Arboviruses

Definition
• Definition: echobiological enthity, having
different families:
• flaviviridae-,
• toga-,
• bunyav-
• reov- şi
• Rhabdoviridae,
• that need vectors for transmission
(mosquitos, flies, etc).
• Pathogenesis

• Arboviruses induce high titres of viraemia in susceptible

vertebrates 1-2 days after parenteral inoculation or
following bites by infected arthropods;
• viraemia persists for several days and serves as a source
of infective blood meals for other biting arthropods.
• The primary site of virus replication is not known but is
likely to be in the reticulo- endothelial cells in lymph
nodes, liver and spleen or endothelial cells of blood
vessels.
• Release of virus from these sites may be associated with
non-specific 'flu-like' symptoms.
• During this period of viraemia (usually at about 5-7 days
after exposure) virus enters the target sites of the central
nervous system, skin, etc.
• There may be a brief period of relief after the initial
symptoms - before the onset of the specific features.
• Thus, the presentation is a biphasic illness.
• Symptoms of encephalitis begin 7 -10 days after exposure
to infection and persist 1 week or more, followed either by
remission or by death.
• Wild birds and mammals regularly exhibit viraemia without
symptoms.
• Antibodies are first detected when the fever
subsides, usually within 2 days after the onset
of encepbalitis, and persist for many years.
• Antibodies are of the IgM class for 1- 7 weeks
after infection, subsequently they are of the
IgG class.
• CLINICAL FEATURES
• Arbovirus infections of humans become clinically
manifest according to the target organ principally
infected.
• These include the following syndromes:
- Encephalitis
- Yellow fever
- Dengue fever and dengue haemorrhagic fever
- Miscellaneous tropical fevers
- Undeferrentiated fever
 Encephalitis
• Characteristically, the cerebrospinal fluid shows
pleocytosis with a predominance of leucocytes,
but sugar and protein levels remain normal.
• The peripheral blood leucocyte count usually
does not exceed 8000 x 106/l and shows a
predominance of leucocytes.
• During most outbreaks of arboviral encephalitis,
a proportion of cases develop aseptic meningitis
only, without significant neuronal involvement.
• Dengue
• This presents as an acute febrile illness with chills, headache, retro-
ocular pain, body aches and arthralgia in more than 90% of cases,
accompanied by nausea or vomiting and a maculo- papular rash
resembling measles lasting 2-7 d in about 60% of cases.
• Illness usually persists for 7 days or longer, with fever remitting
after 3-5 d followed by relapse ('saddleback. fever'), and pains in
the bones, muscles and joints sufficiently severe to earn the epithet
'breakbone fever' .
• Rash occurs more commonly in patients aged less than 14 years.
• The incubation period is 5-11 days.
• Dengue Haemorrhagic fever
• This is a less common manifestation of dengue, affecting mainly children.
• It is occasionally accompanied by a shock syndrome with a case fatality
rate of 50%.
• After an acute onset, fever of 40°C, accompanied by vomiting and
anorexia, enlarged liver and petechiae persists for 5-10 d. This is followed
by a complete recovery unless shock supervenes; this occurs in 7-10% of
cases from 2 to 7 d after onset, usually accompanied by haematemesis
and melaena.
• Although dengue baemorrhagic fever with shock syndrome was initially
recognized in South-East Asia in 1951, it has since occurred in the south-
west Pacific, Puerto Rico and Cuba.
• Sindbis virus
• SYNONYM OR CROSS REFERENCE: Epidemic polyarthritis
