Arbovirus spring

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					ARBO VIRAL DISEASES




              Nishanth B Bhat
              Dept of Microbiology
• Arthropod -borne viruses (arboviruses) are
  viruses that can be transmitted to man by
  arthropod vectors

• It is a collective name for a large group of diverse
  viruses.

• Virus replicates in arthropods & vertebrate hosts
Arthropods
 Mosquitoes, ticks, sandflies
Humans, Monkeys, Kangaroo, Birds, Rabbits
Arboviruses belong to families
1. Togaviridae – Alpha virus
(Mosquito-borne) Eastern Equine Encephalitis
                     Western Equine Encephalitis
                     Venezuelan Equine Encephalitis

2. Bunyaviridae – Bunya virus
                       California encephalitis virus
3. Flaviviridae – Flavi virus
                      St. Louis encephalitis
                       Yellow Fever virus
                     Dengue virus
                     West Nile virus
4. Reoviridae – Orbivirus
                     Colorado tick fever virus
Family & Genus           Encephalitis                   Febrile illness          Haemorrhagic fever

I. Togaviridae-          WEE,                           •Chickengunya            • Chickengunya
   Alphavirus            EEE,                           •O’nyong-nyong
   (Mosquito-borne)      VEE                            •Semliki forest
                                                        •Sindbis
                                                        •Ross river virus
II. Flaviridae-
    Flavivirus
    i) Mosquito-borne    • St. Louis encephalitis       • Dengue, types 1-4      • Dengue
                         •West Nile                                              • Yellow fever
                         • Murray Valley encephalitis
                         • Japanese B encephalitis

                         • Russian spring summer
  ii) Tick-borne          encephalitis                                           • Kyasanur Forest disease
                         • Powassan                                              • Omsk Haemorrhagic fever




III. Bunyaviridae
   a) Bunya virus        • California encephalitis      • Chittor virus
     (Mosquito-borne)    • La Crossie
   b) Phlebovirus                                       •Sandfly fever
     (Phlebotomus or                                    •Rift –valley fever
       mosquito-borne)
   c) Nairovirus                                        •Nairobi sheep disease
      (tick-borne)                                      •Ganjam virus
Family & Genus       Encephalitis   Febrile illness                Haemorrhagic fever



IV. Reoviridae                      • Colorado tick borne virus
    Orbivirus
    (Tick - borne)


V. Rhabdoviridae
   Vesiculovirus
   (Mosquito-borne                  • Vesicular stomatitis virus
    sandfly-borne)                  • Chandipura virus
Properties:
Togaviridae:
          virus contains icosahedral nucleocapsid
  surrounded by an envelope and a single stranded RNA
  genome.


Flaviviridae:
              Similar to toga but are smaller in size.


Bunyaviridae:
             Have helical nucleocapsid surrounded by an
  envelope and a genome consisting of three segments of
  RNA that are hydrogen – bonded together.
• These viruses are spread by haematophagous arthropod
  vectors (blood sucking insects).

• These vectors include mosquitoes and biting flies.
  Arboviruses are vector specific and will replicate only in their
  specific host.

• The virus is usually transmitted to the vector by a blood meal
  and replicates in the vector eventually making its way to the
  salivary glands where it can be transmitted to a second
  animal upon feeding.
• The vector is usually infected for life and does not
  display any signs of sickness

• During winter months in cold climates the vector
  numbers decrease or the vector disappears.

• Thus arbovirus infections tend to be epidemic and
  seasonal based on the presence of a large number of
  infected vectors during warmer months.
• The virus has mechanism for overwintering: this may involve-
    transovarial transmission (adult female to egg) or
    reintroduction of virus by infected migratory birds.

• For many arboviruses vector transmission can also occur-
     Sexually or trans-stadially (larva to nymph to adult).

• Most arboviruses exist in enzootic cycles (natural cycles) of
  transmission in which virus is transmitted by insect vectors
  from bird to bird or among small mammals.

• If the vector should feed on a human or equine the virus may
  be transmitted (epizootic infection) with illness resulting.
  Equines and humans are usually dead end hosts.
Man-Arthropod-Man Cycle
Animal-Arthropod-Man Cycle
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.
ARBOVIRUS TRANSMISSION CYCLE
• A mosquito (vector) picks up a virus (WNV or EEE) from a
  bird (reservoir), and can either cycle that virus through the
  bird population (amplification) or transmit the virus directly
  to a host such as horses and humans (incidental infection).
Incubation period:
Extrinsic incubation period,.is an obligatory length of
 time before the virus has replicated sufficiently for the
 saliva of the vector to contain enough virus to transmit an
 infectious dose
It ranges from 7-14 days.

