Transcript herpes viridae

HERPES VIRIDAE
Prevalent as early as ancient Greek times.
Hippocrates described the cutaneous spreading
of lesions. Shakespeare is thought to have been
familiar with these lesions and their transmission
and mentioned in his Romeo and Juliet. In 1893
Vidal recognized the human transmission of HSV
infection from one individual to another.
In 1919, Lowenstein confirmed experimentally the
infectious nature of HSV. In 1920's and 1930's,
the natural history and range of infections of HSV
were studied. By the 1940's and 1950's, research
established on diseases caused by HSV.
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Herpesviridae, a large family of DNA
viruses that cause diseases in animals and
humans.
The members of this family are
also known as herpesviruses.
Name is derived from the Greek
word herpein ("to creep or
crawl"). Latent, reactivation ,
recurring and lytic infections
are typical of this group of
viruses.
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Medically important viruses – Three subfamilies.
1. Alpha herpes virinae.
•
Rapid growth,
Latent infection in sensory ganglia.
HSV – 1, HSV – 2, V – Z Virus.
2. Beta herpes virinae
Slow growth.
Grow best in Fibroblasts.
Latent infection in salivary gland.
HHV – 5 ( CMV ) HHV– 6 , HHV – 7
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3. Gamma herpes virinae
Grow in Lymphoblastoid cells.
Latent infection in Lymphoid tissue.
HHV – 4 (Epstein – Barr Virus)
HHV – 8 ( Kaposi’s sarcoma herpes virus)
Neurotropic viruses: HSV,VZV; Lymphotropic viruses: EBV,HHV6,HHV7
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Morphology
•Enveloped (Lipid)
•Double stranded DNA
•Icosahedral capsid
•“Tegument”
•Glycoprotein spikes
( Surface spikes)
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Naked virus
Replication and susceptibility
• Virus replicates in host cell nucleus.
• Cowdry type A intranuclear inclusion
bodies.
• Susceptible to Ether
Chloroform
Bile salts.
Heat labile.
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1.Continuous cell line cultures.
Monkey or Rabbit
kidney.
Human amnion cell line
cultures.
HeLa cell cultures.
Cytopathic effects :
Well defined foci with heaped
up cells & syncitial formation.
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2.Growth on Chick embryo CAM
Shiny, non necrotic pocks.
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Pathogenesis
Enters ‘thru’ defects in skin &mucus membranes.
Local multiplication
Retrograde
Local LN involvement.
axonal flow from sensory nerves …. Reaches Ganglia.
Maintains latency
Trigeminal, Sacral
Viral replication in the nerves. Physical, Emotional stress.
Decreased CMI.
Trauma,
Fever.
Sun light.
Centrifugal migration to skin & mucus
membranes.
Recurrence of the disease.
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Primary infection
Vesicle formation
(Ballooning degeneration of intra-epithelial cells)
Site of eruption
shows
Pain, tingling, warmth & itch,
erythema & papule Thin walled
umbilicated vesicle roof
breaks down and forms an ulcer.
with fever (cold sore or fever blisters).
Mucus membrane, non-keratinized
epithelia.
Recurrent infections are seen with severe
pain, ulceration.
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• Neuroinvasiveness
• Neurotoxicity
• Latency in dorsal root ganglion of CNS
•Damaged epithelium is repaired by Natural
killer cells.
•Viral glycoproteins initiates the T-cell
activity which activate primed B cells to
produce antibodies.
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Pathological lesions
1. Mucocutaneous infections
Herpetic gingivostomatitis
Cheeks, chin, forehead.
Napkin rash in infants.
Acute gingivostomatitis
Around the mouth & on lips.
Pre-school children.
Majority of primary infections;
Teething / oral thrush.
Ruptured lesions
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.
Herpetic lesions in oral cavity
Dental anomalies followed
by Herpes viral infections.
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Skin infections
Herpetic whitlow ,
•Toddlers,
•Dentists,
•Nurses,
Herpes gladiatorum
(Wrestlers)
•Painful, swollen,
grouped vesicles with pus.
