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PHARMACEUTICAL
MICROBIOLOGY
PST 05103
⚕
NTA Level 5 Semester 1
BY
PHARM MLACHA JO. jp214479@Gmail.com
Introduction to
Virology
24
BY PHARM MLACHA JO. 2
LearningTasks
By the end of this session students are expected to
be able to:
Define common terms used in virology
Outline the characteristics of virus
Describe general structure and properties of
viruses
Classify viruses according to their genetic and
morphological properties
Describe viral-host-cell interaction and replication
List various drug targets in virus
BY PHARM MLACHA JO. 3
CommonTerms Used inVirology
Virology : Virology is the study of viruses.Their
structures and activities including infections caused
by viruses.
Virus :This is a very small acellular particle that can
only replicate inside cells of another organism.A
virus is capable of infecting cells and potentially cause
disease
Virion: Is complete virus particle.
Capsid: Is the protein shell or coat that encloses the
nucleic acid of a virus
Capsomeres: Morphological units seen in electron
microscopes that make up the capsid
BY PHARM MLACHA JO. 4
Envelope: A lipid-containing membrane
that surrounds some viruses. It is acquired
during maturation by a budding process
through the cell membrane.
Peplomers: Are virus-encoded
glycoproteins that are exposed on the
surface f the envelope
Nucleocapsid : This is the protein-
nucleic acid complex representing the
packed form of the viral genome.
BY PHARM MLACHA JO. 5
 Structural units: The basic protein subunit
which may be assembled into capsomeres;
may consist of one protein subunit or
different protein subunits.The structural unit
is often referred to as a protomer
 Defective virus: A virus particle that is
functionally deficient in some aspect of
replication.
 Provirus: viral DNA that is integrated into
host cell chromosome in latent state and
must be activated before it is transcribed,
leading to production of progeny virions;
transmissible from parent cell to daughter
cells
BY PHARM MLACHA JO. 6
Characteristics ofViruses
They infect prokaryotic and eukaryotic
cells
They are acellular
They contain either DNA or RNA
surrounded by a protein coat
Viruses are obligate intracellular entities
They cannot reproduce outside a host
cell
Viruses are cultivated in living cells e.g.
bacteria
BY PHARM MLACHA JO. 7
Viruses that infect bacteria are called
bacteriophage
Some viruses multiply in cytoplasm of
host cell while others multiply in the
nucleus of host cells
They are very small (the largest virus is the
size of a small bacteria)
Some viruses have envelope outside the
capsid while other are naked
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 Such differences account for the high
diversity of viruses and the differences in
their properties, notably their resistance
to antiviral drugs and viricidal agents
 Viral classification is based on the physical
and chemical properties of viruses, their
structure and morphology
BY PHARM MLACHA JO. 11
Viral Structure
A complete viral particle (virion) consists of;
BY PHARM MLACHA JO. 12
Viral nucleic acid
 The viral genome is composed of either DNA or RNA
 It can be double stranded (ds) or single - stranded (ss),
linear (e.g. poliovirus) or circular (e.g. hepatitis B virus),
containing several segments (e.g. influenza— eight
segments of ss RNA) or one molecule (e.g. poliovirus).
 The nature of the viral nucleic acid is important for the
effectiveness of antiviral treatments
◦ For example, retroviridae such as HIV require a specific virus-
encoded enzyme, a reverse transcriptase, to convert their ss
RNA into ssDNA, to be able to replicate within the host cell.
◦ This enzyme is a primary target site of many antiviral drugs.
BY PHARM MLACHA JO. 13
The viral DNA
single-stranded DNA (ssDNA)
double-stranded DNA (dsDNA)
single-stranded RNA (ssRNA)
The RNA can be of positive sense (+)
which is the same as Mrna or a negative
sense (-) which is complementary to
mRNA
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Protein coat (capsid):
 The nucleic acid is surrounded by a protein coat (the
capsid)
 The capsid is formed from protomers which
collectively form capsomeres.The capsomere is the
basic unit of the capsid
 The capsid protects the virion in the external
environment
 It also helps in transfer of nucleic acid between host
cells
 The capsid and the nucleic acid are collectively called
Nucleocapsid
 Viral Symmetry
BY PHARM MLACHA JO. 17
Capsid is constructed in a highly symmetrical manner
Icosahedral
The capsid is composed of triangular faces
made from capsomeres (hexons)
The virus appears spherical e.g. poliovirus
Helical
Virus is hollow, cylindrical in shape
The virus can be rigid or flexible e.g. tobacco
mosaic virus (TMV)
Complex
Contains several types of symmetry in one virus
BY PHARM MLACHA JO. 18
 Viruses with an icosahedral capsid usually have
capsomeres in the form of pentons and hexons
 Viruses with a helical capsid (e.g. influenza and
mumps viruses) have their subunits
symmetrically packed in a helical array, appearing
like coils of wound rope under electron
microscopy.
BY PHARM MLACHA JO. 19
Viral envelope
 Some viruses have a lipid layer (the
envelope) surrounding the nucleocapsid
 Viruses with the envelope are called
enveloped viruses while those not
containing the envelope are called non
enveloped (or naked) virues
 Contains proteins projecting from the
envelope.These proteins help with
attachment of the virus to the host cells
BY PHARM MLACHA JO. 20
Viral envelope
 The viral capsid can be surrounded by a
lipidic envelope, which originates from the
host cell.
 The envelope is added during the
replication process or following excision of
the viral progeny from the host cells.
 The envelope can come from the host cell
nuclear membrane (e.g. herpes simplex
virus) or the cytoplasmic membrane (e.g.
influenza virus)
BY PHARM MLACHA JO. 21
 Lipids in viruses are generally phospholipids
from the host envelope
 One characteristic of the viral envelope is
that host proteins are excluded, but proteins
encoded by the viral genome are present
 Enveloped viruses are generally con-sidered
to be the most susceptible to chemical and
physical conditions and do not survive well
on their own outside the host cell (e.g. on
surfaces), although they can persist longer in
organic soil (e.g. blood, exudates, faeces).
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Generalized structure of viruses. (a) The simplest virus is a
naked virus (nucleocapsid) consisting of a geometric capsid
assembled around a nucleic acid strand or strands. (b) An
enveloped virus is composed of a nucleocapsid surrounded by a
flexible membrane called an envelope.The envelope usually has
special receptor spikes inserted into it.
Functions of Capsid/Envelope
 The outermost covering of a virus is indispensable to
viral function
 it protects the nucleic acid from the effects of
various enzymes and chemicals when the virus
is outside the host cell.
 Capsids and envelopes are also responsible for
helping to introduce the viral DNA or RNA
into a suitable host cell,
 by binding to the cell surface
 by assisting in penetration of the viral nucleic acid
BY PHARM MLACHA JO. 24
Viral receptors
 Glycoproteins can be found usually protruding
from the viral capsid or embedded in the
envelope.
 These virus - encoded structures are important
for viral infectivity as they recognize the host
cell receptor site conveying viral specificity.
 In bacteriophages, these structures can take the
shape of tail fibres.
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Classification ofViruses
Viruses are not included in the five
kingdom classification
Universal classification of viruses group
viruses into orders, families, sub families,
genera and species.
More than 24 families cause disease in
human)
The nomenclature and classification of
viruses do not use the conventional
taxonomic groups
BY PHARM MLACHA JO. 27
◦ Suffix endings
 Genus –ends in ‘virus’ e.g. coronavirus
 Sub-family –ends in ‘virinae’
 Family –ends in ‘viridae’
 Order –ends in ‘virales’
 Species –contains name of host, the word virus etc.
Viruses are classified based on the
following criteria;
◦ Nucleic acid type: DNA viruses and RNA viruses
◦ Nature of the nucleic acid: linear, circular,
segmented, non-segmented genome or polarity i.e.
positive sense or negative sense of the strands
◦ Enzyme production
BY PHARM MLACHA JO. 28
Reverse transcriptase
Haemaglutinin enzyme (H) –required for
adsorption and penetration of orthomyxoviruses
Neuraminidase (N) –required for invation and
release of influenza viruses
Polymerase enzymes, examples
RNA-dependent RNA polymerase in RNA
viruses
DNA polymerase
RNA-dependent DNA polymerase (reverse
transcriptase)
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Morphology
 Helical viruses
 Icosahendral viruses
 Complex viruses
 Presence or absence of envelope
Enveloped viruses
Naked viruses
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Major families of human viruses
Family Strand
type
Capsid
symmetry
Enveloped or
naked
Example of diseases
DNAViruses
Poxyviridae ds Complex Enveloped Smallpox
Herpesviridae ds Icosahedral Enveloped Cold sores, genital herpes, chickenpox, shingles,
infectious mononucleosis
Adenoviridae ds Icosahedral Naked Common cold, viral meningitis
Papoviridae ds Icosahedra Naked Warts, genital warts, cervical cancer
Hepadnaviridae ds Icosahedral Enveloped Hepatitis B, liver cancer
Parvoviridae ss Icosahedral Naked Fifth disease
RNAViruses
Reoviridae ds Icosahedral Naked Gastroenteritis
Picornaviridae ss (+) Icosahedral Naked Polio, hepatitis A
Caliciviridae ss (+) Icosahedral Naked Gastroenteritis
Togaviridae ss (+) Icosahedral Enveloped Rubella, encephalitis
Flaviviridae ss (+) Icosahedral Enveloped Yellow fever, dengue fever, hepatitis C,West Nile river
fever
Coronaviridae ss (+) Helical Enveloped SARS
Filoviridae ss (-) Helical Enveloped Ebola, Marburg haemorhagic fevers
Bunyaviridae ss (-) Helical Enveloped Hantavirus pulmonary syndrome
Orthomyxoviridae ss (-) Helical Enveloped Influenza
Paramyxoviridae ss (-) Icosahedral Enveloped Mumps, measles
Rhabdoviridae ss (-) Helical Enveloped Rabies
Arenaviridae ss (+) Helical Enveloped Lassa fever
Retroviridae ss (+) Icosahedral Enveloped AIDS, Human adult T-cell leukemia
BY PHARM MLACHA JO. 32
Viral-host cell Interaction andViral
Replication
 Viruses replicate in living cells.They depend
on host cell machinery for replication.
