Mosquito Borne Viruses & Hantavirus

Question 1

Examples of mosquito borne viruses + hantavirus

Answer 1

1. Dengue virus (flavivirus)
2. Alphavirus (Chikungunya) (togavirus)
3. Japanese encephalitis (flavivirus)
4. Hantavirus (bunyavirus)

Question 2

Structure of dengue virus

Answer 2

• enveloped, with glycoprotein containing antigenic determinants - group specific, subgroup specific & type specific
• spherical virion, ssRNA
• 4 serotypes/subgroups

Question 3

Epidemiology of dengue virus

Answer 3

• Aedes aegypti is the main vector, also Aedes albopictus

- man is the main reservoir, man-mosquito-man transmission

Question 4

Pathophysiology of dengue

Answer 4

1. First infection
   - primary type antibody response
   - neutralising IgM production against type specific antigens - IgG production - patient immune to infecting dengue serotypes, partial protection (3-6w) against other serotypes (cross reactive Abs)
2. Second infection
   - IgG predominant, infection enhancing
   - patient protected against clinical disease subsequently
3. Deposited in skin by biting mosquito vector - replicates at site of infection & local lymphatic tissue - viremia (up to 4-5 day after onset of symptoms) - virus replicates in mononuclear phagocytes

Question 5

Clinical presentations of dengue virus

Answer 5

• can be asymptomatic or symptomatic
  1. Undifferentiated fever (infants, young children)
  2. Dengue fever
  3. Dengue hemorrhagic fever/dengue shock syndrome

Question 6

Features of dengue fever

Answer 6

• abrupt onset of high fever
• severe headache
• retro-orbital pain
• muscle & joint pains
• rash

Question 7

Features of dengue haemorrhagic fever/dengue shock syndrome

Answer 7

• fever (acute onset, high, continuous, 2-7 d)
• haemorrhagic manifestations: positive tourniquet test - petechiae (do not blanch), purpura, ecchymosis, epistaxis, gum bleeding, haematemesis, melaena
• enlargement of liver
• DSS - rapid & weak pulse w narrowing of pulse pressure/hypotension w cold clammy skin & restlessness (inadequate perfusion to brain)
• DSS - occurs at time of/shortly after fall in temp (3-7d), acute abdominal pain shortly before onset of shock, warning signs of shocl - restlessness/lethargy, acute abdominal pain, cold extremities, skin congestion, oliguria

Question 8

Pathogenesis of dengue haemorrhagic fever/dengue shock syndrome

Answer 8

1. Viral virulence - varied strains in terms of pathogenic potential
2. Immune enhancement involving infection-enhancing antibodies
   - DSS seen in (A) infants 1yr w 2nd dengue inf
   - in (A) - infants in first 6m protected by maternal, neutralizing Abs - as maternal IgG degrades - dengue neutralising Abs decrease to below protective level (relatively, Abs w enhancing activity reach peak)
   - in (B) - non neutralising Abs from immune complexes w replicating virus, attach to Fc receptors on mononuclear phagocytes, complex internalised, virus continues to replicate in infected cell, mobile cell spreads infection - infection activates phagocytes - release cytokines etc - increase vasc perm & disorder in haemostasis

Question 9

Diagnosis of dengue virus (4)

Answer 9

1. Virus isolation - live mosquitoes, cell cultures
2. Serology - haemagglutination inhibition test; IgM & IgG ELISA; NS1 Ag - ELISA (viraemia)
3. RT-PCR - serum (viraemia)
4. FBC - DHF/DSS - thrombocytopaenia (<100,000/mm3), haemoconcentration due to loss of plasma (vasc perm) - increased haematocrit

Question 10

Treatment of dengue virus (3)

Answer 10

1. Live attenuated tetravalent vaccine - in clinical trial
2. Control of vector mosquitoes - source reduction, adulticiding, health ed, law enforcement
3. DSS/DHF - increased vasc perm - plasma leakage - correct by vol replacement - infuse plasma/plasma expander/electrolyte solution
   - symptomatic treatment - avoid salicylates (cause bleeding), use paracetamol

