CHAPTER

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.

• Characterized by sudden onset of headache, fever,

prostration and cough.

• In more serious cases, it causes pneumonia.

• Fatal particularly for the young and the elderly.

 Infections agent:
• Three types of influenza virus (A, B & C)

• RNA viruses

• Group of family Orthomyxoviridae

• Mostly affects birds and mammals.

Infectious agent
 infections agent…
Influenza virus A:
• Wild aquatic birds are the natural hosts.
• Occasionally transmits to other species and may then
cause devastating outbreaks in domestic poultry or give
rise to human influenza pandemics.
• The most virulent human pathogens and cause the most
severe disease.
• Subdivided into different serotypes:
– H1N1= caused Spanish flu in 1918 and the 2009 flu
pandemic.
– H2N2 = caused Asian Flu in 1957.
– H3N2= caused Hong Kong Flu in 1968.
 infections agent…

Influenza virus B:
• This genus has one species (influenza B
virus).

• It exclusively infects humans.

• It is less common than influenza A.

 infections agent…

Influenza virus C:
• This genus has one species which infects humans,
dogs and pigs.

• Less common than the other types.

• Usually causes mild disease in children.

• Sometimes causing both severe illness and local

epidemics.
 Epidemiology:
• Occurs in pandemics, epidemics and
localized outbreaks (sporadically)

• Epidemics is associated with high mortality.

• Death occurs specially in children's, elderly

and those with chronic disease.
 Reservoir:
• Humans are the primary reservoirs for
human infection.

• Animals (birds, dogs, pigs)

 Mode of transmission:
• Spread in three main ways:
– By direct transmission (when an infected person
sneezes mucus directly into the nose or mouth of
another person).

– The airborne route (inhalation of aerosols produced by

an infected person coughing, sneezing or spitting).

– Through hand-to-nose, or hand-to-mouth transmission,

either from contaminated surfaces or from direct
personal contact such as a hand-shake.
Mode of transmission
 cont…
• The length of time the virus will persist on a surface
varies:

– One to two days on hard, non-porous surfaces such as

plastic or metal.

– For about fifteen minutes from dry paper tissues

– Only five minutes on skin.

– In mucus, longer periods (up to 17 days).

 cont…
Incubation period:
• Short (usually 1-3 days).

Period of communicability:
• 3-5 days from clinical onset in adults; up to 7days in
young children.

• Patients are most infective between the second and third

days after infection and infectivity lasts for around ten
days.

• Children are much more infectious than adults and shed

virus from just before they develop symptoms until two
weeks after infection.
 Susceptibility and Resistance:
• General (adult and children's are equally susceptible if
new subtype appears).

• The disease is severe in children, elderly, immuno-

compromized and those with chronic disease.

• When a new subtype appears, all children and adults are

equally susceptible.

• Infection produces immunity to the specific infecting

agent.
 Clinical picture:
• Symptoms of influenza can start quite suddenly one to two
days after infection.
• Fever with body temperatures ranging from 38-39 °C
• Extreme coldness (chills shivering, shaking)
• Cough (severe and protracted) - in children it causes
abdominal pain.
• Nasal congestion
• Body aches especially joints, back and throat
• Headache
• Myalgia and arthralgia
• Irritated, watering eyes
• Reddened eyes, skin (especially face), mouth, throat and
nose.
Cont…
 Diagnosis:

• Based on clinical ground.

• 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

• Zanamivir (trade name Relenza)

– Are designed to halt the spread of the virus in

the body.
– Often effective against both influenza A and B
 treatment…
• M2 inhibitors (adamantanes):
– Amantadine or
– Rimantadine
• Block a viral ion channel (M2 protein) and prevent the
virus from infecting cells.

• Effective against influenza A if given early in the

infection.

• Ineffective against influenza B (because B viruses do not

possess M2 molecules).
 Prevention:
1. Vaccination:
• Recommended for high-risk groups - may provide 70-80
% protection.
– Children
– Elderly Chronically sick people
– Immuno-compromised.
2. Good personal health and hygiene habits such as:
• Not touching your nose or mouth

• Frequent hand washing (with soap and water, or with

alcohol-based hand rubs)
 Prevention:
3. Preventing MOT:
– Covering coughs and sneezes
– Avoiding close contact with sick people
– Staying home yourself if you are sick.
– Avoiding spitting is also recommended.