 They have no metabolism and cannot
synthesize their own proteins, lipids or
nucleic acids.
 Thus viruses can be considered as true
intracellular parasites that grow within living
cells and use their energy and synthetic
machinery to produce viral components.
BY PHARM MLACHA JO. 33
 The production and excision of viruses from
the host cell will result in cell death, although
this might not be immediate.
 Following the replication of one virus within
the host cell, hundreds of new viruses (virus
progeny or virions ) can be released and infect
adjacent cells (within a tissue).
 The propagation from one infected cell to
new cells, and the subsequent destruction of
tissue or cells, provides signs of the viral
disease.
BY PHARM MLACHA JO. 34
Generally, viral replication involves the
following steps;
BY PHARM MLACHA JO. 35
◦ Attachment
 First step where the virus uses surface proteins to interact
with specific receptors on the target cell surface.
 The viral-specific receptors are necessary for virus to infect
the cell
◦ Penetration
 Enveloped viruses e.g. HIV, penetrate cells through fusion of
the viral envelope with the host cell membrane
 Non-enveloped viruses penetrate cells by endocytosis
◦ Uncoating
 This is also known as disassembly step)
 This step is different in different taxonomic class of the virus
involved
 It involves removal of the protein coat (capsid) and expose
the DNA or RNA to allow multiplication of the viral genome
BY PHARM MLACHA JO. 36
◦ Transcription andTranslation
 The virus uses host cell machinery to replicate and
make functional and structural proteins
◦ Assembly and release
 Involves assembly of newly formed viral nucleic acid
and structural proteins to form the nucleocapsid of
the virus
 Non-enveloped viruses mature in the cytoplasm e.g.
picornavirus or the nucleus e.g. adenoviruses with
disintegration of the cell and release of virions
 Enveloped viruses complete their cycle (maturation) as
the virion exists the cell, and the host cell undergoes
lysis
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General features
in the
multiplication
cycle of an
enveloped animal
virus. Using an
RNA virus (rubella
virus), the major
events are outlined,
although other
viruses will vary in
exact details of the
cycle.
Adsorption and Host Range
 Virus coincidentally collides with a susceptible
host cell and adsorbs specifically to receptor
sites on the cell membrane
 Spectrum of cells a virus can infect – host
range
 hepatitis B – human liver cells
 poliovirus – primate intestinal and nerve
cells
 rabies – various cells of many mammals
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The mode by which animal viruses adsorb to the host cell membrane.
(a) An enveloped coronavirus with prominent spikes.The configuration of the spike
has a complementary fit for cell receptors.The process in which the virus lands on
the cell and plugs into receptors is termed docking
(b) An adenovirus has a naked capsid that adheres to its host cell by nestling surface
molecules on its capsid into the receptors on the host cell’s membrane.
BY PHARM MLACHA JO. 41
Penetration/Uncoating
 Flexible cell membrane is penetrated by the
whole virus or its nucleic acid by:
 endocytosis – entire virus is engulfed
and enclosed in a vacuole or vesicle
 fusion – envelope merges directly with
membrane resulting in nucleocapsid’s
entry into cytoplasm
BY PHARM MLACHA JO. 42
Two principal means by which animal viruses penetrate. (a) Endocytosis
(engulfment) and uncoating (herpesvirus). (b) Fusion of the cell membrane with
the viral envelope (mumps virus).
BY PHARM MLACHA JO. 43
Replication and Protein Production
 Varies depending on whether the virus is
a DNA or RNA virus
 DNA viruses generally are replicated and
assembled in the nucleus.
 RNA viruses generally are replicated and
assembled in the cytoplasm.
 Positive-sense RNA contain the message for
translation.
 Negative-sense RNA must be converted into
positive-sense message.
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Assembly: Filling the capsid
 Capsid proteins made in cytoplasm
 DNA or RNA gets fills empty capsids
 final modifications to capsid
◦ to plug any holes from DNA/RNA
entry
◦ to mature the outer proteins
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Release
 Assembled viruses leave host cell in one of two
ways:
◦ budding – exocytosis; nucleocapsid binds to
membrane which pinches off and sheds the
viruses gradually; cell is not immediately
destroyed
◦ lysis – nonenveloped and complex viruses
released when cell dies and ruptures
 A fully formed, extracellular virus particle that is
virulent (able to establish infection in a host) is
called a virion
 Number of viruses released is variable
◦ 3,000-4,000 released by poxvirus
◦ >100,000 released by poliovirus
BY PHARM MLACHA JO. 46
Maturation and release of enveloped viruses. As parainfluenza virus is
budded off the membrane, it simultaneously picks up an envelope and spikes.
BY PHARM MLACHA JO. 47
VIRAL CHEMOTHERAPY
 Challenges to develop viral chemotherapy:
◦ Viruses are obligate intracellular parasites,
antiviral agents must be capable of selectively
inhibiting viral functions without damaging the
host, making the development of such drugs very
difficult.
◦ Many rounds of virus replication occur during
the incubation period and the virus has spread
before symptoms appear, making a drug
relatively ineffective.
BY PHARM MLACHA JO. 48
DrugTargets inViruses
Drugs that are used in treatment of viral
infections are generally called antiviral drugs
or antivirals
Antiviral drugs inhibit active replication of
viruses
Specific antivirals have specific names e.g.
antiretrovirals are used for infections caused by
retroviruses
BY PHARM MLACHA JO. 49
Targets for antiviral drugs include;
Fusion and penetration of virus to specific
host cell
 Interferes with the ability of viruses to bind to the cells
 The inhibit binding of virus to the viral-specific receptors
on host cells e.g. Enfuvirtide
Uncoating
Interferes with release of viral genome into the host cell
e.g. amantadine (for influenza A)
Integration of viral genome into host genome
Integrase inhibitors e.g. Dolutegravir
BY PHARM MLACHA JO. 50
Inhibition of replication of viral (DNA or
RNA) genome
Polymerase inhibitors; inhibit synthesis of viral DNA or
RNA e.g. reverse transcriptase inhibitors such as
Lamivudine and Tenofovir used in AIDS,Acyclovir used
for herpes infections
Inhibition of assembly of new virions
Protease inhibitors; inhibit post-translational
modification of proteins.These drugs inhibit modification
and assembly of newly formed proteins with nucleic acid
to form new virions e.g. Nevirapine used for treatment
of AIDS
Inhibition of packaging and release of new
virions
 E.g. neuraminidase inhibitors
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Key Points
 Viruses are particles that are capable of
replicating while only in living cells
Viruses differ from bacteria in that viruses are
acellular i.e. they do not have cellular structures
Viruses are classified by several criteria including
morphology and nature of genome
 Viral replication takes place inside living host cells
and involves attachment, penetration, uncoating,
synthesis of macromolecules, assembly and
release of new viral particles
Antiviral drugs target various steps of viral
replication
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Evaluation
What is virology?
What are the characteristics of viruses?
What are classes of viruses?
What are drugs used in treating viral
infection?
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OVERVIEW
 Viral disease is a harmful abnormality
that results from viral infection of
the host organism.
 A viral disease can be:
◦ clinical or
◦ Subclinical (inapparent)
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 Clinical disease in a host consists of
overt signs and symptoms.
 A syndrome is a specific group of signs
and symptoms.
◦ Example:AIDS (Acquired Immuno
Depressant Syndrome)
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 Viral infections that fail to produce any
symptoms in the host are said to be
inapparent or subclinical.
 In fact, most viral infections do not result
in the production of disease
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Types of host and cellular responses to virus
infection
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Important principles that pertain to viral disease include
the following:
1. Many viral infections are subclinical;
2.The same disease may be produced by a variety of
viruses;
3.The same virus may produce a variety of diseases;
4.The disease produced bears no relationship to viral
morphology; and
5.The outcome in any particular case is determined by
both viral and host factors and is influenced by the
genetics of each.
BY PHARM MLACHA JO. 60
VIRAL PATHOGENESIS
 Viral pathogenesis is the process that
occurs when a virus infects a host.
 Disease pathogenesis is a subset of events
during an infection that results in disease
manifestation in the host.
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 A virus is pathogenic for a particular host
if it can infect and cause signs of disease in
that host.
 A strain of a certain virus is more virulent
than another strain if it commonly
produces more severe disease in a
susceptible host
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Steps inViral Pathogenesis
 Specific steps involved in viral pathogenesis are the
following:
◦ 1.Viral entry into the host,
◦ 2. Primary viral replication,
◦ 3.Viral spread,
◦ 4. Cellular injury,
◦ 5. Host immune response,
◦ 6.Viral clearance or establishment of persistent infection,
◦ 7.Viral shedding
BY PHARM MLACHA JO. 63
Mode of viral disease
transmission
Viruses may be transmitted in the following ways:
1. Direct transmission from person to person by
contact.
