EPIDEMIOLOGY OF

VIRAL DISEASES

Hari Kusnanto
EPIDEMIOLOGY
Epidemiology is the study of the
determinants, dynamics, and distribution of
diseases in a population
Why Epidemiology of Viral
Diseases?
The risk of infection and/or disease is
determined by characteristics of the virus (e.g
antigenic variation), the host, and host
population (innate and acquired resistance)
and behavioral, environmental, and ecological
factors that affect virus transmission from one
host to another
 EPIDEMIOLOGY
Know the terms endemic, epidemic,
pandemic. !These terms stem from demos meaning
population
Learn what incidence, prevalence,
case-control, cohort, mathematical
modeling, molecular epidemiology
mean
Transmission routes of viruses
Infection Excretion
Virus
Excretion
 CAUSATIVE ORGANISM
Type of virus: genetics (DNA or RNA), strands
(SINGLE or DOUBLE), tissue tropism, survival in
the environment, integrated into human genome,
cause cell lyses
Origin: human, animal (ZOONOSIS)
 WHAT IS A VIRUS?

Viruses may be defined as acellular

organisms whose genomes consist of
nucleic acid, and which obligately replicate
inside host cells using host metabolic
machinery to different extents, to form a
pool of components which assemble into
particles called virions.
F Viruses cannot be
grown on sterile
media, but require
the presence of
specific host cells.
F A virus differs from a cell in three fundamental ways:
i A virus usually has only a single type of nucleic acid
serving as its genetic material. This can be single or double
stranded DNA or RNA;
ii Viruses contain no enzymes of energy metabolism, thus
cannot make ATP;
iii Viruses do not encode sufficient enzymatic machinery to
synthesize their component macromolecules, specifically, no
protein synthesis machinery.
 Fundamentally then, a
virus is:

A package of genetic information

protected by a protein shell for
delivery into a host cell to be
expressed and replicated
Viruses are distinguished from other obligate parasites, some
of which are even simpler than viruses:
MYCOPLASMA: Small bacterium that grows only in complex medium or attached to
eucaryotic cells.

CHLAMYDIA: Obligate intracellular bacterial parasite which depends on eucaryotic cell for
energy.

PROTOZOA: Obligate intracellular parasite that replicate within eucaryotic cells.

VIROID: Infectious agents of plants that exist as naked nucleic acid (circular single stranded
(ss) ssRNA).

HEPATITIS DELTA VIRUS (HDV): Viroid-like agent whose replication is dependent upon
HBV.
PRION (proteinacious infectious agent): Hypothesized identity of the
unconventional slow viruses (such as the Kuru, Scrapie and Mad cow
disease agents). No nucleic acid is known to be required for prion
function. They are thought by many to consist solely of protein and
perhaps lipids. Study of these agents has resulted in 2 nobel prize awards.
 Kuru

Scrapie BSE vCJD

 BSE
in
Britian

80

70

CJD, 60

50
nvCJD 40

in 30

20
Britian 10

0
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
 Recognition of viruses
F How long viruses have been within our midst?
1500 BC: Leg deformities indicative of poliomyelitis, pock marks indicative of smallpox and.

"Virus" is from the

Greek meaning for
"poison" and was
initially described by
Edward Jenner in 1798.
During the 1800's, all infectious agents were considered to be viruses until Koch developed pure
culture techniques which allowed the separation and growth of bacteria. In the late 1800's: Bacteria
were purified and established as disease causing agents. It then became possible to distinguish them from
the "filterable agents", those able to pass through special filters designed to prevent the passage of
bacteria. The first viruses described were foot and mouth disease (a picornavirus), 1898, Yellow fever (a
flavivirus), 1900, Rous sarcoma virus (an oncogenic retrovirus), 1906.
 Viral diseases have played a major role in human
history over whatever time scale we choose to
explore:
Over the past 1000 years: Smallpox and measles were brought to North
and South America by early European explorers/conquerers. These
diseases, for which the native American populations had no acquired
partial immunity, killed large fractions of the populations, and were a major
factor in the decimation of these societies.

Over the past 100 years: A newly emerged strain

of influenza killed 20 million people in 1918-
1919 in the immediate aftermath of World War I.
A decade later, polio became one of the most
feared infections of children and young adults
(including Franklin D. Roosevelt, the U.S.
President throughout the Depression and World
War II).
As the century entered its final 20 years, a new
~100% lethal virus, HIV, spread rapidly around
the world via body fluid transmission.
Over the past 10 years: As the global HIV epidemic continues, sporadic
cases and outbreaks in humans of some non-human host viruses such as
Ebola and Hanta raise the concern about future epidemics by other viruses
in the new century.

