Download Viral Hepatitis_HIV

Chair of Medical biology, Microbiology,
Virology, and Immunology
Hepatitis Viruses
Human Immunodeficiency
Virus
By as. E.V. Pokryshko
Hepatitis is an inflammation of the liver.
Human hepatitis is caused by at least six
genetically and structurally distinct viruses.
The diseases caused by each of these
viruses are distinguished in part by the
length of their incubation periods and the
epidemiology of the infection.
Characteristics of Human Hepatitis Viruses
Virus
Family/ Genus
Size/
Genome
Length
Transmi
of
ssion of
Incuba
Infection
tion
Vaccine
HAV
Picornaviridae
(enterovirus
72)
27-30
nm,
ss RNA
15-40
days
Mostly
oralfecal
No
HBV
Hepadnaviridae
(hepadnavirus)
142 nm,
circular
ds DNA
50180
days
Parenteral
Recombi
nant
subunit
vaccine
HCV
Flaviviridae
30-50
nm
ssd RNA
14-28
days
Parenteral
No
Characteristics of Human Hepatitis Viruses
Size/
Genome
Length
of
Incubation
Transmis Vaccine
sion of
Infection
Virus
Family/ Genus
HDV
Unclassified
35-40
nm
ss RNA
50-180
days*
Parenteral
No
HEV
Caliciviridae
27-34
nm
sst RNA
6
weeks
Oralfecal
No
Hepatitis A virus
Electron microscopy of fecal extracts
Hepatitis A virus
Family
Genus
Virion
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Picornaviridae
Hepatovirus
27 nm icosahedral
No
ssRNA
Heat- and acid-stable
Fecal-oral
High
Rare
Never
No
Global Prevalence of Hepatitis A
Infection
HAV Prevalence
High
Intermediate
Low
Very Low
Hepatitis A Transmission
Fecal-oral contamination of food or water
Food handlers
Raw shellfish
Travel to endemic areas
Close personal contact
Household or sexual contact
Daycare centers
Natural infection with HAV is seen only in
human.
Hepatitis A - Clinical Features
• Incubation period:
• Jaundice by
age group:
• Complications:
• Chronic sequelae:
Average 30 days
Range 15-50 days
<6 yrs,
<10%
6-14 yrs, 40%-50%
>14 yrs, 70%-80%
Fulminant hepatitis
Cholestatic hepatitis
Relapsing hepatitis
None
Clinical Variants
of Hepatitis A Infection
Asymptomatic (anicteric) disease
Children under 6 years of age, > 90%
Children from 6-14 years old, 40-50%
Symptomatic (icteric) disease
Adults and children over 14, 70-80%
Pathogenesis
of Hepatitis A virus infections
During an asymptomatic incubation period, the
liver is infected and large amounts of virus can be
shed in the feces.
Symptoms usually begin abruptly with fever,
nausea, and vomiting. The major area of cell
necrosis occurs in the liver, and the resulting
enlargement of the liver frequently causes
blockage of the biliary excretions, resulting in
jaundice, dark urine, and clay colored stool. A
fulminant form of hepatitis A occurs in only 1% to
4% of patients. Complete recovery can require 8
to 12 weeks, especially in adults.
Concentration of Hepatitis A Virus
in Various Body Fluids
Body fluid
Feces
Serum
Saliva
Urine
100
102
104
Infection Doses per ml
106
108
1010
During convalescence, patients frequently
remain
weak
and
occasionally
mentally
depressed.
In humans, the severity of the disease varies
considerably with age, most cases occurring in
young children are mild and undiagnosed,
resolving without sequelae. In contrast to HBV,
HAV infections result in no extrahepatic
manifestations of acute infection and no long term
carrier state, and they are not associated with
either cirrhosis or primary hepatocellular
carcinoma.
Diagnosis
of Hepatitis A virus infections.
The diagnosis of individual cases of hepatitis A
usually is not possible without supporting
laboratory findings. Virus particles frequently can
be detected in fecal extracts by use of IFT.
Standard RIA also can be used to detect the
presence of HAV antigens in fecal extracts. An
ELISA using anti-HAV linked to either horseradish
peroxidase or alkaline phosphatase also is used to
detect fecal HAV.
In addition, a specific diagnosis of hepatitis A
can be made by demonstrating at least a four fold
rise in anti-HAV antibody levels in serum.
Typical Serologic Course of Acute
Hepatitis A Virus Infection
Symptoms
ALT
Total anti-HAV
Fecal
HAV
0
1
IgM anti-HAV
2
3
4
5
6
Months after exposure
12
24
Control
of Hepatitis A virus infections.
Proper
sanitation
to
prevent
fecal
contamination of water and food is the most
effective way to interrupt the fecal-oral
transmission of hepatitis A.
Pooled immune serum globulin from a large
number of individuals can be used to treat
potentially
exposed
poisons,
and
its
effectiveness has been well established.
Control
of Hepatitis A virus infections.
Formalin inactivated HAV vaccines have
been developed and some have been
licensed.
Additional approaches using recombinant
DNA techniques also are being used to
generate
subunit vaccines or novel
recombinant vaccine strains.
Structure
of the Hepatitis B virion
HBe
FIGURE. Fraction of the blood serum from a patient with a
severe ease of hepatitis. The larger spherical particles, or Dane
particles, are 42 nm in diameter and are the complete hepatitis B
virus. Also evident are filaments of capsid protein (HBsAg).
Hepatitis B virus
Family
Genus
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Hepadnaviridae
Orthohepadnavirus
Yes (HBsAg)
dsDNA
Acid-sensitive
Parenteral
High
Rare
Often
Yes
HBV - Epidemiology
About 300 million people world-wide are
thought to be carriers of HBV, and many carriers
eventually die of resultant liver disease.
Many HBV infections are asymptomatic
(especially in children). However, many infections
become persistent, leading to a chronic carrier
state. This can lead to chronic active hepatitis and
cirrhosis later in life. The HBV carrier state also is
strongly associated with one of the most common
visceral
malignancies
world-wide,
primary