 The major means of transmission include
◦ droplet or aerosol infection
 eg, influenza, measles, smallpox
◦ by sexual contact
 eg, papillomavirus, hepatitis B, herpes simplex type 2, human
immunodeficiency virus);
◦ by hand–mouth, hand–eye, or mouth–mouth contact
 eg, herpes simplex, rhinovirus, Epstein-Barr virus); or by exchange
of contaminated blood (eg, hepatitis B, human immunodeficiency
virus).
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2. Indirect transmission,
The indirect transmission may be:
◦ By the fecal–oral route
 eg, enteroviruses, rotaviruses, infectious hepatitis A
◦ Or by fomites
 eg, Norwalk virus, rhinovirus.
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 3.Transmission from animal to animal,
with humans an accidental host.
 In this, the spread may be :-
◦ By animal bite
 Eg. rabies
◦ Or by droplet or aerosol infection from
rodent-contaminated quarters
 Eg, arenaviruses, hantaviruses
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 4. Transmission by means of an
arthropod vector
◦ e.g. arboviruses, now classified
primarily as
 togaviruses,
 flaviviruses, and
 bunyaviruses
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Human HerpesVirus
Infections
25
BY PHARM MLACHA JO. 70
LearningTasks
By the end of this session students are
expected to be able to:
Describe causative agents, transmission,
signs and symptoms of herpes infection
Describe treatment, prevention and
control of herpes infections
BY PHARM MLACHA JO. 71
Characteristics of HerpesViruses
Herpes viruses belong to the family
Herpesviridae
They are a group of virus that are widely
spread in human population
They are among the leading cause of human
viral diseases
They can cause overt disease or remain
silent for many years, then reactivated
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These viruses contain double-stranded
DNA which is located at the central core
All herpesviruses establish latent infection
within tissues that are characteristic for
each virus, reflecting the unique tissue
trophism of each member of this family
There are over one hundred viruses in the
family but only eight are pathogenic to
humans.
BY PHARM MLACHA JO. 73
These are known as human herpes viruses
and they are;
Herpes SimplexVirus -1 –causes oral herpes
Herpes SimplexVirus -2 –causes genital herpes
Varicella zoster virus (VZV) –causes chickenpox and
herpes zosters
Cytomegalovirus (CMV) –causes cytomegalovirus
retinitis
Epstein-Barr virus (EBV) –causes infectious
mononucleosis
Hhuman herpesvirus 6 (HH6)
Human herpesvirus 7 (HH7)
Human herpes virus 8/Kaposi's Sarcoma virus causes
cancers
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Members of herpes viruses are grouped into
three subfamilies namely alpha herpesviruses,
beta herpesviruses and gamma herpesviruses
After initial infection, all herpesviruses remain
latent within specific host cells and may
subsequently reactivate
Antiviral drugs that have activity against
herpesviruses include acyclovir, cidofovir,
famciclovir, fomivirsen, foscarnet, ganciclovir,
idoxuridine, penciclovir, trifluridine, valacyclovir,
valganciclovir, and vidarabine
BY PHARM MLACHA JO. 75
Herpes SimplexVirus Infections
Cause,Transmission and Manifestations
Herpes simplex viruses (HSV-1 and HSV-2)
commonly cause recurrent infection affecting the
skin, mouth, lips, eyes, and genitals
Common severe infections include encephalitis,
meningitis, neonatal herpes, and, in
immunocompromised patients, disseminated
infection
Both types of herpes simplex virus (HSV), HSV-1
and HSV-2, can cause oral or genital infection
Most often, HSV-1 causes gingivostomatitis,
herpes labialis, and herpes keratitis
HSV-2 usually causes genital lesions
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Transmission of HSV results from close contact
with a person who is actively shedding virus
HSV -1 is transmitted by respiratory droplets or direct
contact with infected saliva and the infection usually
limited to Oropharynx
HSV -2 is transmitted through sexual contact and from
maternal genital infections to newborn during delivery or
in utero
Viral shedding occurs from lesions but can occur
even when lesions are not apparent.
After the initial infection, HSV remains dormant in
nerve ganglia, from which it can periodically emerge,
causing symptoms
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Recurrent herpetic eruptions are
precipitated by overexposure to sunlight,
febrile illnesses, physical or emotional stress,
immunosuppression and some unknown
stimuli
Generally, HSV infection presents with the
following signs and symptoms
Preceding tingling sensation, discomfort and
itching
Grouped vesicles forming on the skin, and
mucous membranes, particularly the buccal area,
gentalia, conjunctivae, and cornea
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Treatment and Prevention
Antiviral drugs
◦ Acyclovir
◦ Valacyclovir
◦ Famciclovir
Prevention
◦ Hygiene
◦ Treatment of mothers
◦ Safe sex practices
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Varicella (Chickenpox)
 Chickenpox is an acute, systemic, usually childhood
infection caused by the varicella-zoster virus (VZV)
 Chickenpox is an acute invasive phase of the infection
withVZV which lies dormant and reactivate later in life to
cause shingles
 It usually begins with mild constitutional symptoms that
are followed shortly by skin lesions appearing in crops
and characterized by macules, papules, vesicles, and
crusting
 Patients at risk of severe neurologic or other systemic
complications (e.g. pneumonia) include adults, neonates,
and patients who are immunocompromised or have
certain underlying medical conditions
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In immunocompetent children, chickenpox is
rarely severe but in adults and
immunocompromised children, infection can be
serious
Generally, chickenpox presents with the
following signs and symptoms
◦ Red macular rash with a central vesicle (blister) on
the trunk, oral mucosa and scalp
◦ Pustules and crusting
◦ Intense pruritus
◦ Fever
◦ Occasional regional lymphadenopathy
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Treatment options for chickenpox
include;
Antiviral drugs e.g. acyclovir
Antipyretic/analgesic e.g.
Paracetamol
Antipruritic agent i.e. Calamine
lotion with phenol
BY PHARM MLACHA JO. 84
Herpes Zosters (Shingles)
Herpes zosters is an infection due to
resurgence or reactivation of theVaricella
zoster virus (VZV) which also causes
chickenpox
Signs and Symptoms of Herpes zosters
◦ Severe burning pain
◦ Grouped vesicles overlying erythematous skin
following a dermatomal distribution
◦ Typically, lesions do not cross the midline
BY PHARM MLACHA JO. 85
BY PHARM MLACHA JO. 86
Treatment options
Antiviral drugs e.g. acyclovir
Antiseptics for the wounds e.g. Potassium
permanganate 1:4000 solution
Antibiotics for secondary bacterial infections
Topical gentamycin
Mupirocin
BY PHARM MLACHA JO. 87
Key Points
Herpes is a group of over hundred
viruses that belong to family herpesviridae
Eight of the herpes are pathogenic to
humans and they cause an initial illness
then lie dormant in the body to be
reactivated later
Medically important herpes infections
include herpes simplex virus infections,
chickenpox and shingles
BY PHARM MLACHA JO. 88
Evaluation
What is the treatment of chickenpox?
How is oral herpes transmitted?
What are the treatment options for
genital herpes?
BY PHARM MLACHA JO. 89
Measles and Poliomyelitis
26
BY PHARM MLACHA JO. 90
LearningTasks
By the end of this session students are
expected to be able to:
Describe causative agents, transmission,
signs and symptoms of Measle and
poliomyelitis
Describe treatment, prevention and
control of Measle and poliomyelitis
BY PHARM MLACHA JO. 91
Measles
Measles is an acute, highly communicable
infectious disease caused by Measles virus.
The mode of transmission is airborne, by
droplet spread through coughing or
sneezing or by direct contact with nasal
or throat secretions of infected persons
BY PHARM MLACHA JO. 92
Who is at risk
 Unvaccinated young children are at highest risk
of measles and its complications, including death.
 Unvaccinated pregnant women are also at risk.
 Any non-immune person (who has not been
vaccinated or was vaccinated but did not
develop immunity) can become infected.
 Measles is still common in many developing
countries – particularly in parts of Africa and
Asia.The overwhelming majority (more than
95%) of measles deaths occur in countries with
low per capita incomes and weak health
infrastructures.
BY PHARM MLACHA JO. 93
Transmission
 Measles is one of the world’s most contagious
diseases. It is spread by coughing and sneezing, close
personal contact or direct contact with infected nasal
or throat secretions.
 The virus remains active and contagious in the air or
on infected surfaces for up to 2 hours. It can be
transmitted by an infected person from 4 days prior
to the onset of the rash to 4 days after the rash
erupts.
 Measles outbreaks can result in epidemics that cause
many deaths, especially among young, malnourished
children. In countries where measles has been largely
eliminated, cases imported from other countries
remain an important source of infection.