Question 11

Features of chikungunya fever

Answer 11

• alpha virus transmitted by bite of Aedes aegypti & Aedes albopictus
• endemic in Indian subcontinent, outbreaks in Malaysia, Italy

Question 12

Symptoms of chikungunya fever

Answer 12

• fever
• skin rash
• arthralgia (joint pain)
• arthritis
• photophobia

Question 13

Diagnosis of chikungunya fever (2)

Answer 13

1. RT-PCR
2. Serology

to differentiate from dengue: 1. Serology 2. Positive travel history + tend to present more with severe joint pain, dengue more with muscle aches (but not definitive)

Question 14

Epidemiology of Japanese encephalitis

Answer 14

• majority of infections inapparent
• mainly in children < 15 years
• epidemics in India, Thailand, Vietnam, China
• transmitted among mosquitoes & vertebrate hosts - Culex tritaeniorhynchus & Culex gelidus; vertebrate hosts are amplifying hosts mainly domestic pigs & wading birds

Question 15

Pathogenesis of Japanese encephalitis

Answer 15

• Bite by infected mosquito - virus replicates locally in skin/lymphatics/endothelium of blood vessels - transient viraemia
• if viraemia terminates before virus penetrates brain/virus destroys sufficient brain cells to produce overt encephalitis - infection will be asymptomatic/non-encephalitic, generalized, febrile illness
• enters nervous system by - capillary seeding through endothelium into meninges & brain OR inf of nerve endings

Question 16

Symptoms of Japanese encephalitis (5)

Answer 16

1. Abrupt onset w fever, headache, malaise, drowsiness, vomiting, generalised convulsions
2. Marked & increasing disturbances of sensorium & signs of meningeal irritation (neck rigidity, positive Kernig’s sign)
3. CSF abnormalities - pleocytosis, elevated glucose content, raised protein
4. Histopathology of brain: destruction of neurons & glial cells, perivascular infiltration with lymphocytes, sometimes local haemorrhage
5. Motor weakness, mental backwardness, behaviour disorders

Question 17

Diagnosis of Japanese encephalitis

Answer 17

Detect IgM from CSF during encephalitis - ELISA

Question 18

Treatment of Japanese encephalitis

Answer 18

Inactivated vaccines from infected mouse brain

Question 19

Structure of hantavirus

Answer 19

Enveloped, spherical virion with trisegmented ssRNA

Question 20

Variations of hantavirus

Answer 20

• Hantaan, Seoul, Puumala, Dobrava (HFRS)
• Sin Nombre (HPS)
• Prospect Hill (not associated with disease)

Question 21

Transmission of hantavirus

Answer 21

• virus transmitted to humans by infected rodents
• infection in rodents - asymptomatic & lifelong, shed in saliva, urine, faeces
• transmission predominantly after infected rodent excreta are inhaled

Question 22

Clinical presentation of hantavirus (2)

Answer 22

1. Haemorrhagic Fever with Renal Syndrome (HFRS)

2. Hantavirus Pulmonary Syndrome (HPS)

Question 23

Features of haemorrhagic fever with renal syndrome

Answer 23

• Mild to severe (esp in Korea, China, Balkans - Dobrava virus)
• Mild HFRS in Europe is also nephropathia epidemica (Puumala virus)
• Phases of severe clinical course:
  1. Febrile - Sudden onset with influenza-like symptoms, petechiae, conjunctival haemorrhage
  2. Hypotensive - 3-7d later - tachycardia, vomiting, shock, further haemorrhagic signs - haemoconcentration, thrombocytopaenia, leukocytosis
  3. Oliguric - hypotension, severe hemorrhage, abnormal renal fn, most deaths in this phase
  4. Diuretic - +/- electrolyte imbalance
  5. Convalescent - prolonged

Question 24

Features of hantavirus pulmonary syndrome

Answer 24

• fever, myalgia, variable respi symptoms eg-cough

- followed by abrupt onset of acute respiratory distress

Question 25

Diagnosis of hantavirus pulmonary syndrome

Answer 25

Detection of antibody (IgM & total) by indirect IF assay & ELISA