and rash, Sindbis virus disease,
• CHARACTERISTICS: Family Togaviridae, genus
Alphavirus;
• enveloped virions icosahedral with 40-70 nm diameter,
single-stranded, positive-sense RNA genome
• PATHOGENICITY: Self-limiting febrile viral disease.
• Sudden onset of fever, rash, arthralgia or arthritis, lassitude,
headache and myalgia; rash may precede or follow joint
manifestations by 1-2 days ;
• exanthem on trunk progressing to face, legs, palm, soles and lasts
on average 10 days;
• signs of jaundice and myocardial damage are reported but rare;
often no recognized clinical disease manifestations.
• EPIDEMIOLOGY: Common in Africa, Asia,
Australia, Middle East, Eastern Europe,
Scandinavia and the Commonwealth of
Independent States
• HOST RANGE: Humans, mammals, birds
• INFECTIOUS DOSE: Not known
• MODE OF TRANSMISSION: By the bite of an infectious mosquito
• INCUBATION PERIOD: less than 7 days
• COMMUNICABILITY: No evidence of person-to-person transmission
documented
• RESERVOIR: Birds
• ZOONOSIS: by the bite of an infected mosquito
• VECTORS: Mosquitoes (Anopheles, Aedes, Culex and Culista spp.)
• DRUG SUSCEPTIBILITY: No specific antiviral available to date
• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 70% ethanol, 1%
sodium hypochlorite, 2% glutaraldehyde, organic solvents/detergents
• PHYSICAL INACTIVATION: Sensitive to heat, UV and gamma irradiation and
freezing
• SURVIVAL OUTSIDE HOST: Survives in blood up to 2 days at room
temperature
• SURVEILLANCE: Monitor for symptoms; confirm by serological analysis
• FIRST AID/TREATMENT: Mainly supportive therapy
• IMMUNIZATION: None available
• PROPHYLAXIS: None available
• Eastern equine encephalitis virus, Western equine
encephalitis virus
• SYNONYM OR CROSS REFERENCE: Eastern equine
encephalomyelitis, Western equine encephalomyelitis, EEE,
WEE, arbovirus
• CHARACTERISTICS: 60 - 70 nm diameter, posititive ssRNA,
enveloped; Togaviridae, Genus Alphavirus
• PATHOGENICITY: Acute inflammatory disease of short
duration involving brain, spinal cord, and meninges;
• EEE mild cases often occur as febrile headache or aseptic meningitis; severe
infections are marked by acute onset, headache, high fever, meningeal signs,
stupor, disorientation, coma, tremors, occasional spastic convulsions and
paralysis; up to 60% case fatality rate;
• WEE infections are asymptomatic or present as mild, nonspecific illness, mortality
rate is about 3%
• EPIDEMIOLOGY: EEE in eastern and north central USA and
Canada, scattered areas of Central and South America and in
Caribbean; WEE in western and central USA, Canada and
parts of South America (Argentina); cases occur in temperate
latitudes in summer and early fall, and are limited to areas
and years of high temperature and many mosquitoes
• HOST RANGE: Humans, horses, other animals, birds
• INFECTIOUS DOSE: Unknown
• MODE OF TRANSMISSION: By the bite of infective mosquitoes
• INCUBATION PERIOD: Usually 5 to 15 days
• COMMUNICABILITY: Not directly transmitted from person-to-
person;
• virus is usually not demonstrated in blood or CSF of humans
after onset of disease;
• viremia in birds lasts 2 to 5 days;
• mosquitoes are infective for life, possible vertical
transmission (female to egg);
• viremia in horses rarely present in high titres for long periods
• RESERVOIR: Humans and horses are uncommon sources of
mosquito infection;
• virus overwinters possibly in birds, other animals (rodents,
bats, reptiles, amphibians), surviving mosquito eggs or adults
(true reservoir unknown)
• ZOONOSIS: Yes, from infected animals / birds via mosquitoes

