Unprotected People Reports: Yellow Fever
Fatal Yellow Fever in a Traveler Returning from Amazonas, Brazil, 2002
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|On April 19, 2002, the Centers for Disease Control and Prevention (CDC)
published "Fatal Yellow Fever in a Traveler Returning from Amazonas, Brazil,
2002" in the Morbidity and Mortality Weekly Report (MMWR, vol. 51, no.15).
The article describes the case of a previously healthy 47-year-old male who
traveled to Brazil for a fishing trip in March of this year, contracted yellow
fever, returned to his home state of Texas, became severely ill, and died. The
man's death is the third reported death from yellow fever in a U.S. citizen
following travel to the Amazon region since 1996, according to the Editorial
Note to the article.
|The Immunization Action Coalition (IAC) is republishing this story as the
44th in our series of stories about people who have suffered or died from
vaccine-preventable diseases. We usually try to choose stories that are written
for a general audience. Sometimes, however, a powerful story appears in a
technical medical or public-health source that we think almost all readers will
appreciate. Today's MMWR story about an adult traveler's death from yellow fever
infection contains information for clinicians and epidemiologists, but it also
provides case details that are useful for all international travelers.
|Many of us in the United States do not even know what yellow fever is; it's
a viral disease found in parts of Africa and South America that is transmitted
by mosquito bite. The fatality rate for the disease is approximately 20
|Travelers, even if your tour group or company informs you that yellow fever
vaccination certification is not required in the country or countries you plan
to visit, please consult with a travel medicine specialist and weigh the
minor inconvenience and cost of getting vaccinated against the possible cost of
serious or even fatal illness. (Please note that the person whose death is
documented in this article was given incorrect advice about vaccination
from his travel agency, as you will read.) This is a simple, one-dose vaccine
that lasts 10 years. It can be received at a designated yellow fever center,
typically a local health department. As the Editorial Note to this article
states, vaccination should be obtained at least 10 days before departure
in order to allow for an adequate immune response.
|The entire article reads as follows:
|Yellow fever (YF) is a mosquitoborne viral disease that has caused deaths in
U.S. and European travelers to sub-Saharan Africa and tropical South America
(1-5). Although no specific treatment exists for YF and the case-fatality rate
for severe YF is approximately 20%, an effective vaccine is available (6).
This report describes a case of fatal YF in an unvaccinated traveler who had
returned from a 6-day fishing trip on the Rio Negro west of Manaus in the state
of Amazonas, Brazil. Because information from some commercial outfitters and
travel agents might underestimate health risks, health-care providers and
travelers should review vaccination and other traveler's health recommendations
from public health agencies.
On return from Brazil on March 10, 2002, a previously healthy man aged 47
years from Texas presented to an emergency department (ED) with a 4-day
history of crampy abdominal pain and a 1-day history of fever of 102.8 degrees F
(39.3 degrees C) and severe headache. At the ED, he received symptomatic
treatment and doxycyline for a possible rickettsial disease and was discharged.
His fever and headache worsened, and on March 12 he was hospitalized for
On admission, physical examination revealed an ill-appearing, febrile man.
