HERPES SIMPLEX VIRUS Dr. Hani Masaadeh MD, Ph.D

2 HERPES SIMPLEX VIRUS (HSV) HSV-1 and HSV-2 infect more than one-third of the world’s population HSV-2 is responsible for the majority of cases of genital herpes, although HSV-1 can also lead to genital infections

3 Triggers for viral reactivation include: – Immunodeficiency – Fever – Ultraviolet light – Stress ???? – Trauma – Menstruation – Sexual Intercourse HERPES SIMPLEX VIRUS (HSV)

4 Initial episodes are more severe than recurrences After an incubation period of several days patients notice a prodrome: – Itching – Burning – Erythema HERPES SIMPLEX VIRUS (HSV) MANIFESTATIONS

5 Classic vesicles which are painful appear on the: – Cervix – Vagina – Vulva – Rectum – Perineum – Surrounding skin HERPES SIMPLEX VIRUS (HSV) MANIFESTATIONS

6 HERPES

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8 Clinical diagnosis is made by recognition of multiple, shallow and tender ulcerations or vesicles on or around the genitalia Laboratory diagnosis – Viral isolation by tissue culture Gold standard Can take up to 5 days Sensitivity is only 70% - 80% HERPES SIMPLEX VIRUS (HSV) DIAGNOSIS

9 – Antigen Detection and Tzanck Tests Lower sensitivity – Serologic studies Not helpful during the primary illness because of the delay in antibody production – PCR testing Sensitive (96%) and specific (99%) High cost Limited availability HERPES SIMPLEX VIRUS (HSV) DIAGNOSIS

10 Acyclovir binds viral DNA polymerase and ends replication Medications must be administered early in the course of the illness because HSV replication may end as soon as 48 hours into a recurrence Only to be used in pregnancy if there is a severe infection HERPES SIMPLEX VIRUS (HSV) TREATMENT - ACYCLOVIR

Cytomegalovirus

Properties Belong to the betaherpesvirus subfamily of herpesviruses double stranded DNA enveloped virus Nucleocapsid 105nm in diameter, 162 capsomers The structure of the genome of CMV is similar to other herpesviruses, consisting of long and short segments which may be orientated in either direction, giving a total of 4 isomers. A large no. of proteins are encoded for, the precise number is unknown.

Epidemiology CMV is one of the most successful human pathogens, it 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.

Clinical Manifestations Congenital infection - may result in cytomegalic inclusion disease Perinatal infection - usually asymptomatic Postnatal 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.

Congenital Infection Defined as the isolation of CMV from the saliva or urine within 3 weeks of birth. Commonest congenital viral infection, affects % of all live births. The second most common cause of mental handicap after Down's syndrome and is responsible for more cases of congenital damage than rubella. Transmission to the fetus may occur following primary or recurrent CMV infection. 40% chance of transmission to the fetus following a primary infection. May be transmitted to the fetus during all stages of pregnancy. No evidence of teratogenecity, damage to the fetus results from destruction of target cells once they are formed.

Laboratory Diagnosis (1) 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.

Laboratory Diagnosis (2) Virus Isolation – conventional 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 hours. Serology – the presence of CMV IgG antibody indicates past infection. – The detection of IgM is indicative of primary infection although it may also be found in immunocompromised patients with reactivation.

Cytopathic Effect of CMV (Courtesy of Linda Stannard, University of Cape Town, S.A.)

Specimens for Laboratory Diagnosis

Treatment Congenital infections - it is not usually possible to detect congenital infection unless the mother has symptoms of primary infection. If so, then the mother should be told of the chances of her baby having cytomegalic inclusion disease and perhaps offered the choice of an abortion. Perinatal and postnatal infection - it is usually not necessary to treat such patients. Immunocompromised patients - it is necessary to make a diagnosis of CMV infection early and give prompt antiviral therapy. Anti-CMV agents in current use are ganciclovir, forscarnet, and cidofovir.

Human Papillomavirus (HPV) Genital Warts

Human Papillomavirus (commonly called Genital Warts) Human Papillomavirus (HPV) is a virus that can cause various disease states including “genital” or “venereal” warts Papillomaviruses are a complex group of DNA tumor viruses. They can cause benign growths (papillomas), cancers, or more commonly, transient infections HPV infection is causally associated with cervical cancer ; other genital cancers including anal, penile, vulvar, and vaginal cancers may have HPV as co-factor

HPV Prevalence Most common STD An estimated sexually active adolescents and young adults years of age are infected with genital HPV An estimated people infected with genital HPV are infected with multiple types of the virus

Risk Factors for Acquiring a Genital HPV Infection Young age (less than 25 years) Multiple sex partners Early age at first intercourse (16 years or younger) Male partner has (or has had) multiple sex partners

HPV Transmission Direct skin-to-skin contact – Usually, but not always sexual contact Infected birth canal Fomites (very rare)

HPV Incubation Average incubation is 3 weeks to 1 year Possibly years before appearance of warts or cervical abnormalities Some will be transient and may never be detected

Common Symptoms of Genital Warts in Males & Females The symptoms may include single or multiple fleshy growths around the penis, scrotum, groin, vulva, vagina, anus, and/or urethra They may also include: itching, bleeding, or burning, and pain The symptoms may recur from time to time

Perianal Warts Source: Cincinnati STD/HIV Prevention Training Center

Complications of Genital Warts (if untreated) It may destroy body tissue around the genitals and anus For pregnant women – Delivery complications or need for C-section

Testing & Treatment for Genital Warts Can be detected in a clinical exam; Can be treated by removing the warts; The virus cannot be removed, so the warts may grow back.

HPV Diagnostic Techniques History Visual exam Pap smears DNA testing

HPV Treatment Options Chemical agents Cryotherapy Electrosurgery Surgical excision Laser surgery Imiquimod (Aldara) Defer treatment Natural therapies

Perinatal complications

Can a person be re-infected with HPV? There appears to be humoral and probably cellular immunity that develops to a specific type of HPV after a person has been infected with it and “has cleared” it. The risk for re-infection with that specific type of HPV appears to be rare. However, a person can be infected with more than one type of HPV

Molluscum contagiosum Molluscum contagiosum is a common, self- limiting, nonscarring, papular, viral skin infection Groups of papules are found anywhere except palms of hands or soles of feet, containing infectious, white, curd-like material Found mainly in children and young, sexually active adults Transmission by close contact, for

Transmission by close contact, for example, sport, occupational, sexual Adult disease is associated with sexually transmitted infections and may be a marker for late-stage HIV infection Treatment is often unnecessary in children but may prevent further sexual transmission in adults

Transmission by close contact, for example, sport, occupational, sexual Adult disease is associated with sexually transmitted infections and may be a marker for late-stage HIV infection Treatment is often unnecessary in children but may prevent further sexual transmission in adults