VIROLOGY
GENERAL PROPERTIES OF VIRUSES
They don't fall into the category of unicellular organisms
as they don’t possess a cellular organisation
 They don’t have cellular organisation and contains
either DNA or RNA but never both.
 They are obligate intracellular parasites.
 Multiply by complex process
 They cause large number of diseases such as common
cold to rabies ,AIDS
 The control of bacterial infection with antibiotics has
enhanced the role of viral infections in human diseases
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MORPHOLOGY:
 SIZE: smaller than bacteria,can not be seen under
light microscope, the largest of them is 3oonm as large
as the smallest bacteria
 STRUCTURE AND SHAPE:
1.
two types of symmetry are seen: ICOSAHEDRAL AND
HELICAL
 Virions may be enveloped or non enveloped(naked)
 The envelope is lipoprotein in nature
 Envelop confers chemical,antigenic and biological
properties on viruses.
 They are susceptible to the action of lipid solvents like
ether,chloroform and bile salts
 Viruses are of different shape: spherical, irregular,
rabies virus is bullet shaped
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Chemical properties: viruses contain only one
type of nucleic acid either single or double
stranded DNA or RNA
 Resistance : mostly heat labile, can be
inactivated within seconds at 56⁰c, minutes at 37
⁰ c and days at 4 ⁰c. they are stable at low
temperature
 For long term storage they are kept frozen at -70
⁰c or lyophillization /freeze drying
 Viruses can be inactivated by sinlight,UV rays
and ionizing radiations.
 More resistant than bacteria to chemical
disinfection
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VIRAL HEMAGGLUTINATION
Many viruses are shown to agglutinate
erythrocyte fro different species
 In influenza virus Hemagglutinins and
neuroaminidases/receptor destroying enzyme
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CULTIVATION OF VIRUSES
Cannot be grown on any inanimate culture media
 The methods are
1. Animal inoculation :monkeys and mice
2. Embryonated hen’s egg
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3.
Cell culture: organ culture, explant culture ,cell culture
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Detection of Virus-Infected Cells
Multiplication of a virus can be monitored in a variety of ways:
1. Development of cytopathic effects, ie, morphologic changes in the
cells. Types of virus-induced cytopathic effects include cell lysis or
necrosis, inclusion formation, giant cell formation, and cytoplasmic
vacuolization
2. Appearance of a virus-encoded protein, such as the
hemagglutinin of influenza virus. Specific antisera can be used to
detect the synthesis of viral proteins in infected cells.
3. Adsorption of erythrocytes to infected cells, called
hemadsorption, due to the presence of virus-encoded hemagglutinin
(parainfluenza, influenza) in cellular membranes. This reaction
becomes positive before cytopathic changes are visible and in some
cases occurs in the absence of cytopathic effects .
4. Detection of virus-specific nucleic acid. Molecular-based assays
such as polymerase chain reaction provide rapid, sensitive, and
specific methods of detection.
5. Viral growth in an embryonated chick egg may result in death of
the embryo (eg, encephalitis viruses), production of pocks or plaques
on the chorioallantoic membrane (eg, herpes, smallpox, vaccinia), or
development of hemagglutinins in the embryonic fluids or tissues
(eg, influenza).
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INCLUSION BODY FORMATION
In the course of viral multiplication within cells,
virus-specific structures called inclusion bodies may
be produced. They become far larger than the
individual virus particle and often have an affinity for
acid dyes (eg, eosin). They may be situated in the
nucleus (herpesvirus), in the cytoplasm (poxvirus), or
in both (measles virus).
In many viral infections, the inclusion bodies are the
site of development of the virions (the viral factories).
The presence of inclusion bodies may be of
considerable diagnostic aid. The intracytoplasmic
inclusion in nerve cells—the Negri body—is
pathognomonic for rabies.
Viruses may be transmitted in the following ways:
(1) Direct transmission from person to person by
contact. The major means of transmission may be by
droplet or aerosol infection (eg, influenza, measles,
smallpox); by the fecal-oral route (eg, enteroviruses,
rotaviruses, infectious hepatitis A); by sexual contact
(eg, 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).
(2) Transmission from animal to animal, with humans
an accidental host. Spread may be by bite (rabies) or
by droplet or aerosol infection from rodentcontaminated quarters (eg, arenaviruses,
hantaviruses).
(3) Transmission by means of an arthropod vector (eg,
arboviruses, now classified primarily as togaviruses,
flaviviruses, and bunyaviruses).
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DNA viruses
 Group I: viruses possess double-stranded DNA.
 Group II: viruses possess single-stranded DNA.
 Group1. Adenovirus,
Papillomavirus, Parvovirus B19, erpes simplex
virus, varicella-zoster
virus, cytomegalovirus, Epstein–Barr virus,
Smallpox virus, cow pox virus, sheep pox virus,
orf virus, monkey pox virus, vaccinia
virusComplex
coatsComplexd, HepadnaviridaeHepatitis
B virus
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RNA viruses
 Group III: viruses possess double-stranded RNA
genomes, e.g. rotavirus. These genomes are
always segmented.
 Group IV: viruses possess positive-sense singlestranded RNA genomes. Many well known
viruses are found in this group, including
the picornaviruses (which is a family of viruses
that includes well-known viruses like Hepatitis A
virus, enteroviruses, rhinoviruses, poliovirus, and
foot-and-mouth virus), SARS virus, hepatitis
C virus, yellow fever virus, and rubella virus.
 Group V: viruses possess negative-sense singlestranded RNA genomes. The
deadly Ebola and Marburg viruses are well
known members of this group, along
with influenza virus, measles, mumps and rabies.
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VIROIDS
Small infectious agents that cause diseases of plants.
Viroids are agents that do not fit the definition of classic
viruses. They are nucleic acid molecules (MW 70,000–
120,000) without a protein coat. Plant viroids are singlestranded, covalently closed circular RNA molecules
consisting of about 360 nucleotides and with a highly basepaired rod-like structure. Viroids replicate by an entirely
novel mechanism. Viroid RNA does not encode any protein
products; the devastating plant diseases induced by viroids
occur by an unknown mechanism. To date, viroids have
been detected only in plants; none have been demonstrated
to exist in animals or humans.
PRIONS
Infectious particles composed solely of protein with no
detectable nucleic acid. Highly resistant to inactivation by
heat, formaldehyde, and ultraviolet light that inactivate
viruses. The prion protein is encoded by a single cellular
gene. Prion diseases, called "transmissible spongiform
encephalopathies," include scrapie in sheep, mad cow
disease in cattle, and kuru and Creutzfeldt-Jakob disease
in humans. Prions do not appear to be viruses
Route of
transmission
viruses
1. Respiratory tract
Influenza A,B,C, parainfluenza,
rhinovirus,coronavirus,measles,mumps,rubella
2. Alimentary tract
Poliovirus,HAV,HEV, adenovirus,rotavirus,norwalk
and related viruses
3.Skin
Papillomaviruses,herpes simplex and
HBV,arboviruses, rabies virus,HBV,HIV
4.Genital tract
Papillomavirus,herpes simplex
viruses,HIV,HBV,HCV
5. Conjunctiva
Some adenoviruse,few enterovirus
INCUBATION PERIOD:
Time taken for the virus to spread from the site of
entry to the organs of viral multiplication and to
target organs for the production of lesions
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LABORATORY DIAGNOSIS OF VIRAL INFECTIONS
1.
2.
3.
4.
5.
Direct detection of virus:
a) electron microscopy
b) immunoelectronmicroscopy
c) fluoresence microscopy
d) light microscopy
Virus isolation in animal, hens egg
Detection of viral proteins
a) protein patterns by electrophoresis
b) enzyme activities eg: reverse transcriptase
c) hemagglutination and hemadsorption
d) antigen detection by ELISA
Detection of viral genetic material
a)DNA probes
b)Polymerase chain reaction(PCR)
Serological diagnosis
VIRAL VACCINES
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The purpose of viral vaccines is to utilize the immune
response of the host to prevent viral disease.
Tye of vaccine
Disease
Live viral vaccine
i. Measles
ii. Mumps
iii. Rubella
iv. Polio(sabin)
v. Influenza
Killed viral vaccine
i. Polio(salk)
ii. Hepatitis A
iii. Rabies
iv. Influenza
v. Japanese B encephalitis
vi. varicella
Subunit vaccine
i. Heaptitis B
COMPARISON OF CHARACTERISTICS OF KILLED AND LIVE VIRAL VACCINES
Characterstic
Killed
Live
Number of doses
Multiple
single
Number of adjuvents
Yes
no
Shorter
longer
lower
greater
Immunoglobulins produced
IgG
IgG and IGA
Mucosal immuntiy produced
poor
yes
Cell mediated immunity produced
poor
yes
Residual virulent virus in vaccine
possible
No
Reversion to virulence
No
possible
