Posts
Yellow fever is caused by a small virus that is spread by the bite of mosquitoes. This disease is common in South America and in sub-Saharan Africa.
Anyone can get yellow fever, but the elderly have a higher risk of severe infection. If a person is bitten by an infected mosquito, symptoms usually develop 3 - 6 days later.
Yellow fever has three stages:
If you have symptoms of yellow fever, tell your doctor if you have traveled to areas where the disease is known to thrive. Blood tests can confirm the diagnosis.
Tell your health care provider right away if you or your child develop fever, headache, muscle aches, vomiting, or jaundice, especially if you have traveled to an area where yellow fever is known to occur.
Preventive vaccination can be offered through routine infant immunization and one-time mass campaigns to increase vaccination coverage in countries at risk, as well as for travelers to yellow fever endemic area. WHO strongly recommends routine yellow fever vaccination for children in areas at risk for the disease.
The yellow fever vaccine is safe and affordable, providing effective immunity against yellow fever within one week for 95% of those vaccinated. A single dose provides protection for 30–35 years or more, and probably for life. Serious side effects are extremely rare. Serious adverse events have been reported rarely following immunization in a few endemic areas and among vaccinated travelers (e.g. in Brazil, Australia, the United States, Peru and Togo). Scientists are investigating the causes.
The risk of death from yellow fever is far greater than the risks related to the vaccine. People who should not be vaccinated include:
Historically, mosquito control campaigns successfully eliminated Aedes aegypti, the urban yellow fever vector, from most mainland countries of central and South America. However, this mosquito species has re-colonized urban areas in the region and poses a renewed risk of urban yellow fever.
Mosquito control programmes targeting wild mosquitoes in forested areas are not practical for preventing jungle (or sylvatic) yellow fever transmission.
WHO recommends that every at-risk country have at least one national laboratory where basic yellow fever blood tests can be performed. One confirmed case of yellow fever in an unvaccinated population should be considered an outbreak, and a confirmed case in any context must be fully investigated, particularly in any area where most of the population has been vaccinated. Investigation teams must assess and respond to the outbreak with both emergency measures and longer-term immunization plans.
Anyone can get yellow fever, but the elderly have a higher risk of severe infection. If a person is bitten by an infected mosquito, symptoms usually develop 3 - 6 days later.
Yellow fever has three stages:
- Early stage: Headache, muscle and joint aches, fever, flushing, loss of appetite, vomiting, and jaundice are common. After approximately 3 - 4 days, often symptoms go away briefly (remission).
- Period of remission: After 3 - 4 days, fever and other symptoms go away. Most people will recover at this stage, but others may move onto the third, most dangerous stage (intoxication stage) within 24 hours.
- Period of intoxication: Multi-organ dysfunction occurs. This may include heart, liver, and kidney failure, bleeding disorders, hemorrhage, and brain dysfunction including delirium, seizures, coma, shock, and death.
Symptoms
- Arrhythmias, heart dysfunction
- Bleeding (may progress to hemorrhage)
- Coma
- Decreased urination
- Delirium
- Fever
- Headache
- Jaundice
- Muscle aches (myalgia)
- Red eyes, face, tongue
- Seizures
- Vomiting
- Vomiting blood
Exams and Tests
A person with advanced yellow fever may show signs of liver failure, renal failure, and shock.If you have symptoms of yellow fever, tell your doctor if you have traveled to areas where the disease is known to thrive. Blood tests can confirm the diagnosis.
Treatment
There is no specific treatment for yellow fever. Treatment for symptoms can include:- Blood products for severe bleeding
- Dialysis for kidney failure
- Fluids through a vein (intravenous fluids)
Outlook (Prognosis)
Yellow fever varies in severity. Severe infections with internal bleeding and fever (hemorrhagic fever) are deadly in up to half of cases.Possible Complications
- Coma
- Death
- Disseminated intravascular coagulation (DIC)
- Kidney failure
- Liver failure
- Parotitis
- Secondary bacterial infections
- Shock
When to Contact a Medical Professional
Get medical attention at least 10 - 14 days before traveling to an endemic area for yellow fever to find out whether you should be vaccinated against the disease.Tell your health care provider right away if you or your child develop fever, headache, muscle aches, vomiting, or jaundice, especially if you have traveled to an area where yellow fever is known to occur.
