Chapter 4 (Viral Infection) .
Chapter 4 (Viral Infection) .
Chapter 4 (Viral Infection) .
FOUR
VIRAL
INFECTIONS
WHAT
IS
VIRUS??
Introduction
Viruses:
• are ultra-microscopic structures/particles that are
very small to be seen with naked eyes.
• are Small 20-300nm in diameter.
• are obligate Intracellular parasites.
• do not have nucleus and organelles such as
ribosomes, mitochondria
• contain either DNA or RNA.
• can infect all forms of life including bacteria.
Introduction
Viral Structures:
• Viruses are unicellular organisms with following
structures:
1. Nucleic Acids - genetic information (DNA or RNA)
2. Protein Coats:
a. Capsid:
• Protect the genetic material.
• Mediate attachment to specific receptors on the host
cell.
b. Envelop (some viruses):
• It is virus specific lipoprotein composed of lipid
derived from host cell membrane.
I n tr o d u c tio n
c. Matrix Protein:
• Mediates interaction between the capsid
protein and envelope.
• Surface proteins of viruses are the principal
antigen to form protective antibody.
• Determinants of type specificity.
3. Enzymes:
• Protease
• Transcriptase
• Integrase
Introduction
Introduction
Major Groups of Viruses:
1. DNA Enveloped viruses
• Herpes viruses (HSV): Cause painful vesicles on
the face & genitals.
• Hepatitis B virus
– Viral hepatitis
– Hepatocellular carcinoma
2. DNA non-enveloped viruses
• Adenovirus - Causes upper and lower respiratory
infections e.g. Pharyngitis, pneumonia
• Papillovirus - cause papilomas of the skin &
mucous membrane.
I n tr o d u c tio n
3. RNA enveloped viruses
• Influenza viruses
• Para influenza (Common cold)
• Rabies virus
• HIV
• HTLV
4. RNA non-enveloped viruses
• Entero virus -e.g. Poliovirus
• Rhinovirus - cause common cold
• Hepatitis A virus causes hepatitis
(transmission: feco -oral).
Introduction
GENERAL STEPS IN VIRAL REPLICATION
A. Attachment, penetration & un-coating
• Attachment:
– Interaction of a virus with a specific receptor on the
surface of a host cell.
– Example:
• HIV - binds to CD4 receptor on T-cells,
macrophages & monocytes
• Rhinovirus - bind ICAM-1
• EBV -CD21 on B-cells
– The presence or absence of receptors plays an
important role in determining of cell tropism & viral
pathogenesis.
Introduction
• Penetration:
– After binding the virus is taken up inside the
cell by:
• Receptor mediated endocytosis.
• Direct penetration.
• Fusion of viral envelop with plasma
membrane of host cell.
• Un-coating:
– With or after penetration physical separation
of the viral nucleic acid from outer coat.
I n tr o d u c tio n
B. Expression of viral genomes and synthesis of viral
components:
– Transcription of specific mRNA from viral nucleic acid and
translation of mRNA by using cells components.
– Early synthesis of enzymes which enables the virus nucleic
acid to replicate rapidly.
– Late synthesise of capsid proteins.
C. Assembly and Release
• Assembly:
– Newly synthesized Nucleic acids and capsid assemble.
• Release:
– Infected cells lyses and release the virus (non-enveloped)
Influenza
• Influenza, commonly referred to as the flu, is an acute
infectious respiratory tract disease caused by the
influenza viruses.
• RNA viruses
Influenza virus B:
• This genus has one species (influenza B
virus).
Influenza virus C:
• This genus has one species which infects humans,
dogs and pigs.
Period of communicability:
• 3-5 days from clinical onset in adults; up to 7days in
young children.
• Viral culture
Treatment:
Same as common cold:
1. Supportive Management:
– Plenty of rest.
– Drink plenty of liquids.
– Avoid using alcohol and tobacco.
