Yellow Fever Vaccine at the Limits of Age
Yellow Fever Vaccine at the Limits of Age
ABSTRACT & COMMENTARY
By Philip R. Fischer, MD, DTM&H and Amy Yu-Ballard, MD, PhD
Dr. Fischer is Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN, and Dr. Yu-Ballard is a Resident, Department of Internal Medicine, Mayo Clinic, Rochester,
MN.
Dr. Fischer and Dr. Yu-Ballard report no consultants, stockholders, speaker'
s bureaus, research, or other financial relationships with companies having ties to this field of study.
Synopsis: Serious adverse reactions to yellow fever vaccine are significantly more common for individuals aged 60 years or older than for those who are younger. The risk of infection generally outweighs the risk of vaccination, but should be discussed carefully during the pre-travel consultation with older travelers.
Source: Khromava AY, et al. Yellow Fever Vaccine: An Updated Assessment of Advanced Age as a Risk Factor for Serious Adverse Events. Vaccine. 2005;23:3256-3263.
Yellow fever is a serious, mosquito-borne viral illness that is endemic in parts of Africa and South America. Case-fatality rates are approximately 20-50%. Yellow fever is thought to be responsible for 200,000 episodes of illness and 30,000 deaths each year.
The yellow fever vaccine that is available in the United States is an injectable, attenuated, live virus vaccine. During the past decade, yellow fever vaccination has been associated with serious and sometimes fatal viscerotropic and neurotropic illness. Some evidence has suggested that advanced age may be a risk factor for these serious reactions. Khromava and colleagues, in a yellow fever vaccine safety working group, updated the age-related estimated risks of serious adverse reactions to yellow fever vaccine using data from the United States Vaccine Adverse Event Reporting System.
Their study included all Vaccine Adverse Event Reporting System (VAERS) reports following yellow fever vaccination from 1990-2002 in the United States or in US citizens stationed overseas. Serious adverse effects included death, life-threatening illness, inpatient hospitalization, prolongation of existing hospitalization, and persistent or significant disability. Viscerotropic disease encompassed multiple organ system failure following administration of the yellow fever vaccine, including renal, hepatic, respiratory failure, myocarditis, and disseminated intra-vascular coagulation. Cases of neurotropic disease included post-vaccinal encephalitis, Guillain-Barre syndrome, and autoimmune disease with central or peripheral nervous system involvement after yellow fever vaccination. The data were stratified by age and compared to age-related reports of adverse reactions following other travel-related vaccinations (ie, typhoid fever and hepatitis A).
Of 144,072 total reports in the United States submitted to VAERS during this time period, 722 (0.5%) were yellow fever reports that met study criteria. Reporting rates of serious adverse effects following yellow fever immunization were 1.6 per 100,000 doses among civilians and 0.2 per 100,000 doses in the military (P < 0.05). For civilians, the reporting rate for serious adverse effects following administration of yellow fever vaccine increased significantly for age ≤ 60 years (P < 0.00001). Rates of serious adverse events following vaccination in civilians were 0.8 per 100,000 doses for 1-18 year olds, 0.7 for 19-29 year olds, 0.4 for 30-39 year olds, 1.6 for 40-49 year olds, 1.9 for 40-59 year olds, 4.2 for 60-69 year olds, and 7.5 for those at least 70 years of age. Viscerotropic disease following vaccination occurred in 7 individuals, 5 of whom were over 60 years of age, while neurotropic disease followed vaccination in 8 individuals (4 over 60 years of age). For civilians ≥ 60 years, the estimated reporting rate of serious reactions was 5.3 reports per 100,000 doses, as compared to 0.7 reports per 100,000 doses in civilians 19-29 years of age. Compared with other vaccine-associated event reports, there was no significant increase in reports with older age recipients of either hepatitis A vaccine or typhoid vaccine.