Excretion of vaccine virus and transmission
to nonimmune contacts
no
Possible
Interference by other viruses in host
No
possible
Stability at room temperature
high
Low
Duration of immunity
Effectiveness of protection
BACTERIOPHAGES
A bacteriophage (informally, phage) is a virus that
infects and replicates within bacteria.
 Bacteriophages are composed
of proteins that encapsulate a DNA or RNA genome,
 Phages are widely distributed in locations populated
by bacterial hosts, such as soil or the intestines of
animals. One of the densest natural sources for
phages and other viruses is sea water, where up to
9×108 virions per milliliter have been found in
microbial mats at the surface, and up to 70% of
marine bacteria may be infected by phages
 They have been used for over 90 years as an
alternative to antibiotics in the former Soviet
Union and Central Europe, as well as in
 They are seen as a possible therapy against multidrug-resistant strains of many bacteria
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POXVIRUS
Poxviruses are the largest and most complex of
viruses.. Infections with most poxviruses are
characterized by a rash, although lesions induced
by some members of the family are markedly
proliferative. The group includes variola virus,
the etiologic agent of smallpox—the viral disease
that has affected humans throughout recorded
history.
 Even though smallpox was declared eradicated
from the world (in 1980) after an intensive
campaign coordinated by the World Health
Organization, there is concern that the virus
could be reintroduced as a biologic weapon. There
is a continuing need to be familiar with vaccinia
virus (used for smallpox vaccinations) and its
possible complications in humans
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IMPORTANT PROPERTIES OF THE POXVIRUSES
1. Virion: Complex structure, oval or brick-shaped, 400 nm in length x 230 nm
in diameter; external surface shows ridges; contains core and lateral bodies
2. Composition: DNA (3%), protein (90%), lipid (5%)
3. Genome: Double-stranded DNA, linear
4. Proteins: Virions contain more than 100 polypeptides; many enzymes are
present in core, including transcriptional system
5. STRUCTURE, By electron microscopy, they appear to be brick-shaped or
ellipsoid particles. Their structure is complex and conforms to neither
icosahedral nor helical symmetry
6. Envelope: Virion assembly involves formation of multiple membranes
7. Outstanding characteristics:
Largest and most complex viruses; very resistant to inactivation
Virus-encoded proteins help evade host immune defense system
Smallpox was the first viral disease eradicated from the world
VARIOLA
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Pathogenesis & Pathology of Smallpox
The portal of entry of variola virus was the mucous mem
The incubation period of variola (smallpox) was 10–14 days.
The onset was usually sudden. One to 5 days of fever and
malaise preceded the appearance of the exanthems, which
began as macules, then papules, then vesicles, and finally
pustules. These formed crusts that fell off after about 2
weeks, leaving pink scars that faded slowly. In each affected
area, the lesions were generally found in the same stage of
development (in contrast to chickenpox).
Lesions were most abundant on the face and less so on the
trunk. In severe cases, the rash was hemorrhagic. The casefatality rate varied from 5% to 40%. In mild variola, called
variola minor, or in vaccinated persons, the mortality rate
was under 1%
branes of the upper respiratory tract
TREATMENT
Vaccinia immune globulin is prepared from blood
from persons vaccinated with the vaccinia virus.
It is recommended for treatment of all
complications except postvaccinial encephalitis.
 Methisazone is a chemotherapeutic agent of some
value against poxviruses. It is effective as
prophylaxis but is not useful in treatment of
established disease. Cidofovir, a nucleotide
analog, shows activity against poxviruses in vitro
and in vivo
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MOLLUSCUM CONTAGIOSUM
Molluscum contagiosum is a benign epidermal tumor
that occurs only in humans
 The lesions of this disease are small, pink, wart-like
tumors on the face, arms, back, and buttocks. They are
rarely found on the palms, soles, or mucous
membranes. The disease occurs throughout the world
in both sporadic and epidemic forms and is more
frequent in children than in adults.
 It is spread by direct and indirect contact (eg, by
barbers, common use of towels, swimming pools).
 The incidence of molluscum contagiosum as a sexually
transmitted disease in young adults is increasing. It is
seen also in some patients with AIDS.
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HERPESVIRUSES
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The outstanding property of herpesviruses is
their ability to establish lifelong persistent
infections in their hosts and to undergo periodic
reactivation. Their frequent reactivation in
immunosuppressed patients causes serious
health complications. Curiously, the reactivated
infection may be clinically quite different from
the disease caused by the primary infection
IMPORTANT PROPERTIES OF HERPESVIRUSES
1. Virion: Spherical, 150–200 nm in diameter (icosahedral)
2. Genome: Double-stranded DNA, linear,
3. Envelope: Contains viral glycoproteins
4. Outstanding characteristics:
Encode many enzymes
Establish latent infections
Persist indefinitely in infected hosts
Frequently reactivated in immunosuppressed hosts
Some are cancer-causing
OVERVIEW OF HERPESVIRUS DISEASES
Herpes simplex virus types 1 and 2 infect epithelial cells
and establish latent infections in neurons. Type 1 is
classically associated with oropharyngeal lesions and
causes recurrent attacks of "fever blisters." Type 2
primarily infects the genital mucosa and is mainly
responsible for genital herpes. Both viruses also cause
neurologic disease. Herpes simplex virus type 1 is the
leading cause of sporadic encephalitis in the United
States. Both type 1 and type 2 can cause neonatal
infections which are often severe
 Varicella-zoster virus causes chickenpox (varicella) on
primary infection and establishes latent infection in
neurons. Upon reactivation, the virus causes zoster
(shingles). Adults who are infected for the first time
with varicella-zoster virus are apt to develop serious
viral pneumonia
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Cytomegalovirus replicates in epithelial cells of the
respiratory tract, salivary glands, and kidneys and
persists in lymphocytes. It causes an infectious
mononucleosis (heterophil-negative). In newborns,
cytomegalic inclusion disease may occur.
Cytomegalovirus is an important cause of congenital
defects and mental retardation.
 Human herpesvirus 6 infects T lymphocytes. It is
typically acquired in early infancy and causes
exanthem subitum (roseola infantum). Human
herpesvirus 7, also a T-lymphotropic virus, has not yet
been linked to any specific disease
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Epstein-Barr virus replicates in epithelial cells of the
oropharynx and parotid gland and establishes latent
infections in lymphocytes. It causes infectious
mononucleosis and is the cause of human
lymphoproliferative disorders, especially in
immunocompromised patients. Human herpesvirus 8
appears to be associated with the development of
Kaposi's sarcoma, a vascular tumor that is common in
patients with AIDS.
ADENOVIRUSES
Adenoviruses can replicate and produce disease in the
respiratory, gastrointestinal, and urinary tracts and in
the eye. Many adenovirus infections are subclinical,
and virus may persist in the host for months
 Important Properties of Adenoviruses.
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1. Virion: Icosahedral,
2. Genome: Double-stranded DNA, linear
3. Envelope: None
4. Outstanding characteristics: Excellent models for molecular
studies of eukaryotic cell processes
ADENOVIRUS INFECTIONS IN HUMANS
PARVOVIRUSES
IMPORTANT PROPERTIES OF PARVOVIRUSES.
1. Virion: Icosahedral
2. Genome: Single-stranded DNA, linear
3. Envelope: None
4. Outstanding characteristics:
Very simple viruses
Human pathogen, B19, has tropism for red blood cell progenitors
One genus is replication-defective and requires a helper virus
HUMAN DISEASES ASSOCIATED WITH B19
PARVOVIRUS.1
host
Clinical Features
Children (fifth
disease) Adults
Cutaneous rash
Arthralgia-arthritis
Transient aplastic
crisis
Underlying
hemolysis
Severe acute anemia
Pure red cell aplasia
Immunodeficiencies
Chronic anemia
Hydrops fetalis
Fetus
Fatal anemia
Syndrome
Erythema
infectiosum
PICORNAVIRUSES
PROPERTIES OF PICORNAVIRUSES
1. Virion: Icosahedral
2. Genome: Single-stranded RNA, linear
3. Envelope: None
4. Outstanding characteristics: Family is made up of many enterovirus and
rhinovirus types that infect humans and lower animals, causing various
illnesses ranging from poliomyelitis to aseptic meningitis to the common cold.
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They include two major groups of human pathogens:
enteroviruses and rhinoviruses. Enteroviruses are
transient inhabitants of the human alimentary tract and
may be isolated from the throat or lower intestine.
