ARBOVIRUSES

(Arthropod-Borne viruses)

 Originally defined as:

“Viruses transmitted by arthropod (mainly insect) vectors”
 1985 W.H.O criteria:
“Arboviruses: those maintained in nature through biological transmission between
susceptible vertebrate hosts by haematopahous arthropods. They multiply and produce
viraemia in vertebrate, multiply in the tissues of arthropods and are passed on to new
vertebrates when arthropod takes a subsequent blood meal after a period of extrinsic
incubation.”
 International Catalogue of arboviruses
- The term “arbovirus” jas NO taxonomic significance
- 535 heterogenous groups of viruses
- Under 7 taxonomic families
- Many are zoonotic viruses that do not require an arthropod vector!

ARBOVIRUSES (This table is not complete!! I couldn’t type it out in time! Sorry!!!!!)

Toga Alphavirus
Ungrouped
Flavi Flavivirus
Bunya Bunya
Phlebo
Nairo
Uukuu
Hantavirus
Orbovirus
Unassigned
Vesiculovirus

SOME IMPORTANT ARBOVIRUSES

Family: Togaviridae

Genus: Alphavirus

No. of members: 28 (mosquito-borne)

Some important members:-

 Western equine encephalitis (WEE)

 Eastern equine encephalitis (EEE)
 Venezuelan equine encephalitis (VEE)
 Chikugunya
  Ross river

Genus: Rubivirus, spp. Rubella virus (not ar-bo)

Family: Flaviviridae

Genus: Flavivirus

Amount of members: ~80

Some important members:-

A. Mosquito-borne
- St. Louis encephalitis
- Japanese B encephalitis
- Murray Valley encephalitis
- Yellow Fever
- Dengue
- Ilheus
- West Nile
B. Tick-borne
- Louping ill
- Powassan
- Tick-borne encephalitis
- Kyasanur-Forest
- Omsk Haemorrhagic fever

Genus: Hepacivirus

Family: Bunyaviridae

Genus: Bunyavirus

Amount of members: 212

Some important members:

 La Crosse
 Snowshoe hare
 Oropouche

Genus: Phlebovirus

 Rift valley fever

 Punta Toro
 Sandfly fever
 Tascana

Genus: Nairovirus
  Crimeas-Congo haemorrhagic fever

Genus: Hantavirus

 Sin Nombre (not ar-bo)

Family: Rhabdoviridae

Genus: Lyssavirus

Species: rabies virus (not ar-bo), 1 serotype

Other spp: Lagosm Mokota, Duvenhage, Kotonkan, Obodhiang

Important diseases caused by Arboviruses:-

 Yellow fever
 Dengue / DHF
 Japanese encephalitis
 Rubella (not ar-bo)
 Hepatitis C (not ar-bo), also Hep-G
 Rabies (not ar-bo)

DENGUE & Dengue haemorrhagic gever & Dengue shock syndrome (DF, DHF, DSS)
History

 1780: Breakbone fever outbreak in Philadelphia, USA

 1800’s: sporadic outbreaks
 1934: Floridal 1945 – New Orleans
 1897: Australia – Clinical description of dengue complicated by haemorrhages, shock and
death in outnreaks
 1928 – Greece, 1931 – Formosa
 1903: Mosquito-borne transmission of infection by Aedes aegypti demonstrated.
 1944: Sabin
- Isolated virus
- Failure of 2 viral strains to cross protect humans
= evidence of serotypes
 1956: Hammond characterized 2 more
 After WWII: Start of a PENDEMIC with intensidied transmission of multiple viral serotypes in
SEAsia -> Outbreaks of DHF – DSS
 In last 2 decades – similar patterns of intensified transmission and  DHF-DSS in:
- SE Asia
- Americas
- Oceania
 Due to:
- Urbanization
- Population growth
 -  mobility
 If virus introduced into susceptible population (usually by viraemic travelers) epidemic attack
rates can reach 50-70%!!!
 Cross protective immunity among serotypes = LIMITED!
= Epidemic transmission recurs (Pak Nasa: actually, it doesn’t recur. It ‘occurs’) when novel
serotype introduced.
 Secondart infections predispose to DHF
= Virtually all DHF cases are in children with secondary infections
- Relative risk in secondary infection to develop DHF = 100x
 Infants (<1 year old) – DHF!
(Abs -> Maternal)
 DHF in primarily infected persons – rare and anecdotal. ? contributory role of viral strain &
host factors like rate, specific HLA type, etc
 DHA slightly predominant in
- Girls
- Well nourished children
 SEA
= Hyperendemic areas, dengue infection rate : 5-10%
= DHF incidence rate: 10-300/100,000
= DHF usually in children < 15 years, but age range is increasing
 World
= Population at risk: 3 billion
= 100 million dengue cases annually
= 500 thousand DHF cases annually

Cuba
 Early 1970’s
- A. aegypti neatly eradicated
- Control efforts decreased
 Late 70s – A. aegypti reestablished
 Before 1977 – Only D-2 & D-3 viruses (+), DHF (-)
 1977 – D-1 virus introduced
 1981- D-4 virus introfuced
 1981 – Novel D-2 strain introduced
- 116,143 hospitalizations = 10,000 DSS
 1997 - ? last outbreak after intense mosquito control programme!

