Arboviruses and other Arboviruses and other zoonotic viruseszoonotic viruses

Arbovirus: Arbovirus: ArArthropod-thropod-boborne rne Viruses Viruses  maintained  in nature principally, or  to  an  maintained  in nature principally, or  to  an  important important e extent,  through  biological xtent,  through  biological  transmission  beten   susceptible vertebrate  transmission  beten   susceptible vertebrate  hosts by haematophagus arthropods or through  hosts by haematophagus arthropods or through  transovarian and possibly venereal  transovarian and possibly venereal transmission in arthropodstransmission in arthropods

ARBOVIRUSESARBOVIRUSES

FAMILY ENVELOPE

yes

yes

no

SYMMETRY

icosahedral

helical

icosahedral

GENOME

ssRNA (+ve)

ssRNA (-ve)segmented

dsRNA, segmented

Transmission CyclesTransmission Cycles

Man - arthropod -manMan - arthropod -man

– e.g. dengue, urban yellow fever. e.g. dengue, urban yellow fever.

– Reservoir may be in either man or arthropod vector. Reservoir may be in either man or arthropod vector.

– In the latter transovarial transmission may take place.In the latter transovarial transmission may take place.

Animal - arthropod vector - manAnimal - arthropod vector - man

– e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever. e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.

– The reservoir is in an animal. The reservoir is in an animal.

– The virus is maintained in nature in a transmission cycle involving The virus is maintained in nature in a transmission cycle involving the arthropod vector and animal. Man becomes infected the arthropod vector and animal. Man becomes infected incidentally.incidentally.

Both cycles may be seen with some arboviruses such as yellow fever.Both cycles may be seen with some arboviruses such as yellow fever.

Man-Arthropod-Man Cycle Man-Arthropod-Man Cycle

Animal-Arthropod-Man CycleAnimal-Arthropod-Man Cycle

Arthropod VectorsArthropod Vectors

MosquitoesMosquitoesJapanese encephalitis, dengue, yellow fever, St. Louis Japanese encephalitis, dengue, yellow fever, St. Louis encephalitis, EEE, WEE, VEE etc.encephalitis, EEE, WEE, VEE etc.

TicksTicksCrimean-Congo haemorrhagic fever, various tick-borne Crimean-Congo haemorrhagic fever, various tick-borne encephalitides etc.encephalitides etc.

SandfliesSandfliesSicilian sandfly fever, Rift valley fever.Sicilian sandfly fever, Rift valley fever.

Examples of Arthropod VectorsExamples of Arthropod Vectors

Aedes AegytiAssorted Ticks

Phlebotmine SandflyCulex Mosquito

ARTHROPODARTHROPOD HabitatHabitat Diurnal activityDiurnal activity Preferred hostPreferred host Annual activityAnnual activity Overwintering abilityOverwintering ability Transovarial Transovarial

transmissiontransmission

VERTEBRATEVERTEBRATE Migratory activityMigratory activity Persistence of Persistence of

viremiaviremia Clinical Clinical

consequencesconsequences Reservoir ?Reservoir ? Dead end host?Dead end host?

PreventionPrevention

Surveillance Surveillance - of disease and vector populations- of disease and vector populations

Control of vectorControl of vector - pesticides, elimination of breeding - pesticides, elimination of breeding groundsgrounds

Personal protection Personal protection - screening of houses, bed nets, insect - screening of houses, bed nets, insect repellantsrepellants

VaccinationVaccination - available for a number of arboviral - available for a number of arboviral infections e.g. Yellow fever, Japanese encephalitis, infections e.g. Yellow fever, Japanese encephalitis, Russian tick-borne encephalitisRussian tick-borne encephalitis

ARBOVIRAL DISEASEARBOVIRAL DISEASE INITIAL VIRAL INITIAL VIRAL RREPLICATIONEPLICATION

– All are cytolyticAll are cytolytic– endothelial cellsendothelial cells– macrophages/monocyte lineagemacrophages/monocyte lineage

INTERFERON (RNA VIRUSES)INTERFERON (RNA VIRUSES)– headache, fever, myalgiaheadache, fever, myalgia (flulike) (flulike)

VIREMIAVIREMIA– spread to target tissues, spread to target tissues,

depending on tropism of virusdepending on tropism of virus Role of innate immunity in disease Role of innate immunity in disease

progressionprogression Non-neutralizing Ab Non-neutralizing Ab may may

enhance flavivirus infection via Fc enhance flavivirus infection via Fc receptors on macrophagesreceptors on macrophages