hepatocellular carcinoma.
HBV - Epidemiology
Prevalence of HBsAg Carrier State
>8%
28%
<2%
Epidemiology
of Hepatitis B virus infections.
For years, it was believed that a person could
become infected only by the injection of blood or
serum from an infected person or by the use of
contaminated needles or syringes. As a result,
the older name for this disease was serum
hepatitis.
It has now been shown that this supposition is
not true.
Epidemiology
of Hepatitis B virus infections.
Using serologic techniques, HBsAg has been
found in feces, urine, saliva, vaginal secretions,
semen, and breast milk. Undoubtedly, the
mechanical transmission of infected blood or
blood products is one of the most efficient
methods of viral transmission, and infections
have been traced to tattooing, ear piercing,
acupuncture, and drug abuse. Neonatal
transmission also appears to occur during
childbirth. Virus can be sexually transmitted.
Hepatitis B Transmission
1. HBV spread mainly by parenteral route
2. direct percutaneous inoculation of infected serum
or plasma
3. indirectly through cuts or abrasions
4. absorption through mucosal surfaces
5. absorption of other infectious secretions (saliva or
semen during sex)
6. possible transfer via inanimate environmental
surfaces
7. vertical transmission soon after childbirth
(transplacental transfer rare)
8. close, intimate contact with an infected person
Who is at greatest risk
for HBV infection?
drug abusers
 blood product recipients
 accounts for 5-10% postransfusion hepatitis
 hemodialysis patients
 people from southeast asian countries
(70-80%)
Who is at greatest risk
for HBV infection?
 lab personnel working with blood products
 sexually active homosexuals
 persons with multiple and frequent sex
contacts
 medical/dental personnel
In hospitals, HBV infections are a risk for both
hospital personnel and patients because of
constant exposure to blood and blood products.
Pathogenesis
of hepatitis B virus infections.
Acute hepatitis caused by HBV
cannot be clinically distinguished
from hepatitis caused by HAV.
HBV
infections
are
characterized by a long incubation
period, ranging from 50 to 180
days.
Symptoms such as fever, rash,
and arthritis begin insidiously, and
the severity of the infection varies
widely. Mild cases that do not result
in jaundice are termed anicteric.
In more severe cases,
characterized by
headache, mild fever,
nausea, and loss of
appetite, icterus
(jaundice) occurs 3 to 5
days after the initial
symptoms.
The duration and severity of the disease vary from
clinically inapparent to fatal fulminating hepatitis. The
overall fatality rate is estimated to be 1% to 2%, with
most deaths occurring in adults older than 30 years of
age.
Differential Characteristics
of Hepatitis A and Hepatitis B
Characteristic
Hepatitis A
Hepatitis B
Length of incubation
period
15-40 days
50-180 days
Host range
Humans and possibly
nonhuman primates
Humans and some
nonhuman primates
Seasonal occurrence
Higher in fall and winter Year round
Age incidence
Much higher in children All ages
Occurrence of
jaundice
Much higher in adults
Higher in adults
Virus in blood
2-3 weeks before
illness to 1-2 weeks
after recovery
Several weeks before
illness to months or
years after recovery
Differential Characteristics
of Hepatitis A and Hepatitis B
Characteristic
Hepatitis A
Hepatitis B
Virus in feces
2-3 weeks before
illness to 1-2
weeks after
recovery
Rarely present, or
present in very
small amounts
Size of virus
27-32 nm
42 nm
Diagnosis based
on
Liver function
tests,
clinical symptoms,
and history
Liver function
tests, clinical
symptoms, history,
and presence of
HBsAg in blood
Effective vaccine
No
Yes
Chronic Hepatitis B Virus Infections.
Between 6% and 10% of clinically
diagnosed patients with hepatitis B
become chronically infected and continue
to have HBsAg in their blood for at least 6
months, and sometimes for life.
Chronic infections can be subdivided
into two general categories:
1. chronic persistent hepatitis
2. and chronic active hepatitis.
Chronic Hepatitis B Virus Infections.
The latter is the most severe and often
eventually leads to cirrhosis or the development
of primary hepatocellular carcinoma.
The prevalence of chronic carriers varies
widely in different parts of the world, from 0.1%
to 0.5% in the United States to up to 20% in
China, Southeast Asia, and some African
countries.
Diagnosis
of Hepatitis B virus infections.
As in all cases of viral hepatitis, abnormal liver
function is indicated by increased levels of liver
enzymes such as serum glutamic oxaloacetic
transaminase and alanine aminotransferase (ALT).
The presence of HBsAg confirms a diagnosis of
hepatitis B, and its serologic detection is routinely
carried out in diagnostic laboratories and blood
banks using radioimmunoassays or enzyme-linked
immunosorbent assay's.
Diagnosis
of Hepatitis B virus infections.
HBV core protein presence in serum
is believed to reflect active replication
of HBV and is a marker for active
disease. The appearance of anti-HBc
antibodies generally correlates with a
good prognosis and a decline in virus
replication.
Diagnosis
of Hepatitis B virus infections.
All carriers have antibodies to HBcAg, and
some have antibodies to HBeAg. Those who do
not possess antiHBe may have circulating
HBeAg. Carriers with high concentrations of
Dane particles and circulating HBeAg appear to
be more likely to suffer liver damage than those
in whom only HBsAg can be detected. However,
such persons are much more likely to be
transmitters of the disease than are those who
have solely HBsAg in their blood.
PRACTICE
HBsAg
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