• VECTORS: EEE - Culiseta melanura ( USA and Canada) (bird to bird)

- Aedes, Coquillettidia spp. (bird or animal to humans)
• WEE - Culex tarsalis (Western USA and Canada) (major epidemic
vector)
- found in at least 5 genera of mosquitoes

• DRUG SUSCEPTIBILITY: no treatment available

• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to disinfectants -
1% sodium hypochlorite, 2% glutaraldehyde, formaldehyde, 70%
ethanol
• PHYSICAL INACTIVATION: Sensitive to moist and dry heat, drying
• SURVIVAL OUTSIDE HOST: Does not survive outside of host
• SURVEILLANCE: Monitor for symptoms of arthropod-borne viral fever;
serological identification and antibody titre, PCR, ELISA

• FIRST AID/TREATMENT: No specific treatment

• IMMUNIZATION: Investigational vaccines available and recommended for

personnel who work directly and regularly with EEE and WEE in laboratory
• PROPHYLAXIS: WEE immune globulin (human) available but efficacy of
product has not been established
• SPILLS: Allow aerosols to settle;
• wearing protective clothing, gently cover spill with paper towel and apply 1% sodium hypochlorite, starting at
perimeter and working towards the centre; allow sufficient contact time before clean up (30 min)
• DISPOSAL: Decontaminate before disposal; steam sterilization, incineration
• STORAGE: In sealed containers that are appropriately labelled (in locked level 3 facility)
 Crimean-Congo hemorrhagic fever
virus
• SYNONYM OR CROSS REFERENCE: CCHF, Central Asian hemorrhagic fever
• CHARACTERISTICS: Bunyaviridae, Nairovirus group, spherical, enveloped
virion 85-100 nm in diameter, genome contains 3 segments of single-
stranded, negative-sense RNA.

• PATHOGENICITY: Sudden onset of fever, malaise, weakness, irritability, headache,

severe pain in the limbs and loins and marked anorexia; vomiting, abdominal pains and
diarrhea may occur;
• hemorrhagic enanthem of soft palate, uvula and pharynx and a petechial rash are
generally associated with the disease;
• bleeding from the gums, nose, lungs, uterus, intestine can occur, in some cases
associated with liver damage and death due loss of blood;
• case fatality rate ranges from 2 to 50%
• EPIDEMIOLOGY: Observed in western Crimea, Kersch Peninsula,
Kazakstan and Uzbekistan, Rostov and Astrakhan regions of Russia;
also found in Bosnia-Herzogovina, Albania, Bulgaria, Iraq, the
Arabian Peninsula, Pakistan, western China, tropical Africa and
South Africa;
• high risk individuals includes animal husbandry workers and medical
personnel
• HOST RANGE: Humans, birds, ticks (Hyalomma spp. in Eurasia and
South Africa), domestic animals, rodents, and mosquitoes
• INFECTIOUS DOSE: Not known
• MODE OF TRANSMISSION: By the bite of an infective adult tick
(Hyalomma spp.);
• nosocomial outbreaks have occurred due to exposure to blood and
secretions;
• infections also associated with slaughtering infected animals.
• INCUBATION PERIOD: Usually 1 to 3 days (Range
1 to 12 days)
• COMMUNICABILITY: Highly infectious, especially
through the nosocomial route.
• Infective ticks remain so for life
• RESERVOIR: Hares, birds, ticks, rodents, domestic
animals
• ZOONOSIS: Yes - can be acquired from infected
animals
• VECTORS: Ticks (Hyalomma spp.)
• DRUG SUSCEPTIBILITY: Sensitive to ribavirin
• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% hypochlorite, 2%
glutaraldehyde
• PHYSICAL INACTIVATION: Sensitive to heating at 56°C for 30 min
• SURVIVAL OUTSIDE HOST: Virus stable in blood up to 10 days at 40°C
• SURVEILLANCE: Monitor for symptoms; confirm by serological analysis
and virus isolation from blood sample

• FIRST AID/TREATMENT: Administer supportive therapy. Ribavirin may be

effective
• convalescent plasma with high neutralizing antibody titre shown to be
beneficial
• IMMUNIZATION: None available
• PROPHYLAXIS: Convalescent plasma with high neutralizing antibody titre
shown to be beneficial
 Dengue fever virus
(DEN 1, DEN 2, DEN 3, DEN 4)
• SYNONYM OR CROSS REFERENCE: Dengue fever, breakbone fever,
Dengue hemorrhagic fever (DHF), Dengue shock syndrome (DSS)

