herpesvirus

,Herpes viruses,herpein,To creep,Rao Langyu A.P.OFFICE：Exp. Bldg. Rm 413,Section 1 General properties of Herpesviridae,.Biological classification,Herpesviridae3 broad groups (subfamilies):1.-herpesviridae: variable host range, short reproductive cycle, rapid spread in cell culture, e.g. HSV-1，HSV-2 and VZV.2.-herpesviridae: restricted host range, long reproductive cycle, Enlargement of infected cells, e.g.HCMV,HHV-6 and HHV-7.3.-herpesviridae: replicate in lymphoblastoid cells, specific for T or B cells, e.g. EBV and HHV-8.,.common characteristic,Enveloped, double stranded DNA viruses. 180-220nm.Set up latent or persistent infection following primary infectionReactivation are more likely to take place during periods of immunosuppression.Both primary infection and reactivation are likely to be more serious in immunocompromised patients.,Section 2 Herpes simplex virus, HSV,.Biological characterization,-herpesvirusDouble stranded DNA enveloped virus 2 types: HSV-1 & HSV-2 similar characteristics, 50-70% homology, cross-reactive epitopesMan is the only natural host for HSV,. Pathogenesis,Primary infectionLatent infection Reactivation and Recurrence,Mucos membranes and epitheliaHSV-1: above the waist HSV-2: below the waistPersistently infect macrophages and lymphocytesTypical lesion: vesicleDeveloped pathologic changes: multinucleated giant cells, ballooning degeneration of epithelial cells, focal necrosis, eosinophilic intranuclear inclusion bodies,HSV-1: trigeminal ganglia & superior cervical ganglia HSV-2: sacral gangliaEstablish a latent infection in which the neurons survive but continue to harbour the viral genome/ low expression,Stimulating factor: physical or psychological stress, infection, fever, irradiation, a weakened immune system, trauma to the skin or nerves. Recurrence of infection occurs at the same site as the initial infection.,Sensory nerve ending,sensory ganglion,. Clinical features,HSV-1 infection,usually mild/ asymptomatic Primary infection appears most frequently as gingivostomatitis. The infection often initially on the lips spreads to all parts of the mouth and pharynx. The acute illness usually lasts 5 to 12days. Latent within trigeminal ganglia/superior cervical ganglia. Because reactivation is usually from a single latent source, these lesions are typically unilateral.,HSV-2 infection,Sexually transmitted disease- genital herpes. (10% of cases being the result of HSV-1) The mean incubation period from sexual contact to onset of lesion is 5 days. asymptomatic Painful lesions on the penis/vulva/vagina/cervix/urethra. erythematous papules-vesicles-pustules-coalesced ulcers primary infection last an average of 12days. At least 80% of patients with primary genital HSV-2 infection develop recurrent episodes of genital herpes within 12 month.,Clinical Manifestations,HSV is involved in a variety of clinical manifestations which includes:1. Acute gingivostomatitis2. Herpes Genitalis3. Herpes Labialis (cold sore)4. Ocular Herpes 5. Other forms of cutaneous herpes7. Meningitis8. Encephalitis9. Neonatal herpes,Herpetic whitlow on the wrist,Site at which HSV-1 and HSV-2 cause disease in humans,Neonatal herpes,Most of neonatal HSV infections are caused by HSV-2, 15-30% are caused by HSV-1. Fatal/ rareMost cases occur in the intrapartum period.It may be acquired in utero or postnatally.,Neonatal herpes simplex infection of the liver,Jennifer was just 11 days old when she passed away from the virus,Killed by a kiss,Ruth Schofield has written to the Prime Ministers office demanding more warnings be given to pregnant mothers about the deadly virus.,.Laboratory Diagnosis,Direct DetectionElectron microscopy of vesicle fluid - rapid result but cannot distinguish between HSV and VZVImmunofluorescence of skin scrappings - can distinguish between HSV and VZVPCR - now used routinely for the diagnosis of herpes simple encephalitisVirus Isolation HSV-1 and HSV-2 are among the easiest viruses to cultivate. It usually takes only 1 - 5 days for a result to be available.SerologyNot that useful in the acute phase because it takes 1-2 weeks for before antibodies appear after infection. Used to document to recent infection.,Cytopathic Effect of HSV in cell culture: Note the ballooning of cells.,Positive immunofluorescence test for HSV antigen in epithelial cell.,At present, there are only a few indications of antiviral chemotherapy, with the highcost of antiviral drugs being a main consideration. Generally, antiviral chemotherapyis indicated where the primary infection is especially severe, where sight is threatened,and herpes simplex encephalitis.Acyclovir choice for most situations at present. It is available in a number of formulations:I.V. (HSV infection in normal and immunocompromised patients)Oral (treatment and long term suppression of mucocutaneous herpes and prophylaxis of HSV in immunocompromised patients)Cream (HSV infection of the skin and mucous membranes)Ophthalmic ointmentFamciclovir and valacyclovir oral only, more expensive than acyclovir.Other older agents e.g. idoxuridine, trifluorothymidine, Vidarabine (ara-A). These agents are highly toxic and is suitable for topical use for opthalmic infection only.,.Management,Section 3 