黃熱病 衞生署疾病管制局中區傳染病防治醫療網王任賢指揮官

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1 黃熱病 衞生署疾病管制局中區傳染病防治醫療網王任賢指揮官

2 What is Viral Hemorrhagic Fever? Severe multisystem syndrome Damage to overall vascular system Symptoms often accompanied by hemorrhage Rarely life threatening in itself Includes conjunctivitis, petechia, ecchymosis

3 Viral Hemorrhagic Fever Viruses of four distinct families Arenaviruses Filoviruses Bunyaviruses Flaviviruses RNA viruses Enveloped in lipid coating Survival dependent on an animal or insect host, for the natural reservoir

4 Classification Arenaviridae Bunyaviridae Filoviridae Flaviviridae Junin Crimean- Congo H.F. Ebola Kyasanur Forest Disease Machupo Hantavirus Marburg Omsk H.F. Sabia Rift Valley fever Yellow Fever Guanarito Dengue Lassa

5 Flaviviridae History 1648 : Yellow Fever described 17 th 20 th century Yellow Fever and Dengue outbreaks 1927: Yellow Fever virus isolated 1943: Dengue virus isolated 1947: Omsk Hemorrhagic Fever virus isolated 1957: Kyasanur Forest virus isolated

6 Flaviviridae Transmission Arthropod vector Yellow Fever and Dengue viruses Aedes aegypti Sylvatic cycle Urban cycle Kasanur Forest Virus Ixodid tick Omsk Hemorrhagic Fever virus Muskrat urine, feces, or blood

7 Flaviviridae Epidemiology Yellow Fever Virus Africa and Americas Case fatality rate varies Dengue Virus Asia, Africa, Australia, and Americas Case fatality rate 1-10% Kyasanur Forest virus India Case fatality rate 3 5% Omsk Hemorrhagic Fever virus Europe Case fatlity rate 0.5 3%

8 Flaviviridae in Humans Yellow Fever Incubation period 3 6 days Short remission Dengue Hemorrhagic Fever Incubation period 2 5 days Infection with different serotype Kyasanur Forest Disease Omsk Hemorrhagic Fever Lasting sequela

9 Flaviviridae in Animals Yellow Fever virus Non-human primates varying clinical signs Dengue virus Non-human primates No symptoms Kyasanur Forest Disease Virus Livestock No symptoms Omsk Hemorrhagic Fever Virus Rodents No symptoms

10 Yellow fever: I Yellow fever is a devastating viral disease that can cause bleeding from the eyes, nostrils, anus and other mucous membranes. This terrible illness often also causes blackcolored, blood-filled vomit, and the deterioration of the liver, kidneys, and heart. Yellow bile pigments from the damaged liver color the skin, giving the disease its name.

11 Yellow fever: II Those who do not survive usually die between four and eight days after they first show symptoms. There is still no known cure for the disease. Before 1898, yellow fever had always been a puzzle, because it strikes many people at once as an epidemic, yet it isn t directly contagious from one person to another. Sadly, yellow fever epidemics have been common throughout history.

12 YFV History Outbreak in Philadelphia Spanish American War-1898 Dr. Walter Reed Dr. Walter Reed Dr. Carlos Finlay Bold Experiment Dr. Carlos Finlay

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14 The Panama Canal

15 Life for Workers Streets and areas were without sewage and water. This is an example of a street before American occupation and then after. Workers were shipped in from all over the world. Housing and food was provided with wages (but weren t very high)

16 Living conditions for most workers were very poor. This is a workers village. Since fatality rates were so high, new workers were constantly being integrated into the project

17 Quarantine for a Yellow Fever victim Accidents were common place, both due to natural accidents and mechanical ones

18 Fighting Mosquitoes (Disease) Larvicide stockpile Fumigation applied to drainage ditches The canal could not be completed until sanitation problems were solved (Dr. William Gorgas took upon himself the cause of discovering and then fighting the transfer of disease.)

