eMedicine Specialties > Emergency Medicine > Infectious Diseases

Yellow Fever

Emily M Nichols, MD, Clinical Assistant Instructor, State University of New York Downstate, Kings County Hospital Center, Brooklyn
Aleksandr Gleyzer, MD, FAAEM, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Attending Physician, Department of Emergency Medicine, Kings County Medical Center and Brooklyn Veterans Affairs Medical Center

Updated: Oct 22, 2009

Introduction

Background

Yellow fever is one of many causes of viral hemorrhagic fever. It is a member of the flavivirus family (group B arbovirus). The Flavivirus genus is composed of more than 68 arthropod transmitted viruses, of which 30 are known to cause human disease. Other flaviviral infections include dengue, Japanese encephalitis, and tick-borne encephalitis. It is important to consider this group of viruses in the clinical differential of CNS infection, hemorrhagic fever, and acute febrile illnesses with arthropathy.

Yellow fever virus. Image courtesy of the Centers for Disease Control and Prevention.

Yellow fever is transmitted by tree-hole breeding mosquitoes (Haemagogus janthinomys, Haemagogus species, Sabethes chloropterus, and Aedes species) during the tropical wet season and early dry season.¹ Genomic sequence analyses suggest that it evolved from other mosquito-borne viruses about 3000 years ago in Africa. It is surmised that the yellow fever virus was introduced to the Americas by Dutch slave traders during the 17^th century. The first documented epidemic occurred in the Yucatan Peninsula and spread through the Caribbean basin. This was the result of ship travel and continued importation of slaves from West Africa. Vessels infested with Aedes aegypti (mosquitoes) brought yellow fever into New England and several port cities throughout North America.

In the early 20^th century, Carlos Findlay and Walter Reed's discovery of A aegypti as the source of transmission led to the eradication of yellow fever in parts of Latin America. Isolation of the virus and later development of the 17D vaccine by Max Theiler helped eliminate A aegypti and yellow fever from countries in Africa and the Americas during the mid 20^th century.²

A resurgence of yellow fever occurred in South America and sub-Saharan Africa in the late 1980s.³ This was likely the result of fragmentary vaccine implementation, deforestation, urbanization, and climate change.⁴ Today, outbreaks occur regularly in Africa and South America, with significant variation in annual incidence by country and region.³

Pathophysiology

Seventy-three species of flaviviruses have been identified; yellow fever virus was the first to be isolated (1927) and grown in vitro (1932).¹ It is a small (40-60 nm), single-stranded, RNA virus. Although 7 strains exist, there is only one serotype; this enables one vaccine to protect against all strains.³ After a bite from an infected mosquito, the virus replicates initially in local lymph nodes, followed by blood-borne spread and subsequent replication in regional lymph tissue, spleen, and bone marrow. It later spreads to the liver, lungs, and adrenal glands.

The liver is the most important organ affected in yellow fever. Hepatocellular damage is characterized by lobular steatosis, necrosis, and apoptosis with subsequent formation of Councilman bodies (degenerative eosinophilic hepatocytes).⁵ The kidneys also undergo significant pathologic changes. Albuminuria and renal insufficiency evolve secondary to the prerenal component of yellow fever; resultantly, acute tubular necrosis develops in advanced disease. Hemorrhage and erosion of the gastric mucosa lead to hematemesis popularly known as "black vomit." Fatty infiltration of the myocardium, including the conduction system, can lead to myocarditis and arrhythmias.

CNS findings can be attributed to cerebral edema and hemorrhages compounded on metabolic disturbances. The bleeding diathesis of this disease is secondary to reduced hepatic synthesis of clotting factors, thrombocytopenia, and platelet dysfunction. The terminal event of shock can be attributed to a combination of direct parenchymal damage and a systemic inflammatory response.