N.
N.
N.
N.
N.
NO evidence of viral hepatitis viruses.
PRACTICE
HBsAG
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

PAST INFECTION.
N.
P.
P.
N.
N.
PRACTICE
HBsAg
 HBcAB (total)
 HBsAB
 HAV-IGM
 HCV

IMMUNIZATION.
N.
N.
P.
N.
N.
PRACTICE
HBsAg
 HBcAB (Total)
 HBsAB
 HAV-IGM
 HCV

P.
P.
N.
N.
N.
MAY BE ACUTE OR CHRONIC.
Order Hep. B Core IgM to clarify.
The IgM will be positive , If Acute.
PRACTICE
HBsAg
 HBcAB (TOTAL)
 HBsAB
 HAV-IGM
 HCV

P.
P.
N.
P.
P.
Co-infection with HBV, HAV, and HCV
PRACTICE





HBsAG
HBcAB (total)
HBsAB
HAV-IGM
HCV
P.
P.
P.
N.
N.
Past infection with recovery, and
then re-infection that has become
chronic, this is very rare but does
happen.
CONTROL
OF HEPATITIS B VIRUS INFECTIONS.
 The examination of all donor blood for the
presence of HBsAg.
 Passive immunization with hepatitis B immune
globulin (HBIG). One important and effective use
for HBIG, however, is the prevention of active
hepatitis B infections in neonates born to
mothers who are chronic carriers of HBsAg.
HBIG also can be given to nonimmune
individuals known to have been exposed to HBV.
 Active immunization with HBsAg promises to
provide a vehicle for the control of hepatitis B.
Hepatitis C virus.
HCV is RNA virus. Sequence analysis has revealed
that HCV is organized in a manner similar to the
flaviviruses and that it shares biologic characteristics with
this family.
Structural model of the Hepatitis C virus.
Model of Human Hepatitis C Virus
Lipid Envelope
Capsid Protein
Nucleic Acid
Envelope Glycoprotein E2
Envelope Glycoprotein E1
Hepatitis C viruses
Family
Genus
Virion
Envelope
Flaviviridae
Hepacivirus
60 nm spherical
Yes
Genome
Stability
Transmission
ssRNA
Ether-sensitive, acid-sensitive
Parenteral
Prevalence
Fulminant disease
Chronic disease
Oncogenic
Moderate
Rare
Often
Yes
Hepatitis C: A Global Health Problem
170-200 Million (M) Carriers Worldwide
United
States
3-4 M
Americas
12-15 M
Western
Europe
5M
Eastern
Europe
10 M
Far East Asia
60 M
Southeast Asia
30-35 M
Africa
30-40 M
Australia
0.2 M
HCV
accounts for 90-95% of post transfusion
hepatitis
 risk of sexual transmission lower than for HBV
 risk through casual contact low
 vertical transmission possible
 risk increased if mother is positive for HCV
RNA
 risk increased if mother is HIV positive
 overall prevalence estimated
at 1.4%

