.5mg/Ipratropium 0.5mg (1 puff inhaled once) on the 06-Feb-2015 for acute bronchitis. On the 06-Feb-2015 the subject also received 0.9% NS (normal saline) via intravenous bolus three times per day for acute renal failure and intravenous 4mg ondansetron infused over 2 minutes for acute renal failure. On 06-Feb-2015, the subject's urinalysis appeared a dark yellow and 'SL' cloudy with protein measuring at 30 mg/dL, glucose at 100mg/dL and a trace amount of ketones. On 07-Feb-2015, POC (Point of Care) bedside laboratory testing showed glucose tests of 174 mg/dL. On the 09-Feb-2015, POC bedside glucose test was 110mg/dl. On 09-Feb-2015, the subject was discharged from hospital. On 12-Feb-2015, the subject returned to the PCP for a follow up visit. The subject's blood pressure was 118/64, heart rate was 72, and temperature was 96.9. On physical exam, the subject appeared well and was well nourished, with normal bowel sounds. The outcome was recovered on 09-Feb-2015 for both influenza, acute renal failure and acute bronchitis. Investigator assessment: The investigator reported the event of acute renal failure as serious (hospitalisation) and bronchitis acute as serious (hospitalisation) and the event of influenza as non-serious and not related to the study vaccine with the alternative cause being that the subject caught the flu/was secondary to the diagnosis of influenza and then hospitalised for acute bronchitis and acute renal failure. The subject was commenced on cough medicine and oseltamivir phosphate. The subject's chief complaint was flu symptoms with a discharge diagnosis of acute renal/kidney failure, non-traumatic, dehydration, acute bronchitis and constipation secondary to influenza. Diagnosis prior to hospitalisation was influenza and post hospital observation was dehydration secondary to influenza. Follow up (06-Mar-2015): Investigator comments, new AE (influenza), change SAE term, treatments. Follow up (12-Mar-2015): New SAE (bronchitis acute), treatments, route of concomitant medications. Follow up (27-Mar-2015): Influenza test result. Follow up (21-Apr-2015): Prior respiratory medical history. Follow up (22-Jun-2015): Study vaccine unblinded. Case correction (20-Jul-2015): Company comments amended.