Arboviruses and other zoonotic viruses Arbovirus: Arthropod-borne Viruses  maintained  in nature principally, or  to  an  important extent,  through  biological  transmission  beten   susceptible vertebrate  hosts by haematophagus arthropods or through  transovarian and possibly venereal transmission in arthropods

ARBOVIRUSES FAMILY ENVELOPE yes no SYMMETRY icosahedral helical GENOME ssRNA (+ve) ssRNA (-ve) segmented dsRNA,

Transmission Cycles Man - arthropod -man e.g. dengue, urban yellow fever. Reservoir may be in either man or arthropod vector. In the latter transovarial transmission may take place. Animal - arthropod vector - man e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever. The reservoir is in an animal. The virus is maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected incidentally. Both cycles may be seen with some arboviruses such as yellow fever.

Man-Arthropod-Man Cycle

Animal-Arthropod-Man Cycle

Arthropod Vectors Mosquitoes Ticks Sandflies Japanese encephalitis, dengue, yellow fever, St. Louis encephalitis, EEE, WEE, VEE etc. Ticks Crimean-Congo haemorrhagic fever, various tick-borne encephalitides etc. Sandflies Sicilian sandfly fever, Rift valley fever.

Examples of Arthropod Vectors Aedes Aegyti Assorted Ticks Phlebotmine Sandfly Culex Mosquito

Overwintering ability Transovarial transmission VERTEBRATE ARTHROPOD Habitat Diurnal activity Preferred host Annual activity Overwintering ability Transovarial transmission VERTEBRATE Migratory activity Persistence of viremia Clinical consequences Reservoir ? Dead end host? At least 150 species mosquito in US alone. ~3500 species worldwide

Prevention Surveillance - of disease and vector populations Control of vector - pesticides, elimination of breeding grounds Personal protection - screening of houses, bed nets, insect repellants Vaccination - available for a number of arboviral infections e.g. Yellow fever, Japanese encephalitis, Russian tick-borne encephalitis

ARBOVIRAL DISEASE INITIAL VIRAL REPLICATION INTERFERON (RNA VIRUSES) All are cytolytic endothelial cells macrophages/monocyte lineage INTERFERON (RNA VIRUSES) headache, fever, myalgia (flulike) VIREMIA spread to target tissues, depending on tropism of virus Role of innate immunity in disease progression Non-neutralizing Ab  may enhance flavivirus infection via Fc receptors on macrophages

RECOVERY INTERFERON CELL-MEDIATED IMMUNITY ANTIBODY MAY PLAY A ROLE IN PREVENTING SPREAD DURING VIREMIC PHASE

Flaviviruses Spherical, 40-60 nm Positive sense, 11 kb ssRNA 3 structural proteins Replication and essembly in cell cytoplasm

Yellow Fever West Africa and South America Jungle YF is the natural reservoir of the disease in a cycle involving nonhuman primates and forest mosquitoes. Man may become incidentally infected on venturing into jungle areas. The urban form is transmitted between humans by the Aedes aegypti mosquito Some patients may experience an asymptomatic infection or a mild undifferentiated febrile illness.

Mild illness: Fever, headache, pink eye Severe illness (%15 of the infected): Fever, chills, naussea, vomiting (vomitus negra), severe mylagia, lower back pain,yellow colorination of the sklerae (due to hepatic involvement), hemoorhagia, anuria, death

Yellow Fever After a period of 3 to 4 days, the more severely ill patients with a classical YF course will develop bradycardia (Faget's sign), jaundice, and haemorrhagic manifestations. 50% of patients with frank YF will develop fatal disease characterized by severe haemorrhagic manifestations, oliguria and hypotension. Diagnosis is usually made by serology There is no specific antiviral treatment An effective live attenuated vaccine is available against yellow fever and is used for persons living in or traveling to endemic areas.

Yellow Fever 50% of patients with frank YF  fatal disease with severe haemorrhagic manifestations, oliguria and hypotension Diagnosis is usually made by serology, molecular detection There is no specific antiviral treatment Live attenuated vaccine  persons living in or traveling to endemic areas.