– Acetaminophen to relieve the fever and muscle aches.
– Children and teenagers with flu symptoms should
avoid taking aspirin during an influenza infection
(especially influenza type B).
– Because it can lead to Reye's syndrome (potentially
fatal disease of the liver).
Management
Treatment…
2. Pharmacological Treatment:
• Secondary infections such as bacterial
pneumonia can be treated by antibiotic.
• Antiviral medication can be effective, but
some strains of influenza can show resistance
to the standard antiviral drugs.
• The two classes of antiviral drugs used
against influenza are:
– Neuraminidase inhibitors and
– M2 protein inhibitors (adamantane derivatives).
treatment…
• Neuraminidase inhibitors:
– Antiviral drugs such as
• Oseltamivir (trade name Tamiflu) and
4. Chemoprophylaxis:
– Amantadine for IVA - 100mg PO BID is effective in
the chemo prophylaxis of type A virus but not others.
Measles
Definition:
• It is an infection of the respiratory system caused by a virus
specifically a paramyxovirus of the genus Morbillivirus.
• It is a highly contagious acute viral disease characterized by:
– Fever
– Runny nose
– Cough
– Conjunctivitis and lacrimation
– Macula-papular rash.
• 70 million cases develop measles annually & 2 million die.
• Generally the disease affects children less than 5 years.
Infectious Agent
• Measles virus:
– Family – Paramyxovirus.
– Genus - Morbillivirus.
–Enveloped
Reservoir:
• Humans
Modes of Transmission:
– Air droplet inhalation (common)
Pathogenesis:
• Measles virus invades the respiratory
epithelium.
• Spreads via the bloodstream to the reticulo-
endothelial system
• Infects WBCs and establishes infection of the
skin, respiratory tract, and other organs.
• Both viremia and viruria develop.
• The major infected cell in the blood is the
monocyte.
Cont…
Period of communicability
• From 2–4 days prior to rash
• Until 2–5 days following the onset of the rash (i.e.
4–9 days infectivity in total).
• The transmission is minimal after second day of
rash.
Signs and symptoms
• The prodrome develops on day zero following
incubation includes:
– Fever: a temperature often exceeding 104°F (40°C)
begins with the prodrome and persists 7-10 days.
– 3 C's of measles: cough, coryza and conjunctivitis.
– Photophobia are also common during this period.
– These symptoms increase in severity up to 3-4 days
prior to the onset of the morbilliform rash.
cont…
– Convulsion: phenobarbital
Definition:
• It is an acute viral hemorrhagic fever transmitted by an
infected mosquito.
• It is preventable by immunization.
Epidemiology:
• The WHO estimates that yellow fever causes 200,000
illnesses and 30,000 deaths every year in unvaccinated
populations
• Around 90% of the infections occur in Africa.
• A safe and effective vaccine against yellow fever has existed
since the middle of the 20th century and some countries
require vaccinations for travelers.
• Since the 1980s, the number of cases of yellow fever has been
increasing (making it a re-emerging disease).
• Tropical Africa is internationally regarded as “endemic
zone”.
• The disease occurs only in Africa and South America.
Epi…
Infectious agent:
• Yellow fever is caused by the yellow fever virus:
– Enveloped RNA virus
– Belongs to the family Flaviviridae
– 40 to 50 nm wide
Mode of transmission:
• Mainly transmitted through the bite of the yellow fever
mosquito Aedes aegypti, but other mosquitos such as the
" tiger mosquito" (Aedes albopictus) can also serve as a
vector for the virus.
– Intermediate cycle
– Urban cycle
MOT…
Sylvatic cycle:
• Occurs in monkey that are infected by wild mosquito
• The infected monkey passes the virus to other mosquitoes that
fed on them.
• The infected wild mosquito bites humans entering the forest
resulting in sporadic case of YF.
Intermediate cycle:
• Infected mosquito infects both monkey and human hosts.
