Yellow Fever Virus Agent Information Sheet
Boston University
Research Occupational Health Program (ROHP)
617-358-7647
Agent
A member of the genus Flavivirus, and Flaviviridae family. Yellow Fever virus is a spherical, enveloped virus of 40 to 50 nm in diameter, and has a single-stranded, positive- sense RNA genome.
Disease/Infection
Classic Yellow Fever is characterized by three clinical illness stages: infection, remission, and intoxication. Infection is characterized by abrupt fever, chills, headaches, myalgias, nausea, anorexia, and jaundice.
Pathogenicity
It is estimated that 15 to 50 % of people infected with Yellow Fever develop illness. Of those that develop illness, approximately 57 to 85 % will abort their infection and recover without developing classic YF. Case fatality rate can be 20%.
Note: Yellow Fever strain 17D is an attenuated vaccine strain derived from a wild-type YF virus (the Asibi strain) isolated in Ghana in 1927 and attenuated by serial passages in chicken embryo tissue culture. Two substrains of the 17D vaccine virus are currently used for vaccine production in embryonated chicken eggs, namely 17D-204 and 17DD. Some vaccines are also prepared from a distinct substrain of 17D-204 (17D-213). Sorbitol and gelatin are commonly used as stabilizers, and the vaccine preparation is lyophilized and kept under cold-chain conditions. As it is attenuated, the vaccine strain (17D) is infectious, but is less virulent then the wild type.
Biosafety Information
Risk Group/ABSL3
Wild Type Yellow Fever virus Risk Group 3
Biosafety Level 3
Yellow Fever virus 17D Risk Group 2 Biosafety Level 2
Modes of Transmission
Yellow Fever virus is transmitted to humans from infected non-human primates and other humans by the bite of Aedes in Africa and Haemagogus mosquitoes in South America.
| Transmission | |
| Skin Exposure (Needlestick, bite, or scratch): | Yes |
| Mucous Membrane Splash to Eye(s), Nose or Mouth: | Yes |
| Inhalation: | Yes |
| Ingestion: | Yes |
Host Range/Reservoir
In urban areas: humans and mosquitoes (Aedes aegypti); in areas of rainforest: monkeys and mosquitoes; and in savannah areas: humans, monkeys and mosquitoes.
Symptoms
Classic Yellow Fever is characterized by three clinical illness stages: infection, remission, and intoxication.
- a. Infection: This stage typically lasts 3 or 4 days and is characterized by intense viraemia with symptoms including fever, chills, malaise, headache, lower back pain, knee pain, generalized myalgia, jaundice, nausea, and dizziness.
Remission
This stage is typified by an abatement of fever and other constitutional symptoms for a period of about 48 hours. Viraemia may still be present but it is usually waning.
Intoxication
Approximately 15 to 25 % of people who develop any clinical symptoms progress to this stage, which generally occurs 3 to 6 days after the onset of illness and can last for 3 to 8 days. During this period, viraemia disappears, and antibodies, along with the classic signs of YF (jaundice, renal failure and hemorrhage), appear. Common symptoms of this stage include fever, relative bradycardia, vomiting, nausea, epigastric pain, jaundice, oliguria and hemorrhagic manifestations. Many patients will progress to multi-organ failure dominated by hepatic, renal, hematological and cardiovascular involvement. Multi-organ failure due to cytokine release.
Incubation Period
3 to 6 days
Viability
Inactivated by 3-8% formaldehyde, 2% glutaraldehyde, 2-3% hydrogen peroxide, 500-5,000 ppm available chlorine, alcohol, 1% iodine, and phenol idophors, heat (50-60°C for at least 30 minutes), UV light, and gamma irradiation.
Survival Outside Host
Low temperatures preserve infectivity, with stability being greatest below -60°C.