Rhinoviruses are isolated chiefly from the nose and throat
CLASSIFICATION
Enterovirus (enteroviruses), Rhinovirus (rhinoviruses),
Hepatovirus (hepatitis A virus), Parechovirus
(parechoviruses), Aphthovirus (foot-and-mouth disease
viruses), and Cardiovirus (cardioviruses).
 The first four groups contain important human pathogens.
 Enteroviruses of human origin are subdivided into five
species based mainly upon sequence analyses. The former
taxonomy for these viruses included the following:
(1) polioviruses, types 1–3;
(2) coxsackieviruses of group A, types 1–24 (there is no type
23);
(3) coxsackieviruses of group B, types 1–6;
(4) echoviruses, types 1–33 (no types 10, 22, 23, or 28); and
(5) enteroviruses, types 68–78
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POLIOVIRUSES
Poliomyelitis is an acute infectious disease that in its serious
form affects the central nervous system. The destruction of
motor neurons in the spinal cord results in flaccid paralysis.
However, most poliovirus infections are subclinical.
 General Properties
Poliovirus particles are typical enteroviruses (see above). They
are inactivated when heated at 55 °C for 30 minutes, but
Mg2+, 1 mol/L, prevents this inactivation. Whereas purified
poliovirus is inactivated by a chlorine concentration of 0.1
ppm, much higher concentrations of chlorine are required to
disinfect sewage containing virus in fecal suspensions and in
the presence of other organic matter. Polioviruses are not
affected by ether or sodium deoxycholate.
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PATHOGENESIS AND PATHOLOGY
 The mouth is the portal of entry of the virus, and primary
multiplication takes place in the oropharynx or intestine. The
virus is regularly present in the throat and in the stools
before the onset of illness. One week after infection there is
little virus in the throat, but virus continues to be excreted in
the stools for several weeks even though high antibody levels
are present in the blood.
 Clinical Findings
 When an individual susceptible to infection is exposed to the
virus, the response ranges from inapparent infection without
symptoms, to a mild febrile illness, to severe and permanent
paralysis. Most infections are subclinical; only about 1% of
infections result in clinical illness.
 The incubation period is usually 7–14 days, but it may range
from 3 days to 35 days
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Mild Disease:This is the most common form of disease.
The patient has only a minor illness, characterized by
fever, malaise, drowsiness, headache, nausea, vomiting,
constipation, and sore throat in various combinations.
Recovery occurs in a few days.
 Nonparalytic Poliomyelitis (Aseptic Meningitis):In
addition to the above symptoms and signs, the patient
with the nonparalytic form has stiffness and pain in the
back and neck. The disease lasts 2–10 days, and
recovery is rapid and complete. Poliovirus is only one of
many viruses that produce aseptic meningitis. In a small
percentage of cases, the disease advances to paralysis.
 Paralytic Poliomyelitis:The predominating complaint is
flaccid paralysis resulting from lower motor neuron
damage.
 Progressive Postpoliomyelitis Muscle Atrophy
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Laboratory Diagnosis
The virus may be recovered from throat swabs taken soon after
onset of illness and from rectal swabs or stool samples collected
over long periods. No permanent carriers have been identified
among immunocompetent individuals, but long-term excretion
of poliovirus has been observed in some immunodeficient
persons.
Specimens should be kept frozen during transit to the
laboratory. Cultures of human or monkey cells are inoculated,
incubated, and observed. Cytopathogenic effects appear in 3–6
days. An isolated virus is identified and typed by neutralization
with specific antiserum. Virus can also be identified by
polymerase chain reaction (PCR) assays.
Paired serum specimens are required to show a rise in antibody
titer during the course of the disease. Only first infection with
poliovirus produces strictly type-specific responses. Subsequent
infections with heterotypic polioviruses induce antibodies
against a group antigen shared by all three types
Global Eradication
 A major campaign was launched by the World Health
Organization in 1988 to eradicate poliovirus from the
world as was done for smallpox virus. There were an
estimated 350,000 cases of polio worldwide in 1988. The
Americas were certified as free from wild poliovirus in
1994, the Western Pacific Region in 2000, and Europe in
2002. Progress is being made globally, but several
thousand cases of polio still occur each year, principally in
Africa and the Indian subcontinent
Prevention & Control
 Both live-virus and killed-virus vaccines are available
ORTHOMYXOVIRUSES
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Respiratory illnesses are responsible for more than half of all
acute illnesses each year in the United States. The
Orthomyxoviridae (influenza viruses) are a major
determinant of morbidity and mortality caused by
respiratory disease, and outbreaks of infection sometimes
occur in worldwide epidemics.
Important Properties of Orthomyxoviruses
1. Virion: Spherical
2. Genome: Single-stranded RNA, segmented (eight molecules),
3. Envelope: Contains viral hemagglutinin (HA) and neuraminidase (NA)
proteins
Genetic reassortment common among members of the same genus
Influenza viruses cause worldwide epidemics
CLASSIFICATION & NOMENCLATURE
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Genus Influenzavirus A contains human and animal
strains of influenza type A; Influenzavirus B contains
human strains of type B; and Influenzavirus C contains
influenza type C viruses of humans and swine
ANTIGENIC DRIFT & ANTIGENIC SHIFT
 Influenza viruses are remarkable because of the
frequent antigenic changes that occur in HA and NA.
 The two surface antigens of influenza undergo antigenic
variation independent of each other. Minor antigenic
changes are termed antigenic drift; major antigenic
changes in HA or NA, called antigenic shift, result in
the appearance of a new subtype. Antigenic shift is most
likely to result in an epidemic.
Antigenic drift is due to the accumulation of point
mutations in the gene, resulting in amino acid changes
in the protein. Sequence changes can alter antigenic
sites on the molecule such that a virion can escape
recognition by the host's immune system.
 Antigenic shift reflects drastic changes in the sequence
of a viral surface protein, changes too extreme to be
explained by mutation. The segmented genomes of
influenza viruses reassort readily in doubly infected
cells. The mechanism for shift is genetic reassortment
between human and avian influenza viruses. Influenza
B and C viruses do not exhibit antigenic shift because
few related viruses exist in animals.
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CLINICAL FINDINGS
Uncomplicated Influenza
 Pneumonia
 Reye's syndrome is an acute encephalopathy of
children and adolescents, usually between 2 and
16 years of age
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PREVENTION AND TREATMENT
Amantadine hydrochloride and an analog,
rimantadine
 Inactivated viral vaccines are the primary means
of prevention of influenza in the United States.
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PARAMYXOVIRUSES
The paramyxoviruses include the most important
agents of respiratory infections of infants and young
children (respiratory syncytial virus and the
parainfluenza viruses) as well as the causative
agents of two of the most common contagious diseases
of childhood (mumps and measles)
 Important Properties of Paramyxoviruses
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1. Virion: Spherical
2. Genome: Single-stranded RNA, linear, nonsegmented
3. Envelope: Contains viral glycoprotein
4. Outstanding characteristics Antigenically stable, Particles are labile
yet highly infectious
MEASLES(RUBEOLA)
Measles is an acute, highly infectious disease
characterized by fever, respiratory symptoms, and a
maculopapular rash. Complications are common and may
be quite serious. The introduction of an effective livevirus vaccine has dramatically reduced the incidence of
this disease in the United States, but measles is still a
leading cause of death of young children in many
developing countries.
 Clinical Findings The prodromal phase is characterized
by fever, sneezing, coughing, running nose, redness of the
eyes, Koplik's spots, and lymphopenia. The cough and
coryza reflect an intense inflammatory reaction involving
the mucosa of the respiratory tract. The conjunctivitis is
commonly associated with photophobia. Koplik's spots—
pathognomonic for measles—are small, bluish-white
ulcerations on the buccal mucosa opposite the lower
molars
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The most common complication of measles is otitis media
(5–9% of cases).
 Pneumonia is the most common life-threatening
complication of measles, caused by secondary bacterial
infections
 Subacute sclerosing panencephalitis, the rare late
complication of measles infection

