****** The PARVOVIRUSES ******
Characteristics
of the virus:
1.
They
are non–enveloped viruses, with icosahedral symmetry, about 22 nm in diameter
2.
They
have a single stranded nucleic acid. A “hairpin” loop at the end of each genome
initiates replication of the complementary strand. The single strand DNA is 5.5
Kb long.
Parvoviruses
infecting humans:
1.
Dependoviruses
– non–pathogenic, adeno–associated viruses.
2.
Parvoviruses
– B–19 – causes Erythema infectiosum; aplastic crises
– RA–1 – possible implication in rheumatoid
arthritis.
Diseases
associated:
1.
Erythema infectiosum
Also known as “slapped cheek syndrome” or
“fifth disease” (because it is included in the sixth exanthematous illness of
childhood; the others are: measles, rubella, Scarlet Fever, Exanthem subitum
and Duke’s disease)
It is characterized by maculopapular rash
over the malar areas followed within the next 4 days by a rash on the trunk and
limbs which may persist for 2 or 3 weeks. The incubation period is 13–18 days.
There may be some fever and malaise in the early stages and mild febrile
illness without rash is common.
Adults, particularly women may also be
infected with the involvement of the joints, hand and fingers are also affected
by arthropy of the arms, legs and spine are more pronounced. Arthralgia may
persist for a few weeks but there appear to be no long–term sequelae. Infection
in pregnancy may result in fetal death.
2.
Aplastic crisis
Characterized by low hemoglobin value and
disappearance of circulating reticulocytes. This is because the virus
replicates in and damages the rapidly dividing late normoblast.
Laboratory
diagnosis:
1.
Electron
Microscopy
2.
Detection
of IgM antibody by ELISA and RIA
Pathogenesis
and epidemiology
1.
After
primary infection of the upper respiratory tract, there is viremia lasting
about a week. Clearance of virus from the blood coincides with a sharp IgM
antibody response, followed shortly by the appearance of IgG antibody.
2.
Epidemics
occur during late winter and early spring and mainly affect young school
children.
****** The HEPADNAVIRUSES ******
Characteristics
of the virus:
1.
By
electron microscopy, two shapes are revealed:
a.
Consist
of complete virion or Dane particle, 42 nm in diameter and is double–shelled.
b.
The
other are spherical or tubules, 20–22 nm in diameter; they consist only of
excess surface antigen, i.e., the glycoprotein forming the outer layer of the
double–shelled Dane particle. The core of which is icosahedral nucleocapsid
containing:
(1) The DNA genome (double stranded)
(2) A DNA–dependent polymerase
involved in replication
(3) Hepatitis B core antigen (HbcAg)
(4) Hepatitis B envelop antigen
(HbeAg)
2.
It
belongs to the Family Hepadnaviridae (Hepatitis DNA virus). It infects
humans but also ducks, chipmunks and squirrels.
3.
It
causes disease known as Hepatitis B infection.
Serological
markers of Hepatitis B infection
Markers Remarks Present
in
Antigens
1.
HBsAg surface antigen, acute and chronic
infections,
not infective including
antigenemia
2.
HBeAg found in core of
virion acute and chronic
hepatitis
Presence in blood indicates
infectivity
§ HBcAg, the core antigen, is not
readily detectable in blood and is not used as a marker.
Antibodies
1.
Anti
– HBs indicates recovery;
convalescence
2.
Anti
– HBe presence indicates
little convalescence
or no infectivity
3.
Anti
– HBc in IgM forms,
indicates the first
antibody to appear;
recent infection persist in IgG form for life
Mode
of transmission:
1.
Transmitted
only in blood and body fluids, including cervical secretions and semen.
2.
Sexual
intercourse, particularly among male homosexuals.
3.
Intravenous
drug abusers by sharing of needles and syringes.
Pathogenesis:
1.
Postnatal infections
a.
Acute
infections – subclinical, especially in young children or in those with
impaired immunity. However, after an incubation period of 2–3 months, there is
prodromal phase similar to that of Hepatitis A, but sometimes marked by a
transient rash and anthropathy, probably due to virus–antibody interaction.