FourCorners Virus
(Hanta)
 THE DISCIPLINE OF VIROLOGY

The study of virology inherently involves a merging together of what has

traditionally been thought of as two separate "kinds" of science: basic and
applied science. We want to figure out how viruses are transmitted, how they
replicate, and how the host organism responds. We also want to figure out how
to prevent transmission, how to interfere with virus replicaton, and how to
confer immunity on the host. The "applied" follows from, and is dependent
upon, the "basic" in a quite direct way. Virology as it is studied today, is
therefore an outgrowth of both:
Infectious diseases - because of the
recognition of viral pathogens.

Molecular Biology- because of the usefulness

of viruses as probes of cell and molecular
biology and metabolism, and as vectors with
strong potential for gene therapy.

Mouse primary spleen cells transduced with a

GFP (green fluorescent protein)-retrovirus vector
How are viruses classified ?

Hierarchical virus classification: (order) family - subfamily - genus - species -

strain/type

All families have the suffix viridae, e.g.:

* Poxviridae
* Herpesviridae
* Parvoviridae
* Retroviridae

Genera have the suffix virus. Within the Picornaviridae there are 5 genera:

* enterovirus (alimentary tract), species e.g. poliovirus 1, 2, 3

* cardiovirus (neurotropic), species e.g. mengovirus
* rhinovirus (nasopharyngeal region), species e.g. Rhinovirus 1a
* apthovirus (cloven footed animals ), species e.g. FMDV-C
* hepatovirus (liver), species e.g. Hepatitis A virus
 Virus naming and classification
Usually based on data available at the time of
discovery:
i Disease they are associated with, e.g.:
Poxvirus, Hepatitis virus, HIV, measles virus
ii Cytopathology they cause, e.g.:
Respiratory Syncytial virus, Cytomegalovirus
iii Site of isolation, e.g.:
Adenovirus, Enterovirus, Rhinovirus
iv Places discovered or people that
discovered them, e.g.:
Epstein-Barr virus, Rift Valley Fever
v Biochemical features, e.g.: RSV
Retrovirus, Picornavirus, Hepadnavirus
 These naming conventions can lead to confusion
later, e.g.,
viral hepatitis is caused by at least 6 different
viruses
Enterically
Infectious A E transmitted

Viral F, G,
NANB ? Other *
hepatitis

Parenterally
Serum B C transmitted
D

* 10-20% of cases of presumed viral hepatitis are still not

accounted for
Thus,
Different viruses can cause (nearly)
the same symptoms. e.g., the
hepatitis viruses

However, different members of the

same group can cause different
symptoms. e.g., the herpes viruses
 Herpesviruses
HSV Herpes Simplex Virus Cold sores (type 1),
Genital lesions (type 2)
VZV Varicella Zoster Virus Chicken pox
CMV Cytomegalovirus Mononucleosis
EBV Epstein-Barr Virus Mononucleosis,
Burkitts lymphoma,
Nasopharyngeal
carcinoma
and HHV-6, HHV-7, HHV-8..
(Human HerpesVirus-#)
Virus Classification is now based principally on analysis of the
particle:
Morphology:
by electron microscopy
Serology:
antigenic cross-reactivity Rotavirus
Genetic material:
form of nucleic acid
ssDNA (+ or - strand)
dsDNA
ssRNA (+ or - strand)
dsRNA
segmented RNA
genetic organization
sequence homology
DNA sequence
Hybridization
 Animal virus classification: DNA Viruses
Family Pox Herpes Adeno Papova Parvo Hepadna

Genome <---------------------------------------dsDNA--------------------------------------> ssDNA Partial dsDNA

Capsid Complex <---------------------------------------------Icosahedral-------------------------------------------------->

symmetry
Envelope <-----------------Yes------------------> <-----------------------------No------------------------------> Yes

Herpes simplex Human Papilloma Adeno- Hepatitis B

e.g. Vaccinia virus
virus 2 adenovirus Associated

Molluscum
Contagiosum
Plus Sense RNA Viruses
Plus-sense RNA viruses
Family Corona Toga/Flavi Picorna Calici Retro
Genome <-------------------------------------------ss (+) RNA---------------------------------------------> Diploid ( +) RNA

Capsid symme try Helical <--------------------------------------Icosahedral------------------------------------------------->