Treatment, Prevention, & Control:
 A highly effective and safe attenuated live measles virus
vaccine has been available
RUBELLA (GERMAN MEASLES) VIRUS INFECTIONS
Rubella (German measles; 3-day measles) is an acute
febrile illness characterized by a rash and
lymphadenopathy that affects children and young adults.
It is the mildest of common viral exanthems. However,
infection during early pregnancy may result in serious
abnormalities of the fetus, including congenital
malformations and mental retardation. The
consequences of rubella in utero are referred to as the
congenital rubella syndrome
Postnatal Rubella
 Pathogenesis & Pathology
 Neonatal, childhood, and adult infections occur through
the mucosa of the upper respiratory tract. Initial viral
replication probably occurs in the respiratory tract,
followed by multiplication in the cervical lymph nodes

Attenuated live rubella vaccines have been available
 Given as MMR(measles ,mumps and rubella)
Congenital Rubella Syndrome
 The classic triad of congenital rubella consists of
cataracts, cardiac abnormalities, and deafness. Infants
may also display transient symptoms of growth
retardation, rash, hepatosplenomegaly, jaundice, and
meningoencephalitis.
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MUMPS VIRUS INFECTIONS

Mumps is an acute contagious disease
characterized by nonsuppurative enlargement of
one or both salivary glands. Mumps virus mostly
causes a mild childhood disease, but in adults
complications including meningitis and orchitis
are fairly common. More than one-third of all
mumps infections are asymptomatic
ARBOVIRUSES

