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YELLOW FEVER VIRUS

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Yellow fever virus

SYNONYM OR CROSS REFERENCE: YFVFootnote 1, YFFootnote 1 Footnote 2 Footnote 3 yellow feverFootnote 1 Footnote 2 Footnote 3 Footnote 4 Footnote 5 Footnote 6 Footnote 7 Footnote 8 Footnote 9 
Footnote 10
, and black vomitFootnote 1.

CHARACTERISTICS: A member of the genus Flavivirus , and Flaviviridae familyFootnote 2 Footnote 6. YFV is a spherical, enveloped virus of 40 to 50 nm in diameterFootnote 1 Footnote 5, and has a single-stranded, positive- sense RNA genomeFootnote 1 Footnote 4 Footnote 5.

SECTION II – HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: It is estimated that 15 to 50 % of people infected with YF develop illness, beginning abruptly with fever, chills and headacheFootnote 5. Of those that develop illness, approximately 57 to 85 % will abort their infection and recover without developing classic YF. Classic YF is characterised by three clinical illness stages: infection, remission, and intoxication.

Infection : This stage typically lasts 3 or 4 days and is characterised by intense viraemia with symptoms including fever, chills, malaise, headache, lower back pain, knee pain, generalised myalgia, nausea, and dizzinessFootnote 2 Footnote 4 Footnote 5 Footnote 6. On examination, the patient has a heart rate lower than would be expected for a fever (Faget sign), and congestion and erythaema of the conjunctivae, tongue and face. Most infections resolve at this stage. Temperatures up to 40.5°C are associated with severe illness and poor outcomeFootnote 5.

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 waningFootnote 4 Footnote 5.

Intoxication : Approximately 15 to 25 % of people who develop any clinical symptoms (or 10 % of all infected people) 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 haemorrhage), appearFootnote 4 Footnote 5. Common symptoms of this stage include fever, relative bradycardia, vomiting, nausea, epigastric pain, jaundice, oliguria and haemorrhagic manifestations (melena, haematuria, non-menstrual uterine bleeding, petechiae, ecchymoses, epistaxis, and oozing of blood from the gums and needle puncture sites)Footnote 2 Footnote 5. Many patients will progress to multi-organ failure dominated by hepatic, renal, haematological and cardiovascular involvementFootnote 5.

The case fatality rate of patients who develop hepatic and renal failure is 20 to nearly 50 %Footnote 5 Footnote 6. Death is typically preceded by profound hypotension and shock that is difficult to manage with fluids and vasopressorsFootnote 4 Footnote 5.

EPIDEMIOLOGY: YF occurs only in tropical regions of Africa and South AmericaFootnote 4 Footnote 5 Footnote 7. Approximately 200,000 cases of yellow fever occur annuallyFootnote 1, 90 % of them in AfricaFootnote 1 Footnote 7. Up to 5,000 cases of YF in Africa and 300 in South America are reported annually, but the true incidence is believed to be 10 to 50-folds higher than official reportsFootnote 4.

Three distinct transmission cycles exist. A sylvatic (jungle) cycle occurs in the rainforests of Africa and South America whereby YFV is transmitted between non-human primates and mosquitoesFootnote 5. Human cases are rare and usually occur in people who are occupationally exposed in forested or transitional areas. An urban human-mosquito-human transmission cycle occurs in both Africa and South America; and a savannah cycle that occurs only in Africa involves transmission of YFV among monkeys, mosquitoes and humans.

HOST RANGE: HumansFootnote 1 Footnote 2 Footnote 5 Footnote 6, non-human primatesFootnote 1 Footnote 2 Footnote 5, hedgehogs, and golden hamstersFootnote 5.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: YFV is transmitted to humans from infected non-human primates and other humans by the bite of Aedes and Haemagogus mosquitoesFootnote 2 Footnote 4 Footnote 5 Footnote 6 Footnote 8.

INCUBATION PERIOD: 3 to 6 daysFootnote 2 Footnote 4 Footnote 5 Footnote 6.

COMMUNICABILITY: No evidence for direct human-to-human transmission.

SECTION III - DISSEMINATION

RESERVOIR: In urban areas: humans and mosquitoes (Aedes aegypti); in areas of rainforest: monkeys and mosquitoes; and in savannah areas: humans, monkeys and mosquitoesFootnote 1 Footnote 2 Footnote 5 Footnote 8.