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

–Single-stranded (RNA viruses).

 Occurrence:
• All over the world (Africa with no exception).
• Transmits by droplet spread or direct contact with
noise /throat secretions (the transmissibility of the
measles virus is very high).
• According to the World Health Organization (WHO),
measles is a leading cause of vaccine-preventable
childhood mortality.
• The fatality rate has been significantly reduced by a
vaccination campaign.
• Most commonly affects children (before age of 3 years
and in some cases 5yrs) and 90%of the cases occur
before age of 20 years.
Measles incidence/100,000
 Death from measles are determined by:
• Age: generally the younger children are at greatest risk.
• Gender: more in females.
• Socio - economic status: poor are more affected.
• Intensity of exposure: measles acquired in the household
carry greater risk of death.
• Vaccination status: non vaccinated
• Pregnancy
• Vitamin A deficiency
• Immunodeficiency (HIV, leukemia, corticosteroid therapy)
• Travel to areas where measles is endemic
 Cont…

Reservoir:
• Humans

Modes of Transmission:
– Air droplet inhalation (common)

– Direct contact with nasal/throat secretion.

– Indirectly by freshly contaminated articles

(less common)
 Cont…

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…

• Direct invasion of T lymphocytes and increased

levels of suppressive cytokines (interleukin 4) =
depression of cellular immunity.
• Infection of the entire respiratory tract accounts
for the characteristic cough and coryza.
• Generalized damage to mucosa and loss of cilia
 predisposes to secondary bacterial infections
(pneumonia and otitis media).
 Cont…

• Specific antibodies are not detectable before

the onset of rash.

• Immune reactions to the virus in the cells of

dermal capillaries result in development of
Koplik's spots and rash.

• Severe cases result in measles encephalitis

with focal hemorrhage, congestion, and
perivascular demyelination.
 cont…
Incubation period:
• Average 14 days (range 6–19 days)
• Transmission is higher slightly before the
prodromal period to four days after the appearance
of the rash.

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…

• The enanthema (Koplik spots):

– Predate the exanthema by 24-48 hours

– Last approximately 2-4 days.

– It is blue-white spots, about the size of kosher

salt grains, are surrounded by a red halo.
–
– They appear on the buccal mucosa opposite the
premolar teeth.
 cont…

• The rash appears on the skin (Exanthema):

– As slightly elevated papules begins on the face and
behind the ears.
– Within 24-36 hours following the onset of the rash,
– Spreads to the entire trunk and the extremities.
– Initially, the color is dark red
– Reaches its maximum intensity in approximately 3
days.
– It slowly fades to a purplish hue and then to yellow-
brown lesions with a fine scale over the following 5-
10 days.
Examthema
The appearance of the signs and symptoms of
measles are as follows:
• Days 0-1: Prodrome begins.

• Days 2-3: Koplik spots appear.

• Days 4-5: Morbilliform rash appears.

• Day 6: Koplik spots regress.

• Days 7-8: Rash is most intense.

• Day 10: Rash begins to resolve.

 Complications:
• Pneumonia
• Malnutrition (weight loss)
• Gastro-enteritis (diarrhoea, nausea, vomiting)
• Otitis media (red eardrum, ear discharge)
• Xerophthalmia (discharge from the eye, photophobia, hazy
cornea, dryness of the eye)
• Acute Encephalitis: (1 in 1000 cases)
• Cervical Adenitis: (Lymphoid hyperplasia due to immune
response)
• Subacute sclerosing panencephalitis (SSPE): 1 in 100,000
cases due prolonged reaction with defective measles virus.
 Diagnosis:
• History of fever of at least three days together with at least one
of the three C's (cough, coryza and conjunctivitis).
• Positive contact with other patients known to have measles adds
strong epidemiological evidence to the diagnosis.
• Observation of Koplik's spots is also diagnostic.
• Laboratory diagnosis:
– Positive measles IgM antibodies
– PCR: isolation of RNA from respiratory specimens.
• Other diagnostic tests
– Leukopenia especially Lymphopenia.
– Elevated hepatic transaminase levels = measles virus
hepatitis.
 Treatment
1. Supportive:
– Fluid, rest and diet considerations
– Anti-pain and antipyretics - young children should never
be given aspirin without medical advice due to the risk of
inducing a disease known as Reye's syndrome.
– Nutritional support
– Vitamin A supplements have been associated with
reduction in morbidity and mortality (by 50%).
• <6 months: 50, 000IU
• 6 months to 1 year: 100,000 IU PO
• >1 year: 200,000 IU PO
 cont…
2. Human Immunoglobulins or Ribavirin
• Recommended for immunocompromised:
– Infants aged 6 months to 1 year
– Infants younger than 6 months who are born to mother
without measles immunity
– Pregnant women
• Dose:
– Adult: 15 mL IM; divide dose into several muscle sites
to reduce local pain
– Pediatric: 0.25 mL/kg IM (0.5 mL/kg for patients with
HIV); not to exceed a cumulative dose of 15 mL; if dose
exceeds 10 mL, divide dose into several muscle sites to
reduce local pain
 cont…
3. Management of complications:
– Antibiotics: Bronchitis and pneumonia