The arthropod-borne viruses (arboviruses)
and rodent-borne viruses represent ecologic
groupings of viruses with complex transmission
cycles involving arthropods or rodents
RHABDOVIRUSES
Rabies is an acute infection of the central nervous
system that is almost always fatal. The virus is
usually transmitted to humans from the bite of a rabid
animal.
 Important Properties of Rhabdoviruses.

1. Virion: Bullet-shaped
2. Genome: Single-stranded RNA, linear, nonsegmented
3. Envelope: Present
4. Outstanding characteristics: Wide array of viruses with
broad host range, Group includes the deadly rabies virus




Rabies virus has a wide host range. All warm-blooded animals,
including humans, can be infected. Susceptibility varies among
mammalian species, ranging from very high (foxes, coyotes,
wolves) to low (opossums); those with intermediate
susceptibility include skunks, raccoons, and bats
Clinical Findings: Rabies is primarily a disease of lower
animals and is spread to humans by bites of rabid animals or by
contact with saliva from rabid animals.
The disease is an acute, fulminant, fatal encephalitis. The
incubation period in humans is typically 1–2 months but may be
as short as 1 week or as long as many years (up to 19 years). It
is usually shorter in children than in adults.
The clinical spectrum can be divided into three phases: a short
prodromal phase, an acute neurologic phase, and coma. The
prodrome, lasting 2–10 days, may show any of the following
nonspecific symptoms: malaise, anorexia, headache,
photophobia, nausea and vomiting, sore throat, and fever.
Usually there is an abnormal sensation around the wound site.

During the acute neurologic phase, which lasts 2–7 days,
patients show signs of nervous system dysfunction such as
nervousness, apprehension, hallucinations, and bizarre
behavior. General sympathetic overactivity is observed,
including lacrimation, pupillary dilatation, and increased
salivation and perspiration. A large fraction of patients will
exhibit hydrophobia (fear of water). The act of swallowing
precipitates a painful spasm of the throat muscles. This
phase is followed by convulsive seizures or coma and death.
The major cause of death is respiratory paralysis
IMMUNITY & PREVENTION

1.
2.
3.
4.
5.
6.



Types of Vaccines
Human Diploid Cell Vaccine (HDCV)
Rabies Vaccine, Adsorbed (RVA)
Purified Chick Embryo Cell Vaccine (PCEC)
Nerve Tissue Vaccine
Duck Embryo Vaccine
Live Attenuated Viruses
Preexposure Prophylaxis
This is indicated for persons at high risk of contact with
rabies virus (research and diagnostic laboratory workers,
spelunkers) or with rabid animals (veterinarians, animal
control and wildlife workers). The goal is to attain an
antibody level presumed to be protective by means of vaccine
administration prior to any exposure. It is recommended that
antibody titers of vaccinated individuals be monitored
periodically and that boosters be given when required.
Postexposure Prophylaxis
SLOW VIRUS INFECTIONS &
PRION DISEASES

