Lecture 5 Herpes Viruses Human Papilloma Virus Molluscum Contagiosum Virus

Urogenital Microbiology… Lecture 5 Herpes viruses Human papilloma virus Molluscum contagiosum virus 1 _ first: Herpesviruses/Herpesviridae I. General features: a. Large dsDNA enveloped viruses of human, with 8 types:( we will deal with HHV1 & HHV2 as well as HHV5 (CMV) ) b. Icosahedral capsid + Tegument and lipid envelop II. Herpes simplex virus HSV1 and HSV2 a. General features: - They’re closely related , (genomically) - HSV1: Highly prevalent , HSV2: Sexual activity . b. Clinical Diseases: (Herpes simplex type 2 /HHV 2): - Primary Genital Herpes Infection: 1. Incubation period: 5 days, then the disease lasts for 12 days 2. Starts with Papule (raised area of skin tissue), then vesicles ( papules filled with fluid), which turn to pustules (when the fluid turns into pus ). 3. Vesiculopustular painful coalesced ulcers appear bilaterally & extensively in 3-5 days, then they heal without scaring..(Usually they are multiple ~20) 4. Urethra and cervix are usually infected (with ulcers as on exocervix) 5. Painful lymphadenopathy appears and still for months 6. Systemic symptoms: Fever, malaise, myalgia - Recurrent Genital Herpes Infection: 1. Shorter duration (vs primary lesions) 2. Localized genital lesions without systemic symptoms 3. Prodromal paresthesia in perineum, genitalia or buttocks .. 12-24 hours before lesions 2 4. Usually grouped vesicular lesions in external genital region 5. Mild pain and itching last for 4 - 5 days , Lesions last for 2 – 5 days 6. with primary lesions Recurrent in 12m, in 80% of patients: 1. 4-5 episodes/year (e.g monthly) then decreases gradually 2. Recurrences related to reactivation of virus from dorsal root ganglia (we talked about it in CNS1 or 2 🌚). 3. Recurrence with a different strain is RARE 4. Viral shedding occurs without evident diseaseusefu c. Diagnosis : - Cell culture - HSV-1 & HSV-2 distinguished by PCR or type- specific antibody test d. Treatment : - Acyclovir: Mainly for primary herpes, less on recurrent herpes - Valacyclovir, Famciclovir, Penciclovir For recurrent genital herpes . III. Cytomegalovirus (CMV/ HHV-5) : a. Pathogenesis: - Transmission: Close contact, Sexual contact, blood transfusion and transplantation. - CMV Could be isolated from/ Viral excreted in: Saliva, cervical secretion semen, urine & WBC for months after infection (only in patients who are infected) - Latent infection could be primary in CMV seronegative patient (ex. latent infection after blood transfusion in a recipient not infected previously) - reinfection in seropositive patients (infected previously). - High infection rate: Childhood (10-15% of cases) and in early adulthood. - CMV infects: Endothelial cells; Leucocytes Inclusions - Monocytes & stem cells (CD34+) are cells of latency 3 b. Clinical Diseases: - Mechanisms of diseases: Direct immunological damage (as a response to CMV) Via cytotoxic cells and cytokines release , which attack body tissue. - Produces inclusion intranuclear basophilic bodies (Owl’s Eye Cells). - Perinuclear cytoplasmic inclusions - Enlargement of cells (cytomegaly) - Vertical transmission to fetus in utero leading to deafness and other defects (15%-10% of all mothers excrete CMV from cervix at delivery, Breast milk transmission may also occur ) - In adults causes mononucleosis-like syndrome: 1. Blindness in AIDS 2. Infections in immunocompromised c. Immunity against CMV : - Humoral (anti-bodies mediated immunity) and Cellular responses - In immunocompetent: Primary CMV infection is commonly symptomless, Reactivation and viral excretion are Subclinical (not severe) - In immunocompromised: Primary and reactivation are usually symptomatic.. - Start with Monocyte infection, which leads to Dysfunction of phagocytes , increasing susceptibility