• Zone of emergence (small epidemic occur starts)
Urban cycle:
• Large epidemic can occur when migrants introduce the virus
into areas with high human population density.
• Domestic mosquito carries the virus from person to person.
• Monkeys are not involved in this cycle
MOT…
• The virus is carried:
– From animal to animal (from human to human,
monkeys to human) by mosquito Horizontal
transmission.
–Acute phase
–Toxic phase
Acute phase:
• Characterized by:
– Fever (high grade, paradoxically associated with low
pulse)
– Muscle pain (prominent back ache)
– Head ache
– Loss of appetite
– Nausea and vomiting.
• After 3-4 days most patients improve and their
symptoms disappear gradually.
– Metabolic acidosis
– Acute tubular necrosis
– Myocardial dysfunction and arrhythmia
• Relapsing fever
• Typhoid fever
• Viral hepatitis
Complications:
• Hemorrhage
• CNS damage
• Liver damage
Management:
No specific treatment !!!!!!!
1. Supportive management
– V/s monitoring
– Antipain and antipyretics
– Avoid further infection
– Diet and fluid consideration.
2. Histamine H2 antagonists:
– Adjunctive therapy to prevent gastric bleeding.
– Famotidine
– Nizatidine
– Ranitidine
3. Antiviral drugs:
– Ribavirin
Prevention and control:
1. Vaccination of children's greater than 9 month of age who are borne
in endemic areas.
2. Travelers should take the following cares:
– Vaccination should be taken or
– Wear long sleeved clothing
– Treat clothing with insecticide
Note:
• YF vaccination is:
– Live attenuated virus.
– Highly recommended for journeys into affected areas.
– Its protective effect is established 10 days after vaccination in 95%
of the vaccinated people and lasts for at least 10 years.
– Even 30 years later, 81% of patients retained the immunity.
prevention and control…
4. Mosquito control
– Eliminating mosquito breeding sites.
– Insecticide.
– Use insect repellant on the exposed part of the skin.
– Spray living and sleeping areas with insecticide.
– Use bed net
H E PAT I T I S A
Definition:
• Hepatitis A = formerly known as infectious hepatitis.
– Picornavirus
– Non-enveloped
– Single-stranded RNA.
– Has only one serotype but multiple genotypes
exist.
Mode of transmission:
Fecal-oral transmission:
• By drinking food or drinking water becomes
contaminated with stool from an infected person.
• Period of communicability:
– People who are infected can start spreading the
infection about 1 week after their own exposure.
1.Pre-icteric phase
– Nausea and Vomiting
– Low-grade fever
– Loss of appetite
– Rash
2.Icteric phase
– Jaundice - a yellow discoloration of the skin
and the sclera.
– Urine is dark brownish in color, like cola or
strong tea due to excretion of bile.
– Sharp pains in the right-upper quadrant of
the abdomen - in area of liver
– Weight loss
– Feces tend to be light in color due to lack of
bilirubin in bile.
– Dehydration - if the vomiting is severe.
Diagnosis (Exams and Tests):
• Sign and symptoms and history.
• Blood test
• Serum IgG, IgM and ALT following Hepatitis A virus infection are
used in the diagnosis of hepatitis.
– IgM antibody is only present in the blood following an acute
hepatitis A infection.
– The presence of IgG antibody in the blood means that the acute
stage of the illness is past and the person is immune to further
infection.
– The liver enzyme alanine transferase (ALT) is present in the
blood during the acute stage of the infection.
• Hepatitis A virus is present in the blood and feces of infected
people up to two weeks before clinical illness develops.
Management:
• There are no specific medicines to cure infection with hepatitis A.
Most people require no treatment except to relieve symptoms.
• The following measures can help you feel better while you are
having symptoms:
– Rest
– Drink plenty of clear fluids to prevent dehydration.
– Avoid medicines and substances that can cause harm to the
liver.
