Modules 7-9 MCB55

Arboviruses (arthropod-borne viruses)

transmitted primarily by arthropod vectors, such as mosquitoes, flies, ticks and fleas

over 500

How many arboviruses are recognized worldwide?

150

How many arboviruses are known to cause disease in humans?

over 3,000

How many mosquito species are there?

Anopheles, Aedes and Culex

The most dangerous mosquitoes are certain species of

Culex Mosquitoes

Typically bite at night both indoors and outdoors; they prefer avian hosts, but will bite humans (West Nile Virus, Western Equine encephalitis, Eastern Equine encephalitis)

Anopheles Mosquitoes

Bite indoors and outdoors between dusk and dawn and prefer human and mammal hosts. (Malaria)

Aedes Mosquitoes

Unlike the “typical” mosquito of the U.S., they are active day biters and humans are their preferred hosts (Zika, Chikungunya, Yellow Fever, Dengue)

female

only ______ mosquitos bite

produce eggs

Most female mosquitoes must blood-feed on a vertebrate host to

injects saliva into the host, which serves as an anticoagulant (also induces inflammatory response)

While taking a blood meal, the female

The virus circulates and multiplies in the mosquito's hemolymph (blood) for several days. The virus then penetrates and infects the mosquito's salivary glands. After an incubation period of 1-2 weeks, the infected mosquito can transmit viruses to humans and animals while taking blood meals.

How do mosquitos act as vectors?

disease

Arthopods have no apparent

for life

in the arthropod vector diseases persist

ovarilly

virus can be transmitted _____________ to vector progeny (over winter)

birds, rodents, reptiles

Who are the reservoir hosts for arboviruses?

horses, humans

What mammals are dead-end hosts for arboviruses?

Chikunguya, Dengue, Yellow Fever, and Zika

Humans can be the primary vertebrae host for

Russia, Spain, South Africa

Since the 50s several “large” outbreaks of West Nile virus occurred sporadically, including epidemics in

birds → mosquito

mosquito → birds

birds → mosquito → human

birds → mosquito → horse

West Nile virus Transmission Cycle

birds

West Nile virus Reservoir 

more sick

Horses often get _________ than people when infected with WNV

better

WN02 can replicate in mosquitos

lymph nodes → spleen → brain

WNV pathogenesis

Fatigue, swollen lymph nodes

WNV pathogenesis (lymph nodes)

Replicates in brain, inflammation of the brain

WNV pathogenesis (brain)

75%

how many people with WNV are asymptomatic?

25%

How many people with WNV develop West Nile fever?

1%

How many people with WNV get it in their brain?

50%

How many people who have WNV in their brain die?

Unpredictable outbreaks, Economic considerations, Lack of progression to phase 3 trials, Regulatory challenges

Why is there no vaccine for humans?

Surveillance & mosquito control, elimination of standing waters (Plant pots, gutters), Finding and monitoring places where adult mosquitos lay eggs, Tracking mosquito populations and the viruses they may be carrying

Reducing West Nile risk

their hosts

Some herpesviruses (HSV1) have coevolved with

switch

Some herpesviruses (HSV2) _____ hosts

Relatively “large” virus, Genome is made of DNA, Encode 70 to 200+ proteins

Herpes virus

They are successful pathogens extremely well adapted to their hosts, No - or little - clinical symptoms, High infection rates within their host population, infection is lifelong

Some generalities about herpesviruses

latency and the lytic cycles

To persist in their host, Herpesviruses have adopted two different modes of life cycle

Dormant (very little expression - no virions produced)

latency phase

Reactivation (Virions are made - Cell death)

lytic cycle

Upon infection the viral DNA is transported to the nucleus
where it circularizes, The circular form is called an
episome, The episome is maintained in the nucleus of the infected cell, No (or very little) viral expression

How does latency hides infection?