Laboratory tests documented leukopenia (2,300/mm3 [normal: 4,800-10,800/mm3]),
anemia (hemoglobin 10.5 g/dL [normal: 14-18 g/dL]), thrombocytopenia (36,000/mm3
[normal: 150,000-450,000/mm3]), abnormal coagulation (prothrombin time: 29
seconds [normal: 10.5-13.0 seconds] and INR 6.3), renal failure (creatinine: 5.5
mg/dL [normal: 0.6-1.0 mg/dL] and blood urea nitrogen: 65 mg/dL [normal: 6--20
mg/dL]), and liver failure (ALT: 7,600 U/L [normal: 30--65 U/L], AST: 13,700 U/L
[normal: 15--37 U/L], and bilirubin: 3.3 mg/dL [normal: 0--1.0 mg/dL]). The
patient was presumptively treated for malaria. Bacterial cultures of blood,
urine, and cerebrospinal fluid showed no growth, and a malaria smear of
peripheral blood was negative. Three days after admission, the patient developed
shock, seizures, and excessive bleeding at venipuncture sites; he died the
Tests performed at CDC on serum samples collected on the second day of
illness were negative for IgM and IgG antibody to South American arboviruses
(i.e., YF, dengue, St. Louis encephalitis, and Venezuelan equine
encephalomyelitis viruses); serum samples collected on days 3-7 also were
negative for IgM and IgG antibody to YF virus. Serum specimens collected on days
4, 5, and 7 of illness and a postmortem liver sample were positive for YF virus
RNA by RT-TaqMANT PCR tests. Virus isolation was attempted by inoculation of
serum samples onto Vero and AP-61 cells in tissue culture, and by
inoculation of postmortem plasma onto Vero cells in tissue culture and
intracerebrally into suckling mice. No virus was recovered.
Histopathologic examination of a postmortem percutaneous needle sample of
the liver demonstrated massive acidophilic hepatocellular necrosis with minimal
inflammation. Immuno-histochemistry (IHC) tests using a cross-reactive,
polyclonal flavivirus antibody and a polyclonal YF-virus--specific antibody were
positive. IHC tests for New World arenaviruses (Machupo, Guanarito, and Sabia
viruses), spotted fever rickettsiae, dengue virus, and Leptospira spp. were
negative. A postmortem serum sample was negative for IgM and IgG antibody to
Leptospira spp. and New World arenaviruses, and negative for Machupo virus by
ELISA antigen capture. A blood sample collected on day 2 was negative for
malaria by PCR test.
The deceased traveler was one of 15 U.S. citizens who visited the Amazon as
part of a fishing trip. The patient slept aboard an air-conditioned fishing boat
and wore DEET-impregnated clothing while fishing. Before traveling to the
Amazon, the traveler had not received medical consultation, YF vaccine, or
malaria prophylaxis. Information on the outfitter's website stated, "The
International medical community suggests yellow fever and malaria prophylaxis
for the Amazon region. This is not a requirement to enter Brazil, but merely a
suggestion." A brochure from the group's travel agent stated, "We do not suggest
any inoculations of any kind for this trip.... But to make sure you are worry
free, consult with your personal physician. "The
15 U.S. citizens living aboard this fishing boat (including the patient) were
interviewed or investigated by the Texas Department of Health. Other than the
patient, none reported febrile illnesses. Eight (53%) were appropriately
vaccinated for YF according to World Health Organization (WHO) guidelines
(i.e., within the preceding 10 years and 10 or more days before arrival in
Manaus). Of the seven that were not appropriately vaccinated, one had received
YF vaccine 11 years earlier, one had been vaccinated 5 days before arrival
in Manaus, and one was unsure whether he had been vaccinated in the military >30
years earlier. Of the four persons (including the patient) who were never
vaccinated, three stated that they had been "unconcerned" about the risk for YF.
Three (20%) of the 15 reported taking malaria prophylaxis.
Reported by: P Hall, MD, M Fojtasek, MD, J Pettigrove, MD, Corpus Christi
Medical Center--Bay Area; N Sisley, MD, Corpus Christi-Nueces County Public
Health District, Corpus Christi, Texas. J Perdue, K Hendricks, MD, S Stanley,
MD, D Perrotta, PhD, Texas Dept of Health. AA Marfin, MD, GL Campbell, MD, RS
Lanciotti, PhD, LR Petersen, MD, Div of Vector-Borne Infectious Diseases; PE
Rollin, MD, TG Ksiazek, PhD, Div of Viral and Rickettsial Diseases; MS Cetron,
MD, D Sharp, MD, Div of Global Migration and Quarantine, National Center for
Infectious Diseases; KG Julian, MD, EIS Officer, CDC.
This case represents the third reported YF death in a U.S. citizen following
travel to the Amazon region since 1996 (1,2). YF can initially manifest as
fever, headache, myalgias, arthralgias, epigastric pain, or vomiting (6).
