HUMAN HERPES VIRUSES -1

1. HUMAN HERPES VIRUSES -1 Dr. D Kalita, Associate professor, Department of Microbiology, AIIMS Rishikesh Date of Class: 26/4/2017 (4PM to 5PM, LT-4)

3. HERPES VIRUS

4. Introduction to HERPES VIRUS • About100 Enveloped DNA viruses affecting Humans and animals • Can cause Latent infections– enabling virus to persist within infected hosts and to undergo periodic reactivation.

5. Herpes virus morphology • Icosahedral capsid - 162 capsomers- Enclosing the core with dsDNA • Nucleocapsid covered by a lipid envelope (derived from modified host cell membrane) • Envelope carries surface spikes • Tegument (amorphous): between envelope and capsid

6. Herpes virus morphology • Enveloped virion200 nm • Naked virion 100 nm • Replication takes place in the host cell nucleus • Cowdry type A inclusion bodies which is also called Lipschutz bodies

7. CLASSIFICATION

8. Herpes simplex

9. HHV 1 & HHV 2 - Morphology

10. HHV 1 & HHV 2 - Pathogenesis

11. Differentiation of HSV1 and HSV2 • Monoclonal antibodies • Pocks in CAM (HSV2 > HSV1) • HSV2 more neurovirulent in lab animals • HSV2 is more resistant in vitro to antivirals (e.g.Cytarabine & IUDR) • DNA RE studies differentiates (upto strain level) Etc.…………….Ref to a textbook

12. Infections • HSV1 • Acute gingivostomatitis • Herpes labialis (cold sore) • Keratoconjunctivitis • Eczema herpericum • Encephalitis • Dendritic keratitis (above waist…………………but…)

13. HSV2 • Genital herpes (Penile, Urethral, Cervix, Vulval, Vaginal) • Neonatal herpes • Aseptic meningitis (Below waist…..but………….)

14. ACUTE GINGIVOSTOMATITIS • Acute gingivostomatitis is the commonest manifestation of primary herpetic infection. • Pain and bleeding of the gums • Ulcers with necrotic bases • Neck glands are commonly enlarged accompanied by fever. • Usually a self limiting disease lasting around13 days.

16. HERPES LABIALIS (COLD SORE) • Recurrence of oral HSV. • 45% of orally infected individuals will experience reactivation. • Tingling, warmth or itching at the site initially12 hours later, redness appears followed by papules and then vesicles.

17. SYMPTOMS • Mild or severe and may include: • Sores on the inside of the cheeks or gums • Fever • General discomfort, uneasiness, or ill feeling • Very sore mouth with no desire to eat • Halitosis

18. HSV – Cold Sore

19. HHV 1- Clinical manifestations EM of Herpes virus 1

20. OCULAR HERPES Cause of corneal blindness. Include the following:- • Primary HSV keratitis – Keratoconjunctivitis • Dendritic ulcers • Recurrent HSV keratitis • HSV conjunctivitis • Acute necrotising retinitis, chorioretinitis

21. KERATOCONJUNCTIVITIS • Inflammation of the cornea and conjunctiva. • Minor damage to the epithelium (superficial punctate keratitis) to formation of dendritic ulcers.

22. Keratoconjunctivitis

23. HERPES SIMPLEX ENCEPHALITIS • One of the most serious complications of herpes simplex disease. • There are two forms:

24. Neonatal – global involvement and the brain is almost liquefied mortality rate approaches 100%. • Focal disease – • Temporal lobe is most commonly affected. • In children and adults • Many arise from reactivation of virus. • Mortality rate is high (70%) in untreated

25. Early diagnosis and treatment of HSE is very essential. • IV acyclovir is recommended in all cases of suspected HSE • before laboratory results are available.

26. Herpes Simplex Encephalitis CT Scan Autopsy

27. MENINGITIS • Most commonly with primary HSV-2 infection; less likely with recurrences of genital herpes • Benign, self-limited (contrast with encephalitis) • Usually affects sexually active young adults • No neurologic sequelae

28. GENITAL HERPES • Genital lesions may be primary, recurrent • Sites: penis, vagina, cervix, anus, vulva, bladder, the sacral nerve routes, the spinal and the meninges. • Prone to secondary infection eg. Staphylococcus aureus, Streptococcus group, Trichomonas and Candida albicans.

