It will be useful for teaching guide for II year MBBS student

1. Arboviruses
AN OVERVIEW
Dr. Shweta Sharma
MD, Clinical Microbiologist

3. Introduction
• RNA
Viruses, transmitted by arthropod vectors.
• Acronym (ARthropod-BOrne virus)
• Arboviruses can affect both animals,
including
humans, and plants.
•World wide in distribution but far more
numerous in tropical than temperate zones.

4. Types of arboviruses
Many types of arboviruses.
1.Flavivirus
Yellow fever ,West Nile virus, Zika virus, Dengue fever ,Japanese encephalitis,St.louis
encephalitis
2.Togavirus
Ross River virus, Eastern equine virus(EEV), Western equine virus(WEV),chikengunya
3.Bunyavirus
Sandfly fever, Rift Valley fever, California encephalitis, Crimean Congo Haemorrhagic
fever
Rare family includes Reoviridiae, Rhabdoviridae

5. Transmission: Arthropod Vectors
The arboviruses spread mainly through insect bites.
Mosquito(Most Common) :
Japanese encephalitis, dengue, yellow fever, St. Louis
encephalitis, EEE, WEE, etc.
Ticks:
Crimean-Congo haemorrhagic fever, various tick-
borne encephalitides etc.
Sandflies:
Sicilian sandfly fever, Rift valley fever.

6. Man-Arthropod-Man Cycle
e.g. Dengue, urban yellow
fever. Reservoir may be in
either man or arthropod
vector.

7. Animal-Arthropod-Man Cycle
e.g. Japanese encephalitis, EEE, WEE, jungle yellow fever.
The reservoir is in an animal. Though in many cases actual reservoir is not known.
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.

8. Symptoms
Mostly asymptomatic. However, symptoms can range from a mild flu-like illness to
encephalitis.
Fever and rash:
A non-specific illness like other viral illnesses. The patients may develop
encephalitis or haemorrhagic fever.
Encephalitis: e.g. EEE, WEE, St Louis encephalitis, Japanese encephalitis.
Sudden onset of fever, headache, stiff neck, muscle pain, confusion or
disorientation, weakness in the arms and legs, seizures.
Haemorrhagic fever: e.g. yellow fever, dengue, Crimean-Congo haemorrhagic fever.
Fever , headache, muscle aches, joint pain, upset stomach, nausea, vomiting, or
diarrhoea rash, bleeding tendencies.

9. Diagnosis
Serology - Usually used to make a diagnosis of arbovirus infections.
ELISA ,Rapid card test based on Immunochromatography, CFT
Culture - a number of cell lines may be used, However, it is rarely carried out
since many of the pathogens are group 3 or 4 pathogens.
Animal Inoculation - Mice are commonly used for growing arboviruses.
Intracerebral inoculation in suckling mice –most sensitive method.
Direct detection tests - e.g detection of antigen and nucleic acids (PCR)

10. Treatment
• Treatment for most of infections is supportive only.
• In haemorrhagic fevers, bleeding may require phytonadione (vitamin K1).
• Transfusion of packed RBCs or fresh frozen plasma may also be necessary.
• Aspirin and other NSAIDs are contraindicated because of antiplatelet activity.
• Ribavirin is recommended for hemorrhagic fever caused by bunyaviruses
including Rift Valley fever, and Crimean-Congo hemorrhagic fever
• However, Ribavirin has not been effective in animal models of flavivirus
infections.

11. Prevention
More important as no specific treatment is available.
1. Surveillance: of disease and vector populations
2. Vector control:
• Prevention of Diseases transmitted by mosquitoes or ticks : Appropriate clothing ,
Using insect repellants (eg, DEET [diethyltoluamide]), Minimizing the likelihood of
exposure to the insect (eg, for mosquitoes, limiting time outdoors in wet areas )
Larvicides are also used worldwide in mosquito abatement programs. Temefos is a
common mosquito larvicide.
• Prevention of Diseases transmitted by rodent excreta: Sealing sites of potential
rodent entry into homes and nearby buildings, Preventing rodent access to food,
Eliminating potential nesting sites around the home

12. 3. Vaccine:
Vaccine is available for Japnese encephalitis, Yellow fever.
However for Dengue, Zika, West Nile fever vaccine is under
developmental stage.

13. Japnese Encephalitis (JE)
JE is the most important viral encephalities in Asia, especially in rural and
suburban areas where rice culture and pig farming coexist.
First discovered and originally restricted to Japan. Now large scale epidemics occur
in China, India and other parts of Asia.
Virus: Flavivirus, transmitted by Culex mosquitoes, mainly Culex tritaeniorhynchus
Transmission: The virus is maintained in a cycle between mosquitoes and
vertebrate hosts, primarily pigs and wading birds.
Humans are dead-end hosts, as they usually do not develop high concentrations
of JE virus in their bloodstreams to infect feeding.