Varicella-zoster virus, VZV,.Biological characterization,-herpesvirusds DNA enveloped virus One antigenic serotype only, although there is some cross reaction with HSV.Cytopathic effect in cell cultures (multinucleated giant cells and intranuclear eosinophilic inclusion bodies ),Chickenpox-shingles,水痘,水痘,带状疱疹,带状疱疹,. Pathogenesis and symptomatology,Varicella-Primary infectionZoster-Recurrent disease,Transmission: respiratory droplets/ direct contactchickenpox: macule-papule-vesicle-pustule-scab 90% of cases occur before the age of 10 yearsCommunicability is greatest 24 to 48 hours before the onset of rash and lasts 3 to 4 days into the rash.,Latency of VZV occurs in dorsal root gangliaassociated with immunosuppression of the host or mental stress shingles : macule-papule-vesicle-pustule-scab,Pathogenesis,Congenital VZV Infection,90% of pregnant women already immune, therefore primary infection is rare during pregnancy.Primary infection during pregnancy carries a greater risk of severe disease, in particular pneumonia.First 20 weeks of PregnancyUp to 3% chance of transmission to the fetus, recognised congenital varicella syndrome;Scarring of skinHypoplasia of limbsCNS and eye defectsDeath in infancy normal,The clinical presentations of varicella or zoster are so characteristic that laboratory confirmation is rarely required. Laboratory diagnosis is required only for a typical presentations, particularly in the immunocompromised.Virus Isolation - rarely carried out as it requires 2-3 weeks for a results.Direct detection - electron microscopy may be used for vesicle fluids but cannot distinguish between HSV and VZV. Immunofluorescense on skin scrappings can distinguish between the two.Serology - the presence of VZV IgG is indicative of past infection and immunity. The presence of IgM is indicative of recent primary infection.,.Laboratory Diagnosis,Cytopathic Effect of VZV in cell culture: Note the ballooning of cells.,Cytopathic Effect(CPE) of VZV,.Management,Uncomplicated varicella is a self limited disease and requires no specific treatment. However, acyclovir had been shown to accelerate the resolution of the disease and is prescribed by some doctors.Acyclovir should be given promptly immunocompromised individuals with varicella infection and normal individuals with serious complications such as pneumonia and encephalitis.herpes zoster in a healthy individual is not normally a cause for concern. The main problem is the management of the postherpetic neuralgia.The International Herpes Management Forum recommends that antiviral therapy should be offered routinely to all patients over 50 years of age presenting with herpes zoster.Three drugs can be used for the treatment of herpes zoster: acyclovir, valicyclovir, and famciclovir. There appears to be little difference in efficacy between them.,Section 4 Cytomegalovirus, CMV,. Properties, herpesvirus, ds DNA enveloped virusCMV can be transmitted vertically or horizontally usually with little effect on the host.Transmission may occur in utero, perinatally or postnatally. Once infected, the person carries the virus for life which may be activated from time to time, during which infectious virions appear in the urine and the saliva. Reactivation can also lead to vertical transmission. It is also possible for people who have experienced primary infection to be reinfected with another or the same strain of CMV, this reinfection does not differ clinically from reactivation.In developed countries with a high standard of hygiene, 40% of adolescents are infected and ultimately 70% of the population is infected. In developing countries, over 90% of people are ultimately infected.,Cytomegalovirus is named after the swollen appearance fo its cytopathic effect in cell culture. In addition, CMVproduces typical owls eye intranuclear inclusion bodies in infected cells.,Transmission: intrauterine, perinatal, postnatally. Congenital infection- may result in cytomegalic inclusion diseasePerinatal infection- usually asymptomaticPostnatal infection- usually asymptomatic. However, in a minority of cases, the syndrome of infectious mononucleosis may develop which consists of fever, lymphadenopathy, and splenomegaly. The heterophil antibody test is negative although atypical lymphocytes may be found in the blood.Immunocompromised patients such as transplant recipients and AIDS patients are prone to severe CMV disease such as pneumonitis, retinitis, colitis, and encephalopathy.Reactivation or reinfection with CMV is usually asymptomatic except in immunocompromised patients.,. Pathogenesis and symptomatology,Direct detection biopsy specimens may be examined histologically for CMV inclusion antibodies or for the presence of CMV antigens. However, the sensitivity may be low. The pp65 CMV antigenaemia test is now routinely used for the rapid diagnosis of CMV infection in immunocompromised patients. PCR for CMV-DNA is used in some centers but there may be problems with interpretation.Virus Isolationconventional cell culture is regarded as gold standard but requires up to 4 weeks for result. More useful are rapid culture methods such as the DEAFF test which can provide a result in 24-48 hours.Serology the presence of CMV IgG antibody indicat