Adverse Events Associated with
17D-Derived Yellow Fever Vaccination - United States, 2001-2002.
Morbidity & Mortality Weekly Report
Posted 11/15/2002. MMWR 51(44):989-993, 2002. © 2002 Centers for Disease Control and Prevention (CDC)
In June 2001, seven cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) (previously called multiple organ system failure) in recipients of 17D-derived yellow fever vaccine (YEL) were reported to the Advisory Committee on Immunization Practices (ACIP)
MMWR November 8, 2002 / 51(44);989-993 Adverse Events Associated with 17D-Derived Yellow Fever Vaccination --- United States, 2001--2002
Belsher JL et al. Fatal multiorgan failure due to yellow fever vaccine-associated viscerotropic disease.Vaccine. 2007 Dec 5;25(50):8480-5. Epub 2007 Sep 18. PMID: 18023511 [PubMed - indexed for MEDLINE]
Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a rare complication of yellow fever (YF) vaccination. A previously healthy 22-year-old female died following YF vaccination despite aggressive measures. Serial viral load titers, cytokine levels and host genetic factors were evaluated in an attempt to understand this unusual and lethal outcome. The patient's high-titer vaccine viremia and possibly related minor genetic anomalies provide clues to exploring the etiology of YEL-AVD.
B. N. Carle et al. Experiments on the Transmission of an Icterogenic Agent in Yellow Fever Vaccine to Horses and Swine J Bacteriol.1944 July; 48(1): 45–69. PMCID: PMC38144
Jaundice resulting from an apparently transmissible hepatitis of varying degrees of severity has been recognized as a fairly frequent disease of human beings. One form of mild hepatitis with jaundice has recently gained great importance because of the rather widespread occurrence of this disease following inoculation of Army personnel with a yellow fever vaccine containing human serum (A.M.A., 1942; Sawyer, el al., 1944). A similar disease following yellow fever vaccination had previously occurred in England (Findlay, 1940; Findlay and MaeCallum, 1938) and more recentiy in Braxil (Fox, dot, 1942). Findlay (1B40) has reported the occurrence of jaundice apparently resulting from the injection of human measles convalescent serum and was among the first to suggest that the icterus was due to hepatitis involving the liver parenchyma rather than to inflammatory obstraction of the bile ducts or edema of the duodenal mucosa. Other investigators have presented additional evidence of the occurrence of a jaundice-producing agent in certain human sera (Sergiev, et al., L940;Beeson, 1943; Brit. Min. Health, 1943), and experimental transmission of this agent between human beings by injection of serum has been reported (Oliphant, et at., 1943).
Collomb H, et al. [Postvaccinal encephalitis (yellow fever vaccination); neuro-radiological study]. Bull Soc Med Afr Noire Lang Fr. 1966;11(3):587-90. French. No abstract available.PMID: 4382457; UI: 67213214.
Cobelens FG. Yellow fever vaccination and risk of spontaneous abortion. Trop Med Int Health. 1998 Aug;3(8):687. No abstract available.PMID: 9735939; UI: 98405346.
Chan RC, et al. Hepatitis and death following vaccination with yellow
fever 17D-204 vaccine. Lancet 2001;358:121-122.
Died 8 to 11 days after vaccination
Drouet A, et al. [Meningoencephalitis after vaccination against
yellow fever with the 17 D strain: 2 cases]. Rev Med Interne. 1993
Apr;14(4):257-9. Review. French. PMID: 378658; UI: 93391820.
Doblas A, et al. Yellow fever vaccine-associated viscerotropic disease and death in Spain. J Clin Virol. 2006 Jun;36(2):156-8. Epub 2006 Apr 4.
Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) is a recently described severe adverse event after yellow fever vaccination, and some cases have been reported in different countries [Anonymous. Effects of yellow fever and vaccination. Lancet 2001;358(9296):1907-9]. Herein we describe a YEL-AVD case in a young woman, who died after vaccination with 17D-204 strain. Clinical, serological and immunochemical analysis as well as virus detection, quantification, sequence analysis and cytokine release, were performed. Further investigations on yellow fever vaccine adverse events, and carefully analysis of the immune response elicited are important tasks for the future. PMID: 16597510 [PubMed - indexed for MEDLINE]
Vellozzi C, et al. Yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and corticosteroid therapy: eleven United States cases, 1996-2004. Am J Trop Med Hyg. 2006 Aug;75(2):333-6. Links PMID: 16896144 [PubMed - indexed for MEDLINE
During 1996 through 2004, 29 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been reported worldwide; 17 were fatal. Stress-dose corticosteroid (SDS) therapy has recently been found to improve survival among patients with septic shock but benefit for the treatment of YEL-AVD patients in septic shock is unknown. We retrospectively reviewed medical records of 11 U.S. YEL-AVD cases reported to the Vaccine Adverse Event Reporting System (VAERS) from 1996 through 2004. Four of 11 case-patients received SDS; 3 of these 4 (75%) survived. Seven patients did not receive SDS and 2 (29%) survived. Altered mental status was documented on admission for 5 of the 11 patients; 4 of these 5 did not receive SDS and died, whereas one received SDS and survived. The use of stress-dose steroids might be a factor that influenced the survival of these YEL-AVD patients and should be further evaluated in the management of both YEL-AVD and wild-type yellow fever septic shock.