• CHARACTERISTICS: Spherical enveloped virion 40-50 nm in diameter;

single-stranded, positive sense RNA genome surrounded by an
icosahedral nucleo capsid; Flaviridae (Flavivirus)

• PATHOGENICITY: An acute febrile disease characterized by the

sudden onset of fever for 3 to 5 days, with an intense headache,
myalgia, arthralgia, retro-orbital pain, anorexia and rash, symptoms
are usually self-limiting;
• dengue hemorrhagic fever, a more severe manifestation on second
exposure is characterized by abnormal vascular permeability, hypo-
volemia and abnormal clotting mechanisms;
• fatality as high as 40-50%
• EPIDEMIOLOGY: Endemic in most regions of the tropics (Asia, India, Caribbean, Africa,
Central and South America, and Mexico); maintained mostly by a human-mosquito-
human cycle; non-human primate infection common in West Africa
• HOST RANGE: Humans, mosquitoes (as a vector, Aedes spp., Stegomyia spp.) and non-
human primates
• INFECTIOUS DOSE: Not known

• MODE OF TRANSMISSION: By bite of infectious mosquitoes mainly Aedes aegypti; most

bites occur during the 2 hours after sunrise and several hours before sunset: vertical
transmission (infected progeny) does occur, however it is relatively low

• INCUBATION PERIOD: From 3 to 14 days; usually 4 to 7 days

• COMMUNICABILITY: Not directly transmitted from person-to-person; patient infectious
for mosquitoes from shortly before to the end of the febrile period, usually 3 to 5 days:
mosquitoes infectious 8 to 12 days after blood meal and remains so for life.
• RESERVOIR: Humans, mosquitoes (transovarial transmission - extremely
high levels of infectious particles in salivary glands);
• monkey-mosquito cycles common in West Africa and Southeast Asia
• ZOONOSIS: None
• VECTORS: Mosquitoes (Aedes aegypti and other Aedes spp.): eggs of A.
aeypti can withstand long periods of dessication, up to 1 year
• DRUG SUSCEPTIBILITY: No specific antivirals
• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to common
disinfectants; 70% ethanol, 1% sodium hypochlorite, 2% glutaraldehyde
• PHYSICAL INACTIVATION: Sensitive to heat: low pH inactivates dengue
virus
• SURVIVAL OUTSIDE HOST: Virus stable in dried blood
and exudates up to several days at room temperature
• SURVEILLANCE: Monitor for symptoms; confirm
serologically and by isolating virus
• FIRST AID/TREATMENT: No specific treatment,
however no salicylates and maintain adequate
hydration
• IMMUNIZATION: None available
• PROPHYLAXIS: None available
 Yellow fever virus

•  
• SYNONYM OR CROSS REFERENCE: Arbovirus, Yellow fever, YF
• CHARACTERISTICS: Flaviviridae (Flavivirus); 40-50 nm diameter,
ssRNA, enveloped virus

• PATHOGENICITY: acute disease of short duration and varying

severity;
• sudden onset fever, aches, prostration, nausea, vomiting;
• weakened pulse, albuminuria, anuria, leukopenia;
• hemorrhagic symptoms;
• jaundice;
• <5% case fatality rate among indigenous population in endemic
areas, but may reach 50% among non-indigenous groups or in
epidemics
• EPIDEMILOLOGY:
• No cases of urban yellow fever in Americas since 1942;
• urban cases reported in Africa where jungle or sylvan yellow fever is enzootic;
• sylvan yellow fever of tropical America now occurs among adult males who are
exposed in the forest - enzootic in South America, no yellow fever in Asia or
eastern most coast of Africa;
• there have been two cases of fatal yellow fever imported into the USA 1996,1999