ZOONOSIS: Yes, indirectly from mosquitoes infected by non-human reservoir hosts (sylvatic and savannah YF transmission)Footnote 1 Footnote 5 Footnote 6.

VECTORS: The principal arthropod vectors of YF differ depending on their geographical
locationFootnote 5.
Urban YF : Aedes aegypti in both South America and AfricaFootnote 5 Footnote 6.
Sylvatic YF : Aedes africanus in Africa and members of the Haemagogus species in South
AmericaFootnote 5 Footnote 6.
Savannah YF : Aedes furcifer , Aedes vittatus , Aedes luteocephalus , and Aedes africanus in West Africa, and Aedes africanus and Aedes simpsoni in East AfricaFootnote 5.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Ribavirin has activity against YF virus at high (potentially cytotoxic) concentrations in vitroFootnote 5.

SUSCEPTIBILITY TO DISINFECTANTS: Inactivated by 3 to 8 % formaldehyde, 2 % glutaraldehyde, 2 to 3 % hydrogen peroxide, 500 to 5,000 ppm available chlorine, alcohol, 1 % iodine, and phenol iodophorsFootnote 11.

PHYSICAL INACTIVATION: Inactivated by heat (50 to 60°C for at least 30 minutes), ultraviolet light, and gamma irradiationFootnote 11.

SURVIVAL OUTSIDE HOST: Low temperatures preserve infectivity, with stability being greatest below -60°CFootnote 11.

SECTION V – FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Confirmation is via virus isolation from bloodFootnote 1 Footnote 2 Footnote 6 or cerebrospinal fluidFootnote 2 during the viraemic phase. Other methods of detection include immunofluorescenceFootnote 1 Footnote 2 Footnote 6, PCRFootnote 2 Footnote 6, real-time PCRFootnote 2, compliment fixation, haemagglutinin inhibition, neutralizationFootnote 1, and IgM capture ELISAFootnote 1 Footnote 2 Footnote 6.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Treatment is supportive and symptomatic, however it may vary as infection is highly case-dependentFootnote 2. Treatments and care may include maintenance of nutrition and prevention of hypoglycaemia, nasogastric suction to prevent gastric distension and aspiration, intravenous cimetidine to prevent gastric bleeding, treatment of hypotension by fluid replacement and vasoactive drugs, administration of oxygen, correction of metabolic acidosis, treatment of bleeding with fresh frozen plasma, dialysis if indicated by renal failure, and treatment of secondary infections by antibioticsFootnote 4.

IMMUNIZATION: There are 2 attenuated live YF virus vaccines available: the neurotropic French Dakar vaccineFootnote 2 and the 17D strainFootnote 2 Footnote 5 Footnote 6 Footnote 7 Footnote 8, the latter being the only preparation approved for use in Canada. Immunity develops 10 days after primary immunization and persists for more than 10 yearsFootnote 12. Only designated Yellow Fever Vaccination Centre clinics approved by PHAC can administer YF immunizationFootnote 13, which should then be recorded on an appropriately validated International Certificate of Vaccination.

PROPHYLAXIS: Immunisation is required legally for travelers visiting areas of endemicity or traveling from areas of endemicity into counties that are free of YFFootnote 2. Also, passive antibody, interferon, and interferon inducers can be effective if given before YF infection or during incubationFootnote 3. Most often they are used when it is clear that the individual has been exposed to YFV (i.e. in a laboratory setting)Footnote 4 Footnote 5. Travelers should also take precautions against mosquito bites when in areas with yellow fever transmission.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: Thirty-eight cases were reported up until 1980 with 8 deathsFootnote 14.

SOURCES/SPECIMENS: BloodFootnote 1 Footnote 4 Footnote 5 Footnote 6, liver tissueFootnote 6, and cerebrospinal fluidFootnote 2.

PRIMARY HAZARDS: Contact with infected blood and/or tissuesFootnote 9 Footnote 10.

SPECIAL HAZARDS: Direct or indirect exposure to aerosols of concentrated YF 17D vaccineFootnote 8. Evidence also exists of transmission of YFV from the infected blood of a patient to a caregiverFootnote 9, from infected monkey and mouse tissues, and from handling infected laboratory animalsFootnote 10.

