Age: 64.0
Sex: M
Vaccine: HEPA, TYP, YF
Symptoms: Sepsis, Septic shock, Thrombocytopenia, Toxoplasma serology positive, Viraemia
Clinical narrative: Anemia; SGPT increased; SGOT increased; Bilirubinemia; Skin rash; cytolysis; digestive symtoms; hepatitis; Hypotension; Confusion; Disseminated intravascular clotting; Thrombocytopenia; Renal insufficiency; Erythematous rash; Petechiae; Weakness; Nausea; Vomiting; Diarrhea; high fever; Urinary frequency; Septic shock; viscerotropic disease; suspect Yellow fever vaccine-associated viscerotropic disease; From initial information received on 09/Nov/2004 from the Centers for Disease Control and Prevention (CDC) regarding an adverse event occurring, it was reported that a 64-year-old male patient preparing for a fishing trip received YELLOW FEVER VACCINE [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 location 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 Fahrenheit), 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 28/Oct2004.  The patient had Central Nervous System, 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-Viscerotropic-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-Viscerotropic-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.   The patient serum was IgM (immunoglobulin M) positive to yellow fever.  A PCR (Polymerase Chain Reaction) assay on the day 27 post vaccination samples found 100 copies/ml (millilitre) of virus in the plasma.  In the laboratory, a 10 power 6 PBMC/sample (peripheral blood mononuclear cell) was stimulated with recombinant VSV (vesicular stomatitis virus) viruses, each containing a YFV (Yellow fever virus) gene.  Almost all of the response that was seen was in the CD8 (cytotoxic 8) population.    Bun 47, creatinine 2.6, liver enzymes of total Bilirubin was 1.7, Aspartate Aminotransferase (AST) was 210, ASL (argininosuccinate (ASA) lyase) 65, platelets were 36,000 on admission. Liver enzymes continued to increase with bilirubin greater than 4.  His labs were sent to the Centers for Disease Control and to Center for testing.   Results: A serum sample collected on 05/Nov/2004 was positive for IgM to yellow fever and has a neutralization titer of 1:80. This sample also was positive for YF-17D vaccine virus by specific primer for the vaccine strain but there was not enough signal to warrant isolation, and attempts to sequence were unsuccessful due to low yield.  From additional information received on 27-Jan-2005 from the Centers for Disease Control and Prevention, it was reported that this 64-years-old white 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 as 23/Oct/2004.  Upon physical examination, the patient 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 erythematous 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-Medrol 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.  On 27-Oct-2005: The patient was hypokalemic.  A chest x-ray was clear. Hospital admission lab work (28/Oct/2004): ALT (Alanine transaminase) 80, AST (aspartate aminotransferase) 101, Alk phos (Alkaline Phosphatase) 278, Bilirubin 2.6 (direct elevated), BUN (Blood Urea Nitrogen) 40, Creat (creatinine) 3.0, Platelets 36,000, WBC (White blood cell) 12.0 (93% neutro) (neutrophil), DIC (Disseminated Intravascular Coagulation) screen was positive, MRI (Magnetic resonance imaging) of brain was normal, CXR (Chest X- ray) showed bibasilar opacification, CSF (Cerebrospinal fluid) was not obtained. Prior to discharge from hospital: ALT 44, AST 50, Alkaline phosphate 168, Bilirubin 1.4 (direct 0.6), BUN 20, Creatinine 2.1 ( (normal) 0.8-1.5), Platelets 321,000.  Follow-up information was received via a search of the scientific literature on 25-Jul-2008.    The following results were noted in the virologic and immunologic analyses:  YFV Ribonucleic acid (RNA) was detected in the patient 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.  Cluster of differentiation 8 (CD) 8T cell status was also elevated in the patient:  34 days post-vaccination, greater than 50% of CD8 T cells co-expressed Human Leukocyte Antigen-DR isotype (HLA-DR) and cluster of differentiation 38 (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, inducible protein (IP)-10, Monocyte chemoattractant protein (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 demonstrate 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 increase in the numbers CD14 (plus) 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 polymorphism in the CCR5-[triangle]32, which is known 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 RANTES, 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."  Follow up information was received on 02-Mar-2021 regarding an unsolicited valid serious case received from other health professional issued from a literature article.   