Frequency

United States

The last epidemic of yellow fever in North America occurred in New Orleans in 1905. However, during 1970-2002,9 cases of yellow fever were reported in unimmunized travelers from the United States and Europe—disease was acquired in Brazil, Senegal, Venezuela, Ivory Coast, Gambia, and West Africa. Seven of these cases were fatal.^3,6

After the 21st century outbreaks of dengue fever in Hawaii and along the Texas-Mexico border, it has been hypothesized that yellow fever could reemerge in the United States.⁷ Recent virology research has isolated Flaviviridae strains from mosquitoes in eastern Texas, making transmission of yellow fever a potential threat for the United States in the future.⁸

International

Approximately 200,000 cases of yellow fever occur annually, with about 30,000 deaths.⁹ Accurate incidence reporting is limited by the occurrence of asymptomatic disease, underreporting of the disease, and the lack of diagnostic capabilities in endemic areas.³ Ninety percent of reported cases occur in Africa,⁶ where A aegypti species is rampant. Transmission occurs in largely unvaccinated populations of sub-Saharan Africa. The countries at greatest risk lie within a band from 15°N to 10°S of the equator.⁹
 

Global distribution of yellow fever. Image courtesy of the Centers for Disease Control and Prevention.

Mortality/Morbidity

Yellow fever ranges in severity from a self-limited infection to life-threatening hemorrhagic fever. About 15-25% of affected individuals enter into a more severe phase of disease that involves fever, jaundice, and liver and renal failure. Overall mortality ranges from 20-50%.⁴ Case-fatality rates in South America are reportedly higher than in West Africa.³

Mortality is a function of both host susceptibility and the virulence of the infecting strain.⁵ Infancy and age older than 50 years is associated with increased severity of illness and lethality.³ Transaminase levels increase relative to the degree of hepatic injury. Early appearance of jaundice indicates a poor prognosis.

Race

No known racial predilection is known in the transmission or contraction of yellow fever.

Sex

Sylvatic (jungle) yellow fever, which is primarily acquired by forest workers,⁹ is most common among healthy young males because of occupational risk.

Age

Sylvatic disease primarily affects individuals aged 15-45 years who work outdoors in agriculture and forestry. Urban yellow fever and intermediate yellow fever, which occurs primarily in the humid savannas of Africa, affect individuals of all ages.⁹

Clinical

History

To arrive at a diagnosis of yellow fever, consider the patient's clinical features and his or her places and dates of travel, including the epidemiologic history of the places visited, immunizations, and activities.

• An incubation period of 3-6 days indicates that travelers may be viremic before demonstrating symptoms.
• Clinical symptoms manifest in 1:20 partially immune patients and 1:5 immunologically naive patients.
• Initial symptoms correspond to the viremic phase (ie, period of infection). They have an abrupt onset and are followed by a transient (up to 48 h) remission:³
  • Fever and chills
  • Severe headache
  • Back pain
  • Myalgia
  • Nausea
  • Prostration
• The toxic phase (ie, period of intoxication) of yellow fever develops as the fever returns. This phase occurs in approximately 15% of cases.
  • Clinical symptoms include high fever, headache, lumbosacral back pain, nausea, vomiting, abdominal pain, and somnolence.
  • Hepatic-induced coagulopathy produces hemorrhagic manifestations, including the characteristic black vomit (hematemesis), epistaxis, gum bleeding, and petechial and purpuric hemorrhages.
  • Systemic manifestations include deepening jaundice and albuminuria.
• In the late stages of disease hypotension, shock, metabolic acidosis, acute tubular necrosis, myocardial dysfunction, and arrhythmia dominate the clinical picture.
• Confusion, seizure, and coma distinguish the late CNS manifestations of the disease. Death usually follows within 7-10 days of onset.
• Secondary bacterial infections are frequent complications in patients who survive the critical period of illness.

Physical

Physical findings of yellow fever are as follows:

• Altered mental status
• Fever
• Relative bradycardia for the degree of fever (Faget sign)
• Conjunctival injection
• Other physical findings such as jaundice, epigastric tenderness, and hepatomegaly develop as disease progresses.
• Hemorrhagic PE findings as described in History 
• Shock, multiorgan system dysfunction, acute respiratory distress syndrome (ARDS)

Causes

Early signs of disease are likely due to the innate immune response to infection. The release of proinflammatory mediators initiates a cascade of events leading to apoptosis. Additionally, clearance of infected cells by cytotoxic T lymphocytes contributes to the production of oxygen free radicals and subsequent cell damage. The terminal events of shock and multiorgan failure are believed to be due to a combination of direct parenchymal damage and a systemic inflammatory response. With similar cytokines and chemoattractant proteins, the syndrome seen in end-stage yellow fever closely resembles that of overwhelming sepsis.⁵

