- Slides: 36
Varicella –Zoster Virus (VZV) Causes 2 major diseases • Varicella (chicken pox): primary infection usually in childhood • Zoster ( shingles): reactivation of an earlier varicella
Varicella (Chicken Pox) • Mild, highly contagious disease chiefly affecting children • Mode of transmission: - airborne droplets and direct contact from varicella patients - Vesicular fluid of Zoster patients can be the source of Varicella in susceptible children
Pathogenesis • VZV infects the mucosa of the upper respiratory tract • Multiplies in the regional LNs • Primary viremia and spread to liver and spleen • Secondary viremia follows with viral spread to the skin • Typical rash occurs • VZV remains latent in the dorsal root ganglia for life
Clinical Picture • Incubation period: 10 -21 days • Symptoms: mild fever & rash • Rash: first appears on the trunk, then face but sparing distal parts of limbs (Centripetal distribution) • Flat macules become papules then vesicles • Followed by crust formation • The crust is often shed off and heals without scarring
• Cropping is a characteristic feature of varicella rash: fresh vesicles appear in crops, so that all stages of macules, papules, vesicles & crusts are seen at the same time • More severe in adults: Hemorrhagic, bullous lesions, heal with scar
Complications 1 - Pneumonia especially in adults, may be fatal 2 - Rarely: fulminant encephalitis, which may be a manifestation of Reye’s syndrome that occurs as a consequence of salicylates intake during infection 3 - Myocarditis, nephritis, acute cerebellar ataxia, meningitis and encephalitis
Congenital Varicella Syndrome & Neonatal Varicella • Primary maternal infection during the 1 st trimester may lead to congenital varicella syndrome ( serious & fatal): skin lesions, hypoplasia of limbs, chorioretinitis & CNS defects • Primary maternal infection during last trimester can lead to widely disseminated infection in the new born with mortality rate of 35%. • If rash began a week or more before delivery, maternal Abs transferred via placenta – baby gets the infection but escapes clinical disease
Zoster (shingles) • Sporadic disease in adults or immunocompromised patients • Results from reactivation of latent VZV • Rash similar to varicella but limited to a nerve distribution to the skin innervated by a dorsal root ganglion (dermatome)
Varicella-Zoster Virus (VZV) • Initial infection usually in childhood with Varicella virus (HHV-3): Chicken Pox • It is spread by respiratory aerosols or direct contact with lesions • The virus establishes latency within the dorsal root ganglia • Years or decades later, the virus (Herpes zoster) may reactivate -> Shingles
Varicella-Zoster Virus (VZV) Zoster means girdle, from the characteristic rash that forms a belt around the thorax Rash along dermatomes
VZV- Pathology Trigeminal nerve reactivation uveitis, keratitis, conjunctivitis Cranial nerve reactivation Bells palsy: a condition that causes the facial muscles to weaken or become paralyzed. It's caused by trauma to the 7 th cranial nerve and is not permanent.
Ramsay-Hunt syndrome: • Virus spread to facial nerves. • Characterized by intense ear pain, a rash around the ear, mouth, face, neck, and scalp, and paralysis of facial nerves. • Symptoms may include hearing loss, vertigo, and tinnitus. Post-herpetic neuralgia: • chronic burning or itching pain; hyperesthesia (increased sensitivity to touch)
Laboratory Diagnosis • Specimen: Vesicular lesions smears 1 - Direct Virus Demonstration: a) L/M: Tzanck smear – from the base of vesicles, 1% aq. soln. of toluidine blue ‘O’ shows multinucleated giant cells with faceted nuclei & homogenously stained ‘ground glass’ chromatin (Tzanck cells)
B) Direct Immunofluorescence: C) PCR: for detection of viral DNA 2 - serology: Specific VZV Abs using CFT, Nt, or ELISA
Epstein- Barr virus • Ubiquitous human herpes virus. • By adulthood 90 to 95% of most populations are positive. • Spread occurs by intimate contact between susceptible individuals and asymptomatic shedders of EBV. • Mostly causes asymptomatic infections.
Transmission • Source: Oropharymgeal secretions/ saliva of infected persons. • Intimate oral contact, such a kissing leads to transmission (Kissing Disease). • May also follow blood or bone marrow transplants.