Maintenance of the viral reservoir in the host, Viral spread to new hosts, Reactivation is not associated with
disease but under certain circumstances it may be accompanied by clinical symptoms

What happens during the Reactivation stage

well understood

stimuli relating to reactivation are not

innate and active

Herpesviruses excel at evading immune responses

immune evasion

A large fraction of herpesvirus genomes are dedicated to

The apha herpesviruses

Herpes simplex virus 1 (HSV1)
Herpes simplex virus 2 (HSV2)
Varicella Zoster virus VZV)

The beta herpesviruses

Cytomegalovirus (CMV)
Human Herpesvirus 6 (HHV6)
Human Herpesvirus 7 (HHV7

The gamma herpesviruses

Epstein-Barr Virus (EBV)
Kaposi’s sacoma associated herpesvirus (KSHV)

cold sores

HSV1

Genital herpes

HSV2

chicken pox, shingles

VZV

Retinitis, birth defect

CMV

Roseola

HHV6, HHV7

mono, lymphoma, carcinoma

EBV

Sarcoma

KSHV

Filoviridae family, RNA virus but unusual structure and genetic
sequence, virions

Ebola Virus

1000nm

Virions are variable in length but on average are

manifests 2-21 days after exposure (onset of 8-10 days), symptoms progress over time

Ebola virus disease

fruit bats, dead carcasses of antelopes + gorillas

Though Ebola virus is “found” in

Democratic Republic of Congo in 1976

The first outbreak of Ebola virus disease was reported in

318 cases and 218 deaths

the 1978 ebola outbreak in the DRC resulted in

dry to wet

ebola symptoms generally progress from

headache, fever, sore throat, aching muscles, extreme weakness

dry symptoms

nose bleeds, impaired liver function, rash, vomiting, impaired kidney function, diarrhea, internal & external bleeding, multiple organ failure

wet symptoms

macrophages in the liver (fluid loss leads to liver dysfunction)

ebola infects

Viral cytotoxicity, Cytokine storm, Excessive coagulation, Immune collapse, Shock and multi-organ failure

How does Ebola cause mortality?

Viral cytotoxicity

organ damage (especially liver)

Cytokine storm

systemic inflammation and vascular leakage

Excessive coagulation

hemorrhage and microthrombi

Immune collapse

uncontrolled viral spread

ear, testis, eye, brain, uterus, muscle joint

ebola virus clearance might be delayed in

blood, organs or other bodily fluids of infected persons, Contaminated Objects, Infected animals

The Ebola virus is transmitted by direct contact with

symptomatic

Transmission of ebola occurs once someone is

close family contacts, burial ceremonies, in hospitals

Human to human transmission occurred via

nosocomial infections

Hospital acquired infections are referred to as

40

From 1976 to 2022, over __ outbreaks of ebola have occurred

16

How many ebola outbreaks were in the DRC?

25% to 90%

Case fatality for ebola ranges from

zaire

Outbreaks are typically ebola

1,850 identified cases with over 1,200 deaths

1976 - Jan 2014 stats for ebola

28,616 identified cases with 11,310 deaths, This epidemic had 40% mortality but more spread of infection, 6 months for aid organizations to get involved

2014-15 ebola outbreak

a lot of outbreaks in many countries, took aid organizations a long time to get involved, nonspecific treatment, big structures for patients and their families had to be built, aid orgs were inexperienced with ebola, authoritarian tactics scared people

Challenges associated with the 2014-2015 epidemic

re-infection

those who "survive" ebola infection are thought to be protected from

antibody responses (IgG)

There are significant _______________________ to the Ebola virus in people who recover from infection

people with active infection

Passive transfer of IgG antibodies from people who recovered
from Ebola was shown to be beneficial to

Vesicular stomatitis virus (VSV)

causes blister-like lesions in livestock

DNA inserted into VSV utbo

First vaccine for ebola VSV

contact tracing done to follow people for 21 days and vaccinate everyone exposed

ebola outbreak monitoring

they appear

Symptoms of Ebola virus disease (EVD) are treated as

Antiviral Drugs (ebola)

Monoclonal antibodies, stops replication of ebola

vaccine, rapid diagnostic tests, treatment centers, monoclonal antibody therapies, public education, contact tracing, coordination with affected countries, quarantine, surveillance 

new and improved strategy for handling ebola