SECTION VII – EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 3Footnote 15.

CONTAINMENT REQUIREMENTS: Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures.

PROTECTIVE CLOTHING: Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashesFootnote 16.

OTHER PRECAUTIONS: All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animals or large scale activitiesFootnote 16.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (30 min).

DISPOSAL: Decontaminate all materials for disposal by steam sterilisation, chemical disinfection, and/or incinerationFootnote 16.

STORAGE: In sealed, leak-proof containers that are appropriately labelled and locked in a Containment Level 3 laboratoryFootnote 16.

SECTION IX – REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: October 2010.

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada.

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright ©
Public Health Agency of Canada, 2010
Canada

REFERENCES:


Footnote 1
Acha, P. N., & Szyfres, B. (2003). Yellow Fever. Zoonoses and Communicable Diseases Common to Man and Animals (3rd ed., pp. 377-387). Washington D.C.: Pan American Health Organization.
Footnote 2
Krauss, H., Schiefer, H. G., Weber, A., Slenczka, W., Appel, M., von Graevenitz, A., Enders, B., Zahner, H., & Isenberg, H. D. (2003). Viral Zoonoses. Zoonoses: Infectious Disease Transmissible from Animals to Humans (3rd ed., pp. 52-57). Washington D.C.: ASM Press.
Footnote 3
Monath, T. P. (2008). Treatment of yellow fever. Antiviral Research, 78 (1), 116-124.
Footnote 4
Monath, T. P. (2001). Yellow fever: An update. Lancet Infectious Diseases, 1 (1), 11-20.
Footnote 5
Marfin, A. A. (2006). Yellow Fever. In R. Guerrant, D. Walker & P. Weller (Eds.), Tropical Infectious Diseases: Principles, Pathogens, and Practice (2nd ed., pp. 797-812). Philadelphia, PA: Elsevier Churchill Livingston.
Footnote 6
(2004). In D. L. Heymann (Ed.), Control of Communicable Diseases Manual (18th ed., pp. 595-600). Washington, D.C.: American Public Health Association.
Footnote 7
Barnett, E. D. (2007). Yellow fever: Epidemiology and prevention. Clinical Infectious Diseases, 44 (6), 850-856.
Footnote 8
Cetron, M. S., Marfin, A. A., Julian, K. G., Gubler, D. J., Sharp, D. J., Barwick, R. S., Weld, L. H., Chen, R., Clover, R. D., Deseda-Tous, J., Marchessault, V., Offit, P. A., & Monath, T. P. (2002). Yellow fever vaccine. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2002. MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report.Recommendations and Reports / Centers for Disease Control, 51 (RR-17), 1-11; quiz CE1.
Footnote 9
Cook, G. C. (1994). Fatal yellow fever contracted at the Hospital for Tropical Diseases, London, UK, in 1930. Transactions of the Royal Society of Tropical Medicine and Hygiene, 88 (6), 712-713.
Footnote 10
Berry, G. P., & Kitchen, S. F. (1931). Yellow Fever Accidentally Contracted in the Laboratory: A Study of Seven Cases. American Journal of Tropical Medicine and Hygiene, s1-11 (6), 365-434.
Footnote 11
Burke, D. S., & Monath, T. P. (2001). Flaviviruses . In D. M. Knipe, & P. A. Howley (Eds.), (4th ed., pp. 1043-1125). Philadelphia, PA: Lippincott Williams & Wilkins.
Footnote 12
Public Health Agency of Canada. (2010). Yellow Fever. Retrieved 09-09-2010, 2010, from www.phac-aspc.gc.ca/tmp-pmv/info/yf-fj-eng.php
Footnote 13
Public Health Agency of Canada. (2010). Yellow Fever Vaccination Centres in Canada. Retrieved 09-09-2010, 2010, from www.phac-aspc.gc.ca/tmp-pmv/yf-fj/index-eng.php
Footnote 14
Scherer, W. F., Eddy, G. A., & Monath, T. P. (1980). Laboratory safety for arboviruses and certain other viruses of vertebrates. American Journal of Tropical Medicine and Hygiene, 29 (6), 1359-1381.
Footnote 15
Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57- 58 Elizabeth II, 2009. (2009).
Footnote 16
Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.