A.

VECTOR-BORNE
VIRUS DISEASES.
Dr Gordon Abraham/Dr Eva M A Ombaka
April/June 2015

1
INTRODUCTION
 There are >500 described viruses transmitted
by a variety of insects (arthropod vector).
 Primarily Togaviruses, Flaviviruses and
Bunyaviruses
 Many different life cycles exist representing
evolutionary diversity.
 Most viruses ultimately move to the insect’s
salivary gland to facilitate transmission
during feeding.
 Lower vertebrate (e.g. rodent)-arthropod
cycle with tangential infection in human
more common transmission mechanism.
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INTRODUCTION..THE DISEASES
 Most are zoonotic except urban yellow fever and
dengue
 Naming after either disease (dengue, yellow fever) or
geographical area where first isolated (West Nile
fever, St Louis encephalitis)
 Found temperate and tropical but more prevalent in
tropic with its animals and arthropods
 Diseases;
 Fevers of undifferentiated type with or without macula
rash and usually benign
 Encephalitis often with high fatality
 Hemorrhagic fevers often severe and fatal
 Some arbovirus are associated with more than one
syndrome (e.g. dengue)
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 INTRODUCTION
 If a virus is transmitted actively from an insect,
there is a dramatic environmental change from
multiplying inside an insect to the inside of a
mammal.
 Insects must take up sufficient blood from a
host to infect itself and therefore spread an
infection. Often, humans and other animals do
not replicate the virus in high enough numbers
in the circulating blood to infect a new insect so
are regarded as “dead-end” hosts.
 Often, humans try to control the disease by
controlling the vector.
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Examples of insect-carried viruses causing encephalitis/hepatitis/
hemorrhagic fever
Viruses Disease Geographic Vector / Comment
distribution Animal
host
Flaviviridae Fever, Africa, Central Mosquito Humans break the
Yellow fever . hepatitis. and South Aedes jungle cycle by
There are 2 cycles of America spp. chopping down trees .
transmission: Jungle (Europeans Being bitten by the
yellow fever is spread spread in 1640). tree-top mosquito to
Examples of other vector-borne viruses causing fevers and hemorrhagic disease
from monkey-to- start the urban cycle.
monkey by Elimination of Aedes
mosquitoes in trees in urban
and to human by environments stops
mosquito bite. Second the disease.
is from human to
human by Aedes Effective recombinant
aegypti --- the urban vaccine is available.
cycle.
THE JUNGLE AND URBAN CYCLES OF YELLOW FEVER.
(urban yellow human necessary)
 Examples of insect-carried viruses causing
encephalitis/hepatitis / hemorrhagic fever

Virus and disease Geographic Vector for Vertebrate Severity of

distribution human reservoir infection
infection

St Louis USA Culex spp. Wild birds 10% case

encephalitis (Southern, mosquitoes fatality
(flavivirus) Central and
Western
Examples of insect-carried viruses causing encephalitis
States)

Japanese Far East, Culex spp. Birds, pigs. 8-20% case

encephalitis South East Mosquitoes Horses are fatality. ~
(flavivirus) Asia end host. 10,000 deaths
annually in Asia.
Examples of insect-carried viruses causing encephalitis/hepatitis/
hemorrhagic fever
Viruses Disease Geographic Vector / Comment
distribution Animal
host
Fever and Historically in
Human dead end
encephalitis, Africa and Europe
West Nile virus Birds, host. Up to 5%
mosquito but spread to
(Flaviviridae) horses case fatality
(Culex) North America 10
spread. years ago.
Examples of other vector-borne viruses causing fevers and hemorrhagic disease

Bunyaviridae Fever, Africa. A large Mosquito Sheep, cattle,

Rift Valley fever . sometimes outbreak occurred camels can be
hemorrhage in East Africa i infected. 1%
1997. fatality in humans.