 Humans are dead end hosts, because the concentration of
virus in human blood is too low and the duration of
viremia too brief for the next bite to transmit the virus.

In some diseases humans have high level viremia and act
as reservoirs of the virus.
                     e.g. yellow fever, dengue.
Clinical findings & Epidemiology:

The arboviral disease occur primarily in the tropics but are
also found in the temperate zones such as US.

Arboviral infections can manifest as three types of illnesses in
humans. These are

• Acute central nervous system disease including aseptic
  meningitis, encephalitis and encephalomyelitis

• Undifferentiated febrile illness with or without rash, and

• Haemorrhagic fever, a systemic febrile illness with
  haemorrhagic manifestations, cardiovascular instability and
  varying degrees of hepatic and renal insufficiency.
Pathogenesis
         Following the arthropod bite

Virus replicates locally then spreads to regional lymph nodes

It gets disseminated via the lymphatic system into the
bloodstream (primary viraemia).

The primary viraemia seeds target organs which replicate virus
and serve as a source of virus for release into the circulation.



Virus can then enter the neural tissue causing encephalitis.
Symptoms
• The symptoms of arbovirus infection usually have an abrupt
  onset. With constitutional symptoms occurring first-
    Fever, chills, headache, generalized aches and malaise
• Followed in some cases by more severe symptoms of
  encephalitis- drowsiness, nuchal rigidity, confusion,
  convulsions, tremors, coma, death
                             or
• Haemorrhage (yellow fever and dengue [rare]).

• The incubation period can vary from 3 to 21 days.

• Sequelae of encephalitis can be severe.
• Most arbovirus infections are inapparent and immunity is
  life-long.
Eastern Equine Encephalitis virus:

Belongs to genus Alpha virus.

It causes the most severe disease and is associated with the
highest fatality rate – 50%.

Eastern USA, Central & South America.

Birds/mosquitoes.                          Salivary gland of
                                            mosquito showing EEE
                                            virus
 Severe CNS disease in horses and man.
Incubation: 3 - 7 days
Risk Factors
• Exposure to Aedes spp mosquito bites,
• Living near or visiting a wetland area or an area known to have
  incidents of EEE.
Symptoms
   – Fatigue
   – Fever
   – Headache
   – Nausea
   – Restlessness or irritability
   – Difficulty walking or unstableness
   – Confusion, impaired judgment, or an altered mental state
   – Seizures
Eastern Equine Encephalitis Virus Neuroinvasive
  Disease Cases Reported by State, 1964-2009
Lab Diagnosis:
          Isolation of virus
          Demonstration of rise in antibody titer.
 No antiviral therapy available.


 Killed vaccine available for horses but not for
 humans.
Western Equine Encephalitis:
North & South America.

Birds/mosquitoes.

Severe disease in horses. Milder disease in man.

In US the number of cases ranges between 5-20 per year, &
fatality rate is 20%.

Virus is transmitted primarily by Culex mosquitoes among
the wild bird population in areas with irrigated farmland.
Risk factors

• Living in or visiting the plains regions of the western
  and central United States

• Working outdoors

• Participating in outdoor activities
Signs & symptoms:
         –Headache
         –Fever
         –Drowsiness
         –Irritability
         –Nausea
         –Vomiting
         –Confusion
         –Weakness
         –Coma
         –Seizures
Diagnosis:         is done by
                   isolation of the virus
                   demonstration of rise in antibody titer.
Treatment:
 No antiviral therapy.
 Treatment will focus on managing your symptoms and related
  complications.
 Vaccine for horses available.
St. Louis Encephalitis virus (SLE):
Wider geographic area then the EEE & WEE.

Found in southern central and western states of US.
10-30 cases per year.

The virus is spread by several species of Culex mosquito.

Reservoirs: small wild birds – English sparrows.

SLE virus seen in urban areas because these mosquitoes breed
in the stagnant water.