Envelope <----------------------Yes--------------------> <---------------------No----------------------> Yes

e.g. Human corona Rubella virus Polio Norwalk agent HIV-1
virus Hepatitis C vi rus Hepatitis A vi rus Hepatitis E virus
Minus Sense RNA Viruses
Minus-sense RNA viruses
Family Paramyxo Rhabd o Filo Orthomyxo Arena Bunya Reo
Genome <-----------------ss(-) RNA------------------------> ss(-) RNA ss(+) or (+/-) ss(+) or (+/-) ds RNA
segments segments segments segments
Capsid <---------------------------------------------------Helical-------------------------------------------------------> Icosahedral
symmetry
Envelope <----------------------------------------------------Yes-----------------------------------------------------------> No

e.g. Measles Rabies virus Ebola virus Influenza Lassa virus Hanta virus Rotavirus
Mu mps virus
Para-
influenza
Natural history of disease
TIME

Death
Susceptible Subclinical Clinical
host disease disease
Recovery

No
infection
Incubation period

Latent Infectious Non-infectious

Exposure Onset
Simplistic Analysis of the
Mechanisms for Ensuring the
Perpetuation of a Virus

Short cycle infection

Persistent infection
Resistance of the virus to environment
Involvement of an intermediate host
Congenital/vertical transmission
Short cycle infection
(Acute self limiting)

High efficiency of
transmission
Virus excretion of
short duration
Immunity forces
variants; antigenic
drift and shift
Antigenic shift and drift
(evasion of the immune response)
Influenza viruses exhibit SHIFT

Nearly all viruses exhibit some degree of drift. However,

antigenic shift not drift has been associated with the major
pandemics of human influenza in the last century
 Antigenic shift
and drift
Antigenic drift
Seasonal epidemics
New strains
More in influenza A (avian, pig and other mammals)
compared to influenza B (only humans)
Antigenic shift
Causing pandemics
New strain of influenza A with HA or HA & NA
 Typical Course of HIV Infection

Persistent/Latent Infection
Prolonged period of
excretion reduces
population
necessary for
transmission
Antibody and virus
can co-exist
promotes antigenic
variation
Resistance of the virus to the
environment
Survival favors
fomite transmission
Virus is not highly
infectious, hence
number of
susceptibles does
not fall as humans
born compensate for Molluscum
Contagiosum (Pox Virus)
those infected
Perpetuation through
Intermediate Host
Intermediate host is
often an arthropod in
which virus replicates.
Infection is persistent
and can be passed
vertically
There may be several
animal hosts and
several arthropod
vectors
 West Nile Virus Transmission
Mosquito vectors Cycle
Culex species

?
Dead - end Hosts

Virus
Avian reservoirs

Direct
?
VERTICAL
TRANSMISSION
(FROM MOTHER TO
CHILD):
Hepatitis B
Herpes simplex
HIV
Rate of Spread of Epidemic: SARS and Others

R0 Basic reproduction number

average no. of secondary cases generated by 1 primary
case in a susceptible population

Virus diseases R0 % transmission that

must be blocked to
prevent epidemic
SARS 2-5 50-80%
HIV 2-5 50-80%
Smallpox 5-10 80-90%
Pandemic influenza 5-25 80-97.5%
 EPIDEMIOLOGY.
Simplistic Analysis of the Mechanisms for
Ensuring the Perpetuation of a virus

Short cycle infection

Persistent infection
Resistance of the virus to
environment
Involvement of an intermediate
host
Congenital/vertical transmission
How do we use this framework?
We relate it to transmission and the
weak link.
From which we build up an assessment
of risk and control policies
This leads to action in personal and
private prevention, but also government
involvement at local, national and
international levels
 PREVENTING CONTROLING
CURING VIRAL DISEASES
Smallpox: effective vaccine; this is the only viral disease that has been wiped out
worldwide

Measles: effective vaccine since 1963; this disease could be eliminated with a world-
wide effort

Influenza: effective strain-specific vaccine, but new variant strains emerge periodically

Polio: effective vaccine; will soon be the second viral disease wiped out

HIV: no vaccine; effective drugs, but they are costly and toxic, plus resistant strains
appear. World-wide spread continues via intimate contact. 50 million infected thus far

Ebola: no vaccine; important host species unknown (found recently in chimps and
rodents); outbreaks controllable because people die quickly and human-human
transmission is via blood

Hanta: no vaccine; rodent host; easy transmission to humans, but outbreaks controllable