• HOST RANGE: Humans, monkeys, other primates, possibly

marsupials
• INFECTIOUS DOSE: Unknown
• MODE OF TRANSMISSION: By bite of infective mosquitos;
virus is transmitted from monkeys to humans
• INCUBATION PERIOD: three to 6 days
• COMMUNICABILITY: Blood is infective for mosquitoes shortly
before onset of fever and first 3 to 5 days of illness;
• highly communicable where many susceptible persons and
vectors coexist;
• not communicable by contact or common vehicles;
• mosquitos become-infective after 9 to 12 days and remain so
for life
• RESERVOIR:
- urban areas - humans, mosquitoes;
- forest areas - vertebrates other than humans (mainly
monkeys) and possibly marsupials, forest mosquitos;
transovarial transmission in mosquitos contributes to
maintenance of infection
• ZOONOSIS: Yes (jungle yellow fever)
• VECTORS:
• Urban areas - Aedes aegypti mosquitoes; South America forests -
Haemogogus (sylvan mosquitoes); East Africa - Aedes africanus (monkeys);
Aedes bromeliae (Ae. simpsoni) (monkey to humans); West Africa - Ae.
furcifertaylori, Ae. luteocephalus (monkeys to humans)

• DRUG SUSCEPTIBILITY: N/A

• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to many disinfectants - 1%
sodium hypochlorite, 2% glutaraldehyde, 70% ethanol, 3-8% formaldehyde,
2-3% hydrogen peroxide, 1% iodine and phenol iodofors; also susceptible to
organic solvents and detergents due to lipid envelope; 0.1% formalin - 48
hours
• PHYSICAL INACTIVATION: Heating at 60° C for 10 min; ; UV and gamma
irradiation
• SURVIVAL OUTSIDE HOST: Does not survive out of host
• SURVEILLANCE: Monitor for febrile illness: demonstration of viral
antigen in blood using serological techniques, rise in antibody titre
• FIRST AID/TREATMENT: No specific treatment

• IMMUNIZATION: Licensed attenuated live vaccine recommended

for all personnel who work with agents or infected animals, and
those who enter rooms where agents or infected animals are
present;
• the vaccine is contra-indicated to those who are immunosup-
pressed, who have known anaphylaxis to the ingestion of eggs, who
are taking corticosteroids, and who are pregnant;
• vaccine is heat sensitive and should be stored between 5° C and -
30° C in it's un-reconstituted form
• PROPHYLAXIS: None
 ARENAVIRUSES :
Lymphocytic choriomeningitis virus
• SYNONYM OR CROSS REFERENCE: LCM, lymphocytic meningitis

• CHARACTERISTICS: Arenaviridae; ssRNA, enveloped, 50-150 nm diameter

• PATHOGENICITY: Biphasic febrile illness, diversity of clinical manifestations -