West Nile virus Japanese encephalitis virus antigenic complex (Japanese encephalitis, St. Louis encephalitis, Murray Valley encephalitis, and Kunjin)

80% asymptomatic In 20 % Fever Headache Fatigue Skin rash on the trunk of the body (occasionally) Swollen lymph glands (occasionally) Eye pain (occasionally)

In 1/150 cases Fever Gastrointestinal symptoms Ataxia and extrapyramidal signs Optic neuritis Seizures Weakness Change in mental status Myelitis Polyradiculitis A minority of patients with severe disease develop a maculopapular or morbilliform rash involving the neck, trunk, arms, or legs. Flaccid paralysis is sometimes seen. Although not observed in recent outbreaks, myocarditis, pancreatitis, and fulminant hepatitis have been described.

Dengue Fever Vector: Aedes ; epidemic (> 100 countries) Incubation period: 3-14 days (usually 4-7d) 4 serotypes called DENV-1, -2, -3, and -4 Three clinical presentation Undifferentiated Fever; Dengue Fever with or without hemorrhage; or Dengue Hemorrhagic Fever or Dengue Shock Syndrome.

Bunyavirideae Nairovirus Ortho Bunyavirus Bunyavirus Hantavirus Phlebovirus Phlebovirus Hantavirus Nairovirus Tospovirus Tospovirus 7 serogroups; CCHF Grubu: CCHFv* Dugbe* Nairobi koyun hastalığı virusu* Hazara (Patojen değil)

Segmented ss RNA virus L, S and M segments

Tick vectors Hyalomma truncatum Hyalomma marginatum Hyalomma impeltatum Hyalomma impressum Amblyomma variegatum Boophilus decolaratus

CCHF: transmission Tick bite Crushing of ticks Contact with viremic animal’s carcasses Nosocomial Patient contact Tissue & body fluids contact Laboratory

Incubation: - Following tick bite 1-3 d; max. 9 days, - Following exposure to infected blood, tissue or body fluids 5-6 days: max. 13 days

Clinical course Human Animals Flu like signs Haemorrhagies + DIC… Death (10-80%) Animals No disease Temparate fever… Viremia max. 10 days

Symptoms n (%) Fatigue 86 (94) Fever 84 (91) Myalgia 83 (90) Head ache 74 (80) Sore throat 18 (20) Gastrointestinal Naussea 69 (75) Vomiting 63 (68) Diarrhea 36 (39)

Prehemorrhagic period PLTs Incubation 3-7 days Prehemorrhagic period 1-7 days Hemorrhagic period 2-3 days Convelescence Bleeding from various sites (hematemesis, melena, etc.) somnolence AST ALT WBCs Fatality happens Polymerase Chain Reaction: The first 9 days Myalgia, Fever, Nausea-vomiting Diarrhea 7 d 10 d days DIC IgM (7 days-4 months) and IgG (7 days-5 years) viremia Ergonul O. Lancet ID 2006; 6: 203-214

2002-2003:150 cases; 4.5% fatality 2004: 249 cases; 5.2% fatality 2005: 266 cases; 5% fatality 2006: 224 cases..... The largest epidemic in the World

Hantavirus Distinct hantaviruses are associated with specific rodent hosts. Cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary sundrome (HPS) Transmission via: Inhalation of aeresols of rodent excreta

hemorrhagic fever with renal syndrome (HFRS) Interstitiel nephritis  acute renal failure Genralised hemorrhagia and shock CFR is 5-15 % Hantaan and Dobrova viruses in Asia and in Balkans In Euroasia a mild form  nephropathia epidemica  caused by Puumala virus (Scandinavia)

HAntavirus Pulmonary Syndrome (HPS) First described in 1993 in North America Sin Nombre virus Mortality 30 %

Sandfly Fever Phlebovirus Vector  Phlebotomus papatasii Naples virus, Sicilian virus, Cyprus and Toscana virus

Arenaviruses Segmented RNA; two ss RNA molecules Old and new world arenaviruses Establish chronic infections among rodents Lassa fever: Africa, most common seqelae is deafness