Prevention
If you will be traveling to an area where yellow fever is common:- Sleep in screened housing
- Use mosquito repellents
- Wear clothing that fully covers your body
Prevention
1. Vaccination
Vaccination is the single most important measure for preventing yellow fever. In high risk areas where vaccination coverage is low, prompt recognition and control of outbreaks through immunization is critical to prevent epidemics. To prevent outbreaks throughout affected regions, vaccination coverage must reach at least 60% to 80% of a population at risk. Few endemic countries that recently benefited from a preventive mass vaccination campaign in Africa currently have this level of coverage.Preventive vaccination can be offered through routine infant immunization and one-time mass campaigns to increase vaccination coverage in countries at risk, as well as for travelers to yellow fever endemic area. WHO strongly recommends routine yellow fever vaccination for children in areas at risk for the disease.
The yellow fever vaccine is safe and affordable, providing effective immunity against yellow fever within one week for 95% of those vaccinated. A single dose provides protection for 30–35 years or more, and probably for life. Serious side effects are extremely rare. Serious adverse events have been reported rarely following immunization in a few endemic areas and among vaccinated travelers (e.g. in Brazil, Australia, the United States, Peru and Togo). Scientists are investigating the causes.
The risk of death from yellow fever is far greater than the risks related to the vaccine. People who should not be vaccinated include:
- children aged less than 9 months for routine immunization (or less than 6 months during an epidemic);
- pregnant women – except during a yellow fever outbreak when the risk of infection is high;
- people with severe allergies to egg protein; and
- people with severe immunodeficiency due to symptomatic HIV/AIDS or other causes, or in the presence of a thymus disorder.
2. Mosquito control
In some situations, mosquito control is vital until vaccination takes effect. The risk of yellow fever transmission in urban areas can be reduced by eliminating potential mosquito breeding sites and applying insecticides to water where they develop in their earliest stages. Application of spray insecticides to kill adult mosquitoes during urban epidemics, combined with emergency vaccination campaigns, can reduce or halt yellow fever transmission, "buying time" for vaccinated populations to build immunity.Historically, mosquito control campaigns successfully eliminated Aedes aegypti, the urban yellow fever vector, from most mainland countries of central and South America. However, this mosquito species has re-colonized urban areas in the region and poses a renewed risk of urban yellow fever.
Mosquito control programmes targeting wild mosquitoes in forested areas are not practical for preventing jungle (or sylvatic) yellow fever transmission.
3. Epidemic preparedness and response
Prompt detection of yellow fever and rapid response through emergency vaccination campaigns are essential for controlling outbreaks. However, underreporting is a concern – the true number of cases is estimated to be 10 to 250 times what is now being reported.WHO recommends that every at-risk country have at least one national laboratory where basic yellow fever blood tests can be performed. One confirmed case of yellow fever in an unvaccinated population should be considered an outbreak, and a confirmed case in any context must be fully investigated, particularly in any area where most of the population has been vaccinated. Investigation teams must assess and respond to the outbreak with both emergency measures and longer-term immunization plans.
Emergency Department Care
Treatment of yellow fever principally is symptomatic and preventative. Closely monitor patients for hypovolemia, oliguria, hypoxia, acidosis, and electrolyte imbalance. Hypotension and hypoxia may aggravate hepatic and renal injury.
Intravascular volume may decrease secondary to sequestration in the extravascular space and fluid loss through insensible losses, vomiting, and capillary leak. Invasive arterial blood pressure monitoring may be warranted.