RECOVERYRECOVERY

INTERFERONINTERFERON

CELL-MEDIATED IMMUNITYCELL-MEDIATED IMMUNITY

ANTIBODY MAY PLAY A ROLE IN ANTIBODY MAY PLAY A ROLE IN PREVENTING SPREAD DURING VIREMIC PREVENTING SPREAD DURING VIREMIC PHASEPHASE

FlavivirusesFlaviviruses

Spherical, 40-60 nmSpherical, 40-60 nm Positive sense, 11 kb ssRNAPositive sense, 11 kb ssRNA 3 structural proteins3 structural proteins Replication and essembly in cell cytoplasmReplication and essembly in cell cytoplasm

Yellow FeverYellow Fever West Africa and SWest Africa and Southouth America America

Jungle YF is the natural reservoir of the disease in a cycle Jungle YF is the natural reservoir of the disease in a cycle involving nonhuman primates and forest mosquitoes. Man involving nonhuman primates and forest mosquitoes. Man may become incidentally infected on venturing into jungle may become incidentally infected on venturing into jungle

areas.areas.

The urban form is transmitted between humans by the The urban form is transmitted between humans by the Aedes aegypti mosquitoAedes aegypti mosquito

Some patients may experience an asymptomatic infection Some patients may experience an asymptomatic infection or a mild undifferentiated febrile illness.or a mild undifferentiated febrile illness.

Mild illness:Mild illness: Fever, headache, pink eye Fever, headache, pink eye

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

Yellow FeverYellow Fever

After a period of 3 to 4 days, the more severely ill patients with a After a period of 3 to 4 days, the more severely ill patients with a classical YF course will develop bradycardia (Faget's sign), classical YF course will develop bradycardia (Faget's sign), jaundice, and haemorrhagic manifestations. jaundice, and haemorrhagic manifestations.

50% of patients with frank YF will develop fatal disease 50% of patients with frank YF will develop fatal disease characterized by severe haemorrhagic manifestations, oliguria and characterized by severe haemorrhagic manifestations, oliguria and hypotension. hypotension.

Diagnosis is usually made by serologyDiagnosis is usually made by serology

There is no specific antiviral treatmentThere is no specific antiviral treatment

An effective live attenuated vaccine is available against yellow An effective live attenuated vaccine is available against yellow fever and is used for persons living in or traveling to endemic fever and is used for persons living in or traveling to endemic areas.areas.

Yellow FeverYellow Fever

50% of patients with frank YF 50% of patients with frank YF fatal fatal diseasedisease with with severe haemorrhagic severe haemorrhagic manifestations, oliguria and hypotensionmanifestations, oliguria and hypotension

Diagnosis is usually made by serologyDiagnosis is usually made by serology, ,

molecular detectionmolecular detection

There is no specific antiviral treatmentThere is no specific antiviral treatment

LLive attenuated vaccine ive attenuated vaccine persons living in persons living in or traveling to endemic areas.or traveling to endemic areas.

West Nile virusWest Nile virus

Japanese encephalitis virus antigenic complex

(Japanese encephalitis, St. Louis encephalitis, Murray Valley encephalitis, and Kunjin)

80% asymptomatic80% asymptomatic In 20 %In 20 %

– Fever Fever – Headache Headache – Fatigue Fatigue – Skin rash on the trunk of the body (occasionally) Skin rash on the trunk of the body (occasionally) – Swollen lymph glands (occasionally) Swollen lymph glands (occasionally) – Eye pain (occasionally) Eye pain (occasionally)

In 1/150 casesIn 1/150 cases– Fever Fever – Gastrointestinal symptoms Gastrointestinal symptoms – Ataxia and extrapyramidal signs Ataxia and extrapyramidal signs – Optic neuritis Optic neuritis – Seizures Seizures – Weakness Weakness – Change in mental status Change in mental status – Myelitis Myelitis – Polyradiculitis Polyradiculitis – A minority of patients with severe disease develop a maculopapular or A minority of patients with severe disease develop a maculopapular or

morbilliform rash involving the neck, trunk, arms, or legs. morbilliform rash involving the neck, trunk, arms, or legs. – Flaccid paralysis is sometimes seen. Flaccid paralysis is sometimes seen. – Although not observed in recent outbreaks, myocarditis, pancreatitis, and Although not observed in recent outbreaks, myocarditis, pancreatitis, and

fulminant hepatitis have been described. fulminant hepatitis have been described.