Some chronic degenerative diseases of the central
nervous system in humans are caused by "slow"
or chronic, persistent infections by classic
viruses. Among these are subacute sclerosing
panencephalitis and progressive multifocal
leukoencephalopathy. Other diseases known as
transmissible spongiform encephalopathies—eg,
Creutzfeldt-Jakob disease—appear to be caused
by unconventional transmissible agents termed
"prions
HEPATITIS VIRUSES
Viral hepatitis is a systemic disease primarily involving
the liver. Most cases of acute viral hepatitis in children
and adults are caused by one of the following agents:
hepatitis A virus (HAV), the etiologic agent of viral
hepatitis type A (infectious hepatitis); hepatitis B virus
(HBV), which is associated with viral hepatitis B
(serum hepatitis); hepatitis C virus (HCV), the agent of
hepatitis C (common cause of posttransfusion
hepatitis); or hepatitis E virus (HEV), the agent of
enterically transmitted hepatitis. Other viruses are
associated with hepatitis that cannot be ascribed to
known agents, and the associated disease is designated
non-A–E hepatitis
 Hepatitis viruses produce acute inflammation of the
liver, resulting in a clinical illness characterized by
fever, gastrointestinal symptoms such as nausea and
vomiting, and jaundice

CHARACTERISTICS OF HEPATITIS VIRUSES
Virus
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Family
Picornaviridae
Hepadnaviridae
Flaviviridae
Unclassified
Unclassified
Genus
Hepatovirus
Orthohepadnavir Hepacivirus
us
Deltavirus
Hepevirus
Virion
Icosahedral
Spherical
Spherical
spherical
icosahedral
Envelope No
Yes (HBsAg)
Yes
Yes (HBsAg)
No
Genome
dsDNA
ssRNA
ssRNA
ssRNA
Transmis Fecal-oral
sion
Parenteral
Parenteral
Parenteral
Fecal-oral
Prevalenc High
e
High
Moderate
Low, regional
Regional
Fulminan Rare
t disease
Rare
Rare
Frequent
In pregnancy
Chronic
disease
Often
Often
Often
Never
Yes
Yes
?
No
ssRNA
Never
Oncogeni No
c
NOMENCLATURE AND DEFINITIONS OF HEPATITIS VIRUSES, ANTIGENS, AND ANTIBODIES
Disease
Component of System Definition
Hepatitis A
HAV
Hepatitis A virus. Etiologic agent of infectious hepatitis. A
picornavirus, the prototype of a new genus, Hepatovirus.
Anti-HAV
Antibody to HAV. Detectable at onset of symptoms; lifetime
persistence.
IgM anti-HAV
IgM class antibody to HAV. Indicates recent infection with
hepatitis A; positive up to 4–6 months after infection.
CONTN….
Disease
Component Definition
of System
Hepatitis B HBV
Hepatitis B virus. Etiologic agent of serum hepatitis. A hepadnavirus.
HBsAg
Hepatitis B surface antigen. Surface antigen(s) of HBV detectable in
large quantity in serum; several subtypes identified.
HBeAg
Hepatitis B e antigen. Associated with HBV nucleocapsid; indicates
viral replication; circulates as soluble antigen in serum.
HBcAg
Hepatitis B core antigen.
Anti-HBs
Antibody to HBsAg. Indicates past infection with and immunity to
HBV, presence of passive antibody from HBIG, or immune response
from HBV vaccine.
Antibody to HBeAg. Presence in serum of HBsAg carrier suggests
lower titer of HBV.
Anti-HBe
Anti-HBc
Antibody to HBcAg. Indicates infection with HBV at some undefined
time in the past.
IgM antiHBc
IgM class antibody to HBcAg. Indicates recent infection with HBV;
positive for 4–6 months after infection
Hepatitis C
Hepatitis D
Hepatitis E
HCV
Hepatitis C virus, a common etiologic
agent of posttransfusion hepatitis. A
flavivirus, genus Hepacivirus.
Anti-HCV
Antibody to HCV.
HDV
Hepatitis D virus. Etiologic agent of delta
hepatitis; causes infection only in presence
of HBV.
HDAg
Delta antigen (delta-Ag). Detectable in early
acute HDV infection.
Anti-HDV
Antibody to delta-Ag (anti-delta). Indicates
past or present infection with HDV.
HEV
Hepatitis E virus. Enterically transmitted
hepatitis virus. Causes
EPIDEMIOLOGIC AND CLINICAL FEATURES OF VIRAL HEPATITIS TYPES A, B,
AND C
Feature
Viral Hepatitis Type A
Viral Hepatitis Type Viral Hepatitis Type
B
C
Incubation period 10–50 days (avg, 25–30)
50–180 days (avg, 60– 15–160 days (avg, 50)
90)
Principal age
distribution
Children,young adults
15–29 years, babies
Adults
Seasonal
incidence
Throughout the year but
tends to peak in autumn
Throughout the year
Throughout the year
Predominantly
parenteral
Predominantly
parenteral
Route of infection Predominantly fecal-oral
Occurrence of
virus
a.Blood
2 weeks before to 1 week
after jaundice
Months to years
Months to years
b.Stool
2 weeks before to 2 weeks
after jaundice
Absent
Probably absent
c.Urine
Rare
Absent
Probably absent
d.Saliva, semen
Rare (saliva)
Frequently present
Present (saliva)
CONTN………
Feature
Viral Hepatitis
Type A
Viral Hepatitis
Type B
Viral Hepatitis
Type C
Onset
Abrupt
Insidious
Insidious
Fever > 38 °C
Common
Less common
Less common
1–3 weeks
1–6+ months
1–6+ months
(IgM levels)
Elevated
Normal to slightly
elevated
Normal to slightly
elevated
Complications
Uncommon, no
chronicity
Chronicity in 5–10% Chronicity in 70–90%
(95% of neonates)
< 0.5%
< 1–2%
0.5–1%
Absent
Present
Absent
Clinical and
laboratory features
Duration of
aminotransferase
elevation
Mortality rate
(icteric cases)
HBsAg