Fatality rate is 10% . Sequelae is not common.
Risk Factors:

Some factors thought to increase the risk of St. Louis
encephalitis include:

• Elderly age

• Living in or visiting the southern, central, or western
  United States, especially during the summer and fall
Symptoms
      –Headache
      –Fever
      –Neck stiffness
      –Stupor
      –Disorientation
      –Coma
      –Tremors
      –Convulsions (especially in infants)
      –Paralysis
Diagnosis : Serological diagnosis is done.

Treatment:
No antiviral therapy.
California Encephalitis (CE) virus:
Was first isolated from mosquitoes in California in 1952.

La Crosse virus - California serogroup virus

It belongs to family Bunyaviridae

It is the most common arboviral cause of encephalitis in
US.

Approximately 70 cases reported per year
California Serogroup Virus Neuroinvasive Disease Cases*
              Reported by State, 1964-2008
TRANSMISSION
• Virus cycles in woodland habitats between the treehole
  mosquito (Aedes triseriatus) and vertebrate hosts
  (chipmunks, squirrels)
• Virus survives winter in mosquito
• Vector uses artificial containers (tires, buckets, etc.) in
  addition to treeholes

RISK GROUPS
• Residence in woodland habitats environmental risk factor
• Containers at residence environmental risk factor
• Outdoor activities: behavioral risk factor
Clinical picture can be mild, resembling enteroviral
  meningitis or severe resembling herpes encephalitis.

Diagnosis: made serologically.
No antiviral therapy or vaccine available.
Colorado tick fever (CTF)virus:
It is a Reovirus.

Transmitted by wood tick – Dermacentor andersoni
Among small rodents e.g. chipmunks and squirrels.

Geographic range is confined to the western US states and
areas above 5,000 ft. in elevation
The disease occurs primarily in people hiking & camping
  in the Rocky Mountains
100-300 cases per year is seen in US.
Symptoms
               •   High fever
               •   Chills
               •   Severe headache
               •   Pain behind the eyes
               •   Sensitivity to light
               •   Muscle pain
               •   Lethargy
               •   Abdominal pain
               •   Vomiting
               •   Nausea

Complications are extremely rare and include aseptic
  meningitis, encephalitis, and hemorrhagic fever.
Diagnosis: isolation of the virus
           detecting a rise in antibody titer.

Prevention:
• Avoid tick-infested areas, especially during warmer months.
• Wear light-colored clothing to better locate a crawling tick.
• Tuck pants into socks when in tick-infested habitats.
• Use tick repellents.
• Regularly inspect and remove ticks from your body and your
  child’s body when in tick-infested habitats.
• Remove ticks using fine-tipped tweezers by grasping the tick
  close to the skin’s surface and pulling upward steadily.
• Disinfect tick bites with soap and water.
West Nile virus (WNV):
Asia, Central and South Africa (Transvaal). Birds and
  mosquitoes.
Human outbreaks usually after rains.

Out break of encephalitis in New York in the month of
July, Aug & Sept. 1999 was seen with 27 were confirmed
cases.

2000 there were 18 cases & 1 death.

2001 48 cases were seen & 5 deaths.
It not known how the virus entered US, may be through
   infected person or an infected bird.
Reservoirs: wild birds

Transmitted by mosquitoes (Culex species).

Humans are dead end hosts.

Clinical symptoms:
Fever, confusion and striking muscle weakness similar to
Guillain – Barr syndrome.

Laboratory diagnosis:
            Isolation of the virus from brain tissue, blood, or
            spinal fluid.
            Detection of antibodies in spinal fluid or blood
            PCR is also available
Treatment: No antiviral therapy or vaccine available.
Important arbovirus that cause disease outside the US

Yellow fever virus:
The infection is characterized by jaundice and fever.
It is severe, life threatening disease.
Two distinct cycles exist in nature with different reservoirs
   and vectors.

1. Jungle yellow fever – disease of monkeys in tropical
   Africa and South America.
 Vectors: tree top mosquitoes – Haemagogus spp.
 Reservoirs- monkeys
 humans are accidental hosts.
2. Urban yellow fever is a disease of humans.

Vectors: mosquito Aedes aegypti , breeding in the stagnant
Water.

Reservoirs: Humans

Intrinsic incubation period is 3-6 days.
• Risk Factors



• The following factors increase your chance of getting yellow
  fever:
• Living, working, or traveling in jungle or urban areas with
  yellow fever, including:
   – Sub-Saharan Africa
       • 33 countries in Africa have constant cases of yellow fever
   – South America
       • Bolivia, Brazil, Colombia, Ecuador, and Peru provide
         greatest risk
• Symptoms
• Yellow fever has two phases: acute and toxic. All
  individuals infected with yellow fever will experience the
  acute phase. Fifteen percent of people with yellow fever
  will progress into the toxic phase.