14. Less than 1% of infected people develop clinical illness.
In persons who develop symptoms, the IP is 5-15 days.
Initial symptoms: fever, headache, and vomiting.
Mental status changes, neurologic symptoms, weakness, and
movement disorders might develop over the next few days.
Seizures are common, especially among children.
JE contd…. Symptoms

15. JE contd…. Diagnosis
Detection of IgM antibodies in serum or cerebrospinal fluid .
JE virus IgM antibodies are usually detectable 3 to 8 days after onset of illness and
persist for 30 to 90 days, but longer persistence has been documented.
Therefore, positive IgM antibodies occasionally may reflect a past infection or
vaccination.
For patients with JE virus IgM antibodies,(Commercially available) confirmatory
neutralizing antibody testing (Available at reference lab)should be performed.

16. No specific therapy is available.
 Hospitalization for supportive care and close observation is generally
required.
 Among patients who develop encephalitis, 20% – 30% die.
JE contd…. Treatment

17. 4 main types f vaccines available:
i) inactivated mouse brain-derived vaccines, ii)inactivated Vero cell-derived
vaccines, iii) live attenuated vaccines, and iv) live recombinant vaccines.
Inactivated Vero cell culture-derived Japanese encephalitis (JE) vaccine is
mainly used .
•It is recommended for travellers who plan to spend 1 month or more in
endemic It is given as a two-dose series, with the doses spaced 28 days apart.
•The last dose should be given at least 1 week before travel.
JE contd…. Vaccine

18. Worldwide Distribution of Japnese Encephalitis

19. Yellow Fever
YF virus belongs to Flavivirus, mainly found in
West Africa and S America
Transmission:
Transmitted by mosquitoes, belonging to the
Aedes and Haemogogus species.
YF occurs in 2 major forms: urban and jungle
(sylvatic)
• The jungle cycle - Transmission is between
non-human primates (e.g., monkeys) and
mosquito species found in the forest .The virus
is transmitted by mosquitoes from monkeys to
humans when humans are visiting or working
in the jungle.
• Urban cycle - Transmission is between humans
and urban mosquitoes, primarily Aedes
aegypti. The virus is usually brought to the
urban setting by a viremic human who was
infected in the jungle .
Infected people are infectious to mosquitoes (referred to as being
“viremic”) shortly before the onset of fever and up to 5 days after
onset.

20. Symptoms:
Majority no illness or only mild illness. IP is 3–6 days.
• The initial symptoms include sudden onset of fever, chills, severe
headache, back pain, general body aches, nausea, and vomiting,
fatigue, and weakness.
• Most persons improve after the initial presentation.
• After a brief remission of hours to a day, roughly 15% of cases
progress to develop a more severe form of the disease.
• The severe form is characterized by high fever, jaundice, bleeding,
and eventually shock and failure of multiple organs.
Diagnosis: Serology tests
Yellow fever Contd……Symptoms & Diagnosis

21. Treatment:
No specific treatments.
Hospitalization for supportive care and close observation.
Treatment is symptomatic. Rest, fluids, and use of pain relievers.
Avoid aspirin or other nonsteroidal anti-inflammatory drugs
(e.g. ibuprofen, naproxen), which may increase the risk of bleeding.
Protection from further mosquito exposure (staying indoors
and/or under a mosquito net) for up to 5 days after the onset of
fever. This way, YF virus in their bloodstream will not be available
to uninfected mosquitoes, thus breaking the transmission cycle
and reducing risk to the persons around them.
Among those who develop severe disease, 20–50% may die.
Yellow fever Contd……Treatment

22. Vaccine for Yellow fever:
1.Dakar Vaccine:
• French Neurotropic vaccine produced from infected
mouse brain .
• Carries high risk of encephalitis, especially in children.
2. 17D vaccine :
• is an effective live attenuated vaccine .It is developed by
Theiler in 1937 by passaging the Asibi strain (Africian
patient) in mouse embryo.
• It is used for persons living in or traveling to endemic
areas .
• It is administered by subcutaneous inoculation.
• A single dose of yellow fever vaccine provides long-lasting
protection.
Prevention: Protection from mosquito bites .
Vaccination

23. • Dengue, biggest arbovirus problem in the world
today. WHO estimates that 50 to 100 million
infections occur yearly, including 500,000 DHF cases
and 22,000 deaths, mostly among children.
• Dengue is found in SE Asia, Africa and the Caribbean
and S America.
• Flavivirus, 4 serotypes,(DEN 1-4) transmitted by
Aedes mosquitoes which reside in water-filled
containers.
• Human infections arise from a human-mosquito-
human cycle.

