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Herpesviridae. اهداف. خصوصیات ساختمانی مراحل تکثیر طبقه بندی بیماری زایی (آلفا هرپس ویروس ها) بیماری تشخیص آزمایشگاهی کنترل، پیشگیری و درمان (آلفا هرپس ویروس ها). I. Background. 25 viruses in the family Herpesviridae - a number of these are known to infect man:
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اهداف • خصوصیات ساختمانی • مراحل تکثیر • طبقه بندی • بیماری زایی (آلفا هرپس ویروس ها) • بیماری • تشخیص آزمایشگاهی • کنترل، پیشگیری و درمان (آلفا هرپس ویروس ها)
I. Background 25 viruses in the family Herpesviridae- a number of these are known to infect man: • herpes simplex virus (HSV) • Epstein-Barr virus (EBV) • cytomegalovirus (CMV) • varicella-zoster virus (VZV) • human herpes 6 & 7 (exanthumsubitum & roseolainfantum) • HHV 8 (Kaposi’s sarcoma-associated). • Herpes B virus
1- مکان اولیه عفونت: ویروس از طریق تماس با مخاط یا اپی تلیال آسیب دیده وارد بدن می شود. 2- تکثیر در محل ورود 3-ورود تگومنت نورون (retrograde) 5- فعال شدن مجدد و تولید ویروس 4- تکثیر در گانگلیون و ایجاد عفونت Latent
Site of Latency: - HSV-1: Trigeminal Ganglia - HSV-2: Sacral Ganglia
Three manifestations of HSV latency Key Feature: there is a wide spectrum of clinical presentations • Some individuals (5 - 10%) have frequent clinical reactivation • Most individuals reactivation is clinically asymptomatic • In ALL cases, virus is shed
HSV-1 1) Gingivostomatits 2) pharyngotonsilitis 3) herpes Labialis( fever blisters or cold sores) )
2-KeratoconjunctivitisHSV-1 • Recurrent lesions of the eye are common • HSV infections are second only to trauma as a cause of corneal blindness in the United States.
3- Genital Herpes • Genital disease is more often caused by HSV-2. • HSV-1 can also cause clinical episodes of genital herpes. • Complicationsinclude extragenitallesions (~20% of cases) and aseptic meningitis (~10% of cases). • An initial HSV-2 infection in a person already immune to HSV-1 tends to be less severe. • Recurrences of genital herpetic infections are common.
4-Skin Infections • Intact skin is resistant to HSV. • Localized lesions caused by HSV-1 or HSV-2may occur in abrasions(traumatic herpes). • herpetic whitlow • Herpes gladiatorum • Eczema herpeticumis a primary infection, usually with HSV-1, in a person with chroniceczema
HSV Disease:Recurrent Infection Cold sores (labialis) Genital lesions (herpes genitalis) Keratoconjunctivitis Encephalitis Meningoencephalitis
5-Meningitis/Encephalitis • HSV-1 infections are considered the most common cause of sporadic, fatal encephalitis in the United States. • half of patients with HSV encephalitis appear to have primaryinfections, and the rest recurrent infection.
6- Neonatal Herpes • may be acquired in utero, during birth, or after birth • The mother is the most common source of infection in all cases. • (~75% of cases) is for HSV to be transmitted to a newborn during birth by contact with herpetic lesions in the birth canal. • About 75% of neonatal herpes infections are caused by HSV-2. • Neonatal herpes can be acquired postnatallyby exposure to either HSV-1 or HSV-2
HSV-2 1) Genital herpes 2) Neonatal herpes 3) Aseptic meningitis
تشخیص آزمایشگاهی • Polymerase Chain Reaction • most sensitive means of detection and diagnosis of herpesmeningitis/encephalitis. • Isolation and Identification of Virus • Cytopathology • Serology
کنترل، پیشگیری، درمان • acyclovir, valacyclovir, and vidarabine(inhibitors of viral DNA synthesis) • The drugs may suppress clinical manifestations, shorten time to healing, and reduce recurrences of genital herpes.
Acyclovir • Acyclovir, a nucleoside analog, is monophosphorylatedby the HSV thymidine kinase • converted to the triphosphate form by cellular kinases. • The acyclovir triphosphate is efciently incorporated into viral DNA by the HSV polymerase, where it then prevents chain elongation.
Varicella • Subclinical varicella is unusual • Te incubation period of typical disease is 10–21 days • rash, frst on the trunk and then on the face, the limbs, and the buccal and pharyngeal mucosa in the mouth. • macules, papules, vesicles, and crusts may be seen at one time (crops)
Complications of Varicella • Reye’s Syndrome • Bacterial Superinfection of lesions (more common in younger patients) • Varicella pneumonia • Neonatal varicella -- disseminated, 30% mortality
Varicella patients at risk • ADULTS • PREGNANCY (3rd trimester) • IMMUNOCOMPROMISED • The mortality rate for varicella pneumonia in leukemic children receiving chemotherapy is 1,000 times higher than in healthy children. Note: Children with isolated agammaglobulinemia are not at risk!
Complications of Zoster Postherpetic Neuraligia • Affects 25 - 50% of zoster patients over 50 • Pain may persist for months or even years
درمان • Varicella in normal children is a mild disease and requires no treatment. • Neonates and immunocompromised patients with severe infections should be treated. • γ-Globulin of high VZV antibody titer orVaricella zoster immune globulin (VariZIG) is now available for postexposureprophylaxis of high-risk patients • Acyclovir
Varicella Vaccine • Prevents 85% of chickenpox occurrence • Greatly reduces the severity in the rest • Attenuated virus • Can still establish latency and reactivate Question: How long will immunity last?