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Eczema herpeticum
Severe form of Atopic eczema(Kaposi's
varicelliform eruption.)
Extensive ulceration.
Eye infections:
Branching/dendritic
corneal ulcer.
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Visceral HSV:
•
Esophagitis
• Tracheobronchitis
• Pneumonitis
CNS: Sporadic, fatal encephalitis(HSV 1).
Seizures, Hemi paresis and paraesthesia
Congenital infections :
•Transplacental infection.
•Congenital malformations are rare.
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HSV- 2 transmitted by auto infection, sexual
/orogenital contact. Most infections are
asymptomatic.
-Symptomatic infections with sores,
fever and lymphadenopathy of genital
tract, heal within 2-4 weeks.
-Patients may suffer with 4-5
outbreaks (recurrent) within a year.
-Causes psychological distress.
-Infection during late pregnancy poses
a greater risk of transmission to the
baby.
-Sacral radiculopathy common with
urinary retention.
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Genital herpes
Perianal herpes
Labial herpes
Shaft of the Penis
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2.Neonatal herpes
Localized to Skin , eyes,
mouth. Disseminated
infection leads to Multi
organ involvement
(Liver, Adrenals, Brain)
Complication:
Neurological impairment.
3.Aseptic meningitis:
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Laboratory diagnosis
1. Smears
• Scrapings from
base of Vesicle
• CSF,
• Saliva.
Microscopy:
Tzanck smear
1 % Aqu. sol. of Toludine blue.
Multinucleated giant cells
with faceted nuclei ,
ground glass chromatin.
(Tzanck cells)
Best : Giemsa, Papanicolou stain
2. Serum
-Primary infection.
-ELISA most useful.
-CFT.
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3.Antigen detection : Fluorescent antibody , ELISA
4.Viral isolation:
Cell line culture – growth within 1 -3 days.
5.Molecular techniques: PCR and DNA probes.
Treatment :
No cure.
Acyclovir : Primary infection (< 72 hrs).
Reduce the recurrences.
Famciclovir: For resistant cases.
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Varicella-Zoster virus
Varicella
•Mildest childhood exanthemata
•Source: Patient
•Droplet nuclei from Respiratory tract
•Inhalation.
Incubation period 7– 23 days
•Centripetal distribution.
•Macule  Papule  Vesicle Pustule Scab
•Vesicular rash surrounded by a ring (Trunk)
•Superficial “Drop of water”
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Appears in crops, Profuse in adults
•Hemorrhagic & bullous.
Interstetial Pneumonia.
Postviral encephalitis.
Guillain- Barre syndrome.
•Recovery is spontaneous.
•Can cross placenta 
Neuromuscular disorders.
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Lab. Diagnosis :
Same as HSV.
Specimens :
Buccal / Cutaneous lesions
Prophylaxis :
V – Z immunoglobulins.
Live attenuated varicella vaccine.
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Herpes Zoster (Creeping girdle)
Old age (>60 years).
Latent virus in dorsal root or
cranial nerve ganglia
Neuritic pain, Parasthesia for
weeks / months.
Unilateral, painful eruption in
Herpes zoster ophthalmicus.
thoracic region.
Commonest sites:
Areas innervated by spinal cord
segments D3 – L2 & Trigeminal
nerve.
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Complications :
LMN Paralysis.
Meningo-encephalitis
Ramsay Hunt syndrome
Facial palsy + eruption on tympanic
membrane & external auditory canal
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Cytomegalovirus (Salivary gland virus)
Infected cells : Cytomegaly (Owl’s eye appearance)
Most of the infections are unapparent.
Commonest cause for congenital defects.
Pathogenesis:
Latent infection : Mononuclear leucocytes
(Monocytes, B -lymphocytes)
Secretary glands
Kidney.
Replication seen in ductal epithelial cells.
Excretion in body fluids, Milk & Urine.
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Modes of transmission
Transplacental.
Sexual contact.
Blood and its products.
Organ transplantation.
Urine, Saliva, Cervical secretions,
semen, breast milk.