Acute Phase
               •   Fever
               •   Headache
               •   Muscle pain
               •   Backache
               •   Chills
               •   Loss of appetite
               •   Nausea and/or vomiting
Toxic Phase
         – High fever
         – Abdominal pain
         – Bleeding from the gums, nose, eyes, and/or
           stomach
         – “Black” vomit (vomit that appears black due to
           blood content)
         – Low blood pressure
         – Liver failure, which may lead to jaundice (yellowing
           of the skin and whites of the eyes)
         – Kidney failure
         – Confusion
         – Seizure
         – Coma
         – Death (approximately 50% of toxic phase patients
           die)
Diagnosis:
          Isolation of the virus
          Detecting a rise in antibody titer.

Prevention:
Mosquito control

Vaccine: vaccine containing live, attenuated virus available.
Travelers to and residents of endemic areas should be
immunized. Protection lasts for 10 yrs. Booster dose is
required every 10 yrs.
Vaccine:
• "17 D strain" live attenuated virus Good safe long lasting
  protection but labile and expensive to administer.

• Vaccination is required for travel to endemic zones (or
  rather, for return to non-endemic zones!)
Dengue virus: (Break Bone Fever)

The first reported epidemics of DF occurred in 1779-1780
in Asia, Africa, and North America.

It belongs to Flavi virus group.

It is not endemic in US some tourists return with this
disease.

100-200 cases per year seen in US mostly in southern and
eastern states.
About 20 million people get infected each year worldwide.
Vector : Aedes aegypti

Serotypes: virus serotypes DEN-1, DEN-2, DEN-3, and DEN-4
Risk Factors

• Travel to tropical or subtropical areas, such as:
   – Africa
   – India
   – Southeast Asia and China
   – Middle East
   – Countries in the Caribbean and Central and South America
   – Australia
   – Locations in the Central and South Pacific
Symptoms

Classic dengue begins suddenly with an influenza like
  syndrome-
  – Fever
  – Malaise
  – Cough
  – Headache
  – Severe pain in the muscle and joints
  – Enlarged lymphnode, maculopapular rash and leukopenia
    are common.
  – This typical form is rarely fatal.
Dengue hemorrhagic fever:
Fatality rate 10%
Initial picture is same as the classic dengue fever
Later shock and hemorrhage, especially into the
  gastrointestinal tract and skin develop.

Dengue hamorrhagic fever occurs in southern Asia,

Hemorrhagic shock syndrome is due to production of
 large amounts of cross reacting antibody at the time of
 second dengue infection
Lab diagnosis:
               Isolation of virus
               Demonstarte the prescence of IgM antibody
  or a 4 fold or greater rise in antibody titer in acute and
  convalescent stage.

Treatment: No antiviral therapy or vaccine.

Outbreaks are controlled by using insecticides and
  draining stagnant water .
Personal protection – use of mosquito repellent.
    Japanese Encephalitis
• First discovered and originally restricted to Japan.
  Now large scale epidemics occur in China, India and
  other parts of Asia.


• Flavivirus, transmitted by culex mosquitoes.


• The virus is maintained in nature in a transmission
  cycle involving mosquitoes, Ardeid birds ( Herons and
  egrets ) and pigs.
• Most human infections are subclinical: the inapparent
  to clinical cases is 300:1
• In clinical cases,       a    life-threatening
  encephalitis occurs.
• The disease is usually diagnosed by serology.
  No specific therapy is available.
• Since Culex has a flight range of 20km, all
  local control measures will fail. An effective
  vaccine is available.
• A live attenuated SA14-14-2 vaccine
  produced in primary hamster kidney cells
Prevention
• To help reduce your chances of getting Encephalitis,
  take the following steps:
• Avoid areas of mosquito activity, if possible.
• Stay inside when mosquitoes are most active (at dawn
  and at dusk).
• When outside, wear insect repellent, long pants and
  long-sleeved shirts to limit exposure to bites.
• To help limit mosquito populations in and around your
  home, eliminate the insects’ breeding areas. Those
  may include standing water such as pet water bowls,
  rain barrels, and other containers.
• Thank you

				
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