Monitor central venous pressure, peripheral blood pressure, as well as surrogates for organ perfusion and regional blood flow (eg, capillary refill, urinary output, ScvO2). Monitor acid-base disturbances and metabolic acidosis via arterial blood gas sampling.
Replacement of red blood cells and clotting components will be necessary to treat hemorrhage and shock. Consider vasopressor support for those patients who remain hypotensive despite volume resuscitation and further management of shock.
Patients with respiratory failure, acute respiratory distress syndrome (ARDS), or both may require endotracheal intubation and mechanical ventilation. In those cases, nasogastric suction is essential to prevent gastric distention and aspiration of gastric contents.
Other points to remember include the following:
Intravascular volume may decrease secondary to sequestration in the extravascular space and fluid loss through insensible losses, vomiting, and capillary leak. Invasive arterial blood pressure monitoring may be warranted.
Monitor central venous pressure, peripheral blood pressure, as well as surrogates for organ perfusion and regional blood flow (eg, capillary refill, urinary output, ScvO2). Monitor acid-base disturbances and metabolic acidosis via arterial blood gas sampling.
Replacement of red blood cells and clotting components will be necessary to treat hemorrhage and shock. Consider vasopressor support for those patients who remain hypotensive despite volume resuscitation and further management of shock.
Patients with respiratory failure, acute respiratory distress syndrome (ARDS), or both may require endotracheal intubation and mechanical ventilation. In those cases, nasogastric suction is essential to prevent gastric distention and aspiration of gastric contents.
Other points to remember include the following:
- Renal failure may necessitate dialysis
- H2-receptor antagonists and proton pump inhibitors may be valuable in preventing gastric bleeding
- 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
- Consider parenteral alimentation; hypoglycemia can be prevented by infusion of 10-20% glucose solution
Medication Summary
Prior to the development of a vaccine, passive immunization was utilized in the prevention and management of yellow fever. This posed many challenges because of difficulty in obtaining sufficient amounts of human serum and subsequent serum sickness; its use was discontinued in 1936.
Present day supplies of intravenous immunoglobulin (IVIG) have been found to contain high titers of yellow fever antibodies. In 2000, an unpublished case of a patient being treated with IVIG to prevent illness prior to a trip to the Amazon was reported. Vaccination was contraindicated in this individual, who had chronic lymphatic leukemia. Despite this event, no published reports exist of off-label use of IVIG in the treatment of yellow fever.
Currently, no approved antiviral drug against yellow fever is available. 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.
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 started on day 4, after the development of liver infection.[10, 22] 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.[10] Avoid drugs that act centrally, including phenothiazines, barbiturates, and benzodiazepines, because they may precipitate or aggravate encephalopathy. Avoid drugs dependent on hepatic metabolism; in cases of reduced renal function, medications should be renally dosed.
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.[10] Between 1952 and 1959, 15 cases of postvaccination encephalitis were reported after administration of vaccine[5] ; since 1945 a total of 28 cases have been reported. Sixteen of these cases occurred in infants younger than 6 months. This resulted in the restriction of vaccine use in children younger than age 6 months and in limited use in patients aged 6-9 months.
The syndrome of 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 syndrome have been reported. Case- fatality rates are less than 5%; most individuals recover from YEL-AND without sequelae.[11, 21]
YEL-AVD is characterized by fever, jaundice, and multiorgan system failure similar to the wild-type strain. Symptoms begin 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.[11]
The proposed cause of vaccine-associated disease is an unsuited host response to the live-attenuated 17D vaccine. Individuals younger than age 6 months and those older than age 60 years, persons with a history of thymic disease (eg, DiGeorge syndrome, thymomas, and post-thymectomy), and those with a cell-mediated immunodeficiency status (eg, cancer, transplant, human immunodeficiency virus [HIV]) are all considered to be at a greater risk of developing YEL-AND and YEL-AVD with its subsequent sequelae.[23] A careful medical history to exclude the above should be obtained before the vaccine is administered.
