Lecture 3 - Arboviruses

Question 1

What’s a description for viruses that are transmitted between vertebrate hosts by insects?

Answer 1

Arthropod-borne viruses (Arboviruses).

Question 2

A few arboviruses have evolved to use humans as ‘natural hosts’, but what’s a disadvantage of using humans?

Answer 2

Humans are infected ‘dead-end hosts’and do not transmit the disease.

Question 3

What cell types do arboviruses replicate in?

Answer 3

In endothelial cells and macrophage/monocyte lineage cells.

Question 4

From which two main families do mosquito-borne arboviruses consist of?

Answer 4

Family Togaviridae

Family Bunyaviridae

Question 5

The family Togaviridae has two genus types: genus flavivirus and genus alphavirus.

Which known diseases exist from these genus types?

Answer 5

Genus flavivirus: Dengue,Yellow fever, Japanese encephalitis, West Nile Fever, Zika, etc.

Genus alphavirus: Chikungunya, O’nyong nyong, encephalitis, Ross River virus.

Question 6

The family Bunyaviridae consist of two genus types: genus bunyavirus and genus phlebovirus.

To which genus type does Rift Valley Fever belong?

Answer 6

To Genus Phlebovirus.

Question 7

How is the time between blood-feeding and transmission called?

Which factors make this time vary?

Answer 7

Extrinsic incubation period.

It varies with virus, temperature, mosquito spp., etc. Generally 8-14 days in warm climates.

Question 8

The majority of human infections with arboviruses are asymptomatic or cause a mild non-specific febrile illness. When an arbovirus causes disease, it usually leads to one of three clinical syndromes.

Name these clinical syndromes.

Answer 8

1. Fever-Arthralgia-Rash (FAR)
2. Viral Haemorrhagic Fever (VHF)
3. Central Nervous System infection e.g. encephalitis

Note: there can be overlap of these clinical syndromes:

Dengue: FAR, VHF and CNS.

West Nile Virus: CNS and FAR.

Question 9

What is the most common arbovirus?

Answer 9

Dengue.

Question 10

Over the past 50 years, the prevalence of Dengue has increased dramatically. Why is that?

Answer 10

Because of increased human travel, overcrowding populations (refugees; urban areas), transport of car tyres and poor control/expansion of vector.

Question 11

There are four dengue serotypes (DEN-1 to -4). Do you have lifelong immunity against all serotypes if you’re infected by one serotype because of cross-immunity? Why or why not?

Answer 11

You have lifelong immunity against the serotype you got infected from.

Cross-immunity to other serotypes after recovery is only partial and temporary.

Question 12

Subsequent infections by other serotypes increase the risk of developing severe dengue. Because of what mechanism is that?

Answer 12

Antibody-dependant enhancement.

Question 13

Aedes mosquitors are ‘peri-domestic’. What does this mean?

Answer 13

• They breed in collections of fresh water around the house.
• The feed on humans (anthrophilic), mainly by day.
• They feed repeatedly on different hosts (enhancing their role as vectors).

Question 14

Clinical features can be asymptomic but what are specific features of dengue fever?

Answer 14

Fever, Arthralgia and Rash syndrome with retro-orbital pain, photophobia, lymphadenopathy.

In addition there may be petechiae and other bleedings in gum, etc.

Symptoms usually last 2-7 days after incubation period of 4-10 days.

Question 15

Why is severe dengue haemorrhagic fever a potentially deadly complication?

Answer 15

Due to plasma leaking –> fluid accumulation (oedema and effusions), ARDS, severe bleeding, or organ impairment (elevated hematocrit).

In addition, there is thrombocytopenia and haemorrhagic manifestations (GI-bleeding).

Question 16

Classification of dengue: dengue with or without warning signs, and severe dengue. Warning signs occur 3-7 days after first symptoms in conjunction with a decrease in temperature.

Name a few warning signs.

Answer 16

Abdominal pain or tenderness, persistent vomiting, fluid accumulation, mucosal bleeding, lethargy, liver enlargement, or increase in hematocrit.

