Age: 64.0
Sex: M
Vaccine: HEPA, TYP, YF
Symptoms: Confusional state, Culture negative, Delirium, Dermal cyst, Diarrhoea
Clinical narrative: From initial information received on 09/Nov/2004 from the Centers for Disease Control and Prevention (VAERS 228872) regarding an adverse event, it was reported that a 64-year-old male patient preparing for a fishing trip received YF-VAX, lot number UE265AA, administered subcutaneously, TYPHIM VI, lot number AP0862, administered intra-muscularly, and HAVRIX, lot number 0085P, manufactured by GlaxoSmithKline and administered intra-muscularly on 20/Oct/2004. Two days later on 22/Oct/2004, the patient developed nausea, vomiting and diarrhea which lasted for one week. He went fishing and traveled to foreign country and upon returning home became confused and hypotensive. He was admitted to the hospital on 29/Oct/2004 with septic shock and placed in the intensive care unit. The patient had fever (104 F), but the onset date was not reported. It was reported that the patient was improving and no longer requires a ventilator and was moved to an intermediate care unit. From additional information received on 30/Nov/2004 from the Centers for Disease Control and Prevention, it was reported that the patient was admitted to a hospital for confusion, hypotension and septic shock, on 29/Oct/2004. The patient had CNS, renal, and liver involvement. All cultures were negative and no etiology for the illness has been determined. Reportedly, the data at this point tells nothing about why this patient suffered an adverse event. The kinetics of disease onset (two days post vaccination), is far too rapid for it to be due to immunopathology mediated by the T cell response. In addition, there is no similar data (with the VSV recombinants) from normal Yellow Fever vaccine responses. There is some bulk T cell activation data, and there is still a large frequency of activated T cells, maybe up to 20%. This is unusual compared to normal responses (in a younger cohort). This report was considered as a possible case of Yellow-Fever-Vaccine-Associated-Viscertotropic-Disease disease by the CDC. From additional information received on 05/Jan/2005 from the Yellow Fever Work Group Meeting minutes, it was reported that the following were discharge diagnosis: 1> Sepsis; 2> Possible Yellow-Fever-Vaccine-Associated-Visceroptropic-Disease; 3> Disseminated intravascular clotting (DIC); 4> Thrombocytopenia; 5> Fever; 6> Anemia of chronic inflammation; 7> Hypertension; 8> Delirium; 9> Sebaceous cyst on his back; 10> Acute renal failure. The patient recovered and was discharged from the hospital on 18/Nov/2004. From additional information received on 27/Jan/2005 from the Centers for Disease Control and Prevention, it was reported that this 64-year-old male presented to his primary medical doctor on 27/Oct/2004 with a history of five nights of fever and chills, urinary frequency and one day of nausea and vomiting and diarrhea. He had no abdominal pain or dysuria. The onset of symptoms was reported on 23/Oct/2004. Upon physical examination, the patient's blood pressure was 90/70 and his temperature was 101.4 degrees Fahrenheit. He was hypokalemic and a chest x-ray was clear. The primary physician diagnosed viral gastroenteritis. The patient returned to his primary medical doctor the following day on 28/Oct/2004 with increased weakness, diarrhea, vomiting and confusion. His blood pressure at that time was 70/60 and his temperature was 100.5 degrees Fahrenheit. He had a mild erythema rash on his legs and trunk and petechiae on his face. The patient was admitted to the hospital for rehydration. On the first day of admission, the patient decompensated quickly and was transferred to the intensive care unit. Initial treatment included LEVAQUIN and ZOSYN after blood cultures were obtained, and volume resuscitation with vasopressors. He had increased liver function tests. His respiratory function was intact and intubation was not required. Eight doses of SOLU-MEROL were given between 29/Oct/2004 and 01/Nov/2004. The patient required support for several days in the intensive care unit, including total parenteral nutrition. The patient improved and was discharged on 18/Nov/2004 in stable condition, with residual weakness and an elevated creatinine of 2.0. He was discharged on clindamycin (for an infected sebaceous cyst) and was to receive in-home physical therapy for improving strength. Follow-up information was received via a search of the scientific literature on 25 July 2008. The following results were noted in the virologic and immunologic analyses: YFV RNA was detected in the patient's plasma at 27 and 34 days (1/10,240 and 1/40,960, respectively); in five healthy vaccines, viral RNA was undetectable by 11 days post-vaccination. CD8 T cell status was also elevated in the patient: 34 days post-vaccination, greater than 50% of CD8 T cells co-expressed HLA-DR and CD38 activation markers. In the healthy vaccines, maximum CD8 T cell population expansion occurred 14 days post-vaccination, and had reached baseline levels by 30 days post vaccination. The subpopulation of CD14 and CD16 monocytes 34 days post-vaccination was also increased approximately 200-fold over healthy vaccines, who experienced no increase. Analysis of cytokines and chemokines in the plasma revealed elevated levels of pro-inflammatory mediators interleukin, IL-6, IP-10, MCP-1, and RANTES. The patient returned to the clinic 113 days after vaccination for an evaluation of viral load, and virus was undetectable in the blood at that time. However, there was a persistent neutralizing antibody titer and reactivity of CD8 T cells to specific yellow fever vaccine antigens. The following is verbatim from the discussion in the article: "The data presented for this case patient demostrate the following: (1) persistent viremia that lasted at least through 34 days after vaccination, whereas in healthy vaccines, viral loads in declined to baseline levels by day 11; (2) robust induction of T and B cell responses in the blood, by day 34 after vaccination; (3) a 200-fold increased in the numbers CD14 (+) CD16 (bright) monocytes in the blood, and a 20-fold increase that persisted at day 113, even when a virus was no longer detectable in the blood; (4) heterozygosity for a genetic polymophism in the OCR5-[triangle] 32, which is know to reduce the level of CCR5 expression on cells; (5) heterozygosity for a genetic polymorphism in the RANTES-403G/A, which has been reported to be associated with enhanced expression of RANTES; (6) constitutively elevated levels of plasma FANTES, which peaked at day 113 after vaccination." "It is important to stress, however, that while these polymorphisms may have contributed to the development of adverse events in this patient, other host defects could be responsible for the development of adverse events in other patients after YF-17D vaccination. Furthermore, it is entirely possible that other, as yet undetermined, lesions that affect the innate immune system, might have contributed to viscerotropic disease in this individual."