19 Spraying crude oil in ditches to help fight mosquitoes Pay car: men were paid in cash by these mobile cars.

20 Fumigation brigades helped control mosquito populations Buckets, puddles, pans and other potential water collectors were constantly dumped and emptied to minimize mosquito breeding grounds Colon Hospital Grounds - notice wire mesh screen around exterior to restrict Mosquitoes.

21 Endemic Zones

22 What is Yellow Fever? Acute viral disease Caused by an aborvirus RNA virus Mosquitoes are the 1 vector Human and Monkeys are affected

23 Yellow Fever tropical disease viral disease transmitted by female mosquitoes found in Africa & South America 2 kinds: Jungle Yellow Fever (monkeys) & Urban Yellow Fever (humans)

24 Life Cycle of Yellow Fever Parasite Mosquito Environment Humans & Monkeys

25 Mosquito Anatomy mosquitoes/malaria/

26 Aedes aegypti

27 Aedes simpsoni

28 Aedes africanus

29 An Electron Micrograph of YFV

30 Yellow Fever Principally a disease of Africa and South America It is thought that YFV arrived in the Americas during the slave trade Infected slaves, who had some genetic resistance, carried the virus, which then entered the local ecosystem after mosquito bites Two forms Urban Yellow Fever Mosquito-human transmission cycle Aedes aegypti Jungle Yellow Fever Mosquito-primate transmission cycle with spillover to humans Aedes spp. in Africa Haemagogus and Sabethes spp. in South America

31 Yellow Fever Pathogenesis Onset 3-6 days Sometimes a brief (48 hr) recovery period occurs, followed by jaundice Primary replication in lymph nodes Systemic infection Liver, spleen, kidneys, bone marrow, lymph nodes Acute liver failure Apoptosis of hepatocytes Inflammation Immune infiltrates (immunopathology?) 10% mortality

32 Signs & Symptoms 3 to 6 days without signs fever chills severe headache back pain muscle aches nausea fatigue weakness abdominal pain may be remission fever returns symptoms continue

33 Late Stages Hypotension Shock Metabolic acidosis Acute tubular necrosis Myocardial dysfunction Cardiac arrhythmia Confusion Seizures Coma

34 Treatments must be diagnosed by blood test no specific treatment rest helps drink plenty of fluids keep away from mosquitoes

35 YFV Vaccine Used since the 1930 s Scientists at the Rockefeller Foundation in New York developed a live vaccine (17D) The 17D vaccine was first tested in 1936 in New York and in 1937 in Brazil.

36 Yellow Fever Vaccine Virus first isolated in 1928 YFV 17D live attenuated vaccine strain derived amino acid differences between vaccine strain and wild-type Rare adverse events following vaccination Recent report of a death (Doblas et al J Clin Virol. 36:156) 26-year old Spanish woman planning to travel to Africa Developed yellow fever a few days after vaccination Died 10 days after vaccination Genome of recovered virus sequenced Only two silent mutations were found

37 Prevention immunization avoid mosquito bites wear long-sleeved shirts & long pants use insect repellant spray living areas with insecticide use bed net when sleeping in infested area

38 Current Issues: Minas Gerias, Brazil Between January and March 2001, an outbreak of jaundice and hemorrhagic fever occurred in the state of Minas Gerias, Southeast region of Brazil, in which a mortality rate of 53% was reported. Seroconversion, virus isolation, histopathological and immunohistochemical findings, and reverse transcriptionpolymerase chain reaction (RT-PCR) identified yellow fever virus (YFV) as the etiological agent responsible for the outbreak. Partial nucleotide sequence analysis from a fragment of the YFV genome spanning parts of nonstructural (NS) 5 gene and 3 noncoding region (3 UTR) showed that the YFV involved in this outbreak belongs to South American genotype 1 and differs from the Brazilian virus identified in J Med. Virol. 68: , 2002

39 Current Issues: Norfolk, Virginia The steamer Ben Franklin en route to NY from St. Thomas, Virgin Islands which had a YF epidemic raging, made an emergency stop at Hampton Roads. Her cargo contained the larvae of the Aedes aegypti and was a Pandora s Box. By beginning of the winter frost 2,000 people had perished.

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