BY PHARM MLACHA JO. 94
Signs and Symptoms
Generalized, reddish (erythematous), blotchy
(maculopapular) rash;
History of fever usually above 38˚C (if not
measured, then "hot" to touch)
Dry cough, sore throat, runny nose (coryza)
Inflamed eyes (conjunctivitis), tiny white spots with
bluish-white centers on a red background found
inside the mouth on the inner lining of the cheek-
also called Koplik's spots
In addition, children with measles frequently exhibit
a dislike of bright light (photophobia), and often have
a sore red mouth (stomatitis)
BY PHARM MLACHA JO. 95
BY PHARM MLACHA JO. 96
Treatment
◦ No specific antiviral treatment exists for
measles virus
◦ Paracetamol
◦ Vitamin A
◦ Oxyetracycline ointment (for ocular
involvement)
Prevention
◦ Immunization with measles vaccine
BY PHARM MLACHA JO. 97
Poliomyelitis
Poliomyelitis is an acute infection caused by a
poliovirus (an enterovirus)
Humans are the only natural host
Asymptomatic and minor infections (abortive
poliomyelitis) are more common than non-
paralytic or paralytic infections by ≥ 60:1 and are
the main source of spread
The virus enters via the faecal-oral or respiratory
route, then enters the lymphoid tissues of the GI
tract
A primary (minor) viremia follows with spread of
virus to the reticuloendothelial system
BY PHARM MLACHA JO. 98
BY PHARM MLACHA JO. 99
BY PHARM MLACHA JO. 100
Signs and symptoms include;
A nonspecific minor illness (abortive poliomyelitis),
sometimes aseptic meningitis without paralysis (non-
paralytic poliomyelitis), and, less often, flaccid weakness
of various muscle groups (paralytic poliomyelitis)
Treatment
Supportive
Prevention
◦ This disease is preventable by immunization with polio
vaccine starting at birth. Give 4 doses at intervals of 4
weeks.
◦ Parents should be told about theWorld program to
eliminate Polio and the importance of actively
participating.
BY PHARM MLACHA JO. 101
Key Points
Measles is an acute, highly communicable
infectious disease caused by Measles virus.And
transmitted via respiratory droplets
Important signs and symptoms of measles are
cough, runny nose, conjunctivitis and photophobia
Poliomyelitis is a debilitating disease caused by
poliovirus and transmitted via faecal-oral route or
respiratory route
Both measles and poliomyelitis do have specific
treatment and prevented by immunization
BY PHARM MLACHA JO. 102
Evaluation
What are the effects of poliomyelitis?
How is measles prevented?
BY PHARM MLACHA JO. 103
Viral Hepatitis
27
BY PHARM MLACHA JO. 104
LearningTasks
By the end of this session students are
expected to be able to:
Describe causative agents, transmission,
signs and symptoms of viral hepatitis
Describe treatment, prevention and
control of viral hepatitis
BY PHARM MLACHA JO. 105
Cause andTransmission ofViral
Hepatitis
Hepatitis
Hepatitis is the inflammation of the liver, which may result
from various causes, both infectious i.e. viral, bacterial,
fungal, and parasitic organisms and non-infectious e.g.
alcohol, drugs, autoimmune and metabolic diseases
AcuteViral Hepatitis
Acute viral hepatitis is a systemic infection predominantly
affecting the liver caused by hepatotropic viral agents
namely Hepatitis A virus (HAV), Hepatitis B virus (HBV),
Hepatitis C virus (HCV), Hepatitis D virus (HDV), and
Hepatitis E virus (HEV)
In most cases, acute viral hepatitis leads to a self-limiting
disease but can take a fulminant course and lead to
hepatic failure
BY PHARM MLACHA JO. 106
Chronic viral hepatitis
◦ This is a chronic inflammatory reaction that on
going beyond 6monts from the acute infection.
◦ Most common causative agents are HBV, HCV, and
HDV which potentially leads to liver fibrosis,
cirrhosis and portal hypertension, hepatocellular
carcinoma and hepatic failure.
BY PHARM MLACHA JO. 107
Transmission of hepatitis viruses
Hepatitis A virus (HBV) and hepatitis E virus (HEV)
are transmitted by faecal-oral route through
consumption of contaminated food or water
BY PHARM MLACHA JO. 108
Hepatitis A
 Infection occurs in both epidemic and sporadic.Typical
feature are:-
◦ GI upset (anorexia, vomiting, diarrhoea)
◦ Jaundice, tender and enlarged liver
◦ Abnormal liver function tests.
 Clinical presentation
◦ History of direct exposure to a previously jaundiced individual
◦ Consumption of seafood or contaminated water
◦ Initial non-specific symptoms usually precede the development
of jaundice by 5-10 days.
◦ Fever, anorexia and epigastric pain are the usual symptoms
◦ Darkening of the urine precede jaundice, which peaks in 1-2
weeks and then begins to subside.
◦ Tender hepatomegaly and jaundice are typically present;
splenomegaly is variable.
BY PHARM MLACHA JO. 109
BY PHARM MLACHA JO. 110
 Treatment
◦ Supportive treatment: For pain give paracetamol
15mg/kg /dose).
 Prevention
◦ General measures: Sanitation and hygiene that
includes hand washing, proper disposal of infectious
materials.
 Mode of transmission: Mainly fecal - oral
route.
BY PHARM MLACHA JO. 111
BY PHARM MLACHA JO. 112
Hepatitis B virus (HBV)
BY PHARM MLACHA JO. 113
Hepatitis B virus
 Is transmitted through exposure to infective
blood, semen, and other body fluids. HBV can be
transmitted from infected mothers to infants at
the time of birth or from family member to
infant in early childhood.Transmission may also
occur through transfusions of HBV-
contaminated blood and blood products,
contaminated injections during medical
procedures, and through injection drug use
BY PHARM MLACHA JO. 114
 Clinical presentation
◦ The symptoms are non-specific, consisting only of
slight fever (which may be absent) and mild
gastrointestinal upset
◦ Visible jaundice is usually the first significant
finding
◦ Dark urine and pale or clay-coloured stools
◦ Hepatomegaly is present
◦ Occasionally a symptom complex (caused by
antigen-antibody complexes) of macular rash,
urticarial lesion, and arthiritis.
BY PHARM MLACHA JO. 115
Treatment
 Supportive
◦ Low fat diet, oral fluids
◦ Give paracetamol (dose as above) if pain present
 Specific treatment
◦ The use of interferon alfa in children has not yet
established
◦ Lamivudine
 In children 2-11years-3mg/kg/once daily
 In children 12-17 years and adults-100mg daily
BY PHARM MLACHA JO. 116
 Note: Patient Receiving lamivudine for concomitant
HIV infection should continue to receive lamivudine
in appropriate dose for HIV infection
 There are two components for preventing
hepatitis B:
◦ Prevention of transmission of the virus
◦ Immunization
 Mode of transmission
◦ Mainly through parenteral, sexual and vertical transmission
5%
 Immunization recommendations
◦ Hepatitis B vaccine is safe and effective, but should not be
seen as an alternative to a strategy of prevention of
transmission
BY PHARM MLACHA JO. 117
Hepatitis C virus (HCV)
BY PHARM MLACHA JO. 118
Hepatitis C virus (HCV) is mostly
transmitted through exposure to infective
blood.This may happen through transfusions
of HCV-contaminated blood and blood
products, contaminated injections during
medical procedures, and through injection
drug use. Sexual transmission is also possible,
but is much less common.
 Treatment
◦ Interferon alfa: Usual dose: SC, 5–10 million units
3 times weekly for 4–6 months.
BY PHARM MLACHA JO. 119
Signs and Symptoms ofViral
Hepatitis
Acute viral hepatitis
◦ Fever, anorexia, malaise, jaundice and abdominal pain
◦ Enlarged and tender liver
◦ Altered consciousness, coma (hepatic encephalopathy), and
bleeding stigmata (in fulminant cases)
Chronic viral hepatitis
◦ Usually asymptomatic
◦ Right upper quadrant abdominal pains
◦ Fatigue, malaise, anorexia, low grade fever; jaundice is frequent
in severe disease
◦ Ascites, variceal bleeding, encephalopathy, coagulopathy, and
hypersplenism
◦ Urticarial, arthritis, vasculitis, polyneuropathy,
glomerulonephritis, thyroiditis
BY PHARM MLACHA JO. 120
Treatment, Prevention and Control ofViral
Hepatitis
Treatment of Acute Hepatitis
AcuteViral Hepatitis
◦ There is no specific treatment to alter the course of
acute viral hepatitis
◦ Supportive management including hydration, feeding,
control fever and pain if present is required.
◦ Fulminant cases may require specific antiviral
medications
ChronicViral Hepatitis
◦ Hepatits BVirus
 Tenofovir , Entecavir , Lamivudine
◦ Hepatitis CVirus
 Ledpasvir , Sufosvir , Ribavirin
BY PHARM MLACHA JO. 121
Prevention and control of viral hepatitis
Immunization
Personal and environmental hygiene
Safe sexual practices
Safe blood
BY PHARM MLACHA JO. 122
Key Points
Hepatitis is the inflammation of the liver, which may
result from various causes, both infectious i.e. viral,
bacterial, fungal, and parasitic organisms and non-
infectious e.g. alcohol, drugs, autoimmune and metabolic
diseases
Viral hepatitis can be acute or chronic
Acute viral hepatitis is a systemic infection
predominantly affecting the liver caused by hepatotropic
viral agents namely Hepatitis A virus (HAV), Hepatitis B
virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus
(HDV), and Hepatitis E virus (HEV)
Chronic hepatitis is most commonly caused by HBV,
HCV, and HDV which potentially leads to liver fibrosis,
cirrhosis and portal hypertension, hepatocellular
carcinoma and hepatic failure.
BY PHARM MLACHA JO. 123
Evaluation
What is hepatitis?
How is viral hepatitis transmitted?
What are the treatment options for viral
hepatitis?
BY PHARM MLACHA JO. 124
END
ALLTHE BEST
BY
PHARM MLACHA JO.