Congo-Crimean Fever, Asia, Africa Tick Rodents

hemorrhagic fever hemorrhage
(bunyavirus)
Examples of insect-carried viruses causing encephalitis/hepatitis/
hemorrhagic fever
Viruses Disease Geographic Vector / Comment
distribution Animal host
Filoviridae Hemorrhagic Africa Unknown but 60% mortality in
Ebola and Marburg fevers possibly bats humans.
(the only 2 filoviruses or rodents Spreads from
known) human to human
by blood / body
fluids.
Examples of other vector-borne viruses causing fevers and hemorrhagic disease
Arenaviridae. “ Africa Rodents 19% mortality in
Lassa virus. humans.
 HEMORRHAGIC FEVERS….RODENT
There are two main groups to be considered here.
They are termed Risk Group 4 viruses as they pose significant
human health hazards because there are:
• no useful antiviral drugs and
• no protective vaccines are available.

• Arenaviruses transmitted to humans from rodents. Eg. Lassa

fever in Sierra Leone, Liberia and Nigeria. Up to 300,000 cases
and 5,000 fatalities. Blood capillary damage leads to
hemorrhage.

•Filoviruseseg. Marburg and Ebola. Long, filamentous, ssRNA

viruses. Cause periodic infections in tropical African countries.
Ebola is easily transmitted via infected blood or body fluids so
medical and hospital staff face significant risks.
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Virus Virus Disease Animal of Lethality Geographic
group origin distribution

Lymphocytic Arenavirus LCM Mouse, - Worldwide

choriomeningit hamster
is (LCM)

Lassa fever Arenavirus Lassa fever. African bush + ~19% West Africa
Hemorrhage often rat
leads to death. 5-10 (Mastomys
Viral fevers andday incubation.
hemorrhagic natalensis)
diseases acquired from vertebrates or from unknown
sources

Machupo Arenavirus Bolivian Bush mouse + NE Bolivia

hemorrhagic fever (Calomys
callosus)

Junin Arenavirus Argentinian Calomys + Argentina

hemorrhagic fever spp., mice
Virus Virus Disease Animal of Lethality Geographic
group origin distribution

Hantaan Bunyavir Hemorrhagic fever + Far East,

us Scandinavia, E
Europe
Marburg Filovirus Marburg disease. Unknown ++ East Africa (lab.
Fever, rash and ~20% infections in Marburg,
hemhorrhage. Germany)
Ebola, Filovirus •Ebola disease. Probably ++ Africa (Sudan, Zaire,
Ebola Hospital a bat Gabon , Uganda,
Viral fevers and hemorrhagic diseases acquired from vertebrates or from unknown
Reston transmissions sources Sierra Leone,
common via body Liberia).
fluids.
Less pathogenic
•18% of rural Reston strain
residents in Central isolated in
Africa have Philippines.
antibodies so
subclinical infections
must occur.
 B. BLOOD BORNE
VIRUS DISEASES.
Dr Gordon Abraham/Dr Eva M A Ombaka
April/June 2015

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 To consider two examples of blood-borne
diseases:
 Hepatitis
B (although hepatitis C and D are also
blood borne viruses).
 HIV
HEPATITIS….1
(Hepatitis means inflammation of the liver)
•The Hepatitis B virus genome is complex as it is a
partially double-stranded DNA virus. It has 3 important
antigens, and the surface antigen may be found free in
the blood of infected people.

•Hepatitis B is a blood-borne disease. Infection is usually

by direct contact between body fluids or lesions of 2
people.

•Infections are more common in babies (from infected

mothers) and young adults. Blood product transfusions,
body piercing and tattooing are causes of spread.

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HEPATITIS….2
•After entering the blood stream, the virus proceeds to
the liver where hepatitis is caused.
• The incubation is long, 6 weeks to 6 months.
• The immune response is slow and often not effective.
• Blood may remain infectious for many months.

•About 20% of people recover fully, most progress to a

chronic infection state and some (~10%) become life-
long carriers of infection.

•There are estimated to be ~350 million carriers

worldwide, most in Asia or sub-Saharan Africa.

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HEPATITIS….3
•Hepatitis B carriers are 200 times more likely to develop
liver cancer which is one of the most common cancers world
wide. Such cancer cells have integrated copies of the viral
DNA.

•Anal intercourse is a major risk factor for Hepatitis B in

Western societies; most male homosexuals become hepatitis
B positive within 6 months of promiscuous activity.

•Being blood-borne viruses, hepatitis B parallels HIV in its

transmission mechanisms.