WHO IS AT GREATEST RISK
FOR HCV INFECTION?
drug abusers
 blood product recipients (anti-HCV screening
has greatly reduced risk)
 hemodialysis patients
 lab personnel working with blood products
 sexually active homosexuals
 persons with multiple and frequent sexual
contacts
 medical/dental personnel (3-10% via
needlestick from infected patient)

HCV - Diagnosis
Diagnostic Tests
Hepatitis C antibody tests
Qualitative HCV RNA tests
Quantitative HCV RNA tests
Genotyping
Hepatitis Delta virus.
Vírus da Hepatite Delta (HDV)
Vírus da Hepatite B
Vírus da Hepatite Delta
Envelope
AgHBs
Envelope
AgHBs
DNA
polimerase
RNA
42 nm
DNA
Core (27 nm)
AgHBc
AgHBe
Vírus Delta
Core (27 nm)
Virus Delta
Characteristics of hepatitis D viruses
Family
Genus
Envelope
Genome
Stability
Transmission
Prevalence
Fulminant
disease
Chronic disease
Oncogenic
Unclassified
Deltavirus
Yes (HBsAg)
ssRNA
Acid-sensitive
Parenteral
Low, regional
Frequent
Often
?
Two principal models of HDV infection have
been described
1. coinfection (the simultaneous introduction
of both HBV and HDV into a susceptible host),
2. superinfection (the infection of an HBV
carrier with HDV).
HDV INFECTION PATTERNS
Coinfection
acute simultaneous infection with HBV and HDV
often results in fulminant infection


(70% cirrhosis)
survivors rarely develop chronic infection

Superinfection



(< 5%)
results in HDV superinfection in an HBsAg
carrier (chronic HBV)
can occur anytime during chronic disease
usually results in rapidly progressive subacute
or chronic hepatitis
HDV


Transmission
Percutaneous
Sexual
- Common
- Yes, rare
Incubation period
- 21 - 45 (days)
Clinical illness at presentation jaundice 10%, higher with superinfection
Fulminant
- 2 – 7.5%
Case-fatality rate
- 1 – 2%
Chronic infection
Superinfection – 80%
Coinfection < 5%
HDV
Diagnostic tests
Acute infection
Chronic infection
IgM anti-HDV
IgG anti-HDV, HBsAg +
Immunity
Not applicable
Hepatitis E virus.
HEV is a small, nonenveloped RNA virus.
Recent
information
about
the
genomic
organization and other properties of the virus
strongly suggests that it is a calicivirus.
Hepatitis E virus
Family
Genus
Virion
Envelope
Caliciviridae
Unnamed
30-32 nm, icosahedral
No
Genome
Stability
Transmission
ssRNA
Heat-stable
Fecal-oral
Prevalence
Fulminant disease
Chronic disease
Regional
In pregnancy
Never
Oncogenic
No
Hepatitis E virus.
Epidemiology
Many cases of acute viral hepatitis in Asia,
Middle East and North Africa are caused by HEV.
Mainly young adults
Can infect primates, swine, sheep, rats
It is transmitted through the fecal-oral route
(human to human) but is unrelated to HAV. The
disease usually is caused by the ingestion of
fecally contaminated water.
Maternal-infant transmission occurs and is often
fatal.
HEV Clinical Characteristics
Similar to hepatitis A
Incubation period 15 – 60 (days)
Clinical Illness at presentation - 70 – 80% in
adults
Can cause severe acute hepatitis
Subclinical infection is common
Jaundice
Common
Fulminant
<1%, in pregnancy up to 30%
Case-fatality rate 0.5 – 4%
1.5 – 21% in pregnant women
Chronic infection None
HEV
Diagnostic tests
Acute infection IgG anti-HEV (sero-conversion)
Chronic infection Not applicable
Immunity
Not applicable
Hepatitis E
Prevention
Passive (Immune serum globulin)
Does not prevent infection
May ameliorate hepatitis
Active (Vaccine)
Anti-ORF2 prevents infection in chimps and
humans
Clinical trials in progress
Human Immunodeficiency Virus
The first indication of new disease – Acquired
Immunodificiency Syndrom (AIDS) began in the
summer of 1979, when reports came from great city
of USA (New York, Los Angeles, San Francisco) of a
sudden increase in the incidence of two very rare
diseases Kaposi's sarcoma (before registrated only at
elderly Africans) and Pneumocystis carinii pneumonia
(before described as epidemics at the closed
children’s establishments) in young adults who were
homosexuals or addicted to heroin or other injected
narcotics. They appeared to have lost their immnune
competence, rendering them
vulnerable to
overwhelming and fatal infections with relatively
avirulent microorganisms, as well as to lymphoid and
other malignancies.
Pneumocystis carinii
Statistics
Every day in the world infect with HIV 14.000 people,
about 6.000 – young men and women 15 - 24 years old.
The latest statistics on the world
epidemic(UNAIDS/WHO) - 2005
 People living with HIV/AIDS
36,6 million
 Adults living with HIV/AIDS
36,3 million
 Women living with HIV/AIDS
17,3million
 Children living with HIV/AIDS
2,3 million
 New infections with HIV/AIDS
4,1 million
 AIDS deaths in 2005
2,8 million