– Convulsion: phenobarbital

– Xerophthalmia: CAF eye ointment.

– Encephalitis: Monitoring ICP

 Prevention
• Educate the public about measles immunization

• Immunization of all children (<5 years of age)

who had contact with infected children.

• Provision of measles vaccine at nine months of

age.
• Measles vaccination at 6 months of age during
epidemic and repeat at 9 months of age.
 y e l l o w f e v e r

Definition:
• It is an acute viral hemorrhagic fever transmitted by an
infected mosquito.

• Most of the time it is mild but sometimes it may cause

severe life threatening situations.

• The term “yellow” in the name is explained by the

jaundice that affects some patients, causing yellow eyes
and skin.

• 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.

• Has 3 transmission cycle:

– Sylvatic (jungle) cycle

– 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.

– The mosquito can pass the virus via infected

eggs to offspring's Vertical transmission.
 Period of communicability:
• Blood of the patient is infective for mosquito
shortly before the onset of fever and for the
first 3-5 days of fever.

• Mosquito is infective throughout its life and

can pass to generation.
 Susceptibility and resistance:
• Children born to endemic areas.

• Travelers to endemic areas

• Infection is followed by long lasting

immunity.

• Passive immunity in infants born to

immune mothers may persist up to 6month.
 Clinical presentation:
• Has a sudden onset and two disease
phases:

–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.

• Patient surviving till the 7th day of infection

recover spontaneously.
 Toxic phase:
15% of the patients enter the toxic phase in 24hrs and many
organs of the body are affected.
• Fever reappears
• Jaundice (because of the necrosis of liver tissue).
• Abdominal pain with vomiting.
• Headache
• Lumbosacral back pain
• Hepatic-induced coagulopathy produces hemorrhagic
manifestations, including the characteristic black vomit
(hematemesis), epistaxis, gum bleeding, and petechial and
purpuric hemorrhages.
• Kidney function deteriorates (Nephrosis)
• Albuminuria, Anuria and kidney failure
• Confusion, seizure, and coma - late CNS manifestations
 toxic phase:
• In the late stages of disease:
– Hypotensive shock

– Metabolic acidosis
– Acute tubular necrosis
– Myocardial dysfunction and arrhythmia

– Secondary bacterial infections are frequent

• Half of the patients in the toxic phase die within 10-14
days and other recover with significant organ damage.
 Diagnosis:
• Clinical presentation
• History of residence/travel to endemic areas.
• A complete blood count (CBC) often indicates leukopenia
and thrombocytopenia.
• Liver function test results may indicate elevated direct
bilirubin and hepatic transaminases.
• Albuminuria usually is noted with proportional rises in
BUN and creatinine levels.
• Serologic tests such as ELISA aid in making an exact
diagnosis.
• Polymerase chain reaction can be used to identify viral
ribonucleic acid (RNA) during acute infection.
 DDX:
• Malaria

• Relapsing fever

• Typhoid fever

• Viral hepatitis
 Complications:
• Hemorrhage

• Organ system failure

• 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…

3. Surveillance: promote early detection and rapid response

(emergency vaccination campaign)

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.

• It is an acute infectious disease of the liver caused by the

hepatitis A virus (HAV)

• It is most commonly transmitted by the fecal-oral route

via contaminated food or drinking water.

• Unlike hepatitis B and hepatitis C, it does not have a

chronic stage, is not progressive, and does not cause
permanent liver damage.
 Epidemiology:

• It is known to occur throughout the world.