•
•
•
•
•
Hepatitis A virus
Hepatitis A virus (HAV), classified as hepatovirus, is a small,
unenveloped symmetrical RNA virus which shares many of the
characteristics of the picornavirus family, and is the cause of infectious
or epidemic hepatitis transmitted by the fecal-oral route.
Outbreaks of type A hepatitis are common in families and institutions,
summer camps, day care centers, neonatal intensive care units, and
among military troops. The most likely mode of transmission under
these conditions is by the fecal-oral route through close personal
contact. Stool specimens may be infectious for up to 2 weeks before to 2
weeks after onset of jaundice
Prevention & Control
Simple environmental procedures can limit the risk of infection to
health care workers, laboratory personnel, and others. With this
approach, all blood and body fluids and materials contaminated with
them are treated as if they are infectious for HIV, HBV, HCV, and
other blood-borne pathogens.
Formalin-inactivated HAV vaccines are available
Laboratory Features
 HAV can be detected in the liver, stool, bile, and blood of
naturally infected humans and experimentally infected
nonhuman primates by immunoassays, nucleic acid
hybridization assays, or PCR. HAV is detected in the
stool from about 2 weeks prior to the onset of jaundice up
to 2 weeks after.
 Anti-HAV appears in the IgM fraction during the acute
phase, peaking about 2 weeks after elevation of liver
enzymes .Anti-HAV IgM usually declines to
nondetectable levels within 3–6 months. Anti-HAV IgG
appears soon after the onset of disease and persists for
decades. Thus, detection of IgM-specific anti-HAV in the
blood of an acutely infected patient confirms the
diagnosis of hepatitis A.
 ELISA is the method of choice for measuring HAV
antibodies.

INTERPRETATION OF HAV, HCV, AND HDV SEROLOGIC
MARKERS IN PATIENTS WITH HEPATITIS
Assay Results
Interpretation
Anti-HAV IgM-positive
Acute infection with HAV
Anti-HAV IgG-positive
Past infection with HAV
Anti-HCV-positive
Current or past infection with HCV
Anti-HDV-positive, HBsAg-positive
Infection with HDV
Anti-HDV-positive, anti-HBc IgMpositive
Coinfection with HDV and HBV
Anti-HDV-positive, anti-HBc IgMnegative
Superinfection of chronic HBV
infection with HDV
Hepatitis B virus
Hepatitis B virus (HBV), a member of the hepadnavirus group,
double-stranded DNA viruses which replicate, unusually, by
reverse transcription. Hepatitis B virus is endemic in the
human population and hyperendemic in many parts of the
world.
 . There is no seasonal trend for HBV infection and no high
predilection for any age group, although there are high-risk
groups such as parenteral drug abusers, institutionalized
persons, health care personnel, multiply transfused patients,
organ transplant patients, hemodialysis patients and staff,
highly promiscuous persons, and newborn infants born to
mothers with hepatitis B. People have been infected by
improperly sterilized syringes, needles, or scalpels and even by
tattooing or ear piercing..
 HBsAg can be detected in saliva, nasopharyngeal washings,
semen, menstrual fluid, and vaginal secretions as well as in
blood. Transmission from carriers to close contacts by the oral
route or by sexual or other intimate exposure occurs. There is
strong evidence of transmission from persons with subclinical
cases and carriers of HBsAg to homosexual and heterosexual
long-term partners. Transmission by the fecal-oral route has
not been documented

LABORATORY FEATURES

Interpretation of HBV Serologic Markers in Patients with Hepatitis
HBsAg
Anti-HBs Anti-HBc
Interpretation
Positive
Negative
Negative
Early acute HBV infection. Confirmation is required to exclude
nonspecific reactivity.
Positive
(±)
Positive
HBV infection, either acute or chronic. Differentiate with IgM
anti-HBc. Determine level of replicative activity (infectivity)
with HBeAg or HBV DNA.
Negative
Positive
Positive
Indicates previous HBV infection and immunity to hepatitis B.
Negative
Negative
Positive
Possibilities include: HBV infection in remote past; "low-level"
HBV carrier; "window" between disappearance of HBsAg and
appearance of anti-HBs; or false-positive or nonspecific
reaction. Investigate with IgM anti-HBc. When present, antiHBe helps validate the anti-HBc reactivity.
Negative
Negative
Negative
Never infected with HBV. Possibilities include another
infectious agent, toxic injury to liver, disorder of immunity,
hereditary disease of the liver, or disease of the biliary tract.
Negative
Positive
Negative
Vaccine-type response.
PREVENTION
A vaccine for hepatitis B has been available since
1982
 Hepatitis B vaccination is the most effective
measure to prevent HBV and its consequences

Hepatitis C virus
Hepatitis C virus (HCV), is an enveloped singlestranded RNA virus which appears to be distantly
related (possibly in its evolution) to flaviviruses,
although hepatitis C is not transmitted by arthropod
vectors. Several genotypes have been identified.
Infection with this more recently identified virus is
common in many countries. Hepatitis C virus is
associated with chronic liver disease and also with
primary liver cancer in some countries.
 Hepatitis D virus
Hepatitis D virus (HDV) is an unusual, single-stranded,
circular RNA virus with a number of similarities to
certain plant viral satellites and viroids. This virus
requires hepadna virus helper functions for
propagation in hepatocytes, and is an important
cause of acute and severe chronic liver damage in
many regions of the world

Hepatitis E virus
Hepatitis E virus (HEV), the cause of enterically-transmitted nonA, non-B hepatitis, is another non-enveloped, single-stranded
RNA virus, which shares many biophysical and biochemical
features with caliciviruses. The most similar genome to HEV is
found in a plant virus, beet necrotic yellow vein virus, and there
are similarities in the functional domains to rubella virus. Final
taxonomic classification is yet to be agreed upon.
Hepatitis E virus is an important cause of large epidemics of
acute hepatitis in the subcontinent of India, Central and
Southeast Asia, the Middle East, parts of Africa and elsewhere.
This virus is responsible for high mortality (15–20%), during
pregnancy particularly during the third trimester.
 The GB hepatitis viruses
The GB hepatitis viruses (GBV-A, GBV-B and GBV-C). The GB
hepatitis viruses were cloned recently and preliminary genomic
characterization shows that they are related to other positivestranded RNA viruses with local regions of sequence identity
with various flaviviruses. Phylogenetic analysis of genomic
sequences showed that these viruses are not genotypes of the
hepatitis C virus.