BY PHARM MLACHA JO. 125

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Pharm Mlacha virology 1.pdf

  • 1. PHARMACEUTICAL MICROBIOLOGY PST 05103 ⚕ NTA Level 5 Semester 1 BY PHARM MLACHA JO. jp214479@Gmail.com
  • 3. LearningTasks By the end of this session students are expected to be able to: Define common terms used in virology Outline the characteristics of virus Describe general structure and properties of viruses Classify viruses according to their genetic and morphological properties Describe viral-host-cell interaction and replication List various drug targets in virus BY PHARM MLACHA JO. 3
  • 4. CommonTerms Used inVirology Virology : Virology is the study of viruses.Their structures and activities including infections caused by viruses. Virus :This is a very small acellular particle that can only replicate inside cells of another organism.A virus is capable of infecting cells and potentially cause disease Virion: Is complete virus particle. Capsid: Is the protein shell or coat that encloses the nucleic acid of a virus Capsomeres: Morphological units seen in electron microscopes that make up the capsid BY PHARM MLACHA JO. 4
  • 5. Envelope: A lipid-containing membrane that surrounds some viruses. It is acquired during maturation by a budding process through the cell membrane. Peplomers: Are virus-encoded glycoproteins that are exposed on the surface f the envelope Nucleocapsid : This is the protein- nucleic acid complex representing the packed form of the viral genome. BY PHARM MLACHA JO. 5
  • 6.  Structural units: The basic protein subunit which may be assembled into capsomeres; may consist of one protein subunit or different protein subunits.The structural unit is often referred to as a protomer  Defective virus: A virus particle that is functionally deficient in some aspect of replication.  Provirus: viral DNA that is integrated into host cell chromosome in latent state and must be activated before it is transcribed, leading to production of progeny virions; transmissible from parent cell to daughter cells BY PHARM MLACHA JO. 6
  • 7. Characteristics ofViruses They infect prokaryotic and eukaryotic cells They are acellular They contain either DNA or RNA surrounded by a protein coat Viruses are obligate intracellular entities They cannot reproduce outside a host cell Viruses are cultivated in living cells e.g. bacteria BY PHARM MLACHA JO. 7
  • 8. Viruses that infect bacteria are called bacteriophage Some viruses multiply in cytoplasm of host cell while others multiply in the nucleus of host cells They are very small (the largest virus is the size of a small bacteria) Some viruses have envelope outside the capsid while other are naked BY PHARM MLACHA JO. 8
  • 10. BY PHARM MLACHA JO. 10
  • 11.  Such differences account for the high diversity of viruses and the differences in their properties, notably their resistance to antiviral drugs and viricidal agents  Viral classification is based on the physical and chemical properties of viruses, their structure and morphology BY PHARM MLACHA JO. 11
  • 12. Viral Structure A complete viral particle (virion) consists of; BY PHARM MLACHA JO. 12
  • 13. Viral nucleic acid  The viral genome is composed of either DNA or RNA  It can be double stranded (ds) or single - stranded (ss), linear (e.g. poliovirus) or circular (e.g. hepatitis B virus), containing several segments (e.g. influenza— eight segments of ss RNA) or one molecule (e.g. poliovirus).  The nature of the viral nucleic acid is important for the effectiveness of antiviral treatments ◦ For example, retroviridae such as HIV require a specific virus- encoded enzyme, a reverse transcriptase, to convert their ss RNA into ssDNA, to be able to replicate within the host cell. ◦ This enzyme is a primary target site of many antiviral drugs. BY PHARM MLACHA JO. 13
  • 14. The viral DNA single-stranded DNA (ssDNA) double-stranded DNA (dsDNA) single-stranded RNA (ssRNA) The RNA can be of positive sense (+) which is the same as Mrna or a negative sense (-) which is complementary to mRNA BY PHARM MLACHA JO. 14
  • 15. BY PHARM MLACHA JO. 15
  • 16. BY PHARM MLACHA JO. 16
  • 17. Protein coat (capsid):  The nucleic acid is surrounded by a protein coat (the capsid)  The capsid is formed from protomers which collectively form capsomeres.The capsomere is the basic unit of the capsid  The capsid protects the virion in the external environment  It also helps in transfer of nucleic acid between host cells  The capsid and the nucleic acid are collectively called Nucleocapsid  Viral Symmetry BY PHARM MLACHA JO. 17
  • 18. Capsid is constructed in a highly symmetrical manner Icosahedral The capsid is composed of triangular faces made from capsomeres (hexons) The virus appears spherical e.g. poliovirus Helical Virus is hollow, cylindrical in shape The virus can be rigid or flexible e.g. tobacco mosaic virus (TMV) Complex Contains several types of symmetry in one virus BY PHARM MLACHA JO. 18
  • 19.  Viruses with an icosahedral capsid usually have capsomeres in the form of pentons and hexons  Viruses with a helical capsid (e.g. influenza and mumps viruses) have their subunits symmetrically packed in a helical array, appearing like coils of wound rope under electron microscopy. BY PHARM MLACHA JO. 19
  • 20. Viral envelope  Some viruses have a lipid layer (the envelope) surrounding the nucleocapsid  Viruses with the envelope are called enveloped viruses while those not containing the envelope are called non enveloped (or naked) virues  Contains proteins projecting from the envelope.These proteins help with attachment of the virus to the host cells BY PHARM MLACHA JO. 20
  • 21. Viral envelope  The viral capsid can be surrounded by a lipidic envelope, which originates from the host cell.  The envelope is added during the replication process or following excision of the viral progeny from the host cells.  The envelope can come from the host cell nuclear membrane (e.g. herpes simplex virus) or the cytoplasmic membrane (e.g. influenza virus) BY PHARM MLACHA JO. 21
  • 22.  Lipids in viruses are generally phospholipids from the host envelope  One characteristic of the viral envelope is that host proteins are excluded, but proteins encoded by the viral genome are present  Enveloped viruses are generally con-sidered to be the most susceptible to chemical and physical conditions and do not survive well on their own outside the host cell (e.g. on surfaces), although they can persist longer in organic soil (e.g. blood, exudates, faeces). BY PHARM MLACHA JO. 22
  • 23. BY PHARM MLACHA JO. 23 Generalized structure of viruses. (a) The simplest virus is a naked virus (nucleocapsid) consisting of a geometric capsid assembled around a nucleic acid strand or strands. (b) An enveloped virus is composed of a nucleocapsid surrounded by a flexible membrane called an envelope.The envelope usually has special receptor spikes inserted into it.
  • 24. Functions of Capsid/Envelope  The outermost covering of a virus is indispensable to viral function  it protects the nucleic acid from the effects of various enzymes and chemicals when the virus is outside the host cell.  Capsids and envelopes are also responsible for helping to introduce the viral DNA or RNA into a suitable host cell,  by binding to the cell surface  by assisting in penetration of the viral nucleic acid BY PHARM MLACHA JO. 24
  • 25. Viral receptors  Glycoproteins can be found usually protruding from the viral capsid or embedded in the envelope.  These virus - encoded structures are important for viral infectivity as they recognize the host cell receptor site conveying viral specificity.  In bacteriophages, these structures can take the shape of tail fibres. BY PHARM MLACHA JO. 25
  • 26. BY PHARM MLACHA JO. 26
  • 27. Classification ofViruses Viruses are not included in the five kingdom classification Universal classification of viruses group viruses into orders, families, sub families, genera and species. More than 24 families cause disease in human) The nomenclature and classification of viruses do not use the conventional taxonomic groups BY PHARM MLACHA JO. 27
  • 28. ◦ Suffix endings  Genus –ends in ‘virus’ e.g. coronavirus  Sub-family –ends in ‘virinae’  Family –ends in ‘viridae’  Order –ends in ‘virales’  Species –contains name of host, the word virus etc. Viruses are classified based on the following criteria; ◦ Nucleic acid type: DNA viruses and RNA viruses ◦ Nature of the nucleic acid: linear, circular, segmented, non-segmented genome or polarity i.e. positive sense or negative sense of the strands ◦ Enzyme production BY PHARM MLACHA JO. 28
  • 29. Reverse transcriptase Haemaglutinin enzyme (H) –required for adsorption and penetration of orthomyxoviruses Neuraminidase (N) –required for invation and release of influenza viruses Polymerase enzymes, examples RNA-dependent RNA polymerase in RNA viruses DNA polymerase RNA-dependent DNA polymerase (reverse transcriptase) BY PHARM MLACHA JO. 29
  • 30. Morphology  Helical viruses  Icosahendral viruses  Complex viruses  Presence or absence of envelope Enveloped viruses Naked viruses BY PHARM MLACHA JO. 30
  • 31. BY PHARM MLACHA JO. 31
  • 32. Major families of human viruses Family Strand type Capsid symmetry Enveloped or naked Example of diseases DNAViruses Poxyviridae ds Complex Enveloped Smallpox Herpesviridae ds Icosahedral Enveloped Cold sores, genital herpes, chickenpox, shingles, infectious mononucleosis Adenoviridae ds Icosahedral Naked Common cold, viral meningitis Papoviridae ds Icosahedra Naked Warts, genital warts, cervical cancer Hepadnaviridae ds Icosahedral Enveloped Hepatitis B, liver cancer Parvoviridae ss Icosahedral Naked Fifth disease RNAViruses Reoviridae ds Icosahedral Naked Gastroenteritis Picornaviridae ss (+) Icosahedral Naked Polio, hepatitis A Caliciviridae ss (+) Icosahedral Naked Gastroenteritis Togaviridae ss (+) Icosahedral Enveloped Rubella, encephalitis Flaviviridae ss (+) Icosahedral Enveloped Yellow fever, dengue fever, hepatitis C,West Nile river fever Coronaviridae ss (+) Helical Enveloped SARS Filoviridae ss (-) Helical Enveloped Ebola, Marburg haemorhagic fevers Bunyaviridae ss (-) Helical Enveloped Hantavirus pulmonary syndrome Orthomyxoviridae ss (-) Helical Enveloped Influenza Paramyxoviridae ss (-) Icosahedral Enveloped Mumps, measles Rhabdoviridae ss (-) Helical Enveloped Rabies Arenaviridae ss (+) Helical Enveloped Lassa fever Retroviridae ss (+) Icosahedral Enveloped AIDS, Human adult T-cell leukemia BY PHARM MLACHA JO. 32
  • 33. Viral-host cell Interaction andViral Replication  Viruses replicate in living cells.They depend on host cell machinery for replication.  They have no metabolism and cannot synthesize their own proteins, lipids or nucleic acids.  Thus viruses can be considered as true intracellular parasites that grow within living cells and use their energy and synthetic machinery to produce viral components. BY PHARM MLACHA JO. 33
  • 34.  The production and excision of viruses from the host cell will result in cell death, although this might not be immediate.  Following the replication of one virus within the host cell, hundreds of new viruses (virus progeny or virions ) can be released and infect adjacent cells (within a tissue).  The propagation from one infected cell to new cells, and the subsequent destruction of tissue or cells, provides signs of the viral disease. BY PHARM MLACHA JO. 34
  • 35. Generally, viral replication involves the following steps; BY PHARM MLACHA JO. 35
  • 36. ◦ Attachment  First step where the virus uses surface proteins to interact with specific receptors on the target cell surface.  The viral-specific receptors are necessary for virus to infect the cell ◦ Penetration  Enveloped viruses e.g. HIV, penetrate cells through fusion of the viral envelope with the host cell membrane  Non-enveloped viruses penetrate cells by endocytosis ◦ Uncoating  This is also known as disassembly step)  This step is different in different taxonomic class of the virus involved  It involves removal of the protein coat (capsid) and expose the DNA or RNA to allow multiplication of the viral genome BY PHARM MLACHA JO. 36
  • 37. ◦ Transcription andTranslation  The virus uses host cell machinery to replicate and make functional and structural proteins ◦ Assembly and release  Involves assembly of newly formed viral nucleic acid and structural proteins to form the nucleocapsid of the virus  Non-enveloped viruses mature in the cytoplasm e.g. picornavirus or the nucleus e.g. adenoviruses with disintegration of the cell and release of virions  Enveloped viruses complete their cycle (maturation) as the virion exists the cell, and the host cell undergoes lysis BY PHARM MLACHA JO. 37
  • 38. BY PHARM MLACHA JO. 38
  • 39. BY PHARM MLACHA JO. 39 General features in the multiplication cycle of an enveloped animal virus. Using an RNA virus (rubella virus), the major events are outlined, although other viruses will vary in exact details of the cycle.