29. GENITAL HERPES • Dysuria is a common complaint, • Recurrences in 60% . • Recurrent lesions in the perianal area  more numerous and persists longer.

30. HSV – CONGENITAL/PERINATAL • Perinatal infection: • ¾ th are due to HSV 2 acquired during delivery • Post natal infection • HSV-1 acquired from maternal genital, oral or breast lesions or nosocomial infection from other infected babies

32. HERPETIC WHITLOW • A lesion (whitlow) on a finger or thumb caused by the herpes simplex virus. • HSV-1 or HSV-2. • HSV-1 whitlow is often contracted by health care workers  dental workers and medical workers exposed to oral secretions.

34. Laboratory Diagnosis • Direct Detection • Electron microscopy of vesicle fluid - rapid result • Immunofluorescence of skin scrappings - distinguish between HSV and VZV

35. HHV 1& 2 Diagnosis • Multinucleate Giant cells – Tzanck’s smear

36. Laboratory Diagnosis • Viral culture (gold standard) • Preferred test in genital ulcers or mucocutaneous lesions Highly specific (>99%) • Sensitivity declines rapidly as lesions begin to heal • Positive more in primary infection (80%–90%) than with recurrences (30%)

37. CPE of HSV in cell culture: ballooning of cells. IF test for HSV antigen in epithelial cell.

38. Laboratory Diagnosis…cntd • Polymerase Chain Reaction (PCR) • More sensitive than viral culture; has been used instead of culture in some settings not widely available • Preferred test for detecting HSV in spinal fluid (Routinely used in HSE)

39. Serology • Type-specific and nonspecific antibodies • Anti HSV-2 antibody indicates anogenital infection • Anti HSV-1 antibody does not distinguish anogenital from orolabial infection • IgG, IgM - ELISA

40. ANTIVIRAL Several antivirals available for treatment of the conditions: • Aciclovir (acyclovir), • Valaciclovir (valacyclovir), • Famciclovir, • Penciclovir.

41. Varicella zoster

42. VARICELLA • Primary infection results in varicella (chickenpox) • Incubation period : 14-21 days • Presents fever, lymphadadenopathy. a widespread vesicular rash. • Diagnosis can be made on clinical grounds alone.

43. Complications are rare  occurs more frequently and with greater severity in • Adults • Immunocompromised persons • MC complication is secondary bacterial infection. • Life threatening complications Viral pneumonia, Encephalititis, Haemorrhagic chickenpox.

45. NEONATAL VARICELLA • VZV can cross the placenta in the late stages of pregnancy to infect the fetus congenitally. • Mild disease to fatal disseminated infection. • If rash in mother occurs more than 1 week before delivery  sufficient immunity is transferred to the fetus.

46. LABORATORY DIAGNOSIS • C/Fs of varicella or Herpes zoster are characteristic laboratory confirmation is rarely required. • Laboratory diagnosis  for atypical presentations (as seen in immunocompromised patients)

47. LABORATORY DIAGNOSIS….cntd • Direct detection - electron microscopy (no d/d between HSV and VZV). • IF on skin scrapings can distinguish the 2 • VZV IgG is indicative of past infection and immunity.  IgM is indicative of recent primary infection. • Virus Isolation - rarely carried  requires 2-3 weeks for a results.

48. HERPES ZOSTER (Shingles) • Manifestation of recurrent infection following a primary attack of chicken pox. • Caused by varicella zoster • Unlike herpes labialis repeated recurrences of zoster are uncommon. • Infection typically affect adult of middle aged group

49. Pain precedes the rash (vesicles). • Severe pain, and commonly occurs on the trunk on one side. • The trigeminal nerve is affected  15% of cases

50. Lesions localized to one side, along distribution of nerve (e.g. any divisions of the trigeminal nerve up to the midline) • Malaise can be severe. • Regional lymph node are enlarged and can be life-threatening in HIV disease.