Question 17

Which 2 mechanisms can be used to describe the pathogenesis of DHF?

Answer 17

1. Antibody-dependent enhancement
2. Viral strain differences e.g. increased virulence of Asian strains of DEN-2

Question 18

Why is it harder to make vaccines for dengue?

Answer 18

Antibody-dependent enhancement: the immune enhancement by non-neutralizing antibody complicates the prospects for vaccine development.

Question 19

Explain the treatment for dengue.

Answer 19

There’s no specific treatment for dengue fever. Just resting.

For severe dengue: medical care by medical staff experienced with the effects and progression of the disease can save lives.

Maintenance of the patient’s body fluid volume is critical to severe dengue care.

Question 20

What are a couple characteristics of Aedes aegypti and albopticus?

Answer 20

• Anthrophilic, peridomestic
• Repeatedly day biting
• Breed rapidly in tiny water pools
• Vertical transmission of virus
• Breeding sites: tyres, water containers, etc.
• Eggs often laid above water surface.

Question 21

Name the vaccine for dengue that gave these results: 50% efficacy for case reduction (but lower protection against serotype 2), 80% less severe disease, has potential and complex immunology.

Also, describe how they made this vaccine (from which fever it is derived).

Answer 21

The live attenuated vaccine.

It’s chimeric, derived from yellow fever attenuated 17D. The pre-membrane and envelope genes were replaced with those from each four dengue serotypes.

Question 22

Yellow fever:

Between who is it transmitted?

Which insect transmit virus to humans?

Answer 22

YF virus is transmitted between primates by various mosquitos.

Aedes aegypti transmits the virus to humans in urban cycles.

Question 23

Which vaccine is used in yellow fever?

Answer 23

The highly effective 17D live attenuated vaccine.

Question 24

Which zoonosis is transmitted by Culex tritaeniorhynchus mosquitos (rice paddy breeders)?

Who does it mostly infect?

Answer 24

Japanese encephalitis.

It mostly infects mammals and birds.

Question 25

The West Nile Virus is transmitted between passeriform birds by Cules pipiens. Most people with WNV have no symptoms or flu-like symptoms.

Who are more at risk of developing a severe infection?

How are outbreaks caused?

Answer 25

Very young people and elderly people, and people with comorbidites are more at risk of developing severe infection: muscle weakness, confusion, seizures.

Outbreaks are caused by spillover transmission to equids and humans.

Question 26

Chikungunya virus (an alphavirus): an emerging virus – increasing epidemics; Over 50% of population can be infected in epidemics; Zoonosis – monkeys, birds, cattle, rodents.

Describe the symptoms and vectors.

Answer 26

It has similar symptoms to dengue: severe arthralgic disease, painful and debilitating, occasionally fatal. (Fever, rash).

Vectors are ae. aegypti and albopticus.

Question 27

On what does CHIKV act in the body?

What increases risk of CHIKV epidemics?

Answer 27

• It acts primarily in midgut epithelial cells.
• The proximity of mosquito breeding sites to human habitation is a significant risk factor for chikungunya.

–Groups above 65 year old and/or with comorbidities have increased risk of severe disease –

Question 28

Rift Valley Fever virus (Bunyavirus): mostly Africa and Middle East, more than 30 mosquito spp. incriminated (incl. aedes, culex and anopheles), vaccines for ruminant with limited efficacy.

Why can you acquire RVF through direct contact with farmers, butchers, etc.?

Answer 28

It’s a zoonosis – domestic livestock, can cause human epidemics but we are dead-end hosts.

It can be acquired directly by farmers, butchers through livestock trade.

Question 29

ZIKA (a flavivirus): close phylogenetically to dengue, YF, etc., symptoms can last up to a week, complications (neurological) are rare.

By which mosquitoes is it transmitted?

What are the symptoms?

Answer 29

The Zika virus is transmitted by Aedes aegypti, (A. albopictus+ Culex quinquefasciatus).

The infection may present itself as asymptomatic or with a clinical presentation similar to that of other arbovirus infections: including fever, headache, malaise, arthralgia, myalgia, maculopapular rashes, and conjunctivitis.