• The risk of infection is greatest in developing

countries with poor sanitation or poor personal
hygiene standards.

• Occurs as an epidemics and outbreaks - because

of the way it is spread.

• Every year, approximately 10 million people

worldwide are infected with the virus.
 Virology (causative agent):
• The Hepatitis virus (HAV):

– 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.

• By eating raw or undercooked shellfish collected

from water that has been contaminated by
sewage.

• By blood transfusions (this is extremely rare).

 cont…
• Incubation period:
– The time between infection and the appearance of the
symptoms is between two and six weeks and the
average incubation period is 28 days.

• Period of communicability:
– People who are infected can start spreading the
infection about 1 week after their own exposure.

– HAV is excreted in large quantities approximately 11

days prior to appearance of symptoms
 Susceptibility and resistance:
• People at increased risk for hepatitis A infection:

– Household contacts of people infected with HAV.

– Sexual partners of people infected with HAV.
– International travelers, especially to developing
countries.
– Men who have sex with other men
– Users of illegal drugs (injected or non-injected)
 Pathogenesis:
• Following oral ingestion, HAV enters the bloodstream
through the epithelium of the oropharynx or intestine.
• Carried to the liver and multiplies within hepatocytes and
Kupfer cells (i.e., liver macrophages).
• There is no apparent virus-mediated cytotoxicity and liver
pathology is likely immune-mediated.
• Virion are secreted into the bile and released in stool (in
large quantities approximately 11 days prior to
appearance of symptoms).
• Mortality is less than 0.5%.
 Clinical presentation:
• Many people with HAV infection have no
symptoms.
• Sometimes symptoms are so mild that they go
unnoticed.
• Older people are more likely to have symptoms
than children.
• People who do not have symptoms can still
spread the virus.
• The symptoms are usually not too severe and go
away on their own, over time.
 cont…

1.Pre-icteric phase
– Nausea and Vomiting

– Diarrhea, especially in children

– Low-grade fever

– Loss of appetite

– Rash

– Tiredness and fatigue

 cont…

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…

• The rabies virus travels to the brain by

following the peripheral nerves.

• Once the rabies virus reaches the central

nervous system and symptoms begin to
show.

• The infection is effectively untreatable and

usually fatal within days.
 Occurrence:

• Worldwide.

• The vast majority of human rabies cases

(approximately 97%) come from dog
bites.

• Many cases are unreported (or greatly

underreported) in developing countries.
 Infectious agent:
• Rabies viruses: belongs to:
–Genus =Lyssavirus

–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).

• In some cases = longer than 1 year.

• Susceptibility to infection is related to several

factors:
– Size of inoculum
– Size and depth of bite
– Proximity to the CNS.
 Clinical presentation:
1.Prodrome: last from 2-10 days.
– Nonspecific fevers and pharyngitis.

– Pain or paresthesias at the site of bite or

scratch

– Headache

– Anorexia also may be present.

 Clinical presentation:
2. Neurologic stage: (2-7 days)
– Aphasia
– Incoordination and paralysis
– Hyperactivity
– Hypotension
– Disseminated intravascular coagulation
(DIC)
– Cardiac arrhythmias
– Cardiac arrest
– Mental status changes and coma
 Clinical presentation:
3.Late symptoms:
– The production of large quantities of saliva
and tears coupled with an inability to speak or
swallow.

– This can result in hydrophobia (patient has

difficulty swallowing because the throat and
jaw become slowly paralyzed) shows panic
when presented with liquids to drink.
 Physical Finding:
1.High fevers with rapidly progressive
encephalitis.
2.Increased lacrimation.
3.Hyper-salivation.
4.Agitation
5.Anxiety

N.B. The primary cause of death is usually

respiratory insufficiency !!!!
 Diagnosis:
• Cerebrospinal fluid:
– CSF may be normal or
– The protein level usually is elevated.
– Mildly increased CSF white blood cell (WBC)
and red blood cell (RBC)
• The rabies virus may be isolated from saliva, CSF,
serum, or nuchal skin samples.
• Detection of direct fluorescent antibody from the brain
or nerves surrounding hair follicles in the nape of the
neck (definitive diagnosis).
 Management:
• Emergency Department Care:
– Thoroughly cleaning all bite and
scratch wounds with soap and water.
– Provide wound care as needed.
– Tetanus prophylaxis to prevent
bacterial infection)

