HERPES VIRUSES
Herpes means that some of the lesions are creeping in nature Infect both warm and cold blooded animals Infections include - trivial mucocutaneous infection - life threatening cancers Have become successful pathogens due to latency and reactivation
DNA VIRUSES Icosahedral Large baggy envelope DNA polymerase HSV and VZV code for thymidine kinase - activate certain antiviral drugs (SUIZIDING) Replication in nucleus of host cell CLASSIFICATION (Human pathogens)
Herpes viruses have a similar morphology Share common antigens Can differentiate by their genome and by serological tests
Alphaherpesvirinae –Herpes simplex virus type 1HSV-1 –Herpes simplex virus type 2HSV-2 –Varicella-zoster virusVZV Betaherpesvirinae –cytomegalovirusCMV –Human herpesvirus type 6HHV-6 –Human herpesvirus type 7HHV-7 Gammaherpesvirinae –Epstein-Barr virusEBV CLASSIFICATION (Human pathogens)
HERPES SIMPLEX VIRUS (HSV) HSV 1 infect the upper part of the body - mouth and the face HSV 2 infect the lower part of the body - genital infections There is little cross protection Therefore, you can get both the infections
Primary infection-first contact with HSV Latent infection-persistent virus in root ganglia Reactivation-production of infective virus by latently infected cell Recurence-clinically apparent disease produced by reactivation
Man is the only natural host Primary infection occurs - skin - Oral mucous membrane - eyes
Pathogenesis Entry by skin or mucous membranes viral multiplicationsensory nerve lysis of cellsroot ganglia vesicleslatency ulcers REACTIVATION COLD FEVER SURGERY UNKNOWN
Sources of infection - Saliva - Skin lesions - Oropharyngeal lesions - Carriers
Viral DNA may get integrated in to the host genome or virus may just remain in the ganglia Primary infection usually due to type 1 happens at 6 months to 3 yrs of age Only 10-15% of children show acute gingivostomatitis OTHERS ARE ASYMTOMATIC
About 75% of the adults show +ve for HSV 1 infection HSV 1 infections include -i. Oropharyngeal. Children - very painful. due to kissing of elders. acute gingivostomatitis. problem of feeding
ii. Dermal - mainly among the health care workers - Herpetic whitlow - painful - heals without treatment - no pus/is it necessary to do a stain - Herpes gladiatorum - among wrestlers - eczema herpeticum
ECZEMA HERPETICUM
Iii. Ophthalmic - Keratoconjunctivitis with dendritic ulcers - Repeated attacks can lead to blindness 1V. Meningitis and encephalitis HSV 2 infections include Genital - male and female
Male - metaus with dysuria (you may not see ?) - hepatic proctitis Females - infection of the labia/vulva/perineus - cervicitis Neonatal infections At what stage ?
During the delivery What are the other infections acquired by this mode
Candida can super infect, So what ?
Immune response There will be IgM and IgG BUT NOT PROTECTIVE
High antibody titres do not prevent latent infections Latent infections - recurrent herpes labialis - acute keratoconjunctivitis Recurrent lesions may lead to - dendritic ulcers - corneal ulcers
Childhood infections common Second peak at onset of sexual activity Viral shedding – persons with recurrences –infected but asymptomatic persons Mucocutaneous lesions can be diagnosed clinically Laboratory diagnosis
Useful –genital & eye infections –HVZ & HSV in immunocompromised patients –herpes encephalitis Specimens –aspirate from vesicle –scraping from base of ulcer –serum / CSF for antibody
EM detection Cell culture Stained smears - for multinucleated giant cells with intranuclear inclusions
Treatment –Acyclovir –Idoxyuridine Treatment
HERPES VARICELLA ZOSTER HVZ Causes chicken pox -fever + characteristic rash variable incubation period days usually mild in children and more severe in adults complications –secondary infection - uncommon –varicella pneumonia –seconday bacterial pneumonia S aureus & pneumococci –post-infetious encephalitis –generalised varicella (in immunocompromised patients) –congenital and neonatal varicella
HERPES ZOSTER Reactivation of HVZ dermatomal distribution may recur can disseminate in immunocompromised patients complications –post herpetic pain –ophthalmic zoster -corneal scarring and loss of vision DIAGNOSIS CLINICAL EM of vesicle fluid SEROLOGY IgM detection