Illness can progress to liver and renal failure, and thrombocytopenia and
abnormal coagulation can cause hemorrhagic symptoms and signs. Definitive
diagnosis is made by viral culture of blood or tissue specimens or by
identification of YF virus antigen or nucleic acid in tissues (especially liver)
using IHC, ELISA antigen capture, or PCR tests. Although antibodies are not
always present in the first week of illness, detection of YF-specific IgM
antibody by capture ELISA with confirmation of >4-fold rise in neutralizing
antibody titers between acute- and convalescent-phase serum samples also is
On returning home, viremic travelers can establish new foci of YF
transmission where susceptible vectors are present. The geographic range of
Aedes aegypti, a mosquito that transmits YF virus among humans, includes the
southern United States. Patients with suspected or confirmed YF should be
isolated from contact with mosquitoes during at least the first 5 days of
illness, and local or state health departments must be notified immediately (7).
YF is one of three diseases (along with cholera and plague) designated by the
International Health Regulations as internationally quarantinable and requires
international reporting of all suspected and confirmed cases within 24 hours
Commercial outfitters and travel agents should ensure that health
information provided to travelers is consistent with CDC and WHO YF vaccination
and malaria prophylaxis recommendations. Undervaccination of travelers at risk
for YF might be an increasing problem. Using a mathematical
model based on U.S. arrivals to countries where YF transmission occurs and
on YF vaccine doses sold to U.S. civilians, overall coverage among U.S.
travelers to regions where YF is endemic might have declined 50% from 1992 to
1998 (9). The degree to which inaccurate health information contributes to
apparently decreasing coverage is unknown.
Because of the severity of YF illness, the potential for epidemics, and the
availability of an efficacious vaccine, CDC recommends vaccination of persons
aged 9 months or greater traveling to nonurban areas where YF is endemic (i.e.,
sub-Saharan Africa and tropical South America, including Amazonas states in
Brazil and Venezuela). To allow for an adequate immune response, vaccination
should be completed at least 10 days before travel. Some countries, other than
the United States, require YF vaccination for travelers returning from countries
where YF is endemic and may impose quarantine if the traveler does not
have official vaccination documentation or a written medical waiver. Although
recent reports described occurrence of severe systemic illness potentially
related to recent YF vaccination (10), the rarity of these events does not
warrant changes in YF vaccination recommendations. Before international travel,
persons should review CDC recommendations (http://www.cdc.gov/travel)
for prevention of vectorborne and other travel-related diseases.
- McFarland JM, Baddour LM, Nelson JE, et
al. Imported yellow fever in a United States citizen. Clin Infect Dis
- CDC. Fatal yellow fever in a traveler
returning from Venezuela, 1999. MMWR 2000;49:303-5.
- Barros MLB, Boecken G. Jungle yellow fever
in the central Amazon. Lancet 1996;348:969-70.
- World Health Organization. Yellow fever,
1998-1999. Wkly Epidem Rec 2000;75:322-8.
- World Health Organization. Outbreak news:
imported case of yellow fever, Belgium (update). Wkly Epidem Rec
- Monath TP. Yellow fever. In: Plotkin SA,
Orenstein WA, eds. Vaccines. 3rd ed. Philadelphia, Pennsylvania: WB
- Chin J, ed. Control of communicable
diseases manual. 17th ed. Washington, DC: American Public Health
- World Health Organization. International
health regulations (1969): 3rd annotated ed. Geneva, Switzerland: World
Health Organization, 1983.
- Monath TP, Cetron MS. Preventing yellow
fever in travelers to the tropics. Clin Infec Dis (in press).
- CDC. Fever, jaundice, and multiple organ
system failure associated with 17D-derived yellow fever vaccination,
1996-2001. MMWR 2001;50:643-5.
|4/22/02 • REPORT #44
|Disclaimer: The Immunization Action Coalition (IAC) publishes
Unprotected People Reports for the purpose of making them available
for our readers' review. We have not verified the content of this