HIV, the etiologjcal agent of AIDS, belongs to the
lentivirus subgroup of the family Retroviridae.
Structure. HIV is a spherical enveloped virus,
about 90-120 nm in size. The nucleocapsid has an
outer icosaedral shell and an inner coneshaped core,
enclosing the ribonucleoproteins. The genome is
diploid, composed of two identical single stranded,
positive sense RNA copies. In association with viral
RNA is the reverse transcriptase enzyme, which is a
characteristic features of retroviruses. When the virus
infects a cell, the viral RNA is transcribed by the
enzyme, first into single stranded DNA and then to
double stranded DNA (provirus) which is integrated
into the host cell chromosome.
Types of HIV Virus
HIV 1



Most common in sub-Saharan Africa and
throughout the world
Groups M, N, and O
Pandemic dominated by Group M

HIV 2

Group M comprised of subtypes A - J
Most often found in West Central Africa,
parts of Europe and India
Viral genes and antigens. The genome of
HIV contains the three structural genes (gag,
pol and env) characteristic of all retroviruses,
as well as other nonstructural and regulatory
genes specific for the virus. The products of
these genes, both structural and nonstructural,
act as antigens. Sera of infected persons
contain antibodies to them. Detection of these
antigenes and antibodies is ofgreat value in the
diagnosis and prognosis of HIV infections.
Pathogenesis.
The receptor for the virus is the CD4 antigen and
therefore the virus may infect any cell bearing the
CD4 antigen on the surface. This is primarily the T4
(helper/inducer) lymphocyte. Some other immune
cells also possess the CD4 antigen on the surface
and so are susceptible to infection. Thus about 3 –
10 per cent of B lymphocytes and 10-20 per cent of
monocytes and macrophages, including specialised
macrophages such as alveolar macrophages in the
lungs and Langerhans cells in the dermis are
susceptible. Glial cells and microglia in the central
nervous system are also found infected. Folicular
dendritic cells from tonsils can be infected by HIV
without the involvemnent of CD4.
Specific binding of the virus to CD4 is by the
envelope glycoprotein gp120. However, for
infection to take place, cell fusion is essential.
This is brought about by the transmembrane
gp41.
Infection is transmitted when the virus enters the
blood or tissues of a person and comes into
contact with a suitable host cell, principally the
Th lymphocyte. Infection is likely to result more
often following the introduction of HIV infected
cells (as in blood transfusion or sexual contact)
than of cell free virus (as in injection of blood
products),
In an infected individual,
HIV can be isolated from
the blood,
lymphocytes,
cell free plasma,
semen,
cervical secretions,
saliva,
tears,
urine
and breast milk.
The primary pathogenic mechanism in HIV
infection is the damage caused to the T4
lymphocyte. The T4 cells decrease in numbers
and the T4:T8 (helper: killer) cell ratio is
reversed. Viral infection can suppress the
function
of infected cells without causing
structural damage. Infected T4 cells do not
appear to release normal amounts of
interieukin-2, gamma interferon and other
lymphokines. This has a marked dampening
effect on cell mediated immune response.
Window Period
Time from initial infection with HIV until
antibodies are detected by a single test
 Usually 3-8 weeks before antibodies are
detected
 May test false-negative for HIV antibodies
during this time period
 Can still pass the virus to others during this
period