25. Symptoms: Usually begin 4 – 7 days after the
mosquito bite and typically last 3 – 10 days.
High fever- Breakbone fever lymphadenopathy,
myalgia, bone and joint pains, headache, and a
maculopapular rash.Bre
Severe cases: Haemorrhagic fever and shock.
Mortality is 5-10%.
Dengue haemorrhagic fever and shock syndrome
appear most often in patients previously
infected by a different serotype of dengue, thus
suggesting an immunopathological mechanism.
Dengue symptoms

26. Immunological Response to Dengue Infection:
• Production of IgM and IgG antibodies
primarily directed against the virus
envelope proteins.
• The immune response varies depending on
whether the individual has a primary (first
dengue ) versus a secondary (had dengue
infection in past) dengue infection.
Tests:
1.PCR
2.(MAC-ELISA):IgM antibody capture enzyme-
linked immunosorbent assay
3. IgG and
4. NS1 ELISA
5.PRNT- Plaque Reduction and Neutralization
Test
Diagnosis Of Dengue
Secondary Infection
NS1 Antigen
Common to all dengue serotypes and can
be used to detect either primary or
secondary infections.
Primary Infection
IgM antibodies first to appear after the
onset of symptoms, followed by IgG at
about 14 days post-onset.
IgM levels peak after 1 to 2 weeks, but
may be elevated for 2 to 3 months after
illness.
Secondary Infection
IgG rises rapidly within 1 to 2 days of
symptoms and often exceeds previous
levels;
IgM may not appear for up to 20 days and
may be undetectable in 20-30% of
secondary infections

28. Dengue Treatment
No specific therapy only supportive care
Prevention : Mosquito Eradiation
The population should be removed from all containers which serve
as vessel for egg deposition
Vaccine: A live attenuated vaccine is under trial in Thailand with
encouraging results.

29. Zika Virus
Virus and Transmission:
Flavivirus ,transmitted by Aedes mosquitoes. It can also be sexually
transmitted and possibly via blood transfusions.
Zika outbreaks are currently happening in many countries and territories.
The mosquitoes that can become infected with and spread Zika, live in many
parts of the world.
The specific areas where Zika virus is spreading are often difficult to
determine and are likely to change over time.

30. Zika Virus Symptoms & Treatment
Symptoms: Most are asymptomatic. fever, rash, headache, joint pain, red eyes,
and muscle pain.
Zika virus infection during pregnancy can cause microcephaly, a condition in
which the fetus has a smaller head than normal. Other problems before birth,
such as eye and hearing defects and impaired growth.
Rarely causes Guillain-Barré syndrome, a serious condition of the nervous
system.
Treatment: There is no medicine or vaccine for Zika at present.
Mainly prevention from mosquito bite is important.

31. West Nile fever
Flavivirus , commonly found in Africa, Europe, the Middle East, North America and West Asia.
West Nile Virus (WNV) was first isolated in a woman in the West Nile district of Uganda in 1937.
Transmission: Human infection is often the result of bites from infected mosquitoes.
Birds are the natural hosts. Mosquitoes become infected when they feed on infected birds, which circulate
the virus in their blood for a few days.
The virus eventually gets into the mosquito's salivary glands. During later blood meals (when mosquitoes
bite), the virus may be injected into humans and animals, where it can multiply and possibly cause illness.
The virus may also be transmitted through contact with other infected animals, their blood, or other
tissues.
A very small proportion of human infections have occurred through organ transplant, blood transfusions and
breast milk.

32. WNF contd…
Symptoms: Asymptomatic in 80% of cases.
In rest, virus can cause a fatal neurological disease .
The symptoms of severe disease (also called neuroinvasive disease, such as
West Nile encephalitis or meningitis or poliomyelitis) include headache, high
fever, neck stiffness, stupor, disorientation, coma, tremors, convulsions,
muscle weakness, and paralysis.
Diagnosis: ELISA for IgM antibodies and PCR
Treatment: Supportive often involving hospitalization, intravenous fluids,
respiratory support, and prevention of secondary infections.
No vaccine is available for humans.