Event rash, cytolysis, gastrointestinal disorder and hepatitis were added.  Abstract: Yellow fever virus (YFV) live attenuated vaccine could, in rare cases, cause life-threatening disease, typically in patients with no previous history of severe viral illness. Autosomal recessive (AR) complete Interferon-alpha/beta receptor alpha chain (IFNAR1) deficiency was reported in one 12-year-old patient. Here, we studied seven other previously healthy patients aged 13 to 80 year with unexplained life-threatening YFV vaccine associated disease. One 13-year-old patient had adverse reaction (AR) complete interferon alpha/beta receptor chain 2 (IFNAR2) deficiency. Three other patients vaccinated at the ages of 47, 57, and 64 year had high titers of circulating antibodies (auto-Abs) against at least 14 of the 17 individual type I interferons (IFNs). These antibodies were recently shown to underlie at least 10 % of cases of life-threatening corona virus disease (COVID)-19 pneumonia. The auto-Abs were neutralizing in vitro, blocking the protective effect of IFN-alpha 2 against YFV vaccine strains. AR interferon (alpha, beta and omega) receptor 1 (IFNAR1) or IFNAR2 deficiency and neutralizing auto-Abs against type I IFNs thus accounted for more than half the cases of life-threatening YFV vaccine-associated disease studied here. Previously healthy subjects could be tested for both predispositions before anti-YFV.  This case is linked to cases 2021SA072289, 2021SA072302 and 2021SA072200. (Same literature)  This case involves a 64 years old male patient ( 80-years-old et the time of reporting) who experienced YFV vaccine-associated disease (yellow fever vaccine-associated viscerotropic disease) along with other symptoms.  The patient had no previous history of severe viral infections.  The Inborn errors of type I IFN (interferons) was negative.  Past medical treatment, past vaccination, concomitant medications and family history were not reported.   The vaccine was administered for prophylactic vaccination.  On an unknown date, the patient developed a serious hepatitis, (unknown latency) following the administration of YELLOW FEVER VACCINE.  On an unknown date in 2004, the patient presented with a serious digestive symptoms (gastrointestinal disorder), two days following the administration of YELLOW FEVER VACCINE. The condition of patient was quickly deteriorated.  On an unknown date in 2004, two days later patient was admitted to the hospital for cytolysis (cell death), skin rash (rash) and hypotension, four days following the administration of YELLOW FEVER VACCINE.  All the reported events were assessed as medically significant and life-threatening and patient was hospitalized for these events.  Relevant additional laboratory test results included:  On an unknown date: Autoantibodies (auto-Abs) for type I interferons (IFNs) test was Positive with high high titers of IgG (immunoglobulin G) auto-Abs against IFN-a2 and IFN-? (omega). The blood sample positive for auto-Abs was taken 16 days after the onset of YFV-17D disease.  Auto-Abs for type I IFNs presence was not tested before vaccination or during YFV-17D disease.  The outcome of the additional events/symptoms reported in this article was not reported at the time of reporting.  According to the authors, the presence of these Abs 16 days later provides compelling evidence for an association with the disease.; Sender's Comments: Follow up received on 02-Mar-2021 changes the medical assessment of the case as follows:  This literature case was newly mentioned in a recently published article. In 2004, at age of 64, the patient with no prior history of severe viral infections and no family medical history, reported life-threatening yellow fever vaccine-associated viscerotropic disease (YEL-AVD) 2 days after vaccination with YF-VAX. This case was considered as suspect YEL-AVD by the CDC YF WG. A serum sample collected on 05-Nov-2004 was positive for IgM to yellow fever and has a neutralization titer of 1:80. This sample also was positive for YF-17D vaccine virus by specific primer for the vaccine strain but there was not enough signal to warrant isolation, and attempts to sequence were unsuccessful due to low yield. However, septic shock and confusion occurred when the patient came back from the fishing trip. Infection from flood water transmission, i.e., leptospirosis, Lyme disease and other spirochetes, as well as ictero-hemorrhagic fever, i.e., West Nile disease, which is an emerging severe infection might be considered as potential etiologies. Sixteen days after the onset of YEL-AVD, the patient was found positive for auto-Abs to type I IFNs in blood. Further information regarding previous vaccinations and tolerance, as well as CNS involvement would be needed to fully assess this case. Based on available information the role of vaccine cannot be ruled out.