This is followed by overt, jaundice, after which 90% of patients recover
uneventfully within a month or so. In others, the outcome may be chronic
infections or rapid death.
Other signs and symptoms include:
(1) Elevated serum transaminases and
HbsAg
(2) Elevated HBeAg and DNA polymerase
(3) Appearance of anti–HBc followed
by anti–HBe (a good prognostic sign since its production heralds the
disappearance of HbeAg and thus infectivity)
·
HBsAg
is the first antigen to appear while the anti–HBs are the last antibody to
appear. The arrival of anti–HBs indicates complete recover and immunity to
reinfection.
Fulminant hepatitis – result of an abnormally active destruction
of infected hepatocytes by cytotoxic T lymphocytes. Usually infected are females
who die within 10 days in hepatic coma.
b.
Chronic carriers – occurs in 10% of patient’s which appears
when the serological profile has not reverted to the normal post–recovery
pattern within six months of onset. It has three varieties:
(1) Chronic antigenemia – patient fails to form anti–HBs and the
appearance of anti– HBe may be delayed. Although HbsAg persists in the blood
for many years, liver function is normal, the patient is well and is of little
or no danger to others. This picture is often seen in those with impaired
immunity. The serological pattern is similar in chronic persistent hepatitis,
in which , however, there is a mild degree of liver damage.
(2) Chronic aggressive (active)
hepatitis – patient fails to produce
either anti–HBs or anti–HBe, as a result they continue to carry both HBsAg and
infectious virions in their blood and are thus infectious for others and are
referred to as supercarriers. There is significant damage to the liver
parenchyma and raised transaminase levels. These patients are liable to repeat episodes
of hepatitis and are at risk of developing cirrhosis; some may eventually
succumb to malignant disease of the liver.
(3) Hepatocellular carcinoma or
primary liver cancer – result of
integration of viral genome into the DNA of hepatocytes. This happens only
after a chronic infection with continuing production of complete virions has
been in progress for at least 2 years.
2.
Perinatal infections
a.
HBeAg –
positive carriers are at risk of cirrhosis of the liver and the hepatocellular
carcinoma. Babies acquiring the infection at birth nearly all come into the
category.
Laboratory
diagnosis:
1.
Specific test
a.
Reverse
passive hemagglutination
b.
Latex
slide test
c.
HbsAg
by ELISA
d.
Electron
microscopy
2.
Non–specific test
a.
Alanin
aminotransferase (ALT) test
b.
Prothrombin
Time
c.
Bilirubin
assay
Treatment,
epidemiology and control:
1.
Alpha–interferon
is the treatment of choice; however, DNA polymerase inhibitors like vidarabine,
acyclovir, and foscarnet have been tried.
2.
It
is estimated that there are 200 million HBV carriers in the world; of these,
75% were infected at birth.
3.
Control
measures include active immunization of “first generation” vaccines prepared
from the blood plasma of carriers given intramuscularly at 0,1 and 6 months
with booster at 5 year intervals. Human immunoglobulin with a hight titre
anti–HBs (HBIG) can be used to provide immediate passive protection:
a.
With
vaccine, for infants born to carrier mothers.
b.
For
health care staff who suffer “needle stick” or other penetrating injuries while
attending actual or suspected high–risk patients.
****** The PAPOVAVIRUSES ******
Characteristics
of the virus in general:
1.
The
name itself is an acronym for:
a.
pa
– papillomavirus (55 nm in diameter)
b.
po
– polyomavirus (45 nm in diameter)
c.
va
– vacuolating agents
·
– oma – a suffix meaning tumors
2.
Their
virion are icosahedral and has no envelope.
3.
The
genomes are circular double stranded DNA and code for a comparatively small
number of polypeptides.
4.
Replication
takes place within the host – cell nucleus except for papillomavirus which
multiply in differentiating stratified squamous epithelium.
THE PAPILLOMAVIRUS
Specific characteristics:
1.
They
are classified on the basis of their degree of DNA homology, i.e., on how
closely their nucleotide sequences correspond.