  • 40. Adsorption and Host Range  Virus coincidentally collides with a susceptible host cell and adsorbs specifically to receptor sites on the cell membrane  Spectrum of cells a virus can infect – host range  hepatitis B – human liver cells  poliovirus – primate intestinal and nerve cells  rabies – various cells of many mammals BY PHARM MLACHA JO. 40
  • 41. The mode by which animal viruses adsorb to the host cell membrane. (a) An enveloped coronavirus with prominent spikes.The configuration of the spike has a complementary fit for cell receptors.The process in which the virus lands on the cell and plugs into receptors is termed docking (b) An adenovirus has a naked capsid that adheres to its host cell by nestling surface molecules on its capsid into the receptors on the host cell’s membrane. BY PHARM MLACHA JO. 41
  • 42. Penetration/Uncoating  Flexible cell membrane is penetrated by the whole virus or its nucleic acid by:  endocytosis – entire virus is engulfed and enclosed in a vacuole or vesicle  fusion – envelope merges directly with membrane resulting in nucleocapsid’s entry into cytoplasm BY PHARM MLACHA JO. 42
  • 43. Two principal means by which animal viruses penetrate. (a) Endocytosis (engulfment) and uncoating (herpesvirus). (b) Fusion of the cell membrane with the viral envelope (mumps virus). BY PHARM MLACHA JO. 43
  • 44. Replication and Protein Production  Varies depending on whether the virus is a DNA or RNA virus  DNA viruses generally are replicated and assembled in the nucleus.  RNA viruses generally are replicated and assembled in the cytoplasm.  Positive-sense RNA contain the message for translation.  Negative-sense RNA must be converted into positive-sense message. BY PHARM MLACHA JO. 44
  • 45. Assembly: Filling the capsid  Capsid proteins made in cytoplasm  DNA or RNA gets fills empty capsids  final modifications to capsid ◦ to plug any holes from DNA/RNA entry ◦ to mature the outer proteins BY PHARM MLACHA JO. 45
  • 46. Release  Assembled viruses leave host cell in one of two ways: ◦ budding – exocytosis; nucleocapsid binds to membrane which pinches off and sheds the viruses gradually; cell is not immediately destroyed ◦ lysis – nonenveloped and complex viruses released when cell dies and ruptures  A fully formed, extracellular virus particle that is virulent (able to establish infection in a host) is called a virion  Number of viruses released is variable ◦ 3,000-4,000 released by poxvirus ◦ >100,000 released by poliovirus BY PHARM MLACHA JO. 46
  • 47. Maturation and release of enveloped viruses. As parainfluenza virus is budded off the membrane, it simultaneously picks up an envelope and spikes. BY PHARM MLACHA JO. 47
  • 48. VIRAL CHEMOTHERAPY  Challenges to develop viral chemotherapy: ◦ Viruses are obligate intracellular parasites, antiviral agents must be capable of selectively inhibiting viral functions without damaging the host, making the development of such drugs very difficult. ◦ Many rounds of virus replication occur during the incubation period and the virus has spread before symptoms appear, making a drug relatively ineffective. BY PHARM MLACHA JO. 48
  • 49. DrugTargets inViruses Drugs that are used in treatment of viral infections are generally called antiviral drugs or antivirals Antiviral drugs inhibit active replication of viruses Specific antivirals have specific names e.g. antiretrovirals are used for infections caused by retroviruses BY PHARM MLACHA JO. 49
  • 50. Targets for antiviral drugs include; Fusion and penetration of virus to specific host cell  Interferes with the ability of viruses to bind to the cells  The inhibit binding of virus to the viral-specific receptors on host cells e.g. Enfuvirtide Uncoating Interferes with release of viral genome into the host cell e.g. amantadine (for influenza A) Integration of viral genome into host genome Integrase inhibitors e.g. Dolutegravir BY PHARM MLACHA JO. 50
  • 51. Inhibition of replication of viral (DNA or RNA) genome Polymerase inhibitors; inhibit synthesis of viral DNA or RNA e.g. reverse transcriptase inhibitors such as Lamivudine and Tenofovir used in AIDS,Acyclovir used for herpes infections Inhibition of assembly of new virions Protease inhibitors; inhibit post-translational modification of proteins.These drugs inhibit modification and assembly of newly formed proteins with nucleic acid to form new virions e.g. Nevirapine used for treatment of AIDS Inhibition of packaging and release of new virions  E.g. neuraminidase inhibitors BY PHARM MLACHA JO. 51
  • 52. BY PHARM MLACHA JO. 52
  • 53. Key Points  Viruses are particles that are capable of replicating while only in living cells Viruses differ from bacteria in that viruses are acellular i.e. they do not have cellular structures Viruses are classified by several criteria including morphology and nature of genome  Viral replication takes place inside living host cells and involves attachment, penetration, uncoating, synthesis of macromolecules, assembly and release of new viral particles Antiviral drugs target various steps of viral replication BY PHARM MLACHA JO. 53
  • 54. Evaluation What is virology? What are the characteristics of viruses? What are classes of viruses? What are drugs used in treating viral infection? BY PHARM MLACHA JO. 54
  • 55. BY PHARM MLACHA JO. 55
  • 56. OVERVIEW  Viral disease is a harmful abnormality that results from viral infection of the host organism.  A viral disease can be: ◦ clinical or ◦ Subclinical (inapparent) BY PHARM MLACHA JO. 56
  • 57.  Clinical disease in a host consists of overt signs and symptoms.  A syndrome is a specific group of signs and symptoms. ◦ Example:AIDS (Acquired Immuno Depressant Syndrome) BY PHARM MLACHA JO. 57
  • 58.  Viral infections that fail to produce any symptoms in the host are said to be inapparent or subclinical.  In fact, most viral infections do not result in the production of disease BY PHARM MLACHA JO. 58
  • 59. Types of host and cellular responses to virus infection BY PHARM MLACHA JO. 59
  • 60. Important principles that pertain to viral disease include the following: 1. Many viral infections are subclinical; 2.The same disease may be produced by a variety of viruses; 3.The same virus may produce a variety of diseases; 4.The disease produced bears no relationship to viral morphology; and 5.The outcome in any particular case is determined by both viral and host factors and is influenced by the genetics of each. BY PHARM MLACHA JO. 60
  • 61. VIRAL PATHOGENESIS  Viral pathogenesis is the process that occurs when a virus infects a host.  Disease pathogenesis is a subset of events during an infection that results in disease manifestation in the host. BY PHARM MLACHA JO. 61
  • 62.  A virus is pathogenic for a particular host if it can infect and cause signs of disease in that host.  A strain of a certain virus is more virulent than another strain if it commonly produces more severe disease in a susceptible host BY PHARM MLACHA JO. 62
  • 63. Steps inViral Pathogenesis  Specific steps involved in viral pathogenesis are the following: ◦ 1.Viral entry into the host, ◦ 2. Primary viral replication, ◦ 3.Viral spread, ◦ 4. Cellular injury, ◦ 5. Host immune response, ◦ 6.Viral clearance or establishment of persistent infection, ◦ 7.Viral shedding BY PHARM MLACHA JO. 63
  • 64. Mode of viral disease transmission Viruses may be transmitted in the following ways: 1. Direct transmission from person to person by contact.  The major means of transmission include ◦ droplet or aerosol infection  eg, influenza, measles, smallpox ◦ by sexual contact  eg, papillomavirus, hepatitis B, herpes simplex type 2, human immunodeficiency virus); ◦ by hand–mouth, hand–eye, or mouth–mouth contact  eg, herpes simplex, rhinovirus, Epstein-Barr virus); or by exchange of contaminated blood (eg, hepatitis B, human immunodeficiency virus). BY PHARM MLACHA JO. 64
  • 65. 2. Indirect transmission, The indirect transmission may be: ◦ By the fecal–oral route  eg, enteroviruses, rotaviruses, infectious hepatitis A ◦ Or by fomites  eg, Norwalk virus, rhinovirus. BY PHARM MLACHA JO. 65
  • 66.  3.Transmission from animal to animal, with humans an accidental host.  In this, the spread may be :- ◦ By animal bite  Eg. rabies ◦ Or by droplet or aerosol infection from rodent-contaminated quarters  Eg, arenaviruses, hantaviruses BY PHARM MLACHA JO. 66
  • 67.  4. Transmission by means of an arthropod vector ◦ e.g. arboviruses, now classified primarily as  togaviruses,  flaviviruses, and  bunyaviruses BY PHARM MLACHA JO. 67
  • 68. BY PHARM MLACHA JO. 68
  • 69. BY PHARM MLACHA JO. 69
  • 71. LearningTasks By the end of this session students are expected to be able to: Describe causative agents, transmission, signs and symptoms of herpes infection Describe treatment, prevention and control of herpes infections BY PHARM MLACHA JO. 71