Disease Progression
Severity of illness is determined by amount of
virus in the body (increasing viral load) and
the degree of immune suppression
(decreasing CD4+ counts)
As the CD4 count declines, the immune
function decreases.
What body fluid transmit AIV?
blood
 semen
 vaginal fluid
 breast milk

AIDS is primarily a sexually transmitted
infection. In the USA it was transmitted
predominantly among male homosexuals. The
danger of infection is more for the passive
partner because mucosal tears are very
frequent during anal intercourse and virus
laden lymphocytes in the semen can directly
enter through these. In homosexual men, the
relative risk of infection in the various sexual
practices has been estimated in the
descending order as ano-receptive, ororeceptive, ano-insertive and oro-instertive.
The second mode of transmission is
through blood and blood products. Before
the danger of HIV transmission was
recognised, many persons had received
blood and blood products containing the
infectious virus. Screening of blood donors
is now mandatory. Even screening may not
completely eliminate the danger as the early
infectious case may be missed but the risk is
reduced considerably.
This restriction also applies to the
donation of semen, cornea, bone marrow,
kidney and other organs as infection can be
transmitted through any of these.
However, such restraints may not be
enforced in the developing countries, where
professional donors constitute a real hazard.
Contaminated needles can transmit the
infection. This is particularly relevant in
drug addicts who share syringes and
needles.
The use of unsterile syringes and
needles by qualified and unqualified
health workers makes iatrogenic infection
likely. Even in large hospitals, sterilisation
and asepsis are often unsatisfactory. The
use of disposable syringes, needles and
other equipment should be obligatory.
The danger of needlestick injury is present in
medical and paramedical personnel, though the
chances of infection are much less than with HBV.
The risk of infection following needlestick injury or
injury with sharp instruments used on seropositive
patients has been estimated to be about one per
cent. The risk to medical and nursing personnel
appears to be minimal provided they take
adequate precautions. However, considering the
unsatisfactory asepsis and hygiene in many
hospitals in the poor countries, the risk may be
real. Medical and paramedical staff need to be
educated on caring for patients infected with HIV.
Transmission of infection from
mother to baby can take place before,
during or after birth. As infection occurs
in about half such babies. HIV may be
present in breast milk and may rarely
be transmitted through breast feeding.
Normal social and domestic contact
does not transmit the infection. Shaking
hands, hugging, putting cheeks together or dry
kissing are safe. There has been no confirmed
case of transmission through saliva, though the
virus may be present in the saliva of infected
persons. 'Wet kissing' is considered risky.
Sharing rooms, bathrooms, and cooking and
eating facilities are not considered dangerous.
There is no evidence that mosquitoes, bed bugs
or other bloodsucking insects can transmit the
virus. Infection is not transmitted through air,
food, water or formites.
ACQUIRED DEFICIENCY
SYNDICOME (AIDS)
Clinical features of HIV infection. AIDS is only
the last stage in the divide spectrum of clinical
features in HIV infection.
The natural evolution of HIV infection can be
considered in the following stages:
I. Acute HIV infection.
II. Asymptomatic infection.
III. Persistant Generalised Liphadenopathy
(PGL).
IV. AIDS Related Complex (ARC).
V. AIDS.
Acute HIV infection.
Within a few weeks of infection with HIV, about 1015 per cent of persons experience low grade fever,
malaise, headache, 1ymphadenopathy, sometimes
with rash and arthropathy resembling glandular fever.
Rarely, there may be acute encephalopathy. Tests for
HIV antibodies are usually negative at the onset of the
illness but become positive during its course. Hence
this syndrome has been called «seroconversion
i1lness», though in the majority of those inflected
with HIV, seroconversity occurs without any apparent
illness. HIV antigenemia (p24 antigen) can be
demonstrated at the beginning of this phase.
Asymptomatic infection.
All persons infected with HIV, whether they
experience seroconversion illness or not, pass
through a phase of symptom1ess infection; lasting
for several months or years. They show positive
HIV antibody tests during this phase and are
infectious. In some, the infection may not progress
any further, while in others it may lead to full
brown AIDS, either directly or through cytopenias,
minor
opportunistic
infection,
persistent
generalised lympnadenopathy or AIDS related