– Post exposure rabies prophylaxis

 Management:
• Vaccines:
– The 2 rabies vaccines currently available are:
• The human diploid cell vaccine (HDCV
Imovax) and
• RabAvert (rabies vaccine produced by Chiron).
– They are equal in efficacy and safety.
– Administered in the deltoid region with a dose
of 1 mL on days 0, 3, 7, 14, and 28.
– The vaccine takes 7-10 days to induce an
active immune response
– They last for approximately 2 years.
 Management:
• Passive immunization:
– With human rabies immune globulin (HRIG,
Hyper-ab) provides immediate protection with a
serum half-life of 21 days.
– Dose: 20 IU/kg infiltrated in and around the
wound (if wound location allows);
– Administer the rest intramuscularly in the gluteal
region, using a needle long enough to ensure an
intramuscular injection.
 Medication summary:
• Rabies immune-prophylaxis requires passive and active
immunization!!!
1. Human rabies immune globulin (HRIG, Hyperab,
Imogam):
– Provides passive protection to individuals exposed to rabies virus.
– 20 U/kg IM once after exposure.
– Preferably with first dose of rabies vaccine.
2. Rabies vaccine (RabAvert)
– Pre-exposure immunization: 1 mL IM on days 0, 3, 7, 14, and 28;
then every 2-5years depending on antibody titers.
– Post-exposure prophylaxis (previously unvaccinated patients):
HRIG (20 IU/kg) ASAP post exposure; followed by 1 mL/dose
vaccine IM on days 0, 3, 7, 14, and 28 (1 dose/d)
– Previously immunized patients (documented titers): IM doses on
days 0 and 3 (1 dose/d); do not administer HRIG.
 Medication summary:
3.Human diploid cell vaccine (HDCV, Imovax Rabies
Vaccine ID, Imovax Rabies Vaccine):
– Pre-exposure immunization: 1 mL Imovax IM
or 0.1 mL Imovax ID on days 0, 7, and 21-28;
then q2-5y, depending on antibody titers.
– Post-exposure prophylaxis: HRIG (20 IU/kg)
ASAP post-exposure, followed by 1 mL/dose
vaccine IM on days 0, 3, 7, 14, and 28 (1
dose/d).
– Previously immunized patients: 1 mL IM on
days 0 and 3; do not administer HRIG.
 Prevention:
• Avoid wild and unknown domestic
animals.

• Seek treatment immediately if

bitten.
Poliomyelitis
 Definition:
• It is often called polio or infantile paralysis.
• The term is derived from the word:
– Poliós (πολιός) meaning "grey"
– Myelós (µυελός) referring to the “spinal cord“ and

– The suffix - itis which denotes inflammation.

• It is an acute viral infectious disease which spread

from person to person, primarily via the fecal-oral
route.
 Ac
ute
wi
tho Flac
ut cid
Se
nso Para
ry lysi
Lo s
ss
 Epidemiology:
• Wild polioviruses can infect the entire human population.
• It is seasonal in temperate regions with peak transmission
occurring in summer and autumn.
• An outbreak mostly affects children, pregnant women,
and the elderly.
• 90% of polio infections cause no symptom at all.
• In about 1% of cases the virus enters the CNS, infecting
and destroying motor neurons, leading to:
– Muscle weakness;
– Acute flaccid paralysis without sensory loss
 Infectious agent:
• The poliovirus:
– Enteroviruses within the Picornaviridae family.
– Three serotypes of poliovirus each with a slightly
different capsid protein.
• Poliovirus type 1 (PV1)
• Poliovirus type 2 (PV2), and
• Poliovirus type 3 (PV3).
– All three are extremely virulent and produce the
same disease symptoms.
– PV1 = the most common form and closely
associated with paralysis.
 Occurrence:
• They multiply in the GI tract and can be
potentiated by factors such as exercise and
tonsillectomy.
• Patients who are immune-compromised: are
particularly at high risk when exposed to both
wild-type polioviruses and vaccine-attenuated
viruses
– HIV infection
– B-cell dysfunction
– Immunoglobulin A (IgA) deficiency or
– Severe combined immunodeficiency
 Mode of transmission:
• By contact with infected feces.

• By direct person-to-person contact.

