Age: 22.0
Sex: F
Vaccine: FLU3, YF
Symptoms: Diarrhoea, Laboratory test abnormal, Liver function test abnormal, Nausea, Pyrexia
Clinical narrative: From information received at manufacturer on 1/13/03, it was reported that a 22 year old female was administered FLUZONE SV 2002-2003 (lot # U0983WA) IM in the deltoid and YF-VAX (lot # U0253AA) SC in the deltoid on 10/17/02. On 10/21/02 at 08:05AM she experienced fever, nausea, vomiting, diarrhea and mildly elevated liver function tests. She was admitted to hospital. A spinal tap was performed on 10/23/02, which was within normal limits except for an elevated CSF glucose level 72.0 (normal range 40-70mg/dL). On 10/25/02, an exploratory laparotomy, partial colectomy, and lymph node biopsy were performed. Path results showed areas of colon and terminal ileum with mucosal acute inflammation, epithelial erosion and necrosis, as well as marted submucosal edema with acute and chronic inflammation. The muscularis propria and serosa showed mild acute and chronic inflammation, which were interpreted as being consistent with ischemic bowel disease. There were rare mucosal and submucosal lymphoid follicles with evidence of hemophagocytosis. No vascular emboli or evidence of vasculitis were identified. No parasite, granulomas or neoplastic changes were identified. Colonic and terminal ileum surgical margins were inflammed, margins viable. The appendix showed mild acute and subacute appendicitis. Lymph node biopsy showed marked interfollicular hyperplasia and sinus histiocytosis with hemaphagocytosis, suggestive of hemophagocytic syndrome. 30cc of bile was also removed for analysis. Pre and post-operative diagnoses were sepsis of unknown origin. On 10/26/02, aerobic and anaerobic blood cultures were positive for gram negative rods and grew bacterium klebsiella pneumoniae. The patient died on 10/26/02 of distributive shock and multisystem organ failure. An autopsy was performed at the hospital; results are pending. A section of formalin fixed liver was submitted to the CDC for evaluation of hepatic failure and suspected Yellow Fever. This report was previously submitted to VAERS by the reporter. This case is closed.  Reported on 02/27/2003: "Follow-up #1 correspondence received on 02/11/2003- A pathology report received from the CDC indicated that Immunohistochemical (IHC)tests using a two-step indirect immunoalkaline phosphatase technique were performed.  The primary antibodies used in the tests include a monoclonal mouse anti-yellow fever virus D-17 strain antibody* and a polyclonal rabbit anti-K pneumoniae antibody.  Appropriate positive and negative controls were run in parallel.  No immunohistochemical staining of yellow fever virus antigen was found in multiple organs, including liver, lung, heart, spleen, kidney and lymph node.  Abundant and widespread antigens were present in mononuclear phagocytic cells and mesenchymal cells of these organs, including liver.  In comparison, smaller amounts of antigen were observed in hepatocytes.  The distribution of viral antigen is different from the pattern seen in fatal wild-type yellow fever virus infection, in which viral antigens are usually present in hepatocytes and Kupffer cells and never in our experience seen outside the liver.  Electron microscopic examination of spleen and lung tissues revealed cells with foci of smooth membrane vesicles compatible with flavivirus replication complexes.  The viral nature of these vesicles was further confirmed by immunogold label experiments using the same anti-yellow fever virus antibody.  In conclusion, the abundance and widespread distribution of viral antigens as well as the ultrastructural findings indicate yellow fever virus infection was a major cause of death in this case.  Confirmation with serology and molecular techniques is highly recommended. Correction of info reported 02/11/2003, Page 4; follow-up #1, line 5-6: Should have stated "No immunohistochemical evidence of Klebsiella pneumonia infection was found in the heart and lung. Positive immunohistochemical staining of yellow fever virus antigen was found in multiple organs, including liver, lung, heart, spleen, kidney and lymph node." Code for death removed as it is an outcome and a MedDRA term was added for Multi organ failure. From additional info received on 09/10/2003, the U.S. military will not release autopsy results. This case is closed as no further info is anticipated. Follow up on 03/30/04: "From information received at manufacturer on 01/13/03 from the CDC, it was reported that a 22 year old female was administered Fluzone SV '02-03 USP (Lot # U0983WA) IM in the deltoid and YF-VAX (Lot # U0253AA) SC in the deltoid on 10/17/02.  On 10/21/02 at 8:05AM she experienced fever, nausea, vomiting, diarrhea and mildy elevated liver function tests.  She was admitted to the medical center.  A spinal tap was performed on 10/23/02, which was within normal limits except for an elevated CSF glucose level 72.0 (normal range 40-70 mg/dl).  On 10/25/02, an exploratory laparotomy, partial colectomy, and lymph node biopsy were performed.  Pathology results showed areas of colon and ternimal ileum with mucosal acute inflammation, epithelial erosion and necrosis, as well as marked submucosal edema with acute and chronic inflammation.  The muscularis propria and serosa showed mild acute and chronic inflammation, which were interpreted as being consistent with ischemic bowel disease.  There were rare mucosal and submocusal lyphoid follicles with evidence of hemophagocytosis.  NO vascular emtoli or evidence of vasculitis were identified.  No parasites, granulomas or neoplastic changes were identified.  Colonic and terminal ileum  surgical margins were inflammed, margins viable.  The appendix showed mild acute and subacute appendicitis.  Lymph node biopsy showed marked interfollicular hyperplasia and sinus histiocytosis with hemophagocytosis, suggestive of hemophagocytic syndrome.  30cc of bile was also removed for analysis.  Pre-and post-operative diagnosis were sepsis of unknown origin.  On 10/26/02, aerobic and anaerobic blood culture were positive for gram negative rods and grew bacterium klebseilla pneumoniae.  The pt died on 10/26/02 of distributive shock and multisystem organ failure.  An autopsy was performed at the medical center, results are pending.  A section of formalin fixedliver was submitted to the CDC for evaluation of hepatic failure and suspected Yellow Fever.  This report was previously submitted to VAERS by the reporter (192477-1).  The case is closed.