mild influenza-like illness or occasionally, meningeal or
meningoencephalomyelitic symptoms, transverse myelitis, a Guillain-Barre-
type syndrome; orchitis or parotitis;
• usually short duration;
• no chronic infection, infection asymptomatic in one third of individuals;
• rarely fatal, mortality <1%, recovery from severe disease without sequelae
in most cases;
• temporary or permanent neurological damage is possible;
• pregnancy-related infection has been associated with abortion, congenital
hydrocephalus, chorioretinitis and mental retardation
•  
• EPIDEMIOLOGY: Initially isolated in 1933;
• prevalence in humans 2-10%;
• individuals of all ages are susceptible, infrequent occurrence, sporadic
cases have been reported;
• outbreaks have occurred from infected pet hamsters or laboratory
animals;
• cases reported in Europe, the Americas, Australia and Japan
• HOST RANGE: Humans, guinea pigs, hamsters, mice,
monkeys
• INFECTIOUS DOSE: Unknown
•  
• MODE OF TRANSMISSION: Infected mice excrete virus in saliva,
urine and feces;
• man is infected through inhalation of infectious aerosolized particles
of rodent urine, feces or saliva, food contaminated with virus,
contamination of mucus membranes, skin lesions or cuts with
infected body fluids
• INCUBATION PERIOD: 8-13 days; 15-21 days (meningeal symptoms)
• COMMUNICABILITY: No evidence of person to person spread;
vertical transmission from mother to child is possible
• RESERVOIR: House mouse (Mus musculus) - virus is harboured
throughout life of mouse and transmitted to offspring which
become healthy carriers;
• natural infections also occur in non-human primates (including
macaques and marmosets), swine, dogs, hamsters, guinea pigs
• ZOONOSIS: Yes VECTORS: None
• DRUG SUSCEPTIBILITY: evidence of ribavirin susceptibility from in
vitro studies
• SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% sodium
hypochlorite, 2% glutaraldehyde, 70% ethanol, formaldehyde
• PHYSICAL INACTIVATION: Sensitive to heat inactivation
• SURVIVAL OUTSIDE HOST: Virus survives out of host - mice
droppings
• SURVEILLANCE: Monitor for symptoms; confirmation by virus
isolation, serology
• FIRST AID/TREATMENT: No specific treatment; anti-inflammatory
drugs may be useful
• IMMUNIZATION: None available
• PROPHYLAXIS: None available
 LABORATORY DIAGNOSIS
• Diagnosis of arbovirus infections depends on the isolation of
virus from blood, cerebrospinal fluid or tissues, or on
serology.
• Whenever possible, attempts should be channelled towards
virus isolation, especially in febrile illnesses.
• Virus isolation
• The causative virus can be isolated from blood collected
during the initial 3 d febrile illness induced by serotypes such
as dengue, Ross River and yellow fever, when viraemia titres
are maximum.
• Collect cerebrospinal fluid or brain biopsy during life, or
brain at autopsy of fatal cases of encephalitis.
• Obtain liver from fatal cases of yellow feyer .
• The isolation procedures are as follows:
• Inoculate mammalian tissue cultures, e.g. continuous
polyploid grivet monkey kidney (Vero) or baby
hamster kidney (BHK) and incubate at 37°C under
agarose overlay until plaques appear after 7-14 d.
• Determine the serotype in an extract of an excised
plaque by neutralization, immuno- fluorescence or
ELISA tests using appropriate monoclonal antibodies.
• Inoculate continuous cultures of Aydes albopictus
mosquito cells and incubate at 28°C for up to 10
days;
• examine cells for arbovirus antigen by immuno-
fluorescence.
• Inoculate acute-phase blood from dengue patients
intrathoracicaly into male mosquitoes and incubate
at 30°C for 14 d.
• Detect viral antigen in head squashes by direct
immunofluorescence.
• Inoculate acute-phase blood, or brain or liver
suspensions, intracerebrally into suckling mice
aged less than 48 h and examine daily up to 14 d
for development of encephalitis (hunching, rumed fur,
convulsions, spasticity and, eventually, death).
• Remove brains from moribund mice and perform
preliminary serogrouping by haemagglutination
inhition tests on sucrose-acetone extracts of brain suspension,
followed by final serotypic identification by
neutralisation tests in suckling mice or by plaque
reduction in Vero or BHK tissue cultures.
 Serology

• Serological tests frequently offer the only available means of laboratory

diagnosis of encephalitis.
• The detection of a four-fold or greater rise of antibody titre by haemag-
glutinin isolation or ELISA tests on paired sera collected during the initial
week and several days later after defervescence provide good evidence of
concurrent infection.
• Antibodies detected by complement fixation first appear 2 or more weeks
after onset and become undetectable by 3 years.
• Serotype- specific IgM antibody may be detected within 1-3 days after
onset using an IgM capture ELISA test.
• IgM antibody wanes 6 weeks after onset and is replaced by IgG
antibodies.