Differential Diagnoses

Other Problems to Be Considered

Crimean-Congo hemorrhagic fever
Rift valley fever
Typhoid fever
Typhus
Sepsis/multiorgan system dysfunction
DIC
Other viral hemorrhagic fevers
Other flaviviruses

Workup

Laboratory Studies

• A complete blood count (CBC) often indicates leukopenia and thrombocytopenia. Leukopenia is an early manifestation of disease.³
• Liver function test results may indicate elevated direct bilirubin and hepatic transaminases.Levels begin to rise as early as 2-3 days into the viremic phase.³
• Prothrombin time, activated partial thromboplastin time, international rationalized ratio (INR), and clotting times are prolonged invariably.
• Diminished levels of factor VIII, fibrinogen, and platelets, along with the presence of fibrin split products, indicate the presence of disseminated intravascular coagulation (DIC).
• Albuminuria usually is noted with proportional rises in BUN and creatinine levels.
• Serologic tests such as enzyme-linked immunosorbent assay (ELISA) aid in making an exact diagnosis. Confirmation is difficult because of cross-reactivity with other viruses, particularly in Africa where multiple flaviviruses exist.³
• Laboratory diagnosis of yellow fever in travelers depends principally on serological testing of serum immunoglobulins. Immunoglobulin M (IgM) testing by ELISA is the preferred method of testing. This assay is 95% sensitive when serum specimens are collected 7-10 days after the onset of illness.
• Paired acute and convalescent sera indicate the diagnosis.
• Polymerase chain reaction can be used to identify viral ribonucleic acid (RNA) during acute infection, but clinical experience is limited.
• Immunohistochemical staining of tissues (liver, heart, or kidneys) for the yellow fever antigen would also provide a definitive diagnosis.³ One should not attempt a liver biopsy during infection because of the risk of complications from hemorrhage.

Other Tests

• ECG may identify prolongation of PR and QT intervals.¹

Treatment

Prehospital Care

Patients with yellow fever with hemodynamic instability should undergo prehospital fluid resuscitation. Adherence to universal precautions is mandatory to prevent transmission to health care workers.

Emergency Department Care

Treatment of yellow fever is principally symptomatic and preventative.

• Closely monitor patients for hypovolemia, oliguria, hypoxia, acidosis, and electrolyte imbalance. Hypotension and hypoxia may aggravate hepatic and renal injury.
• Invasive arterial blood pressure monitoring may be warranted.
• Intravascular volume may decrease secondary to sequestration in the extravascular space or to fluid loss through insensible losses, vomiting, and capillary leak.
• If oxygenation and hydration do not improve hemodynamic parameters, or if myocardial dysfunction is present, monitor pulmonary artery pressures.
• Monitor central venous pressure, peripheral blood pressure, as well as surrogates for organ perfusion and regional blood flow (eg, capillary refill, urinary output, ScvO₂). Swan-Ganz catheter monitoring of hemodynamic parameters may be helpful in some situations.
• Monitor acid-base disturbances and metabolic acidosis via arterial blood gas sampling
• Use of cooling blankets and tepid sponging can reduce fever and, thus, oxygen consumption.
• Hypothermia frequently occurs late in the disease course and is corrected with gradual rewarming.
• Nasogastric suction is essential to prevent gastric distention and aspiration of gastric contents. H2-receptor antagonists and sucralfate may also be valuable in preventing gastric bleeding.
• Consider parenteral alimentation. Hypoglycemia can be prevented by infusion of 10-20% glucose solution.
• Replacement of red blood cells, clotting components, and other volume expanders are used to treat hemorrhage and shock.
• Renal failure may necessitate dialysis. Consider dopamine for patients not responding to hydration, but dobutamine may offer the advantage of its positive chronotropic effect. Avoid drugs that are dependent on hepatic metabolism while medication doses should be adjusted for reduced renal function.