  • 72. Characteristics of HerpesViruses Herpes viruses belong to the family Herpesviridae They are a group of virus that are widely spread in human population They are among the leading cause of human viral diseases They can cause overt disease or remain silent for many years, then reactivated BY PHARM MLACHA JO. 72
  • 73. These viruses contain double-stranded DNA which is located at the central core All herpesviruses establish latent infection within tissues that are characteristic for each virus, reflecting the unique tissue trophism of each member of this family There are over one hundred viruses in the family but only eight are pathogenic to humans. BY PHARM MLACHA JO. 73
  • 74. These are known as human herpes viruses and they are; Herpes SimplexVirus -1 –causes oral herpes Herpes SimplexVirus -2 –causes genital herpes Varicella zoster virus (VZV) –causes chickenpox and herpes zosters Cytomegalovirus (CMV) –causes cytomegalovirus retinitis Epstein-Barr virus (EBV) –causes infectious mononucleosis Hhuman herpesvirus 6 (HH6) Human herpesvirus 7 (HH7) Human herpes virus 8/Kaposi's Sarcoma virus causes cancers BY PHARM MLACHA JO. 74
  • 75. Members of herpes viruses are grouped into three subfamilies namely alpha herpesviruses, beta herpesviruses and gamma herpesviruses After initial infection, all herpesviruses remain latent within specific host cells and may subsequently reactivate Antiviral drugs that have activity against herpesviruses include acyclovir, cidofovir, famciclovir, fomivirsen, foscarnet, ganciclovir, idoxuridine, penciclovir, trifluridine, valacyclovir, valganciclovir, and vidarabine BY PHARM MLACHA JO. 75
  • 76. Herpes SimplexVirus Infections Cause,Transmission and Manifestations Herpes simplex viruses (HSV-1 and HSV-2) commonly cause recurrent infection affecting the skin, mouth, lips, eyes, and genitals Common severe infections include encephalitis, meningitis, neonatal herpes, and, in immunocompromised patients, disseminated infection Both types of herpes simplex virus (HSV), HSV-1 and HSV-2, can cause oral or genital infection Most often, HSV-1 causes gingivostomatitis, herpes labialis, and herpes keratitis HSV-2 usually causes genital lesions BY PHARM MLACHA JO. 76
  • 77. BY PHARM MLACHA JO. 77
  • 78. Transmission of HSV results from close contact with a person who is actively shedding virus HSV -1 is transmitted by respiratory droplets or direct contact with infected saliva and the infection usually limited to Oropharynx HSV -2 is transmitted through sexual contact and from maternal genital infections to newborn during delivery or in utero Viral shedding occurs from lesions but can occur even when lesions are not apparent. After the initial infection, HSV remains dormant in nerve ganglia, from which it can periodically emerge, causing symptoms BY PHARM MLACHA JO. 78
  • 79. Recurrent herpetic eruptions are precipitated by overexposure to sunlight, febrile illnesses, physical or emotional stress, immunosuppression and some unknown stimuli Generally, HSV infection presents with the following signs and symptoms Preceding tingling sensation, discomfort and itching Grouped vesicles forming on the skin, and mucous membranes, particularly the buccal area, gentalia, conjunctivae, and cornea BY PHARM MLACHA JO. 79
  • 80. Treatment and Prevention Antiviral drugs ◦ Acyclovir ◦ Valacyclovir ◦ Famciclovir Prevention ◦ Hygiene ◦ Treatment of mothers ◦ Safe sex practices BY PHARM MLACHA JO. 80
  • 81. Varicella (Chickenpox)  Chickenpox is an acute, systemic, usually childhood infection caused by the varicella-zoster virus (VZV)  Chickenpox is an acute invasive phase of the infection withVZV which lies dormant and reactivate later in life to cause shingles  It usually begins with mild constitutional symptoms that are followed shortly by skin lesions appearing in crops and characterized by macules, papules, vesicles, and crusting  Patients at risk of severe neurologic or other systemic complications (e.g. pneumonia) include adults, neonates, and patients who are immunocompromised or have certain underlying medical conditions BY PHARM MLACHA JO. 81
  • 82. BY PHARM MLACHA JO. 82
  • 83. In immunocompetent children, chickenpox is rarely severe but in adults and immunocompromised children, infection can be serious Generally, chickenpox presents with the following signs and symptoms ◦ Red macular rash with a central vesicle (blister) on the trunk, oral mucosa and scalp ◦ Pustules and crusting ◦ Intense pruritus ◦ Fever ◦ Occasional regional lymphadenopathy BY PHARM MLACHA JO. 83
  • 84. Treatment options for chickenpox include; Antiviral drugs e.g. acyclovir Antipyretic/analgesic e.g. Paracetamol Antipruritic agent i.e. Calamine lotion with phenol BY PHARM MLACHA JO. 84
  • 85. Herpes Zosters (Shingles) Herpes zosters is an infection due to resurgence or reactivation of theVaricella zoster virus (VZV) which also causes chickenpox Signs and Symptoms of Herpes zosters ◦ Severe burning pain ◦ Grouped vesicles overlying erythematous skin following a dermatomal distribution ◦ Typically, lesions do not cross the midline BY PHARM MLACHA JO. 85
  • 86. BY PHARM MLACHA JO. 86
  • 87. Treatment options Antiviral drugs e.g. acyclovir Antiseptics for the wounds e.g. Potassium permanganate 1:4000 solution Antibiotics for secondary bacterial infections Topical gentamycin Mupirocin BY PHARM MLACHA JO. 87
  • 88. Key Points Herpes is a group of over hundred viruses that belong to family herpesviridae Eight of the herpes are pathogenic to humans and they cause an initial illness then lie dormant in the body to be reactivated later Medically important herpes infections include herpes simplex virus infections, chickenpox and shingles BY PHARM MLACHA JO. 88
  • 89. Evaluation What is the treatment of chickenpox? How is oral herpes transmitted? What are the treatment options for genital herpes? BY PHARM MLACHA JO. 89
  • 90. Measles and Poliomyelitis 26 BY PHARM MLACHA JO. 90
  • 91. LearningTasks By the end of this session students are expected to be able to: Describe causative agents, transmission, signs and symptoms of Measle and poliomyelitis Describe treatment, prevention and control of Measle and poliomyelitis BY PHARM MLACHA JO. 91
  • 92. Measles Measles is an acute, highly communicable infectious disease caused by Measles virus. The mode of transmission is airborne, by droplet spread through coughing or sneezing or by direct contact with nasal or throat secretions of infected persons BY PHARM MLACHA JO. 92
  • 93. Who is at risk  Unvaccinated young children are at highest risk of measles and its complications, including death.  Unvaccinated pregnant women are also at risk.  Any non-immune person (who has not been vaccinated or was vaccinated but did not develop immunity) can become infected.  Measles is still common in many developing countries – particularly in parts of Africa and Asia.The overwhelming majority (more than 95%) of measles deaths occur in countries with low per capita incomes and weak health infrastructures. BY PHARM MLACHA JO. 93
  • 94. Transmission  Measles is one of the world’s most contagious diseases. It is spread by coughing and sneezing, close personal contact or direct contact with infected nasal or throat secretions.  The virus remains active and contagious in the air or on infected surfaces for up to 2 hours. It can be transmitted by an infected person from 4 days prior to the onset of the rash to 4 days after the rash erupts.  Measles outbreaks can result in epidemics that cause many deaths, especially among young, malnourished children. In countries where measles has been largely eliminated, cases imported from other countries remain an important source of infection. BY PHARM MLACHA JO. 94
  • 95. Signs and Symptoms Generalized, reddish (erythematous), blotchy (maculopapular) rash; History of fever usually above 38˚C (if not measured, then "hot" to touch) Dry cough, sore throat, runny nose (coryza) Inflamed eyes (conjunctivitis), tiny white spots with bluish-white centers on a red background found inside the mouth on the inner lining of the cheek- also called Koplik's spots In addition, children with measles frequently exhibit a dislike of bright light (photophobia), and often have a sore red mouth (stomatitis) BY PHARM MLACHA JO. 95
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  • 97. Treatment ◦ No specific antiviral treatment exists for measles virus ◦ Paracetamol ◦ Vitamin A ◦ Oxyetracycline ointment (for ocular involvement) Prevention ◦ Immunization with measles vaccine BY PHARM MLACHA JO. 97