Commentary
Yellow fever vaccine is commonly administered, and is appropriately believed to be fairly safe. Nonetheless, as this study shows, reported viscerotropic reactions, neurotropic reactions, and other serious reactions were disproportionately more frequent in older individuals. Despite the small numbers of viscerotropic disease cases, the actual risk of such reactions was significantly higher in vaccinees 70 years of age and older (3.2 cases per 100,000 vaccine doses). This increased risk of reported reactions seems to be specific for yellow fever vaccine, since it is not seen with other vaccines.
Nonetheless, the proven risk of adverse reactions in older individuals must be kept in context. In fact, there were only 35 serious adverse events (including 7 of viscerotropic disease and 8 of neurotropic disease) reported from 1990 to 2002 following 2,230,760 doses of yellow fever vaccine in civilians. Even for the oldest group (≤ 70 years), there were only 7 serious events following nearly 100,000 vaccine doses.
What is the risk of getting yellow fever when traveling to an endemic area? Based on estimates of yellow fever incidence in populations residing in endemic areas, the risk of yellow fever illness in an unvaccinated traveler to an endemic area is estimated to be about 1:1000 per month, and the risk of death would be approximately 20% of that (1:5000).1 Nonetheless, there were only 11 reported cases of yellow fever in travelers from developed countries between 1950 and 2002.1 With the use of mosquito protection measures, the actual risk of yellow fever infection in an unvaccinated traveler might be somewhat less than 1:1000.
Thus, the risk of an adverse reaction to yellow fever vaccine in an elderly individual (possibly 1:13,000) must be balanced against the risk of disease in an unprotected traveler (potentially 1:1000). Cognizant of vaccine risks, immunization should still be seriously considered for elderly travelers going to an area where yellow fever is endemic.
At the same time, travelers should be advised to maximize other means of protection against yellow fever, including aggressive avoidance of mosquito bites. DEET has been effective as a repellent for decades. Now, a newer insect repellent, picaridin, is available in the United States. Picaridin is comparable to DEET in effectiveness and in duration of protection when used in comparable concentrations.2 Currently, however, picaridin is available only in lower concentrations in the Unites States, but could still provide 1-2 hours of protection.
What about travelers at the other end of the age spectrum? A majority of cases of vaccine strain encephalitis (neurotropic disease) have been in infants less than 4 months of age.3 Indeed, the incidence of vaccine-associated encephalitis in young infants (0.5-4 cases per 1000) approximates, or perhaps exceeds, the risk of yellow fever in unvaccinated travelers. Thus, yellow fever vaccine is not recommended for anyone under 6 months of age, and should be used only with extreme caution and expert consultation in infants between 6 and 9 months of age.3,4
Thus, Khromava et al's study emphasizes the importance of pre-travel risk assessment, especially in the elderly, and careful vaccination of only those traveling to yellow fever-endemic or epidemic regions. This study also highlights the importance of educating patients regarding the risks and benefits of vaccination.
References
1. Monath TP, Cetron MS. Prevention of Yellow Fever in Persons Traveling to the Tropics. Clin Infect Dis. 2002; 34:1369-1378; Erratum in: Clin Infect Dis. 2002;35:110.
2. Badolo A, et al. Evaluation of the Sensitivity of Aedes aegypti and Anopheles gambiae Complex Mosquitoes to Two Insect Repellents: DEET and KBR 3023. Trop Med Int Health. 2004;9:330-334.
3. Mackell SM. Vaccinations for the Pediatric Traveler. Clin Infect Dis. 2003;37:1508-1516.
4. Centers for Disease Control and Prevention. Yellow Fever Vaccine; Recommendations of the Advisory Committee on Immunization Practices.
By Philip R. Fischer, MD, DTM&H and Amy Yu-Ballard, MD, PhD Dr. Fischer is Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN, and Dr. Yu-Ballard is a Resident, Department of Internal Medicine, Mayo Clinic, Rochester, MN. Dr. Fischer and Dr. Yu-Ballard report no consultants, stockholders, speakers bureaus, research, or other financial relationships with companies having ties to this field of study.Subscribe Now for Access
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