2.
There
are 60 types of human papillomavirus (HPV) which has been identified.
3.
They
cause disease only on skin and mucous membrane.
Types of lesions produced by HPV:
1.
Benign lesions
a.
Cutaneous warts
Mode of transmission:
(1) Through infected skin, either by
direct contact or through fomites and enters its new host through abrasions.
(2) Through swimming pools and
changing rooms.
Types of cutaneous warts
(1) Common warts (verruca vulgaris) – has a characteristically roughened
surface; the excrescences are usually a few millimeters in diameters and may
occur in quite large numbers anywhere on the skin, but especially on hands,
knees and feet.
(2) Flat warts (verruca planae) – are flatter and smoother than common warts
and predominantly affects young children.
(3) Butcher’s warts – cause by HPV–7 and is an occupational
hazard, it has no relationship with bovine papillomavirus (BPV).
b.
Genital warts or condylomata acuminate – they are fleshy, moist and vascular and
may grow much larger than the common in skin warts.
Mode of transmission:
(1) Through sexual contact
(2) Through vaginal contact in
delivery cases
Sites in men:
(1) On the penis, affecting the area
around the glans and prepuce more than the shaft.
(2) Within the urethral meatus and
urethra itself.
(3) Around the anus and within the
rectum, particularly in homosexuals practicing receptive anal intercourse.
Sites in woman:
(1) On the vulva
(2) Occasionally, in the vagina
(3) On the cervix. Here, the typical
lesion is the flat, intraepithelial type, rather than the fleshy variety seen
on the external genitalia. It is difficult to distinguish clinically between
this lesion, caused by a papillomavirus and other forms of cervical dysplasia.
(4) Around the anus and perineum.
2.
Malignant lesions
a.
Bowenoid papulosis – manifested by multiple papules on the
penis or vulva (name taken from Bowen’s disease thought not associated).
b.
Premalignant intra–epithelial dysplasia – cause by HPV 16 and 18 and cause carcinoma
of penis and cervix
(1) Vulvar Intraepithelial Neoplasia
(VIN)
(2) Vagina Intraepithelial Neoplasia
(VAIN)
(3) Cervix Intraepithelial Neoplasm
(CIN)
c.
Laryngeal infection – cause by HPV 6, 11 and 16.
d.
Epidermodysplasia verruciformis – a rare autosomal recessive disease
associated with T cell defects, function and number.
Clinical features of papillomavirus lesions
1.
Hyperkeratosis – massive proliferation of the keratinized
layers of the dermis. Large, pale, vacuolated cells are present in the granular
layer. There are also eosinophilic cytoplasmic inclusions which are not of
viral origin but which consist of abnormally large keratohyalin granules.
Basophilic inclusions in the nuclei of the epidermal cells in which typical
papillomavirus virions can be seen by electron microscopy.
e.g.
flat warts, common warts
2.
Koilocytes or empty cells – vacuolated cells in cervical scrapings.
e.g. condylomata acuminata
Laboratory diagnosis:
1.
Papanicolau
staining of smear
2.
Antiserum
against disrupted BPV particles – for HPV but not its type.
Treatment:
1.
For skin warts
a.
Podophyllin
– extracted from roots of the American mandrake
b.
Freezing
with liquid nitrogen
2.
For cervical lesions
a.
Freezing
b.
Electrodiathermy
c.
Cone
biopsy
d.
Injection
of interferon
THE POLYOMAVIRUS
Specific characteristics:
1.
Poly
– oma means “many tumors.”
2.
They
have oncogenic potential (ability to cause malignant cells or tumors)
3.
They
have the ability to grown and induce cytopathic effects in cultured cells,
notably those from embryo mice.
Associated diseases:
1.
JC
virus – primarily affects senile patients,
it causes persistent infection, primarily in the urinary tract, until stirred
into more dangerous activity by immunosuppression. It causes a disease known as
progressive multifocal leukoencephalopathy (PML).
Clinical features:
a.
Chronic
lymphatic leukemia
b.
Hodgkin’s
disease
c.
Demyelination
d.