• By contact with infected mucus from

the nose or mouth.
PATHOGENESIS
 Cont…
• Incubation period:
– Ranges from 5 - 35 days (average 7 -
14 days).

• Susceptibility and resistance:

– Lack of immunization against polio.

– Travel to an area that has experienced

a polio outbreak.
Clinical Manifestation:
• Asymptomatic
A (unapparent infection) –
90-95%

• 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:

The goal of treatment:

To To save life
control especially
symptom breathing
help.
s
 Management:

1.Medical care:

• No antivirals
are effective
NB against
polioviruses.
 2. Supportive Rx:

Antibiotics for urinary tract infections.

Medications (such as bethanechol) for urinary retention.

Analgesics for headache, muscle pain and spasms.

Moist heat (heating pads, warm towels) to reduce muscle pain

and spasms.

Mechanical ventilation is often needed in patients with bulbar

paralysis.

Tracheostomy care is often needed in patients who require long-

term ventilator support.

Laxatives: to treat fecal impaction.

 3. Physical Therapy

•Braces or corrective shoes, or

orthopedic surgery to help recover
muscle strength and function.
 4. Surgical care:
• Total hip arthroplasty = for patients with
paralytic sequelae of poliomyelitis who
develop hip dysplasia and degenerative
disease.

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.

• Brain or spinal cord involvement is a medical

emergency (may result in paralysis or death).

• Disability is more common than death.

• Infection high in the spinal cord or in the brain

increases the risk of breathing problems
 Possible Complications:
• Aspiration pneumonia
• High blood pressure
• Kidney stones
• Lack of movement
• Lung problems
• Myocarditis
• Paralytic ileus (loss of intestinal function)
• Permanent muscle paralysis, disability, deformity
• Pulmonary edema
• Shock
• Urinary tract infections
 Prevention:
• Polio vaccine effectively prevents poliomyelitis in most people (over
90% effective):
– Decrease the prevalence of disease throughout the world.
– Induce mucosal immunity and herd immunity.
– Increase vaccine uptake because of oral administration.
– Cost-effective, especially in countries in the developing world.
• The major disadvantage of trivalent OPV is its association with
vaccine-associated paralytic poliomyelitis (VAPP).
• VAPP occurs most frequently after the first dose of OPV but may also
occur after administration of the second or third doses.
• Administered at 6, 10 and 14 week and with a booster at age 4 years.
HIV/AIDS
 History of HIV/AIDS:
• AIDS was first recognized in the United States in
the summer of 1981 in the U.S. CDC.
• It is recognized following the occurrence of PCP
in five previously healthy homosexual men in
Los Angeles.
• In 1983 HIV was isolated from a patient with
lymphadenopathy
• By 1984, HIV was demonstrated clearly to be the
causative agent of AIDS.
 Etiology:
• HIV: is human immunodeficiency virus:
– Belongs to the family Retroviridae and the
subfamily of lentiviruses.
– The four recognized human retroviruses belong
to two distinct groups:
• The human T lymphotropic viruses (HTLV)-I
and
• The human T lymphotropic viruses (HTLV-
II)
– The HIV -1 and HIV -2 cause cytopathic
effects either directly or indirectly.
 Etiology…

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

• Are zoonotic infection: which is reserved

in Pan troglodytes troglodytes species of
chimpanzees .
• More virulent.
• Associated with faster disease progression

• Higher mother to child transmission

MTCT/ rate.
• Higher transcription rate.
 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…

5.Reverse transcription of the genomic RNA into DNA and

the protein coat opens to release the DNA (by viral
reverse transcriptase enzyme).
6.The pre-integration complex traverses the cytoplasm to
reach the nucleus.
– At this point in the replication cycle, the viral genome
is vulnerable to cellular factors that can block the
progression of infection.