Consultations

• Intensivist consultation for severe disease or hemorrhagic fever
• Infectious disease consultation
• Centers for Disease Control and Prevention/reportable disease

Medication

Currently, no antiviral drug against yellow fever is approved. To date, nonclinical testing of antiviral agents has yielded modest results. Ribavirin, given at high doses to hamsters challenged with yellow fever, has been shown to reduce mortality when administered as late as 120 hours after infection. Interferon-α has also been found to reduce mortality when administered to monkeys with yellow fever; however, it was only effective when given within 24 hours of infection. These findings suggest that antiviral therapies may only be effective early in the course of disease when clinical symptoms are nonspecific and indistinguishable from other viral infections. Recent trials by Julander et al involving an active carboxamide drug [AT-1106 (2,4-dihydro-3-oxo-4-β-D-ribofuranosyl-2-pyrazinecarboxamide)] have been effective in hamsters when treatment was started on day 4, after the development of liver infection.⁵ Ongoing research and advances show promise for the future.Adjunctive measures include nonhepatotoxic antipyretics to reduce fever and pain and an H2-receptor antagonist to prevent gastric bleeding. Use of heparin for documented cases of DIC is controversial. Additionally, the use of stress-dose corticosteroids is currently under investigation.⁵ Avoid drugs that act centrally, including phenothiazines, barbiturates, and benzodiazepines, because they may precipitate or aggravate encephalopathy. Avoid drugs dependent on hepatic metabolism, and, in cases of reduced renal function, medications should be renally dosed.

Histamine H2 antagonists

These agents are useful as an adjunctive therapy to prevent gastric bleeding. H2-receptor antagonists are highly selective, do not affect the H1 receptors, and are not anticholinergic agents. These are potent inhibitors of all phases of gastric acid secretion. They inhibit secretions caused by histamine, muscarinic agonists, and gastrin.

Famotidine (Pepcid)

Competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Dosing

Adult

20-40 mg PO qhs or 20 mg IV q12h

Pediatric

0.5 mg/kg PO/IV qh; not to exceed 40 mg/d

Interactions

May decrease efficacy of ketoconazole, itraconazole, cefpodoxime, delavirdine, digestive enzymes, and iron salts

Contraindications

Documented hypersensitivity; phenylketonuria; impaired renal function

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If changes in renal function occur during therapy, adjust dose or discontinue treatment; serious reactions include thrombocytopenia, leukopenia, pancytopenia, and cholestatic jaundice

Nizatidine (Axid)

Competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Dosing

Adult

300 mg PO hs or 150 mg bid

Pediatric

<6 months: Not established
6-10 mg/kg PO qd (for 6 months to 12 years, divide dose bid)
>12 years: Administer as in adults

Interactions

May reduce efficacy of cefpodoxime, delavirdine, digestive enzymes, iron salts, and ketoconazole

Contraindications

Documented hypersensitivity; impaired renal function

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

If changes in renal function occur during therapy, adjust dose or discontinue treatment; serious reactions include thrombocytopenia, leukopenia, pancytopenia, and cholestatic jaundice

Ranitidine (Zantac)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Dosing

Adult

150 mg PO bid or 300 mg PO qhs; alternately, 50 mg/dose IV/IM q6-8h

Pediatric

<2 weeks: 2 mg/kg PO divided bid ; alternately, 1.5 mg/kg IV initial, then 1.5 mg/kg IV divided bid
Infusion: 0.04 mg/kg/h IV
Children: 4-5 mg/kg PO IV/IM divided bid/tid; alternately, 2-4 mg/kg IV/IM divided tid/qid; infusion 0.1-0.125 mg/kg/h

Interactions

May decrease effects of ketoconazole, itraconazole, cefpodoxime, delavirdine, and digestive enzymes; may alter serum levels of ferrous sulfate, nondepolarizing muscle relaxants, diazepam, and oxaprozin

Contraindications

Documented hypersensitivity; porphyria; impaired liver and renal function

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dosage or discontinuing treatment; may cause thrombocytopenia and hepatotoxicity

Antipyretics

Treatment of yellow fever is symptomatic and supportive. Bed rest and mild analgesic-antipyretic therapy often help relieve associated lethargy, malaise, and fever.

Acetaminophen (Tylenol, Aspirin-Free Anacin, Feverall)

Inhibits action of endogenous pyrogens on heat-regulating centers; reduces fever by direct action on the hypothalamic heat-regulating centers, which, in turn, increase dissipation of body heat via sweating and vasodilation.