•An effective recombinant (genetically engineered) vaccine is

available, replacing the original purified antigen vaccine
prepared from the blood of donors.
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AIDS…..1
•The only cause of acquired immunodeficiency syndrome (AIDS) we shall
consider is human immunodeficiency virus (HIV).

•AIDS is not a single disease but a syndrome; that is, a groups of signs
and symptoms associated with a common cause.

•HIV members of lentiviruses of Retroviridae family

• HIV 1 subtype B is found mainly in Europe, North America and Australia

while subtypes A (West Africa and C in Southern Africa)

•HIV 2 is found mainly in West Africa.

•Both viruses are probably derived by mutation from simian

immunodeficiency virus (SIV) isolated from African primate animals, eg.
chimpanzees.

•The disease caused by HIV 1 is generally more severe.

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AIDS…..2
HIV is a member of the Retroviridae of which there are
two main sub-families;

• the oncoviruses can transform target cells to become

cancerous or become immortal in that they keep dividing
indefinitely. Such tumour viruses are found in many
animal species.
• Endogenous retroviruses is the term used to describe
virus DNA copies that have been integrated into the
chromosome of many host animals and thereafter,
transmitted vertically.

• the lentiviruses, including HIV, are slow growing viruses

associated with neurologic and immunosuppressive
diseases.
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AIDS…..3
• Retroviruses are enveloped and HIV has two
prominent surface glycoproteins, gp120 and gp41.

• The larger glycoprotein binds specifically to cells

carrying the CD4 surface antigen (eg. helper T
lymphocytes and macrophages) and some other cells
in the liver and brain.

• Retroviruses are:
• single-stranded RNA viruses with (+) polarity.
• The infecting virus particle also includes enzymes
( reverse transcriptase, protease and integrase) and
some tRNA molecules that act as primers for the
reverse transcriptase.
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AIDS…..4
• Reverse transcriptase is very prone to error and
miscopies a nucleotide every 2000 base pairs.

• This produces very rapid mutation and explains the

enormous genetic variability shown by HIV, even within
the one person.

• Thus, HIV is never a single virus but a heterogeneous

collection known as a quasispecies.

• Inside the infected cell, the virus RNA is copied to

double-stranded DNA and delivered to the host cell
nucleus where it is spliced (integrated) into the host cell
chromosome.
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AIDS…..5
• The virus is thus latent or hidden ---- known as a
provirus state. The virus genes are then
transcribed and translated as if they were part
of the cell.

• The 3 unique enzymes carried by HIV provide

targets for chemotherapy (to be covered later).

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HIV...PROGRESS OF THE DISEASE…1
•Initial infection usually leads to an influenza-like illness;
fever, diarrhoea and nausea may last for 2-3 weeks.
Weight loss and fatigue are common.

•The virus infects target cells (CD4 lymphocytes and

macrophages) and is carried to lymph nodes by
macrophages during this phase.

•The clinical symptoms subside but there is a major

battle occurring between virus replication and the
immune reactions of cytotoxic T cells and delayed type
hypersensitivity (DTH) activity.

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HIV...PROGRESS OF THE DISEASE…2
•There is humoral (circulating) antibody that can be
detected by ELISA tests but it is not a neutralising antibody.

•There is virus in the blood (and in other fluids such as

semen to a lesser extent) and the person is still very
infectious and capable of transmitting the AIDS to others.

•This asymptomatic state may persist for some years while

the battle is waged. The infection lasts for life and is
ultimately fatal.

•The disease progress is seen best by plotting average values

for virus, antibody and CD4 lymphocyte levels in blood. (See
next slide).

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USUAL PROGRESSION OF HIV INFECTION.
HIV...PROGRESS OF THE DISEASE…3
• The virus life cycle takes ~2.5 days and up to 10
billion HIV particles may be produced each day.

• Gradually, the number of CD4 cells (helper

lymphocytes) falls. The body’s capacity to
regulate / control its immune response fails.
Antibody production by B cells falls as there are
no helper T cells. HIV levels rise.

• It is the attack on the CD4 cells by the virus

that causes the immunosuppression.