Abnormal
oligodendrocytes
e.
Astrocytosis
2.
BK
Virus – isolated from the urine of an immunocompromised renal transplant
patient. It readily grows in monkey kidney (VERO) cells.
3.
SV
40 virus or Simian Vacuolating viruses – oncogenic for hamsters but not in
monkey where it was first isolated. It is resistant to formalin which is used
in inactivating polio vaccine.
4.
Merkel
cell polyomavirus (MCV) – is the causative agent of Merkel cell carcinoma, a
rare but aggressive form of skin cancer.
5.
Trichodysplasia
spinulosa–associated polyomavirus – causative agent of trichodysplasia
spinulosa, a rare skin disease only seen in immunocompromised patients.
****** The ADENOVIRUSES ******
Characteristics
of the virus:
1.
They
have an icosahedral DNA, 80 nm in diameter.
2.
The
capsid is formed from 252 capsomeres, which are arranged in icosahedron with 20
sides and 12 ventrices (with slender fiber projections).
3.
The
CELO (chick embryo lethal orphan) virus, an avian adenovirus which is used for
vaccine production causes cancer in animals.
4.
It
has an incubation period of 5–10 days.
Two
generas of Adenovirus:
1.
Avian
adenovirus
2.
Human
adenovirus
Classification
of Human Adenovirus:
Subgroup Representative Virus Target organ
A 12, 18, 31 Gastrointestinal
Tract
B 3, 7, 11, 21 Pharynx,
Lungs, Urinary Tract,
Conjuntiva
C 1, 2, 5, 6 Pharynx
D 8, 9, 19 Eye
E 4 Upper
Respiratory Tract
F 40, 41 Gastrointestinal
Tract
Other
adenovirus associated diseases:
1.
Acute
intussusception in infants
2.
Necrotizing
enterocolitis
3.
Acute
cystitis
4.
Meningoencephalitis
5.
Pneumonia
Laboratory
diagnosis:
1.
Cell
culture using Human diploid, HeLa, Hep–2 medium – the pH of the medium usually
falls rapidly as the virus – infected cells become swollen, rounded and
refractile, clustering together like bunches of grapes.
****** The HERPESVIRUSES ******
Characteristics
of the virus:
1.
The
morphology of all herpesviruses is similar and distinctive. Although they share
a number of antigens, they can be distinguished by difference in their genomes
and by serological tests.
2.
They
are distinguished by electron microscopy by their large baggy envelope.
Unenveloped particles may also be present.
3.
They
have an icosahedral nucleocapsid. The virion are 120–200 nm in diameter.
4.
The
genome is double stranded DNA and codes for about 100 polypeptides. HSV–1, HSV–2
and VZV code for thymidase kinase, a phosphorylating enzyme which helps to
mediate the action of certain antiviral drugs.
Classification
of Human Herpesviruses:
Subfamily Virus Abbreviation
Alphaherpesvirus Herpes simplex virus
type 1 HSV–1
Herpes
simplex virus type 2 HSV–2
Varicella
zoster virus VZV
Betaherpesvirus Cytomegalovirus CMV
Human
Herpes virus type 6 HHV–6
Human
Herpes virus type 7 HHV–7
Gammaherpesvirus Epstein–Barr virus EBV
HERPES SIMPLEX VIRUS (HSV)
Two varieties:
1.
HSV–1
– primarily affects the upper part of the body
2.
HSV–2
– usually but not extensively causes genital infection.
Types of infection produced by HSV
1.
Primary infection – refers to the first infection with either
HSV. Since there is little cross –protection between HSV–1 and HSV–2 it is
impossible to be infected later with other variety; to distinguish it from a
primary infection in a completely non–immune person, such an episode is known
as an initial infection.
2.
Reactivation – production of infective virus by
latently–infected cell.
3.
Recurrence / Recrudescence – result of clinically apparent disease.
Diseases produced by HSV:
1.
Oropharyngeal infection – primary infection is acquired through oral
contact of infant with adult by kiss. It maybe asymptomatic otherwise it may
present as acute gingivostomatitis characterized by vesicle on gums and oral
mucosa ulcers. The time of onset to healing is 2 weeks.