Pathogenesis Attaches to CR 2 (CD 21) receptor (same as C 3 d complement receptor) Entry and multiplies locally Invades blood stream Infects B Lymphocytes Polyclonal activation Latency and immortalisation of B cells
Lytic Infection • The ZEBRA protein is expressed in epithelial cells • This transcription factor promotes the expression of early genes -> active virus replication and lytic infection Latency • B lymphocytes are only semi-permissive for replication and EBV infection is often latent • The infected B-lymphocyte contains a few episomes • Only a few genes are expressed from the episome, including two membrane proteins that are oncogenic • Burkitts lymphoma • Nasal pharyngeal carcinoma
Epstein Barr Virus (EBV) In addition: • Infectious mononucleosis • Chronic fatigue syndrome
Infectious Mononucleosis (Glandular fever) • Acute self limited illness following primary infection with EB virus. • Incubation period is 4 -8 weeks. • Fever, sore throat, lymphadenopathy, tonsillitis, enlarged spleen and liver • Occasional rash. • Ampicillin treated patients develop more rashes due to immune complex reactions. • The severity of disease often depends on age, but usually resolves in 1 to 4 weeks • In some Chronic fatigue (Mental and physical)
Laboratory diagnosis Peripheral blood smear: • Initially leucopenia • Prominent lymphocytosis • Abnormal mononuclear cells: Deeply basophilic & vacuolated cytoplasm, kidney shaped nuclei, lattice of fenestrated chromatin. • Not infected B cells • T cells reactive to virus infection.
Paul-Bunnell test • Standard diagnostic procedure • Heterophile agglutination test • Inactivated serum in doubling dilutions are mixed with equal volumes of 1% sheep erythrocytes • Incubate at 370 C for 4 hours • Examined for agglutination • Titre of 100 or above is suggestive of EBV • Confirmation: • Differential adsorption of agglutinins with guinea pig and Ox red cells
Normal serum Antibody after serum therapy Infectious mononucleosis Result of Absorption by Guinea Pig kidney Ox red cells Absorbed Not Absorbed This test appears early in infection and disappears within two months
Other tests • Ig. M VCA (Virus capsid antigen) rises and disappears in 1 -2 weeks: Reliable indicator for primary infection. • VCA Ig. G antibodies persist throughout life: Indicates past infection. • Appearance of Ab to EBNA (EB nuclear Ag): useful marker for primary infection
Cytomegalovirus (CMV) • Formerly known as salivary gland virus • Characterised by enlargement of infected cells and prominent intra-nuclear inclusions. • Prolonged latency in infected hosts • In neonate and immunodeficient: severe disease • Virus exhibits strict host specificity. • Human CMV is unrelated genetically with other herpes and even with CMV of other species.
Pathogenesis CMV (HHV-5) derives its name from the fact that it can form multinucleated cells (syncytia) Some cells such as macrophages and fibroblasts support a productive infection Other cells such as T lymphocytes and stromal cells of the bone marrow set up latent infection
Pathogenesis • The virus is spread via most secretions, particularly saliva, urine, vaginal secretions and semen • CMV may also be spread by blood transfusion and organ transplant • CMV causes no symptoms in children and mild disease in adults
Pathogenesis • Primary infection in older children and adults are asymptomatic. • Clinical infection is caused during to intrauterine or postnatal infections. • Intrauterine infection leads to fetal death or cytomegalic inclusion disease. • Cytomegalic inclusion disease is often fatal, associated with hepatosplenomegaly, jaundice, thrombocytopenic purpura & hemolytic anaemia. • Chorioretinitis, & cerebral calcification, mental retardation.
CMV The virus elicits both humoral and cell-mediated immunity but the infection is not cleared The virus may reactivate, particularly in cases of immunosuppression • Organ transplant patients • Immunosuppressive disease (CMV-retinitis occurs in up to 15% of all AIDS patients; also pneumonia, colitis, esophagitis and encephalitis)
Lab Diagnosis • Urine, saliva or other body fluids. • Human fibroblast cell cultures • Demonstration of cytomegalic cells in the centrifuged deposits from the saliva Owl’s eye appearance
Prevention • No licensed vaccine is available. • There is a candidate live attenuated vaccine known as the Towne strain 125 and AD 169 strains. • But there are concerns about administering a live vaccine which could become latent and reactivate
Human Herpes virus 6 • Human B cell lymphotrophic virus • Ubiquitous and spreads through saliva in early infancy • Two variants A & B • Variant B causes Exanthem subitum (Roseola infantum or sixth disease)
Human Herpes virus 8 • Human Herpes virus 8 (HHV-8), or Kaposi Sarcoma Herpes Virus (KSHV), is associated with the development of Kaposi’s Sarcoma in AIDS patients. • Kaposi's sarcoma is a type of cancer that affects men and is rarely seen in women. • Although KS mainly affects the skin, the mouth, and the lymph nodes, it can also involve the bowels and lungs. • HHV 8 is sexually transmitted.