33. Chikungunya
Togavirus , transmitted by infected mosquitoes of Aedes species.
Outbreaks have occurred in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans.
In Mauritius ,after the epidemic of chikungunya in 2005 and 2006, only 10 cases, all imported, have
been reported between 2007 and 2014; no case was reported in 2015.
The name “chikungunya” derives from a word in the Kimakonde language, meaning “to become
contorted”, and describes the stooped appearance of sufferers with joint pain (arthralgia).
Symptoms: The most common symptoms are fever and severe joint pain.(stooped appearance).
Other symptoms may include headache, muscle pain, joint swelling, or rash.
Diagnosis: Serology test mainly rapid card test, ELISA and molecular test PCR
Treatment: no specific antiviral drug treatment. Only supportive. No vaccine
There is a risk that the virus will be imported to new areas by infected travellers.
Travelers can protect themselves by preventing mosquito bites by using appropriate measures

36. Arbovirus
Incubation
Period
Symptoms Complications Vectors Primary Host
Geographic
distribution
Dengue 3–14 days Asymptomatic in most
cases; fever, headache,
rash, muscle, and joint
pains
Shock internal
bleeding, and organ
damage
Aedes mosquitoes,
especially Aedes
aegypti
Humans Globally
Japanese encephalitis
virus
5–15 days Asymptomatic in most
cases; fever, headache,
fatigue, nausea, and
vomiting
Encephalitis, seizures,
paralysis, coma, and
long-term brain
damage
Culex mosquitoes,
especially Culex
tritaeniorhynchus
Domestic Pigs and
wading birds
Southeast and East
Asia
Yellow fever virus 3–6 days Fever, headache, back
pain, loss of appetite,
nausea, and vomiting
Jaundice, liver damage,
gastrointestinal
bleeding, recurring
fever
Aedes mosquitoes,
especially Aedes
aegypti
Primates Tropical and
subtropical regions of
South America and
Africa
West Nile fever,
encephalitis
2–15 days Asymptomatic in most
cases; fever, headache,
fatigue, nausea,
vomiting, rash
Swollen lymph nodes,
meningitis,
encephalitis, acute
flaccid paralysis
Culex mosquitoes Passerine birds North America,
Europe, West and
Central Asia, Oceania,
and Africa
Zika Asymptomatic fever,
rash, headache, joint
pain, red eyes, and
muscle pain
pregnancy can cause
microcephaly,eye and
hearing birth defects
,impaired growth.GBS
Aedes mosquitoes Human Many countries and
territories
Chikungunya Fever,heqdache, Joint
pain,muscle pain,rash
Stooped appearance
due to severe joint
pain and swelling.
Aedes mosquitoes Humans Africa, Asia, Europe,
and the Indian and
Pacific Oceans.

37. Case 1
A 20 year-old Spanish man, travelled to Thailand to participate in a martial art competition. The
expected duration of the trip was a month and a half.Upon arriving in Thailand, he visited
Bangkok for two days where he stayed in a hotel. Then he travelled by bus to Surat Thani, and
on the same day he took the ferry to Koh Samui island. He stayed at bungalows in the beach
during all the stay. In Koh Samui, he was trained every day but he also visited rural areas, went
in the forest and visited waterfalls where was bitten by mosquitoes.
He developed fever. 24 hours after admmition his condition worsened .
Photophobia, vomiting and decreased level of consciousness occurred.
Physical examination revealed neck stiffness.

38. Case 1 contd…
48 hours later he presented with seizures, V and VII left peripheral nerves palsy with right
hemiparesis. Intubation and invasive mechanical ventilation were required.
Empiric treatment was initiated with ceftriaxone, doxycycline, aciclovir, dexamethasone and
phenytoin. After five days his condition worsened and did not respond to simple commands.
Initial full blood count, urine test and chest X-ray were normal. CT showed meningeal
enhancement.
Cerebrospinal fluid (CSF) analyses revealed a clear fluid with 960 leucocytes/mm3 (norm:
4,000–10,000/mm3) with 86% of mononuclear cells, and normal glucose and proteins.

39. Japnese Encephalitis

40. Case 2
History : A 56-year-old man admitted with high fever, headache, myalgia, arthralgia, retro-
orbital pain, and nausea that began two days earlier. On admission, he had body temperature
of 39°C and petechia in the lower limbs.
Investigation: His total leukocyte count decreased from 7,400 to 2,200 cells/mm3 , his
lymphocyte count decreased from 2,590 to 946 cells/mm3 , and his platelet count decreased
from 232,000 to 13,700 cells/mm3 .Serum albumin levels decreased from 4.9 to 3.1 g/dL. He
remained in the hospital for five days and had a fever for three days. His only hemorrhagic
manifestation was petechia in the lower limbs.

41. Dengue fever

42. Thank you