HUMAN IMMUNODEFICIENCY
VIRUS

Human immunodeficiency virus (HIV) types, derived
from primate lentiviruses, are the etiologic agents of
AIDS. The illness was first described in 1981, and
HIV-1 was isolated by the end of 1983. Since then,
AIDS has become a worldwide epidemic, expanding in
scope and magnitude as HIV infections have affected
different populations and geographic regions. Millions
are now infected worldwide; once infected, individuals
remain infected for life. Within a decade, if left
untreated, the vast majority of HIV-infected
individuals develop fatal opportunistic infections as a
result of HIV-induced deficiencies in the immune
system. AIDS is one of the most important public
health problems worldwide at the start of the 21st
century
Pathogenesis & Pathology
The typical course of untreated HIV infection spans
about a decade .Stages include the primary
infection, dissemination of virus to lymphoid
organs, clinical latency, elevated HIV expression,
clinical disease, and death. The duration between
primary infection and progression to clinical
disease averages about 10 years. In untreated
cases, death usually occurs within 2 years after
the onset of clinical symptoms.



Clinical Findings
Symptoms of acute HIV infection are nonspecific and
include fatigue, rash, headache, nausea, and night sweats.
AIDS is characterized by pronounced suppression of the
immune system and development of a wide variety of
severe opportunistic infections or unusual neoplasms
(especially Kaposi's sarcoma). The more serious symptoms
in adults are often preceded by a prodrome ("diarrhea and
dwindling") that can include fatigue, malaise, weight loss,
fever, shortness of breath, chronic diarrhea, white patches
on the tongue (hairy leukoplakia, oral candidiasis), and
lymphadenopathy. Disease symptoms in the
gastrointestinal tract from the esophagus to the colon are a
major cause of debility. With no treatment, the interval
between primary infection with HIV and the first
appearance of clinical disease is usually long in adults,
averaging about 8–10 years. Death occurs about 2 years
later



Opportunistic Infections
The predominant causes of morbidity and mortality among patients with late-stage
HIV infection are opportunistic infections, ie, severe infections induced by agents
that rarely cause serious disease in immune-competent individuals.
The most common opportunistic infections in untreated AIDS patients include the
following:

(1) Protozoa: Toxoplasma gondii, Isospora belli, Cryptosporidium species.

(2) Fungi: Candida albicans, Cryptococcus neoformans,




(3) Bacteria: Mycobacterium avium-intracellulare, Mycobacterium tuberculosis,
Listeria monocytogenes, Nocardia asteroides, Salmonella species, Streptococcus
species.
(4) Viruses: Cytomegalovirus, herpes simplex virus, varicella-zoster virus,
adenovirus, polyomavirus, JC virus, hepatitis B virus, hepatitis C virus.
Cancer
. AIDS-associated cancers tend to be those with a viral cofactor and include nonHodgkin's lymphoma (both systemic and central nervous system types), Kaposi's
sarcoma, cervical cancer, and anogenital cancers. the occurrence of Kaposi's
sarcomas but has had less of an effect on the incidence of non-Hodgkin's lymphomas
in HIV-infected individuals.
Laboratory Diagnosis of AIDS
 Evidence of infection by HIV can be detected in
three ways: (1) virus isolation, (2) serologic
determination of antiviral antibodies, and (3)
measurement of viral nucleic acid or antigens.

EPIDEMIOLOGY OF AIDS


1.
2.
3.

Routes of Transmission
High titers of HIV are found in two body fluids—blood
and semen. HIV is transmitted during
sexual contact (including genital-oral sex),
through parenteral exposure to contaminated blood
or blood products, and
from mother to child during the perinatal period.
Asymptomatic virus-positive individuals can
transmit the virus. Since the first description of
AIDS, promiscuous homosexual activity has been
recognized as a major risk factor for acquisition of
the disease. The risk increases in proportion to the
number of sexual encounters with different
partners.
Transfusion of infectious blood or blood products is an
effective route for viral transmission
CONTROL MEASURES FOR AIDS








Without control by drugs or vaccines, the only way to avoid epidemic
spread of HIV is to maintain a lifestyle that minimizes or eliminates the
high-risk factors discussed above. No cases have been documented to
result from such common exposures as sneezing, coughing, sharing meals,
or other casual contacts.
Public health authorities have recommended that persons reported to
have an HIV infection be given the following information and advice:
(1) Almost all persons will remain infected for life and will develop the
disease.
(2) Although asymptomatic, such individuals may transmit HIV to others.
Regular medical evaluation and follow-up are advised.
(3) Infected persons should refrain from donating blood, plasma, body
organs, other tissues, or sperm.
(4) There is a risk of infecting others by sexual intercourse (vaginal or
anal), by oral-genital contact, or by sharing of needles. The consistent and
proper use of condoms can reduce transmission of the virus, though
protection is not absolute.
(5) Toothbrushes, razors, and other implements that could become
contaminated with blood should not be shared.
(6) Seropositive women or women with seropositive sexual partners are
themselves at increased risk of acquiring AIDS. If they become pregnant,






7) After accidents that result in bleeding, contaminated surfaces should
be cleaned with household bleach freshly diluted 1:10 in water.
(8) Devices that have punctured the skin—eg, hypodermic and
acupuncture needles—should be steam-sterilized by autoclaving before
reuse or should be safely discarded. Dental instruments should be heatsterilized between patients. Whenever possible, disposable needles and
equipment should be used.
(9) When seeking medical or dental care for intercurrent illness,
infected persons should inform those responsible for their care that
they are seropositive, so that appropriate evaluation can be undertaken
and precautions taken to prevent transmission to others.
(10) Testing for HIV antibody should be offered to persons who may
have been infected as a result of their contact with seropositive
individuals (eg, sexual partners, persons with whom needles have been
shared, infants born to seropositive mothers).
(11) Most persons with a positive test for HIV do not need to consider a
change in employment unless their work involves significant potential
for exposing others to their blood or other body fluids. There is no
evidence of HIV transmission by food handling.
(12) Seropositive persons in the health care professions who perform
invasive procedures or have skin lesions should take precautions
similar to those recommended for hepatitis B carriers to protect