complex (ARC) as described below.
Persistant Generalised Liphadenopathy
(PGL).
This has been defined as the presence of
enlarged lymph nodes, at least 1,0 cm, in
diameter, in two or more noncontiguous
extrainguinal sites, that persist for at least
three months, in the absence of any current
illness or medication that may cause
lymphadenopathy. This by itself is benign but
a proportion of the cases may progress to
ARC or AIDS.
AIDS Related Complex (ARC).
This group inc1udes patients with considerable
immunodeficiency,
suffering
from
various
constitutional symptoms
or having minor
opportunistic infections. The typical constitutional
symptoms are fatigue, unexplained fever, persistent
diarrhea and parked weight loss of more than 10 per
cent of body weight. The common opportunistic
infections are oral candidiasis,
herpes zoster,
salmonellosis
or
tuberculosis.
Generalized
lyrnphadenopathy and splenomegaly are usually
present. ARC patients are usually severely ill and
many of them progress to AIDS in a few months.
AIDS.
This is the end stage disease representing the
irreversible breakdown of immune defense
mechanisms, leaving the patient a prey to
progressive
opportunistic
infections
and
malignancies. The clinical severity of AIDS varies
with the type of infection or malignancy present.
In early AIDS, many patients are ill only during
episodes of infection which may respond to
treatment. Between
episodes they may be
relatively well and able to resume normal life.
Dermatomycosis
Herpes zoster
Dermatitis
Herpes
Kaposi's sarcoma
Kaposi's sarcoma
Warts
Sarcoma
Herpetic infection
Еczema
Dementia. HIV may cause direct cytopathogenic
damage in tire central nervous system. It can
cross the blood brain barrier and cause
encepfialopathy leading to loss of higher
functions, progressing to dementia.
Pediatric AIDS. About one third to one half the
number of babies born to infected mothers are
infected with HIV. Many of them may not survive
for a year. Children may also acquire the infection
from blood transfusions or blood products.
There are many differences between adult
and pediatric AIDS.
Children develop humora1 immunodeficiency
early, leading to recurrent bacterial infections.
Failure
to
thrive,
chronic
diarrhea,
lymphadenopathy,
tuberculosis
and
opportunistic bacteria1 infections are common
manifestations in pediatric AIDS Lymphocytic
interstital pneumonia is seen exclusively in
children,
while
Kaposi's
sarcoma,
toxoplasmosis and cryptococcosis are less
common than adults.
Laboratory diagnosis
Laboratory procedures for the diagnosis of HIV infection
include tests for immunodificiency as well as specific tests
for HIV.
A. Immunological tests. The following parameters help to
establish the immunodeficiency in HIV infection:
l . Total leucocyte and lymphocyte count to demonstrate
leucopenia and a lymphocyte count usually below
2,000 /c.mm.
2. T cell subset assays. Absolute T4 cell count will be
usually less than 200/c.mm. T4: T8 cell ratio is reversed.
3. Platelet count will show thrombocytopenia.
4. Raised IgG and IgA levels.
5. Diminished CMI as indicated by skin tests.
6. Lymph node biopsy showing profound abnormalities.
B. Specific tests for HIV infection. These
inc1ude demonstration of HIV antigens and
antibodies and isolation of the virus.
I. Antigen detection. The time course of
appearance of detectable antigens and antibodies
after VIIV infection is generally as follows:
Following a single massive infection, as by blood
transfusion, the virus antigens (p24) may be
detectable in blood after about two weeks. IgM
antibodies appear in about 4-6 weeks, to be
followed by IgG antibodies.
If the infecting dose is small, as following a
needlestick injury, the process may be considerably
delayed. The appearance of p24 antigenemia and
viremia followed by the early antibody response
coincide with the acute or seroconversion illness.
Afterwards, p24 antigen disappears from circulation
and remains absent during the long asymptomatic
phase, to reappear only when severe clinical disease
sets in. Tests for antigen detection are available only
in specialized laboratories and therefore not used
routinely.
2. Virus isolation. Once infected with HIV, a person
remains infected for life. The virus is present in
circulation and body fluids,
mostly within the
lymphocytes but some are also cell free. Virus titres are
high early in infection, about a week before antibodies
start appearing. Antibodies do not neutralize the virus and
the two can coexist in the body. During the phase of
asymptomatic infection, the virus titre is low and may not
be detectable but when clinical AIDS sets in, the titre
rises once again. An infected person may therefore be
infectious throughout but the infectivity is highest in the
early phase of infection (when the antibody tests are