Anecdotes:-

1. Transmission via accidental needlestick: 1

2. From BM donor: 1
From blood donors: ??

DENGUE
EPIDEMIOLOGY

 4 serotypes of dengue virus transmitted in tropics (DEN1, DEN2, DEN3, DEN4)

- Area between 35N & 35S (Latitude)
- Directly proportional to the distribution of A. aegypti
 Principal vector: A. aegypti
 Others:
- A. albopictus
- A. polynesiensi (Tahiti)
- A. scutellaris hebrideus (N. Guinea)
- A. cooki (Niue)
 Definitive host: Human
 Reservoir: Human
 So, it is NOT a zoonosis
 After feeding on viraemic patient, viral replication in mosquito = 1-2 weeks (extrinsic
incubation period)
 Feed: Several times during 1-4 weeks life span
 A.aegypti
- Breed around humans
- Oviposits in stagnant water
- Adults -> shelter indoor bite during 1-2 hours intervals in mornings and late afternoons
- In endemic areas, 1 in 20 mosquitoes infected
- 0.8 – 2.0 km flying distance
 Transmission in tropical areas maintained throughout the year and  during rainy season
  humidity,  lifespan
  temperature,  extrinsic incubation period

Pathogenesis

 Usually Dengue Fever – self-limited infection

 Bite -> tissues (2-3 days, hematogenous)
 Virus circulate for 4-5 days in:
- Infected monocytes & macrophages
- B cells
- T cells
 Fever – viraemia
 Fever , viraemia  1 day later
Typify DF - ? cytokine response
 Myalgia – cardinal feature of DF
Histophatological Exmination:
- Perivascular mononuclear infiltrate + lipid accumulation
- Some cases – mitochondrial changes + muscle necrosis
- CPK  (creatinine phosphokinase)
 Musculoskeletal pain (breakbone fever)
People wonder whether there is viral infection of bone marrow. Because:
 - Peripheral cytopenias
- Haemophagocytosis (+)
 Rash – lymphatic dermal vasculitis
  hepatic transaminases in 80%
Fatal cases
- Kuppfer cell hypertrophy
- Focal ballooning and necrosis of hepatocytes
- Mild fatty change
- Occasional councilman’s body
 Shock in DHF-DSS due t sudden extravasation of plasma into extravascular compartment
including pleura and abdominal cavity.
 Usually when fever has 
-  TNF
-  IL-8
-  IFN-gamma
- Complement activation
 Result: “loss” of fluid, and hypoproteinaemia/albuminaemia
 Reversal usually within 48 hours

Dengue Hemorrhagic Fever (DHF)

 Role of heterologous Abs in secondary infection

- Enchancing Abs
- i.e  uptake of virus and  replication in Fc-bearing cells
(Ab-mediated immune enhancement)
 TNF-alpha, CD8, IL-2
= Cross reactive CD4+ amd CD8+ cells 
= IFN-gamma  and IL-2 
 DHF -> Propensity after DEN-2 & DEN-3 infections (Pak Nasa: that’s for you to remember)

VIROLOGY

 Etiology
- Family: Arboviridae
- Genus: Flaviviridae
- Species: Dengue virus
- Serotypes: 4 (1,2,3,4)
 Virion
- Spheric/cubic
- 40-60 nm
- Consist of
i. Lipid enveolope
ii. Covered densely with surface projections (Membrane glycoproteins and
envelope glycoproteins)
- E gp (envelope glycoproteins) organized as dimmers paired horizontally head to tail on
virion surface
  Viruses – unstable, sensitive to:-
- Heat
- UV
- Disinfectants (alcohol, iodine, etc)
- Acid/low pH
- Ether & deoxycholate
 (+) ssRNA of 11kb
 E gp exhibits important biological properties
- Viral-cellular attachment
- Endosomal membrane fusion
- Site for hemagglutination and neutralization

Clinical Features of Dengue Fever

Acute febrile disease with:

 Headache
 Musculoskeletal pain
 Rash (Hess test)

80% asymptomatic in infants/children

If ill:

 Fever
 Malaise
 Irritability
 Pharyngeal injection (URTI)
 Rash

Adult:

 > Sever & > acute

 Chills, severe frontal headache
 Retro-orbital pain
 Severe musculoskeletal pain
 Severe lumbal back pain
 Skin flushed
 General signs and symptoms

Then fever 

Second episode of fever and symptoms recur -> SADDLEBACK PATTERN

Followed by:

 Listlessness
 Fatigability
  Depression

DHF-DSS

 Hemorrhagic phenomena
 Hypovolaemic shock
o (Usually after fever has )
 Effusion
i. Pleura (80%)
ii. Ascites (>95%)
iii. Gallbladder oedema (>95%)
iv. Peri/parerenal (77%)
v. Heptaic/splenic
vi. Pericardial
 -> Myocardial dysfunction, metabolic acidosis, respiratory distress -> death
 Fatality rate
- Up to 50%
- Least reported 1%
 Encephalopathy -> CNS hemorrhage
 Liver & Renal failure

Laboratory Diagnosis

 Viral isolation
- 1st week after onset
- Serotype (Personal health reasons)
 Specimen
- Biopsy
- Autopsy
 Culture
- Suckling mice
- Mosquito cell lines (C6/36, AP61
- Vero
- LLCMK2
- PS, etc
 PCR
 Serology
- Blood/serum
- CSF
- Elisa (IgM, IgG)
i. 7-10 days after onset: 95% sensitive
ii. IgM & IgG -> 100% (as early as 4-5 days)
 Other tests
- IIF
- HA
Treatment

 Symptomatic
 Supportive

Prevention

 Mainstay
- Public health
- Personal (home)

Public Health

 Insecticidal fogging (? Usefulness)

 Vaccine – under development