People can bet varicella from zoster Therefore, having immunocompromised patients in the hospital is a problem These patients should be looked after by the staff who are immune to chickenpox
Pain and hyperaesthesia
Prevention of Chickenpox Susceptible population children adults living in close proximity Do nothing Immunize live attenuated vaccine Protect if contact with patient with chickenpox and at risk of severe disease Zoster Immune Globulin (ZIG)
Treatment Acyclovir10mg/Kg x 5 times/day Famcyclovir NO RELIABLE DATA ON ROLE OF ACYCLOVIR IN PREVENTION OF CHICKENPOX
EPSTEIN BARR VIRUS EBV Discovered in 1964 by Epstein & colleagues Definite association with malignancy is able to ‘transform’ cells resulting in ‘immortalization” of cell 2 types of virus A & B which may co-exist in same person
Replication and induction of antigens InfectionEBNAEMAPersistent infection EAVCA Late MA LYSIS EBNA- EB nuclear antigen MA - membrane antigen VCA -Viral capsid antigen EA- Early antigen
Infectious mononucleosis Affects adolescents and young adults worldwide distribution called ‘kissing’ disease IP - one month presents with fever, sore throat, rash & lymph nodes COMPLICATIONS ampicillin rash guillain barre syndrome rupture of spleen COMPLICATIONS ampicillin rash guillain barre syndrome rupture of spleen DIAGNOSIS raised wbc with >20% lymphocytes Paul-Bunnell test (heterophile antibodies) or monospot DIAGNOSIS raised wbc with >20% lymphocytes Paul-Bunnell test (heterophile antibodies) or monospot
AMPICILLIN RASH
Syndromes caused by EBV Burkitts lymphoma –children 4-12 years –subsaharan Africa and New Guinea Nasopharyngeal carcinoma –adults years old –southern China B cell lymphome –children and adults –primary immunodeficiency –patients with AIDS
BURKITTS LYMPHOMA
NASOPHARYNGEAL CARCINOMA
Cytomegalovirus infections Ubiquitous virus most populations -infections in early childhood often asymtomatic Latency Clinical disease increasing due to increasing number of immunocompromised patients
Foetus –transmission from mother via placenta –clinically normal 80% –causes congenital CMV –death 1% –Cytomegalic inclusion disease % –late onset hearing defect / mental retardardation 15% Infant –transmission during birth or breast feeding –usually asymptomatic Cytomegalovirus infections
Young children –transmission from other children –usually asymptomatic adolescent/adult –transmission during kissing, sexual intercourse or blood transfusion –occasionally IM like syndrome immunocompromised –Exogenous PRIMARY INFECTION –EndogenousREACTIVATION pneumonitis, GI infection Cytomegalovirus infections
Diagnosis – presence of virus or antibody to CMV does not indicate that current disease is due to CMV –Different strategies used in different clinical situations isolation of virus from urine within 30 days of birth * antigen detection in buffy coat - indicates viraemia Cytomegalovirus infections DIFFICULT Congenital CMV immunocompromised patient * CMV specific Ig G positive indicates past infection
Treatment and prevention Congenital CMV –prevention not possible –treatment ? CMV in transplant recipients –prevention –treatment Test IgG before transplant If seronegative - use only seronegative donors Early diagnosis Reduce immunosuppression Ganciclovir
CMV retinitis
CMV encephalopathy
OTHER HUMAN HERPES VIRUSES HHV6 –Discovered in 1988 –Worldwide –virus replicates in T and B cells –infection occurs in first 3 years of life –Clinical Exanthem subitum (roseola infantosum ) mild acute febrile illness incubation period of 2 weeks fever lasts several days macular papular rash appears within 2 days of fever –85% of adults carry virus in saliva
Exanthem subitum (roseola infantosum)
HHV7 –isolated from CD4 positive cells –virus present in saliva of >75% of adults –role in disease unclear –Evidence of infection present (seroconversion) HHV8 –detected in epithelial cells of Kaposi sarcoma –also present in semen –postulated as cause of Kaposi sarcoma OTHER HUMAN HERPES VIRUSES