Perinatal & Postnatal infections:
Infected birth canal,Breast milk.
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1.Transplacental route:
Condition severe if infection occurs during first
trimester of pregnancy.
Cytomegalic Inclusion disease of Newborn(10%)
characterised by varied type of clinical manifestations.
Hepatospleenomegaly
Jaundice
Thrombocytopenic purpura
Haemolytic anaemia
Microcephaly
Cerebral calcifications.
Mental retardation.
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IMN like disease:
Young adults.
Hepatitis, fever, atypical lymphocytosis.
(No pharyngitis, no lymphadenopathy,
Negative for heterophile antibody)
Respiratory tract infections:
Pneumonitis in infants.
Immunocompromised individuals:
Pneumonia
Fatal encephalitis
Chorioretinitis
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Lab. Diagnosis:
Adults: Urine, Saliva, BAL,
Semen & Cervical secretions.
Neonate: Urine
1. Microscopy:
Centrifuged deposits of secretions.
Giemsa stain: Cytomegalic cells
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2.Isolation:
“Human diploid fibroblast cell” culture.
Large retractile cells with cytoplasmic
granules.
3.Serology:
Anti CMV IgM Ab estimation by ELISA.
Treatment: Ganciclovir & Foscarnet.
Prophylaxis: Acyclovir.
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Epstein – Barr (EB) Virus
Burkitt's lymphoma in 1964 .
Affinity for B – lymphocytes (CD 21 receptors.)
80 – 90% of children by three years of age.
Asymptomatic.
Not highly contagious.
Droplets are not infectious.
Source : Saliva, Oropharyngeal secretions
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Infected saliva.
Pathogenesis
Pharyngeal epithelial cells (Multiplies locally).
Persistence
Shed in saliva
Invades blood stream
Infects B. lymphocytes.
Liver
Spleen
Polyclonal activation
cell death .
Unchecked replication results in Lymphomas
Neoantigen formation
Atypical lymphocytosis.
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Clinical Diseases
Incubation period : 4 – 7 weeks
1.Infectious Mononucleosis
(Glandular disease, Kissing disease)
Acute self limiting illness.
Fever, sore throat.
Lymphadenopathy.
Sub clinical Hepatitis, Tender spleenomegaly
Abnormal lymphocytes in PS
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2.Chronic fatigue syndrome.
3.Malignancies associated with EB.
Burkitt’s lymphoma
(Malignant B cell lymphoma of jaw)
Nasopharyngeal carcinoma
Lymphomas in HIV infected
persons.
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Lab diagnosis
1.Blood smear examination :Atypical Lymphocytosis.
2.Paul - Bunnel test:
Heterophile antibody detection test.
Inactivated serum + 1% sheep RBC
suspension  370C  4 hrs 
Agglutination (>100)
3. EBV Specific antibodies:
EBNA
Ab EBNA
Ig M VCA,
Ig G VCA
4. PCR:
More sensitive.
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HHV – 6
Isolated in 1986 from AIDS patient
T - lymphocytotropic (CD+)
Transmission through Oral secretions.
Roseola infantum (Exanthema subitum)
High fever with generalized rash.
Chronic fatigue syndrome.
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HHV – 7
HHV – 8
Kaposi's sarcoma related
Isolated from AIDS
patient in 1990.
herpes virus.
No disease
association.
In 1994 : Association
Remains as orphan
virus.
(Rare type of “B cell
with Kaposi's sarcoma.
lymphoma” from
AIDS patients).
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Research is currently ongoing into a
variety of side-effect or co-conditions
related to the herpesviruses.
Alzheimer's disease
atherosclerosis
cholangiocarcinoma
Crohn's disease
chronic fatigue syndrome
fibromyalgia
Irritable bowel syndrome
multiple sclerosis
pancreatic cancer
pityriasis rosea
Type II Diabetes
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Prepared for e-learning by
Dr .P.SRINIVASULU REDDY , M D.,
Professor, Department of Microbiology
Narayana Medical College
NELLORE
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