  • 98. Poliomyelitis Poliomyelitis is an acute infection caused by a poliovirus (an enterovirus) Humans are the only natural host Asymptomatic and minor infections (abortive poliomyelitis) are more common than non- paralytic or paralytic infections by ≥ 60:1 and are the main source of spread The virus enters via the faecal-oral or respiratory route, then enters the lymphoid tissues of the GI tract A primary (minor) viremia follows with spread of virus to the reticuloendothelial system BY PHARM MLACHA JO. 98
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  • 101. Signs and symptoms include; A nonspecific minor illness (abortive poliomyelitis), sometimes aseptic meningitis without paralysis (non- paralytic poliomyelitis), and, less often, flaccid weakness of various muscle groups (paralytic poliomyelitis) Treatment Supportive Prevention ◦ This disease is preventable by immunization with polio vaccine starting at birth. Give 4 doses at intervals of 4 weeks. ◦ Parents should be told about theWorld program to eliminate Polio and the importance of actively participating. BY PHARM MLACHA JO. 101
  • 102. Key Points Measles is an acute, highly communicable infectious disease caused by Measles virus.And transmitted via respiratory droplets Important signs and symptoms of measles are cough, runny nose, conjunctivitis and photophobia Poliomyelitis is a debilitating disease caused by poliovirus and transmitted via faecal-oral route or respiratory route Both measles and poliomyelitis do have specific treatment and prevented by immunization BY PHARM MLACHA JO. 102
  • 103. Evaluation What are the effects of poliomyelitis? How is measles prevented? BY PHARM MLACHA JO. 103
  • 104. Viral Hepatitis 27 BY PHARM MLACHA JO. 104
  • 105. LearningTasks By the end of this session students are expected to be able to: Describe causative agents, transmission, signs and symptoms of viral hepatitis Describe treatment, prevention and control of viral hepatitis BY PHARM MLACHA JO. 105
  • 106. Cause andTransmission ofViral Hepatitis Hepatitis Hepatitis is the inflammation of the liver, which may result from various causes, both infectious i.e. viral, bacterial, fungal, and parasitic organisms and non-infectious e.g. alcohol, drugs, autoimmune and metabolic diseases AcuteViral Hepatitis Acute viral hepatitis is a systemic infection predominantly affecting the liver caused by hepatotropic viral agents namely Hepatitis A virus (HAV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), and Hepatitis E virus (HEV) In most cases, acute viral hepatitis leads to a self-limiting disease but can take a fulminant course and lead to hepatic failure BY PHARM MLACHA JO. 106
  • 107. Chronic viral hepatitis ◦ This is a chronic inflammatory reaction that on going beyond 6monts from the acute infection. ◦ Most common causative agents are HBV, HCV, and HDV which potentially leads to liver fibrosis, cirrhosis and portal hypertension, hepatocellular carcinoma and hepatic failure. BY PHARM MLACHA JO. 107
  • 108. Transmission of hepatitis viruses Hepatitis A virus (HBV) and hepatitis E virus (HEV) are transmitted by faecal-oral route through consumption of contaminated food or water BY PHARM MLACHA JO. 108
  • 109. Hepatitis A  Infection occurs in both epidemic and sporadic.Typical feature are:- ◦ GI upset (anorexia, vomiting, diarrhoea) ◦ Jaundice, tender and enlarged liver ◦ Abnormal liver function tests.  Clinical presentation ◦ History of direct exposure to a previously jaundiced individual ◦ Consumption of seafood or contaminated water ◦ Initial non-specific symptoms usually precede the development of jaundice by 5-10 days. ◦ Fever, anorexia and epigastric pain are the usual symptoms ◦ Darkening of the urine precede jaundice, which peaks in 1-2 weeks and then begins to subside. ◦ Tender hepatomegaly and jaundice are typically present; splenomegaly is variable. BY PHARM MLACHA JO. 109
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  • 111.  Treatment ◦ Supportive treatment: For pain give paracetamol 15mg/kg /dose).  Prevention ◦ General measures: Sanitation and hygiene that includes hand washing, proper disposal of infectious materials.  Mode of transmission: Mainly fecal - oral route. BY PHARM MLACHA JO. 111
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  • 113. Hepatitis B virus (HBV) BY PHARM MLACHA JO. 113
  • 114. Hepatitis B virus  Is transmitted through exposure to infective blood, semen, and other body fluids. HBV can be transmitted from infected mothers to infants at the time of birth or from family member to infant in early childhood.Transmission may also occur through transfusions of HBV- contaminated blood and blood products, contaminated injections during medical procedures, and through injection drug use BY PHARM MLACHA JO. 114
  • 115.  Clinical presentation ◦ The symptoms are non-specific, consisting only of slight fever (which may be absent) and mild gastrointestinal upset ◦ Visible jaundice is usually the first significant finding ◦ Dark urine and pale or clay-coloured stools ◦ Hepatomegaly is present ◦ Occasionally a symptom complex (caused by antigen-antibody complexes) of macular rash, urticarial lesion, and arthiritis. BY PHARM MLACHA JO. 115
  • 116. Treatment  Supportive ◦ Low fat diet, oral fluids ◦ Give paracetamol (dose as above) if pain present  Specific treatment ◦ The use of interferon alfa in children has not yet established ◦ Lamivudine  In children 2-11years-3mg/kg/once daily  In children 12-17 years and adults-100mg daily BY PHARM MLACHA JO. 116
  • 117.  Note: Patient Receiving lamivudine for concomitant HIV infection should continue to receive lamivudine in appropriate dose for HIV infection  There are two components for preventing hepatitis B: ◦ Prevention of transmission of the virus ◦ Immunization  Mode of transmission ◦ Mainly through parenteral, sexual and vertical transmission 5%  Immunization recommendations ◦ Hepatitis B vaccine is safe and effective, but should not be seen as an alternative to a strategy of prevention of transmission BY PHARM MLACHA JO. 117
  • 118. Hepatitis C virus (HCV) BY PHARM MLACHA JO. 118
  • 119. Hepatitis C virus (HCV) is mostly transmitted through exposure to infective blood.This may happen through transfusions of HCV-contaminated blood and blood products, contaminated injections during medical procedures, and through injection drug use. Sexual transmission is also possible, but is much less common.  Treatment ◦ Interferon alfa: Usual dose: SC, 5–10 million units 3 times weekly for 4–6 months. BY PHARM MLACHA JO. 119
  • 120. Signs and Symptoms ofViral Hepatitis Acute viral hepatitis ◦ Fever, anorexia, malaise, jaundice and abdominal pain ◦ Enlarged and tender liver ◦ Altered consciousness, coma (hepatic encephalopathy), and bleeding stigmata (in fulminant cases) Chronic viral hepatitis ◦ Usually asymptomatic ◦ Right upper quadrant abdominal pains ◦ Fatigue, malaise, anorexia, low grade fever; jaundice is frequent in severe disease ◦ Ascites, variceal bleeding, encephalopathy, coagulopathy, and hypersplenism ◦ Urticarial, arthritis, vasculitis, polyneuropathy, glomerulonephritis, thyroiditis BY PHARM MLACHA JO. 120
  • 121. Treatment, Prevention and Control ofViral Hepatitis Treatment of Acute Hepatitis AcuteViral Hepatitis ◦ There is no specific treatment to alter the course of acute viral hepatitis ◦ Supportive management including hydration, feeding, control fever and pain if present is required. ◦ Fulminant cases may require specific antiviral medications ChronicViral Hepatitis ◦ Hepatits BVirus  Tenofovir , Entecavir , Lamivudine ◦ Hepatitis CVirus  Ledpasvir , Sufosvir , Ribavirin BY PHARM MLACHA JO. 121
  • 122. Prevention and control of viral hepatitis Immunization Personal and environmental hygiene Safe sexual practices Safe blood BY PHARM MLACHA JO. 122
  • 123. Key Points Hepatitis is the inflammation of the liver, which may result from various causes, both infectious i.e. viral, bacterial, fungal, and parasitic organisms and non- infectious e.g. alcohol, drugs, autoimmune and metabolic diseases Viral hepatitis can be acute or chronic Acute viral hepatitis is a systemic infection predominantly affecting the liver caused by hepatotropic viral agents namely Hepatitis A virus (HAV), Hepatitis B virus (HBV), Hepatitis C virus (HCV), Hepatitis D virus (HDV), and Hepatitis E virus (HEV) Chronic hepatitis is most commonly caused by HBV, HCV, and HDV which potentially leads to liver fibrosis, cirrhosis and portal hypertension, hepatocellular carcinoma and hepatic failure. BY PHARM MLACHA JO. 123
  • 124. Evaluation What is hepatitis? How is viral hepatitis transmitted? What are the treatment options for viral hepatitis? BY PHARM MLACHA JO. 124
  • 125. END ALLTHE BEST BY PHARM MLACHA JO. BY PHARM MLACHA JO. 125