7.The viral DNA integrates in to the host’s nucleus by

enzyme “integrase”. The viral DNA accesses the nuclear
pore and is exported from the cytoplasm to the nucleus,
where it is integrated into the host cell chromosomes.
 Replication…

8. Transcription of HIV DNA to mRNA then translated into

proteins (undergo modification through glycosylation,
phosphorylation and cleavage) = Nucleic acid and Capsid
protein are produced).
9. The viral particle is formed by the assembly of HIV
proteins, enzymes and genomic RNA at the plasma
membrane of the cells.
10.Budding of the progeny virion in the lipid bilayer of the
host cell membrane (known as lipid rafts) = core acquires
its external envelope.
11.The virally encoded protease then catalyzes the cleavage
to yield the mature virion.
 Modes of Transmission:
• MTCT: pregnancy, labor, delivery
and breastfeeding.
• Sexual ( anal, vaginal, oral) abuse.
• Blood transfusion
• Use of syringes and needles which
are contaminated
 Modes of Transmission:

HIV cannot be transmitted by:

• Other body fluids: tears, saliva, Urine
• Personal contact, social kisses
• Social contact: eating from same plate.
• Insect bites: mosquitoes
• Air or water…
 Mother to child transmission of HIV:
• MTCT of HIV could occur:
– Intrauterine – less common (36%) without any
intervention or Rx.
– During labor and deliver: is most common route.
– Through breast feeding
• Intrauterine transmission is less common.
– Without any intervention ≈ 35% of infants born
from HIV positive mothers become infected.
– With current available interventions this can be
reduced up to 5-10%
 Factors associated with Increased MTCT:
• High maternal viral load and • Anemia
low CD4 count • Malaria
• Advanced stage of HIV • Prolonged duration of breast
• Maternal nutritional status feeding and mixed feeding
• Presence of breast abscess,
• Prolonged labor
mastitis, nipple crack
• Presence of STD
• Oral or GI lesions in the child
• Premature rupture of • Twin pregnancy – 1st twin is a
membrane high risk during birth
• Vaginal delivery compared
to CS
• Obstetric procedures e.g.
episiotomy, artificial ROM
CD4 Count and Opportunistic Infections:
 WHO Grading of HIV:
Stage I – asymptomatic:
– Asymptomatic or

– Persistent generalized lymphadenopathy

(PGL): is painless swollen lymph nodes will
present bilaterally in the cervical area, under
the arm, or groin.

– Performance scale 1: able to carry on normal

activity
 WHO Grading of HIV:
Stage II
– Moderate unexplained weight loss (<10% of
body weight)
– Recurrent upper respiratory tract infections.
– Herpes zoster
– Angular cheilitis and recurrent oral ulcerations
– Papular pruritic eruptions
– Seborrheic dermatitis
– Fungal fingernail infections
– Performance scale 2
 WHO Grading of HIV:
Stage III:
– Severe weight loss (>10% body weight)
– Unexplained chronic diarrhea > 1months.
– Unexplained persistent fever (intermittent or constant >
1mo.)
– Oral candidiasis
– Oral hairy leukoplakia
– Pulmonary tuberculosis (TB)
– Severe bacterial infections
– Ulcerative stomatitis, gingivitis or periodontitis
– Unexplained anemia (<8 g/dl)
– Neutropenia (<500/mm3) and Thrombocytopenia (<50
000)
 WHO Grading of HIV:
Stage IV:
– HIV wasting syndrome
– Pneumocystis carinii pneumonia
– Chronic herpes simplex infection (orolabial, genital or an-rectal of more
than one month’s duration)
– Esophageal candidiasis
– Extra pulmonary TB
– Kaposi’s sarcoma
– Central nervous system (CNS) toxoplasmosis
– HIV encephalopathy
– Extra pulmonary cryptococcosis including meningitis
– Disseminated non-tuberculous mycobacteria infection
– Progressive multifocal leukoencephalopathy (PML)
– Candida of trachea, bronchi or lungs
– Cryptosporidiosis
– Isosporiasis
– Visceral herpes simplex infection
 Diagnosis:
• Serology
– Enzyme Linked Immunosorbent Assay (ELISA)
– Western blot (Confirmatory Test)
– Rapid test
– p24 antigen
• Virus culture
• Polymerase Chain Reaction
– Qualitative: detect early infection
– Quantitative (viral load): Amount of viruses.
• Lymphocyte phenotyping: CD4 count“flow-
cytometry”
 Diagnosis:
T e st 1 ,2

Pos 1 & 2 D isco rd a nt Neg 1 & 2

p o sitive T e st 3 N e ga tive

R e p ort p ositive R e po rt n e ga tive

P o sitive N e ga tive
 Serial Testing Aligorisms

SERIAL TESTING ALGORITHM

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.

• The second-line regimen is stronger because the

virus has not yet developed a way to avoid the
drugs.
• Even second-line regimen can fail, if not taken
well.