Dosing

Adult

325-1000 mg PO/PR q4-6h; not to exceed 4 g/d
Alternatively, administer 1000 mg tid/qid; not to exceed 4 g/d

Pediatric

<12 years: 10-15 mg/kg/dose PO/PR q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO/PR q4h; not to exceed 4 g/d

Interactions

Because of induction of microsomal enzymes by barbiturates, carbamazepine, hydantoins, isoniazid, rifampin, and sulfinpyrazone, long-term administration of these agents or large doses of acetaminophen may increase acetaminophen hepatotoxicity (therapeutic effects of acetaminophen also may decrease)

Contraindications

Documented hypersensitivity; G-6-PD deficiency, phenylketonuria, impaired liver and renal function, and long-term alcohol use

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Hepatotoxicity possible in patients with chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate serious illness; acetaminophen is contained in many OTC products and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose

Aspirin (Anacin, Bufferin, Ecotrin)

Lowers elevated body temperature by vasodilating peripheral vessels, thereby enhancing dissipation of excess heat. Also acts on the heat-regulating center of hypothalamus to reduce fever.

Dosing

Adult

325-650 mg PO/PR q4h

Pediatric

10-15 mg/kg PO/PR q4-6h; not to exceed 60-80 mg/kg/d

Interactions

Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants, antiplatelets, COX-2 inhibitors, sulfinpyrazone, thrombolytics, and valproic acid derivatives; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs and insulin; mesalamine may increase aspirin toxicity; combo therapy may increase methotrexate toxicity

Contraindications

Documented hypersensitivity; liver damage, GERD, G-6-PD deficiency, hypoprothrombinemia, TTP, vitamin K deficiency, bleeding disorders, asthma; because of association of aspirin with Reye syndrome, do not use in children (<16 y) with flu

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, with history of blood coagulation defects, or taking anticoagulants

Ibuprofen (Motrin, Advil, Nuprin)

NSAID with analgesic and antipyretic activities. Although exact mode of action not known, appears to inhibit cyclooxygenase activity and prostaglandin synthesis. May inhibit lipoxygenase, leukotriene synthesis, lysosomal enzyme release, neutrophil aggregation, and various cell-membrane functions.

Dosing

Adult

200-400 mg PO q4-6h prn; not to exceed 3.2 g/d; take with food

Pediatric

4-10 mg/kg PO q6-8h, not to exceed 50 mg/kg/d; take with food

Interactions

Coadministration with aspirin, probenecid, and leflunomide increases risk of inducing serious NSAID-related adverse effects; anticoagulants, antiplatelets, corticosteroids, COX-2 inhibitors, thrombolytics, valproic acid derivatives, and aspirins may increase risk of bleeding; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, ACE inhibitors, angiotensin II receptor blockers, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase lithium toxicity, phenytoin levels may be increased when administered concurrently, acetaminophen, cyclosporin, may increase risk of nephrotoxicity, all quinolones may increase risk of CNS stimulation

Contraindications

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding; CHF

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Follow-up

Further Inpatient Care

• There is mandated reporting to the World Health Organization (WHO) of all suspected or confirmed yellow fever cases within 24 hours of detection. Cases should also immediately be reported to one’s local health department.
• All cases of yellow fever identified in the United States warrant inpatient admission because of unfamiliarity with this disease.
• In settings outside urban areas, admission is predicated on the illness of the patient and the medical resources available.
• For patients with any evidence of end-organ injury (eg, jaundice, renal failure, bleeding) or hemodynamic instability, intensive care is optimal.
• From a systems perspective, improving the local infrastructure is more practical than evacuation of patients.
• Suggested improvements include improved surveillance, early rapid diagnostic services, and specialized mobile teams to augment local clinical facilities.

Deterrence/Prevention

• Protect patients from mosquitoes with bed nets or screened rooms to avoid development of urban yellow fever. Travelers should consider using DEET(N,N-Diethyl-meta-toluamide)-containing insect repellent spray.
• The currently available vaccine confers near lifelong immunity in 95% of patients.³ For travel certification, revaccination is recommended every 10 years.

Complications

Complications of yellow fever include the following:

• Hemorrhage
• Organ system failure
• CNS damage
• Liver damage

Prognosis

See Mortality/Morbidity.

Patient Education

Current information, including new outbreaks and information for travelers, can be obtained online from the World Health Organization and the Centers for Disease Control and Prevention.