– Avoid alcoholic beverages, as these can worsen the effects of
HAV on the liver.
– Avoid prolonged, vigorous exercise until symptoms start to
improve.
– Eat fat free diet
– Carbohydrate high diet (Balanced diet)
Prevention and control:
• Hepatitis A can be prevented by vaccination, good hygiene and
sanitation.
• Avoid surfing or going in the ocean after rains in coastal areas
that are known to have bad runoff.
• Proper human excreta disposal.
• Safe and adequate water supply.
• Proper processing of foods (specially vegetables and fruits).
• Screening food handlers.
• The vaccine protects against HAV in more than 95% of cases
for 10 years.
– The vaccine is given in two doses in the muscle of the upper arm.
– The first dose provides protection two to four weeks after initial
vaccination;
– The second booster dose, given six to twelve months later, provides
protection for up to twenty years.
Rabies
Definition:
• Rabies is a viral disease of the central nervous system
(CNS); it is one of the oldest and most feared diseases
reported in medical literature.
• Causes acute encephalitis (inflammation of the brain) in
warm-blooded animals.
• It is zoonosis acquired most commonly by a bite from an
infected animal but occasionally by other forms of
contact.
• Invariably fatal if post-exposure prophylaxis is not
administered prior to the onset of severe symptoms.
cont…
• Worldwide.
–Family = Rhabdoviridae
–Has bullet-shape
–RNA viruses
Mode of transmission:
• Bite of terrestrial animals = 5-80% carry the risk.
• Non-bite exposures include being scratched, being licked
over an open wound or mucus membrane, or exposure to
brain tissue or cerebrospinal fluid (CSF) of a rabid
animal.
• Non-bite exposures from bats are the exception and
respiratory exposure from bats.
• Woodchucks are an exception and have been shown to
carry rabies.
• Direct human-to-human transmission of rabies has not
been documented.
• Intact skin contact with urine, blood, or feces of an
animal is not infectious except in bats.
Incubation period:
• 5 days to 1 year (average 20-90 days).
– Headache
• Pre-paralytic Phase:
• Fever
• Sore throat and redness
B • Myalgia
• Anorexia
• Stomach upset (nausea,
vomiting and Stomach aches)
• Loose stool
Clinical Manifestation…
•None – paralytic
poliomyelitis: last 1 - 2 weeks
•Involvement of CNS without
signs of paralysis and
subsides without sequale.
•Signs of meningeal irritation
C (neck stiffness and pain, back
pain,…)
•Headache
•Diarrhea and vomiting
•Excessive tiredness and
fatigue
•Leg pain (calf muscles)
Clinical Manifestation…
• Paralytic poliomyelitis:
• Flaccid paralysis of a group
of muscles associated with
fever, myalgia, neck rigidity,
• Abnormal sensation (No loss
of sensation)
• Bloated and Constipation
D • Breathing difficulty
• Difficulty in beginning to
urinate
• Drooling
• Headache
• Asymmetrical muscle
weakness
• Sensitivity to touch
Diagnosis:
• Clinical:
– Signs of meningeal irritation : stiff neck or back stiffness with
difficulty bending the neck.
– Difficulty lifting the head or lifting the legs when lying flat on
the back and their reflexes might be abnormal.
• Epidemiological Grounds
• Tests include:
– Routine CSF examination
– Antibodies to the polio virus
– Viral cultures of throat washings, stools, or CSF
– A 4-fold increase in the immunoglobulin G (IgG) antibody titers
during acute stage is diagnostic.
Management:
To To save life
control especially
symptom breathing
help.
s
Management:
1.Medical care:
• No antivirals
are effective
NB against
polioviruses.
2. Supportive Rx:
5. DIET:
– Diet rich in fiber is usually indicate:
because they are prone to develop
constipation.
Prognosis:
• Complete recovery is likely in case more than
90% - if CNS are not involved.
HIV 1:
• The most common cause of HIV disease
throughout the world.