Recurrence is characterized by a cluster of
vesicles around the mouth with itching sensation. The lesion is often watery.
They are milder, more localized and of shorter duration than primary infection.
2.
Dermal infection
a.
Herpetic
whitlow – a lesion on a finger which is
very painful but heals without treatment. Opening such lesion must be
discourage since it contains not pus but necrotic material and incision tends
to spread the infection.
b.
Eczema
herpeticum – an infection acquired by
people.
3.
Genital infection
a.
Herpetic
proctitis with meningitis is sometimes seen in male homosexuals. The pain
presents a crop of vesicles, lesions also occur in meatus causing dysuria.
b.
Cervicitis
with vesicular in females. Lesions are found in labia, vulva and perineum,
sometimes extending to the inner surface of thighs.
c.
Herpetic
vulvovaginitis in children occurs as an indication of sexual abuse though it
may also be a result of auto–inoculation from oral lesions.
4.
Ophthalmic infection
a.
Herpetic
keratoconjuctivitis – characterized by dendritic ulcers.
b.
Disciform
keratitis
c.
Iridocyclitis
5.
Encephalitis – characterized by fever and malaise lasting
a few days followed by headache and changes in behavior. Clouding of
consciousness proceeding to coma is a bad prognostic sign.
Laboratory diagnosis:
1.
Immunofluorescent
staining – using monoclonal antibodies
2.
Electron
microscopy – a drop of fluid is taken by opening the top of a vesicle with a
large gauge needle or the point of a scalpel blade, spreading it on an ordinary
microscope slide and observing for characteristic morphology.
VARICELLA–ZOSTER VIRUS (VZV)
Disease produced by VSV:
1.
Varicella
– causes chickenpox
2.
Herpes
Zoster – causes shingles or hives
Clinical manifestations of Varicella:
1.
Incubation
period: 2 weeks but may vary by several days
2.
In
children, rash and mild feverish illness
3.
In
adults, a rash is centripetal (confined on face and trunks than on limbs). It
first appears as flat macules, which rapidly become raised into papules; these
are succeeded by vesicles, which finally form crusts that are shed from skin.
4.
Transmitted
by respiratory route.
Complications of Varicella infection:
1.
Bacterial
infection of the vesicular fluid leading to pustule formation.
2.
Hemorrhage
in patients with thrombocytopenia
3.
Post–infection
encephalitis
4.
Varicella
pneumonitis in leukemic children
5.
Generalized
varicella (involvement of viscera, joints and CNS)
6.
Congenital
and neonatal infections resulting in a severe scarring of the skin with
hydrocephalus and other malformations.
Clinical manifestations of Zoster:
“Zoster” is derived from the Latin word for a
belt or girdle and refers to the characteristic distribution of the rash when a
thoracic dermatome is involved. The attack is heralded by hyperaesthesia and
sometimes by pain in the affected area, followed within a day or so by a crop
of typical herpetic vesicles which eventually crust over and heal in the usual
way.
CYTOMEGALOVIRUS (CMV)
Category of patient Mode of infection
Fetus from mother,
across the placenta
Infant contact with
maternal body fluids during birth;
Breast–feeding
(colostrum)
Young child Contact
with urine or saliva of other children
Adolescent and adults kissing; sexual intercourse;
blood transfusion
Transplant recipient Exogenous – through
donated tissues and blood transfusion
Endogenous
– reactivation due to immunosuppression
Diseases produced by CMV:
1.
Glomerulonephritis
with rejection of transplanted kidney
2.
Febrile
illness
3.
Interstitial
pneumonitis with edema and pronounced cellular infiltration
EPSTEIN–BARR VIRUS (EBV)
Two varieties:
1.
EBV–A
2.
EBV–B
– more prevalent
EBV antigens:
1.
EB
viral nuclear antigen (EBNA) – found in nuclei of cells.
2.
Lymphocyte
detected membrane antigen (LYOMA) – hard to stain but is the target for
cytotoxic T cells.
3.