The WHO, United Nations Children's Fund (UNICEF), and the World Bank have recommended that yellow fever vaccine be added to the routine Expanded Program on Immunization in developing nations. However, poor financing remains a problem and a major reason for low vaccination rates among residents of endemic areas. In the United States, the yellow fever vaccine is available at designated state health departments and selected travel clinics.
Up-to-date information on yellow fever vaccination and travel requirements may be obtained by contacting Health Information for Travelers, Centers for Disease Control and Prevention, Atlanta, GA 30333, fax (404) 332-4265, document number 220022#, phone (404) 332-4559.
This vaccine should be administered to residents of and travelers to endemic areas. The seroconversion rate for adults and children receiving the vaccine is 99%. Protective antibodies form within 7-10 days, and protection lasts for at least 10 years. The vaccine is safe and effective in asymptomatic adult patients with HIV and CD4 counts of greater than 200/μL. The vaccine appeared ineffective when administered to 1-year-old infants who were HIV positive (CD4 count >200/μL).
Famotidine competitively inhibits histamine at the H2 receptor of the gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Nizatidine competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Ranitidine competitively inhibits histamine at the H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, reduced gastric volume, and reduced hydrogen concentrations.
Present day supplies of intravenous immunoglobulin (IVIG) have been found to contain high titers of yellow fever antibodies. In 2000, an unpublished case of a patient being treated with IVIG to prevent illness prior to a trip to the Amazon was reported. Vaccination was contraindicated in this individual, who had chronic lymphatic leukemia. Despite this event, no published reports exist of off-label use of IVIG in the treatment of yellow fever.
Currently, no approved antiviral drug against yellow fever is available. 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.
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 started on day 4, after the development of liver infection.[10, 22] 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.[10] Avoid drugs that act centrally, including phenothiazines, barbiturates, and benzodiazepines, because they may precipitate or aggravate encephalopathy. Avoid drugs dependent on hepatic metabolism; in cases of reduced renal function, medications should be renally dosed.
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.[10] Between 1952 and 1959, 15 cases of postvaccination encephalitis were reported after administration of vaccine[5] ; since 1945 a total of 28 cases have been reported. Sixteen of these cases occurred in infants younger than 6 months. This resulted in the restriction of vaccine use in children younger than age 6 months and in limited use in patients aged 6-9 months.
The syndrome of 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 syndrome have been reported. Case- fatality rates are less than 5%; most individuals recover from YEL-AND without sequelae.[11, 21]
YEL-AVD is characterized by fever, jaundice, and multiorgan system failure similar to the wild-type strain. Symptoms begin 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.[11]
The proposed cause of vaccine-associated disease is an unsuited host response to the live-attenuated 17D vaccine. Individuals younger than age 6 months and those older than age 60 years, persons with a history of thymic disease (eg, DiGeorge syndrome, thymomas, and post-thymectomy), and those with a cell-mediated immunodeficiency status (eg, cancer, transplant, human immunodeficiency virus [HIV]) are all considered to be at a greater risk of developing YEL-AND and YEL-AVD with its subsequent sequelae.[23] A careful medical history to exclude the above should be obtained before the vaccine is administered.
Vaccines
Class Summary
The live attenuated virus (17D) vaccine was created by serial passages of yellow fever virus through chick and mouse embryo cells. Dr. Max Theiler of the Rockefeller Institute developed this vaccine in 1937. Since 1945, more than 200,000,000 doses have been administered.The WHO, United Nations Children's Fund (UNICEF), and the World Bank have recommended that yellow fever vaccine be added to the routine Expanded Program on Immunization in developing nations. However, poor financing remains a problem and a major reason for low vaccination rates among residents of endemic areas. In the United States, the yellow fever vaccine is available at designated state health departments and selected travel clinics.
Up-to-date information on yellow fever vaccination and travel requirements may be obtained by contacting Health Information for Travelers, Centers for Disease Control and Prevention, Atlanta, GA 30333, fax (404) 332-4265, document number 220022#, phone (404) 332-4559.