Dengue FeverDengue Fever

Vector: Aedes ; epidemic (> 100 countries)Vector: Aedes ; epidemic (> 100 countries) Incubation period: 3-14 days (usually 4-7d)Incubation period: 3-14 days (usually 4-7d) 4 serotypes called DENV-1, -2, -3, and -4 4 serotypes called DENV-1, -2, -3, and -4 Three clinical presentationThree clinical presentation

– Undifferentiated Fever; Undifferentiated Fever; – Dengue Fever with or without hemorrhage; or Dengue Fever with or without hemorrhage; or – Dengue Hemorrhagic Fever or Dengue Shock Dengue Hemorrhagic Fever or Dengue Shock

Syndrome.Syndrome.

BunyavirideaeBunyavirideae

Bunyavirus Hantavirus Nairovirus Phlebovirus TospovirusOrthoBunyavirus

Hantavirus Nairovirus TospovirusPhlebovirus

7 serogroups; CCHF Grubu: -CCHFv*-Dugbe*-Nairobi koyun hastalığı virusu*-Hazara (Patojen değil)

Segmented ss RNA virusSegmented ss RNA virus L, S and M segmentsL, S and M segments

Tick vectorsTick vectors

– Hyalomma truncatumHyalomma truncatum

– Hyalomma marginatumHyalomma marginatum

– Hyalomma impeltatumHyalomma impeltatum

– Hyalomma impressum Hyalomma impressum

– Amblyomma variegatumAmblyomma variegatum

– Boophilus decolaratusBoophilus decolaratus

CCHF: transmissionCCHF: transmission

Tick biteTick bite Crushing of ticksCrushing of ticks Contact with viremic animal’s carcassesContact with viremic animal’s carcasses NosocomialNosocomial

– Patient contactPatient contact– Tissue & body fluids contactTissue & body fluids contact– LaboratoryLaboratory

Incubation:Incubation:

- Following tick bite 1-3 d; max. 9 days,- Following tick bite 1-3 d; max. 9 days,

- Following exposure to infected blood, tissue - Following exposure to infected blood, tissue or body fluids 5-6 days: max. 13 daysor body fluids 5-6 days: max. 13 days

Clinical courseClinical course

HumanHuman– Flu like signsFlu like signs– Haemorrhagies + DIC…Haemorrhagies + DIC…– Death (10-80%)Death (10-80%)

AnimalsAnimals– No disease No disease – Temparate fever…Temparate fever…– Viremia max. 10 daysViremia max. 10 days

•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)

n

(%)

SymptomsSymptoms

PLTs

Incubation

3-7 days

Prehemorrhagic period1-7 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-vomitingDiarrhea

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

HantavirusHantavirus

Distinct hantaviruses are associated with Distinct hantaviruses are associated with specific rodent hosts.specific rodent hosts.

Cause hemorrhagic fever with renal Cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HFRS) or hantavirus pulmonary sundrome (HPS)sundrome (HPS)

Transmission via: Inhalation of aeresols of Transmission via: Inhalation of aeresols of rodent excretarodent excreta

hemorrhagic fever with renal hemorrhagic fever with renal syndrome (HFRS)syndrome (HFRS)

Interstitiel nephritis Interstitiel nephritis acute renal failure acute renal failure Genralised hemorrhagia and shockGenralised hemorrhagia and shock CFR is 5-15 %CFR is 5-15 % Hantaan and Dobrova viruses in Asia and in Hantaan and Dobrova viruses in Asia and in

BalkansBalkans In Euroasia a mild form In Euroasia a mild form nephropathia nephropathia

epidemica epidemica caused by Puumala virus caused by Puumala virus (Scandinavia)(Scandinavia)

HAntavirus Pulmonary Syndrome HAntavirus Pulmonary Syndrome (HPS)(HPS)

First described in 1993 in North AmericaFirst described in 1993 in North America Sin Nombre virusSin Nombre virus Mortality 30 %Mortality 30 %

Sandfly FeverSandfly Fever

PhlebovirusPhlebovirus Vector Vector Phlebotomus papatasii Phlebotomus papatasii

Naples virus, Sicilian virus, Cyprus and Toscana virus

http://upload.wikimedia.org/wikipedia/commons/9/9d/SandFlyFeverMap.jpg

ArenavirusesArenaviruses

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

is deafnessis deafness