Falvo C, et al. Adverse reactions associated with simultaneous administration of multiple vaccines to travelers. J Gen Intern Med. 1994 May;9(5):255-60. PMID: 8046527; UI: 94322133.
Furmanski M. Unlicensed vaccines and bioweapon defense in World War
II. JAMA. 1999 Sep 1;282(9):822. No abstract available.PMID: 10478686; UI:
In a letter to the editor, Dr. Martin Furmanski of Newport Beach, California, notes that the use of unapproved vaccines for use against biological agents occurred long before Operation Desert Storm. In 1942, the U.S. military vaccinated all active duty personnel against tetanus, typhoid, smallpox, and yellow fever. The vaccine for yellow fever had not yet been licensed for civilian use and a Food and Drug Administration version would not be available for more than a decade; however, the military decided to use the vaccine anyway in response to the Imperial Japanese Army's attempts to develop biological weapons. Despite the fact that the 1942 yellow fever vaccine had been reported to possibly cause jaundice after inoculation, the vaccinations began. The yellow fever vaccine used human serum, some lots of which were contaminated with hepatitis B. The result of the mass inoculation with the yellow fever vaccine was the largest point source outbreak of hepatitis B ever recorded. The hepatitis B outbreak began in March 1942, and yellow fever vaccinations ended in April 1942. Serologic investigation of those inoculated found 330,000 people infected after the vaccination program. A similar use of unlicensed vaccines almost occurred in 1944. The U.S. government considered vaccinating the entire D-Day assault force with botulinum toxoid following an erroneous report of Nazi weapons using botulinum toxin, but the U.S. Army Surgeon General refused to let the unapproved vaccination be used.
Fitel, M. Encephalitis after yellow fever vaccine. Pediatrics
A case of encephalitis after yellow fever vaccination in a young infant is reported. The results of efforts to identify a virus and the probable etiology are discussed. From the negative results of attempts at virus isolation and from epidemiologic criteria, it is concluded that there is a cause and effect relationship between the administration of yellow fever vaccine and the occurrence of subsequent encephalitis in this infant.
Freestone DS, et al. Stabilized 17D strain yellow fever vaccine: dose
response studies, clinical reactions and effects on hepatic function. J Biol
Stand. 1977;5(3):181-6. No abstract available.PMID: 893464; UI: 77249685.
Jennings AD, et al. Analysis of a yellow fever virus isolated from a fatal case of vaccine-associated human encephalitis. J Infect Dis. 1994 Mar;169(3):512-8. PMID: 7908925; UI: 94209744.
Kelso JM, et al. Anaphylaxis from yellow fever vaccine. J Allergy Clin Immunol 1999;4:698--701. PMID: 10200022; UI: 99216472.
Monath TP. Yellow Fever. Plotkin SA, Orenstein WA (eds. ). Vaccines.
3rd Edition, WB Saunders Company. 1999;815-879.
One study conducted in Kenya in 1993 detected four cases of encephalitis temporally associated with vaccination, one in a 2-year-old child and three in adults, for an incidence of 5. 3 cases per million vaccinees of all ages.
McMahon AW, et al. Neurologic disease associated with 17D-204 yellow
fever vaccination: a report of 15 cases. Vaccine. 2007 Feb 26;25(10):1727-34.
Epub 2006 Nov 27. PMID: 17240001 [PubMed - indexed for MEDLINE]
Yellow fever (YF), can be prevented by an attenuated vaccine (YEL). We reviewed neurologic adverse events (AE) following YEL that were reported to the national Vaccine Adverse Events Reporting System (VAERS). VAERS is a passive reporting system with inherent limitations for causality assessment. Based on defined criteria, five cases of encephalitis were classified as 'definitely' and one of acute disseminated encephalomyelitis (ADEM) as 'probably' caused by YEL. Six cases of Guillain-Barre Syndrome (GBS), one of encephalitis, and two of ADEM, were classified as 'suspect' vaccine-associated disease. Laboratory and epidemiological evidence suggests that YEL caused encephalitis. Additional studies will be required to confirm whether YEL can rarely result in GBS and/or ADEM.
Muñoz J, et al. Yellow fever-associated viscerotropic disease in
Barcelona, Spain. J Travel Med. 2008 May-Jun;15(3):202-5. PMID: 18494699 [PubMed
- indexed for MEDLINE]
Yellow fever vaccine is a live, attenuated viral preparation from the 17D virus strain. Since 1996, 34 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been described. We report a new case of YEL-AVD. Given the potential risks associated with the vaccine, physicians should consider vaccination only for patients truly at risk for exposure to yellow fever, especially for primovaccination.