negative and the case may not be detected in screening
tests) and again when the person becomes clinically ill,
3. Antibody detection. Demonstration of antibodies
is the simplest and most widely employed technique
for the diagnosis of HIV infection. However, it needs
to be emphasized that it may take several weeks to
months for antibodies to appear after infection, and
during the later part of this period, the individual may
be infectious. This seronegative infective stage is
known as the window period. For this reason,
antibody screening is not totally dependable for
spotting infectious persons, for example, from among
blood donors.
Once antibodies appear they increase in titre
and broaden in spectrum for the next
several months. IgM antibodies disappear in
8-10 weeks while IgG antibodies remain
throughout.
When
immunodeficiency
becomes severe following clinical AIDS,
some components of anti HIV antibody
(e.g., anti-p24) may disappear.
Serological tests for anti HIV antibodies are
of two types screening and confirmatory
tests.
Screening tests possess high sensitivity,
have a broadly reactive spectrum, are
simple to perform and can be automated for
handling large numbers of samples at a
time. They are not highly specific and may
give a few false positive results. All sera
positive on screening tests are to be checked
by a confirmatory test before the sample is
declared as positive. The most widely used
screening test is ELISA.
ELISA tests. Direct solid phase antiglobulin ELISA
is the method most commonly used. The antigen
obtained from HIV grown in continuous T
lymphocyte cell line or by recombinant techniques is
coated on microtitre wells or other suitable solid
surface. The test serum is added, and if the "antibody
is present, it binds to the antigen. After washing
away
the
unbound
serum,
antihuman
immunoglobulin linked to a suitable enzyme is
added, followed by a colour-forming substrate. If the
test serum contains anti HIV antibody, a visible or
photometrically detectable colour is formed which
can be read visually or by special ELISA readers.
The confirmatory test commonly employed is
immunoblotting (the Western Blot test). In this test, IIIV proteins separated according to their
electrophoretic mobility (and molecular weight) by
polyacrylamide gel electrophoresis are blotted onto
stops of nitrocellulose paper. These strips are made to
react with test sera and then with enzyme conjugated
antihuman globulin. A suitable substrate is then
added, which produces a prominent colour band
where the specific antibody has reacted with the
separated viral protein.
The confirmatory test
In a positive serum, bands will be seen with multiple
proteins, typically with p24 (gag gene, core protein),
p31 (pol gene, reverse transcriptase) and gp41, gpl20
or gpl60 (env gene, surface antigen). However,
interpretation becomes difficult when bands appear
only at one or two sites, as with p24 or gpl20. This
may happen in early infection but may also be
nonspecific.
Western blot is a very useful
confirmatory test but the interpretation remains
subjective and demands considerable experience.
Applications of serological tests.
Serological tests for HIV infection are employed in the
following situations.
A person found positive for anti HIV antibody should never
donate blood or other biological materials (semen, cells, tissues
and organs).
As the infection can be transmitted from mother to baby,
before, during or after birth, antenatal screening may be
considered.
Some countries have laws requiring screening of incoming
foreigners.
Diagnosis. Serology after two months and, if negative, after six
months would be sufficient. If serology is negative six month
after exposure, infection is unlikely to have occurred.
Prognosis. In a person infected with HIV
Therapy of HIV Infection:
Several distinct classes of drugs are now used to
treat HIV infection:
Nucleoside-Analog Reverse Transcriptase
Inhibitors (NRTI). These drugs inhibit viral RNAdependent DNA polymerase (reverse transcriptase)
and are incorporated into viral DNA (they are chainterminating drugs).
Zidovudine (ZDV, Retrovir)
Didanosine (ddI, Videx)
Zalcitabine (ddC, Hivid)
Stavudine (d4T, Zerit)
Lamivudine (3TC, Epivir)
Therapy of HIV Infection:
Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs). In contrast to NRTIs,
NNRTIs are not incorporated into viral DNA; they
inhibit HIV replication directly by binding noncompetitively to reverse transcriptase.
Nevirapine (Viramune)
Delavirdine (Rescriptor)
Therapy of HIV Infection:
Protease Inhibitors. These drugs are specific for
the HIV-1 protease and competitively inhibit the
enzyme, preventing the maturation of virions
capable of infecting other cells.
Saquinavir (Invirase) first approved in 1995
Ritonavir (Norvir)
Indinavir (Crixivan)
Nelfinavir (Viracept)