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HIV...PROGRESS OF THE DISEASE…4
• DTH functions cease and the body becomes
susceptible to diseases normally eliminated
by cell mediated immunity such as
intracellular bacteria eg.
• TB which has infection rates 20 X higher
in HIV-infected people,
• fungi (Pneumocystis jiroveci, thrush) ,
• cancers ( Kaposi’s sarcoma, lymphomas),
• herpes viruses, etc.

• These are called opportunistic infections

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HIV...PROGRESS OF THE DISEASE…5
• This is the phase of immunosuppression.

• Virus begins to replicate in the brain

leading to neurologic abnormalities and
dementia.

• Death soon follows.

• Pediatric AIDS acquired in utero , during or

after birth progresses rapidly to death
within 2 years.
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MAJOR AND MINOR HIV TRANSMISSION
ROUTES
(IVDU = INTRAVENOUS DRUG USE)
 Epidemiology.
•AIDS is a disease (more accurately, it is a syndrome)
associated with HIV that has spread to humans from other
primate animals, probably 50 years or more ago.

•It has spread rapidly since the 1980s due to social,

behavioural or economic changes.

•There are 33 x 106 HIV-infected people in the world & more

than half are in sub-Sarahan Africa where males & females
are about equally infected.

•In East Africa, up to 40% of young adults are infected.

•In Western countries, infected males outnumber females by

about 4:1.
 Epidemiology....some stats 2005
Sub-Saharan Africa has just over 10% of the world’s
population, but is home to more than
60% of all people living with HIV—25.8 million.

In 2005, an estimated 3.2 million people in the region

became newly infected,
while 2.4 million adults and children died of AIDS.

Declines in adult national HIV prevalence appear to be

underway in Kenya and Uganda (10-15%)

In Zimbabwe HIV prevalence among pregnant women

fell from 26% in 2002 to 21% in 2004.
 Transmission....1.

•AIDS was first observed in homosexual men

in New York and San Francisco in 1981.

•The causative virus was identified in 1983.

•Experimentation has subsequently shown

that blood and tissue fluid exchanges between
people represents the biggest threat of
disease spread.
 Transmission....1.
•The lining of the rectum is very thin and specially
designed through evolution for the extraction of
water from faeces. Large blood vessels are close to
the surface.

•Anal intercourse frequently causes bleeding and

facilitates HIV transmission, particularly to the
passive partner.

•In contrast, the female vagina has a much thicker,

tougher lining without large blood vessels close to
the surface and has evolved to withstand friction.
 Transmission....2

•HIV transmission via orthodox heterosexual

contact does occur but less frequently, in
most countries.

•Female to male transmission occurs more

frequently in Africa and Asia.

•In summary, a tear or lesion facilitates an

exchange of blood / other body fluids.
 Transmission...3.
•The presence of other sexually-transmitted diseases also
contributes to the transmission of HIV as lesions and
discharges are more common.

•Although transmission can occur via other body fluids,

blood contains the highest titre of infectious material
(viruses and infected white cells).

•People most at risk are :

• male homosexuals,
• other humans sexually-active in unsafe practises,
• intravenous drug users, and
• babies of HIV-positive mothers.
 Transmission....4
•Transmissions by blood transfusion and organ transplants
have almost been eliminated.

•Virus in breast milk may be spread to young babies. Mother-

to-child transmission rates were very high in sub-Saharan
Africa. Introduction of preventive measures addressing this
problem.

•AIDS is not contracted by casual contact, touching, hugging,

kissing, sneezing, insect bites, water, food, toilets, swimming
pools, etc.

•The most certain way to stop AIDS is by behavioural change;

maintain a lifestyle that minimises or eliminates the risk
factors described above!!!!!!
 Treatment.
•Some effective drug treatments delay the onset of terminal
disease but do not eliminate the infection as the virus is in
the integrated “provirus” state. Such include ARVs.

•Effective vaccines have not been successfully produced

despite >20 years efforts by researchers.

•A vaccine is unlikely to be successful because of the rapid

mutation rates of HIV and because the natural (“best”)
immune response does not neutralise / eliminate the virus.

•Public education programs demanding the avoidance of risk

factors are the best option for stopping the disease.