• Comprises several subtypes with different
geographic distributions:
– Group M (major) worldwide and has nine subtypes
or clades: (designated as A, B, C, D, F, G, H, J, and
K)
– Group O (outlier), a relatively rare viral form found
originally in Cameroon, Gabon, and France; and
– Group N first identified in a Cameroonian woman
with AIDS
Etiology
HIV 2:
• First identified in 1986 in West African.
• More closely related to the simian
immunodeficiency virus (SIV).
• Less pathogenic when compared to
HIV -1.
Structure of HIV:
• HIV has outer double lipid layer.
• Surface glycoproteins or envelope proteins: Gp120 and
gp41
• Core with several proteins: P24, p17 …
• Two single stranded RNA;
• HIV contains 3 enzymes:
– Reverse transcriptase: converts RNA to DNA.
– Integrase: integrate newly formed DNA into host
DNA.
– Protease: splits the synthesized proteins which can be
incorporated in new virion.
Replication Cycle of HIV:
1.Binding of the gp120 protein to its receptor on the host
cell surface (the CD4 molecule).
2.Once gp120 binds to CD4, the gp120 undergoes a
conformational change that facilitates binding to one of a
group of co-receptors (CCR5 and CXCR4) - used for entry
into the cell.
3.Fusion and penetration with the host cell membrane via
the newly exposed gp41 molecule.
4.Following fusion, the pre-integration complex (viral RNA
and enzymes surrounded by a capsid coat) is released into
the cytoplasm of the target cell.
Replication…
p o sitive T e st 3 N e ga tive
P o sitive N e ga tive
Serial Testing Aligorisms
Test 1
STEP - 1
SCREENING
REACTIVE
NEGATIVE
A second test to confirm
Client receives the result of the first test
NEGATIVE result
STEP - 2
CONFIRMATORY
NEGATIVE Positive
Use a third test Client receives
to break the tie POSITIVE result
STEP - 3
TIE- BREAKER
NEGATIVE REACTIVE
Client receives Client receives
NEGATIVE result POSITIVE result
Treatment:
The main classes of drugs used against HIV are:
• Nucleoside analogues (Inhibit DNA synthesis and make it useless)
– Zidovudine
– Stavudine
– Lamivudine
• Non-nucleoside reverse transcriptase inhibitors (Bind to enzyme reverse
transcriptase and prevent conversion of RNA to DNA)
– Neverapine
– Delaverdine
– Efavirenz
• Protease inhibitors (Block enzyme protease and prevent the virus not to infect new
cells)
– Saqiunavir
– Nelfinavir
– Indinavir
– Retonavir, etc
• Fusion inhibitors (Prevent fusion of HIV to CD4 cells)
– Fuzeon
Requirements to Start ART at Health Center
Level:
• Requirement 1: HIV positive with written documentation
of a positive test).
• Requirement 2: Medical eligibility—start only patients
with medical eligibility for ART:
• If CD4 count available:
– WHO stage IV irrespective of CD4.
– WHO stage III with CD4 ≤ 350/mm3.
– CD4 < 200/mm3 irrespective of the clinical stage.
• If CD4 count not available:
– WHO stage IV irrespective of TLC.
– WHO stage III irrespective of TLC.
– WHO stage II with TLC < 1200/ mm3.
Treatment:
• A first-line regimen is a combination of drugs that will
be used in a patient who has no prior ART experience.
• This means that the patient has never taken ARV drugs
before.
• Most commonly, a first-line regimen will consist of two
NRTI's and one NNRTI.
• There are four main first-line regimens:
– d4T-3TC-NVP
– d4T-3TC-EFV
– AZT-3TC-NVP
– AZT-3TC-EFV
Treatment:
• Second Line Regimens are used when the first-
line therapy will not be effective anymore.
• Usually, the second-line regimen will consist of 2
NRTIs (previously unused) + 1 PI.