Information for Lab Workers
Laboratory PPE
a. Wild Type Yellow Fever virus
Biosafety Level 3 practices and facility are recommended for working involving wild type Yellow Fever virus. Such practices may include dedicated laboratory clothing and shoes, or don full coverage protective clothing. Additional protection may be worn over laboratory clothing respiratory protection may be utilized. Eye protection must be used where there is a known or potential risk of exposure to splashes. Animal experiments are conducted at ABSL-3.
b. Yellow Fever virus 17D
Biosafety level 2 practices and facility are recommended for work involving the Yellow Fever 17D virus. Animal experiments are conducted at ABSL-2. PPE includes Lab coat. Gloves and eye protection when direct skin contact with infected materials or animals is unavoidable.
Containment
a. Wild Type Yellow Fever virus
BSL-3 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.
b. Yellow Fever virus 17D
BSL-2 facilities, equipment and practices are recommended.
In Case of Exposure/Disease
- For injuries in the lab which are major medical emergencies (heart attacks, seizures, etc…):
- Medical Campus: call or have a coworker call the Control Center at 617-414-4144.
- Charles River Campus: call or have a coworker call campus security at 617-353-2121.
You will be referred to or transported to the appropriate health care location by the emergency response team.
- For lab exposures (needle sticks, bite, cut, scratch, splash, etc.) involving animals or infectious agents, or for unexplained symptoms or illness call the ROHP 24/7 hour number (1-617-358-ROHP (7647); or, 8-ROHP (7647) if calling from an on-campus location) to be connected with the BU Research Occupational Health Program (ROHP) medical officer. ROHP will refer you to the appropriate health care location.
- Under any of these scenarios, always inform the physician of your work in the laboratory and the agent(s) that you work with.
- Provide the wallet-size agent ID card to the physician.
Vaccination
The attenuated live 17D strain preparation of Yellow Fever vaccine is approved for use in US. Immunity develops in more than 95% of recipients 10 days after primary immunization and persists for more than 10 years. Vaccine administration has been associated with anaphylaxis in 1 of every 116,000 doses. There have also been potentially fatal cases of vaccine-associated CNS infection or systemic illness, mimicking wild-type infection reported from multiple countries. We offer vaccination every 10 years based on MMWR/ACIP recommendations.
Information for First Responders/Medical Personnel
Public Health Issues
Yellow fever is not usually transmitted person to person via casual contact without the intermediate mosquito vector. There has been one report of an infant acquiring the infection through breast milk, from a mother with recent yellow fever vaccination. Blood of an infected patient in the acute phase of illness is potentially infectious, and virus can theoretically be transmitted via transfusion or needlesticks. Standard precautions should be used. Clinical laboratory staff should be alerted.
Diagnosis/Surveillance
Monitor for symptoms. Confirmation is via virus isolation from blood or cerebrospinal fluid during the viraemic phase. Other methods of detection include immunofluorescence, PCR, real-time PCR, compliment fixation, hemagglutinin inhibition, neutralization, and IgM capture ELISA.
First Aid/Post Exposure Prophylaxis
No antiviral therapy exists
Perform one of the following actions:
| Skin Exposure (Needlestick or scratch): | Immediately go to the sink and thoroughly wash the wound with soap and water for 15 minutes. Decontaminate any exposed skin surfaces with an antiseptic scrub solution. |
| Mucous Membrane Splash to Eye(s), Nose or Mouth: | Exposure should be irrigated vigorously. |
| Splash Affecting Garments: | Remove garments that may have become soiled or contaminated and place them in a double red plastic bag. |
Treatment
Treatment is supportive and symptomatic.
References
Public Health Agency of Canada; http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/yfv-vfj-eng.php
UptoDate: March 30, 2018, Monath, T. P. et al, https://www.uptodate.com/contents/yellow-fever
Biosafety in Microbiological and Biomedical Laboratories, 5th Edition: https://www.cdc.gov/biosafety/publications/bmbl5/bmbl.pdf
MMWR Wkly Rep. Yellow Fever Booster Doses, ACIP 2015 , June 19; 64(23) 647-650.