Miscellaneous

Medicolegal Pitfalls

• Vaccine-associated complications
  • The yellow fever vaccine has been regarded as one of the safest and most effective vaccines in use. Nonetheless, the live attenuated 17D vaccine has been shown to cause wild-type disease in a subset of patients.⁵ Between 1952 and 1959, 15 cases of postvaccination encephalitis were reported after administration of vaccine;¹² since 1945, a total of 28 cases have been reported. Sixteen of these cases occurred in infants younger than 6 months old. This resulted in the restriction of vaccine use in children younger the age of 6 months and limited use in those between 6 and 9 months of age.
  • The syndrome of yellow fever vaccine-associated neurologic disease (YEL-AND) is characterized by fever, headache, and focal or generalized neurologic dysfunction. Symptomatic onset ranges from 4-23 days after vaccination. In addition to encephalitis, cases of disseminated encephalomyelitis and Guillain-Barré have been reported. Case-fatality rates are less than 5%; most individuals recover from YEL-AND without sequelae.³
  • A condition known as yellow fever vaccine-associated viscerotropic disease (YEL-AVD) has also been described within the last 15 years. This syndrome is characterized by fever, jaundice, and multiorgan system failure similar to the wild-type strain. Symptoms began 2-5 days after immunization; they are usually mild but can be fatal. As of August 2006, more than 30 cases of YEL-AVD had been described worldwide; it has occurred only in nonimmune first-time vaccinees. Unlike YEL-AND, YEL-AVD has been reported primarily in individuals of advanced age.³
  • The proposed cause of vaccine-associated disease is an unsuited host response to the live attenuated 17-D vaccine. Individuals younger than 6 months and older than 60 years, persons with a history of thymic disease (eg, DiGeorge syndrome, thymomas, post thymectomy), and those with a cell-mediated immunodeficiency status (eg, cancer, transplant, HIV patients) are all considered to be at a greater risk of developing YEL-AND and YEL-AVD with its subsequent sequelae.¹³ A careful medical history to exclude the above should be obtained before the vaccine is administered.
• Failure to recognize yellow fever in the returned traveler is an important pitfall.
• Failure to vaccinate individuals traveling to affected areas is a pitfall.

Special Concerns

Yellow fever will likely not be eradicated in the near future. Various mosquito species transmit the sylvatic form via nonhuman primates in the jungles and moist savannas;² this ongoing life cycle does not require humans for the spread of disease. Additionally, urbanization and deforestation have reintroduced the virus into areas of previous inactivity. New outbreaks and epidemics continue to reemerge in regions of Africa and South America previously not considered at risk.

At present, the burden of disease is greater than the resources available for proper surveillance and mass vaccination. Furthermore, the vaccine supply is rapidly dwindling. According to the WHO, the current stockpile is likely to be depleted in 2010.¹⁴ Without additional funding, it is doubtful that the goal of herd immunity will be achieved in endemic regions. Yellow fever also carries the potential threat of use as a bioterrorist agent;¹ however, other viral hemorrhagic fevers pose a greater risk because of their lack of prophylactic protection.

Multimedia

Media file 1: Global distribution of yellow fever. Image courtesy of the Centers for Disease Control and Prevention.

Media file 2: Yellow fever virus. Image courtesy of the Centers for Disease Control and Prevention.

References

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Keywords

yellow fever symptoms, yellow fever vaccine, flavivirus, , group B arbovirus, attenuated 17D vaccine, flaviviral infections, dengue, Japanese encephalitis, tick-borne encephalitis, hemorrhagic fever, acute febrile illnesses with arthropathy

Contributor Information and Disclosures

Author

Emily M Nichols, MD, Clinical Assistant Instructor, State University of New York Downstate, Kings County Hospital Center, Brooklyn
Emily M Nichols, MD is a member of the following medical societies: American College of Emergency Physicians, Emergency Medicine Residents Association, and National Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Aleksandr Gleyzer, MD, FAAEM, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Attending Physician, Department of Emergency Medicine, Kings County Medical Center and Brooklyn Veterans Affairs Medical Center
Aleksandr Gleyzer, MD, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine and International Society of Travel Medicine
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Medical Editor

Dan Danzl, MD, Chair, Department of Emergency Medicine, Professor, University of Louisville Hospital
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CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
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Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
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The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Natalie T Shum, MD, Judith C Brillman, MD, and Malini K Singh, MD, to the development and writing of this article.

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