HERPES VIRUSES

Dr F Noordeen Department of Microbiology Faculty of Medicine Peradeniya April 2013

Learning outcomes
Mechanisms by which herpes viruses cause disease in humans Host defenses against viruses Main clinical features of viral infections/disease Principles of diagnosis treatment and prevention viral infections/disease in humans

EM of a Herpes Virus

CLASSIFICATION
Genome - DNA Viruses Morphology - Icosahedral - Large baggy envelope Enzymes - DNA polymerase - HSV & VZV thymidine kinase

Reproduction - Nucleus of host cell

CLASSIFICATION
Alphaherpesvirinae
Herpes Simplex Virus type 1 Herpes Simplex Virus type 2 Varicella-Zoster Virus Betaherpesvirinae Cytomegalovirus Human Herpesvirus type 6 Human Herpesvirus type 7 Human Herpesvirus type 8 HSV-1 HSV-2 VZV

CMV HHV- 6 HHV- 7 HHV- 8

Gammaherpesvirinae
Epstein-Barr virus EBV

HERPES SIMPLEX VIRUS

Primary infection Latent infection Reactivation - Contact with HSV - Virus persists in root ganglia - Production of infective virus by latently infected cell - Clinical disease produced by reactivation

Recurrence

Pathogenesis
Entry by skin or mucous membranes viral multiplication lysis of cells vesicles ulcers sensory nerve root ganglia latency REACTIVATION
Cold Fever Surgery Unknown

Stomatitis with secondary skin lesions

Primary infection of the skin

Recurrent infection

Herpetic infection of the eye

Herpetic whitlow

Vulvovaginitis in child

Genital herpes in an adult male

Genital herpes in an adult female

Genital herpes in adult female (Herpetic cervicitis)

Epidemiology
Childhood infections common Second peak at onset of sexual activity Viral shedding/reservoirs
persons with recurrences infected but asymptomatic persons

Laboratory diagnosis
Useful Genital & eye infections HVZ & HSV in immunocompromised Herpes encephalitis Specimens Aspirate from vesicle Scraping from base of ulcer Serum/CSF for antibody

Laboratory diagnosis
1. Microscopy - Light - giant cells & inclusions
- Electron microscopy

2. Antigen detection - ELISA and IFT 3. Virus culture & identification 4. DNA detection - PCR (Encephalitis) 5. Antibody detection - ELISA and IFT

Treatment for HSV infections

1. Acyclovir : Topical and oral formulations 2. Idoxyuridine

HERPES VARICELLA ZOSTER - HVZ

Chicken pox - Fever + characteristic rash Variable incubation period 14-21 days Usually mild in children and more severe in adults Complications
Secondary infection - uncommon Varicella pneumonia Secondary bacterial pneumonia S aureus & pneumococci Post-infectious encephalitis Generalised varicella (in immunocompromised patients) Congenital and neonatal varicella

Varicella rash in child

Varicella vesicles on palate

Varicella vesicles on conjunctiva

HERPES ZOSTER
Reactivation of VZV Dermatomal distribution and may recur Can disseminate in immunocompromised patients Complications
Post herpetic pain Ophthalmic zoster - corneal scarring and loss of vision

Diagnosis of Zoster
Clinical features and lesion distribution EM/IFA of vesicle fluid Serology - IgM detection

Skin supplied by cervical roots 4 & 5 are affected

Thoracic segments are affected

Prevention of chicken pox

Children & adults living in close proximity

Do nothing

Immunise with live attenuated vaccine

Protect contact with patient with chickenpox and at risk of severe disease Zoster Immuno Globulin (ZIG)

EPSTEIN-BARR VIRUS - EBV

Discovered in 1964 by Epstein and Barr Definite association with malignancy Is able to transform cells resulting in immortalisation of cells 2 types of virus A & B which may co-exist in a same person

Infectious mononucleosis
Affects adolescents and young adults Worldwide distribution Called kissing disease IP - one month Presents with fever, sore throat, rash and swollen lymph nodes
DIAGNOSIS Raised WBC with >20% lymphocytes Paul-Bunnell test (heterophil antibodies) or mono spot

Blood film with abnormal mononuclear cells

1st week - normal/raised neutropenia 2nd week - leukoctosis with (lymphoctosis)

Enanthum - Rashes on the palate

Inflamed throat without exudate

Follicular exudate

Patch of white exudate Patches of white exudate

Syndromes caused by EBV

Burkitts lymphoma
Children 4-12 years Subsaharan Africa and New Guinea

Nasopharyngeal carcinoma
Adults 20-50 years old Southern China

B cell lymphoma
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

Cytomegalovirus infections
Foetal infection
Transmission from mother via placenta Clinically normal 80% Causes congenital CMV Death 1% Cytomegalic inclusion disease 4% Late onset hearing defect/mental retardation 15%

Infantile infections
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 Endogenous REACTIVATION Pneumonitis, GI infection

Cytomegalovirus infections
Diagnosis - Difficult
Presence of virus or antibody to CMV does not indicate a current CMV infection/disease Different strategies used in different clinical situations

Congenital CMV Immunocompromised

Isolation of virus from urine within 30 days of birth

Antigen detection in buffy coat - indicates viraemia * CMV specific IgG positive indicates past infection

Treatment and prevention

Congenital CMV
Prevention not possible

CMV in transplant recipients

Prevention Treatment Test IgG before transplant Use only seronegative donors

Early diagnosis Reduce immunosuppression Ganciclovir

OTHER HUMAN HERPES VIRUSES

Human Herpes Virus 6 (HHV6) Discovered in 1988 Worldwide Virus replicates in T and B cells Infection occurs in first 3 years of life Clinical disease - Exanthem subitum (Roseola infantum) 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 infantum)

OTHER HUMAN HERPES VIRUSES

HHV7
Isolated from CD4 positive cells Virus present in saliva of >75% of adults Role in disease is unclear Evidence of infection present (seroconversion)

HHV8
Detected in epithelial cells of Kaposi sarcoma Also present in semen Postulated as cause of Kaposi sarcoma

1.1 Name three (5) herpes viruses that cause disease in humans (25 Marks) 1.2 How can you make an aetiological diagnosis of 3 diseases you have named in 1.1? (75 Marks) SAQ September 2011