Nishioka SA, et al. Yellow fever vaccination during pregnancy and spontaneous abortion: a case-control study. Trop Med Int Health 1998;3(1):29-33.
Louis JJ, et al. [A case of encephalitis after anti-yellow fever vaccination with the 17 D strain]. Pediatrie. 1981 Oct-Nov;36(7):547-50. French. No abstract available.PMID: 6119675; UI: 82105325
Mar ID, et al. [Encephalitis following anti-yellow fever vaccination]. Ann Pediatr (Paris). 1967 Mar 2;14(3):181-91. French. No abstract available.PMID: 4387264; UI: 69064560.
Merlo C, et al. Possible association of encephalitis and 17D yellow fever vaccination in a 29-year-old traveller. Vaccine. 1993;11(6):691. No abstract available.PMID: 8100665; UI: 93311098.
No authors listed] Fatal viral encephalitis following 17D yellow fever vaccine inoculation. Report of a case in a 3-year-old child. JAMA. 1966 Nov 7;198(6):671-2. No abstract available.PMID: 4380787; UI: 67043249.
Nishioka S de A, et al. Yellow fever vaccination during pregnancy and spontaneous abortion: a case-control study. Trop Med Int Health. 1998 Jan;3(1):29-33. PMID: 9484965; UI: 98143496.
Nottebart HC Jr. Yellow fever vaccine and avian leukosis virus. Ann Intern Med. 1984 Jul;101(1):148. No abstract available.PMID: 6329052; UI: 84229633.
Oyelami SA, et al. Severe post-vaccination reaction to 17D yellow fever vaccine in Nigeria. Rev Roum Virol. 1994 Jan-Jun;45(1-2):25-30. PMID: 7756161; UI: 95275719.
Rosa I. Mateo. Yellow Fever 17-D Vaccine Is Neurotropic and Produces
Encephalitis in Immunosuppressed Hamsters. Am. J. Trop. Med. Hyg., 77(5), 2007,
These findings support current recommendations against yellow fever vaccination of immunosuppressed/ immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.
Tsai TF, et al. Congenital yellow fever virus infection after immunization in
pregnancy. J Infect Dis 1993;168:1520-1523. PMID: 8245539; UI: 94065281.
Described two fatal cases of encephalitis possibly associated with 17D-204 vaccination among 67, 325 children between the ages of 6 months and 2 years, for an incidence rate of 3 per 100, 000.
Tauraso NM, et al. Yellow fever vaccine. I. Development of a
vaccine seed free from contaminating avian leukosis viruses.Proc Soc Exp Biol
Med. 1968 Apr;127(4):1116-20. No abstract available.PMID: 4297696; UI: 68281850.
Vogt D, et al. [Chromosomal changes following yellow fever vaccination]. Monatsschr Kinderheilkd. 1970 Jun;118(6):316-7. German. No abstract available.PMID: 5523671; UI: 72074875.
Vasconcelos PFC, et al. Serious adverse events associated with yellow
fever 17DD vaccine in Brazilia report of two cases. Lancet 2001;358:91-97.
Two Brazilian citizens (age 5 and 22 years) became ill three to four days after receiving 17DD vaccine in Brazil, all of whom died 8 to 11 days after vaccination.
PMID: 18023511 [PubMed - indexed for MEDLINE]
Payet M, et al. [Meningo-encephalitis after yellow fever
vaccination. Forms observed in adults (apropos of 7 cases]. Bull Soc Med Afr
Noire Lang Fr. 1966;11(3):597-600. French. No abstract available.PMID: 4382458;
Philipps J, et al. [Side effects of travel vaccinations. Data collection via telephone survey in Berlin]. Wien Klin Wochenschr. 1996;108(19):615-20. German. PMID: 9012147; UI: 97079943.
Pivetaud JP, et al. [Reactions to vaccination against yellow fever]. Bull Soc Pathol Exot Filiales. 1986;79(5 Pt 2):772-6. French. PMID: 3829216; UI: 87159732.
Receveur MC, et al. [Ketoacidotic coma 4 days after yellow fever vaccination]. Presse Med. 1995 Jan 7;24(1):41. French. No abstract available.PMID: 7899340; UI: 95207222.
Schoub BD, et al. Encephalitis in a 13-year-old boy following 17D yellow fever vaccine. J Infect. 1990 Jul;21(1):105-6. PMID: 2384674; UI: 90347226.
Wheelock EF, et al. Lymphocytes and yellow fever. I. Transient virus refractory state following vaccination of man with the 17-D strain. J Immunol. 1970 Nov;105(5):1304-6. No abstract available.PMID: 5496134; UI: 71088409.