“Early”
membrane antigen
4.
Viral
capsid antigen (VCA)
5.
“Late”
membrane antigen
EBV antibodies useful in diagnosis
1.
Anti–EA
2.
Anti–VCA
Diseases associated with EBV
1.
Infectious
mononucleosis (IM) or Glandular Fever –
transmitted by oral route and primarily affects adolescents and young adults. The
incubation period is a month or more. There is fever, pharyngitis and
enlargement of the lymph nodes, first in the neck and later elsewhere. In most
patients, the spleen is palpable and there is some liver dysfunction,
occasionally with frank jaundice. There may be transient macular rash; it is a
peculiarity of the disease that patients given ampicillin develop a more severe
rash due to the formation by transformed B cells of antibody to this
antibiotic.
Complications include Guillain–Barre’
syndrome with CNS involvement and rarely, ruptures of spleen.
2.
Burkitt’s
Lymphoma (BL) – hyperendemic in children in
Africa with ages 6–7 years old. It presents as a tumor of the jaw, less often
of the orbit and other sites. This highly malignant neoplasm is responsive to
cyclophosphamide which, if given early enough, may affect a cure.
3.
Nasopharyngeal
Carcinoma (NPC) – prevalent
in Southern China affecting 20–50 years old males usually. This neoplasm is
similar to BL. It is also said to be associate with certain Human Leukocyte
Antigen (HLA) haplotypes and high consumptions of nitrosamine in salted foods.
Laboratory diagnosis depends on:
1.
Raised
leukocyte count and atypical T lymphocytes in the blood film.
2.
Presence
of heterophil (Formann) antibodies detectable by Paul–Bunnell or Monospot
hemagglutination test.
HUMAN HERPESVIRUS (HHV)
1.
HHV–6
– first isolated in 1986. It causes:
a.
Exanthema
subitum or Roseala infantum – characterized by rash in young children with mild
febrile illness.
b.
Lymphadenopathy
in adults
2.
HHV–7
– isolated in mononuclear cells in blood of healthy individual but not
associated with any disease
Laboratory diagnosis:
1.
IgG
antibody
2.
IgM
antibody
3.
Cell
culture in lymphoid cell line
****** The POXVIRUSES ******
Characteristics
of the virus:
1.
The
largest virus of all measuring 230 x 270 nm and when suitably stained can be
seen with an ordinary microscope.
2.
Their
structure is complex. They are either icosahedral or helical. The capsid is
consist of network of tubules and is sometimes surrounded by an envelope.
3.
Their
nucleic acid is double stranded.
4.
They
replicated only in the cytoplasm in which they form Inclusion Bodies.
Classification
of Human Poxviruses:
Genus Virus Primary Host Clinical
features in human
Orthopoxvirus Variola Man Smallpox
Vaccinia Man, cattle, cats, vesicular vaccination lesion
Cowpox
Rodents Lesion in hands
Monkeypox Monkeys, squirrels resembles smallpox
Parapoxvirus pseudocowpox Cattle Localized nodular lesion
Orf Sheep,
goats Localized
Vesicogranulomatous
lesion
Unclassified Tanapox monkeys vesicular skin lesion and
Febrile
Illness
Molluscum Man multiple
small skin nodules
Diseases
associated with Poxvirus
1.
Smallpox
Two varieties: a. Variola major b. Variola
Minor or alastrim
Signs and symptoms:
It has an incubation period of 10–12 days,
with a range of 8–17 days; a febrile illness of sudden onset lasting 3–4 days
was followed by the appearance of a rash progressing from macules to papules,
vesicles and pustules which then forms crusts. The distribution of the rash is
centrifugal (affects extremities).
2.
Molluscum contagiosum – characterized by small nodular lesions,
mostly on trunks. They become umbilicated and contain caseous material in which
“molluscum bodies” can be readily demonstrated. These are quite large (30 µm
long) ovoid structure containing many virions. It is transmitted via skin
abrasion or sexual penetration. Cryotherapy, curettage or treatment with
caustic agents such as phenol helps eradicate the disease.
No comments:
Post a Comment