to infections , then Activation of infected monocytes by T cells … Transmits CMV, e.g. transplantation . d. Diagnosis : - CMV detection: 1. (cytopathic effect, antigens, DNA) in tissues or blood 2. Ag and DNA can be detectable In fluid 3. DNA detection is by PCR (> sensitive than culture) - Virus isolation : From tissue, fluid or blood. - Seroconversion (Negative to Positive, e.g. in AIDS, i.e. usually positive) 4 e. Treatment : - Ganciclovir Combining immunoglobulin reduces mortality - Foscarnet is the second choice - Valacyclovir also approved for CMV therapy - Cidofovir: For resistant cases - No vaccine . f. Prevention : - Ensure that the blood is free of the CMV in blood transfusion : 1. Seronegative donors 2. Removed WBC (reservoir of the virus) - Ensure that organs are CMV free tissue in transplantations Seronegative donors Safe sexual practice & _ Second: Papillomavirus (HPV) : I. II. General features: a. HPV is a DNA virus, which has more than 100 genotypes, related to: - The Family: Papovaviridae - Genus: Papillomavirus Epidemiology: a. The main reservoir is infected humans b. Transmitted by: - Direct contact - Sexual (genital warts) contagious ( highly infectious) - It’s the Most common sexually transmitted infection c. Major cause of cervical cancer in women, also causes other cancers, e.g. penile or vaginal tumors d. Causes non-genital cutaneous warts genotypes e. More than 40 genotypes cause genital lesions: - Type 6 and 11: Genital warts in 90% of cases, and Other areas warts - Types 16,18, 31, 45, & 56 :Genital lesions - Type 16 & 18: Cause 70% of cervical , which is a serious tumor 5 III. Pathogenesis: a. infects squamous and columnar epithelium (e.g. cervix and anus) b. HPV gene products (E6 and E7) implicated in oncogenicity (precancerous) , E5 in benign papilloma c. HPV DNA found in 95% of cervical carcinoma (tested by PCR) Harald Zur Hausen discovery; “he took Nobel Prize” 2008 . d. Causes Condylomata acuminata , is also known as anogenital warts . IV. Diagnosis : a. HPV does NOT grow in tissue culture & Antibody tests is NOT useful (stay +ve) b. Poikilocytosis = Perinuclear cytoplasmic vacuolization and nuclear enlargement in cervix or vagina epithelium in Papanicolaou smear (Pap) c. Viral Ag by immunoassay, Nucleic Acid Hybridization and PCR: more sensitive than Pap . NOTE: CIN stands for cervical intra-epithelial neoplasia, e.g. CIN 1, 2 or 3 to be determined by Pap . V. Treatment : a. Cytotoxic drugs or surgical operation (Laser, or freezing with liquid nitrogen) b. Carcinoma: Radiation therapy or radical surgery 6 VI. Prevention : a. Two recombinant vaccines: - Bivalent “Cervarix” (HPV 16 & 18): For cervical cancer protection - Quadrivalent “Gardasil” (HPV 6,11, 16, 18): (Produce neutralizing antibodies, Protect against cervical cancer and genital wart ) For girls at age 9 -12 years & women - at age 13 – 26 years; males 13-26 years Three doses 6 months apart _Third Molluscum contagiosum/ MC virus: I. Benign cutaneous poxvirus with DsDNA, Enveloped II. Transmitted by direct contact( In shower rooms, pools and sexual contact) III. I.P.: 2-8 weeks IV. Nodular, pale, firm (pearl-like) lesions 2-10mm V. painless umbilicated, with cheesy material called Mollusca (means wart) , usually pink in color (eosinophilic inclusions ) VI. Disappear 2 -12 months; limited to epidermis VII. Diagnosis: Clinical or eosinophilic inclusions (histopathology) VIII. Treatment: Curettage ‫تنظيف طبي‬ Past years’ questions: _Not true about HPV:. No vaccine _Not true about CMV: Efficient immune reaction against it _Not true about Molluscum contagiosum: No curettage treatment. _No true Regarding CMV: AIDS patients usually have Anti-HIV Antibodies (-) test False about HHV : HSV2 and CMV is not latent Not true about HPV vaccine:. It’s an inactive killed vaccine 7