1. Viral Infections of Reproductive System

2. The most common viral causes are:
Herpes simplex virus type 2 (HSV-2)
Human papillomavirus (HPV).

3. Herpesviridae Family:
Icosahedral, enveloped Ds DNA viruses.
Three subfamilies:
Alpha herpes viruses: HSV-1 & 2, VZV
Beta herpes viruses: CMV, HHV-6, HHV-7
Gamma herpes viruses: EBV, HHV-8
Latent or persistent infection after primary infection. Reactivations take place during periods of immunosuppression.

4. Herpes virus Particle All herpes viruses have identical
morphology and cannot be
distinguished from each
other under electron microscopy

5. Herpes Simplex Virus Type 2 (HSV-2):
HSV-1 and HSV-2 show 50-70% genetic homology and cross-reactive epitopes .
Man is the only natural host for HSV.
Transmission of HSV-2:
Sexual contact.
Perinatal infection (during birth).
Pathogenesis:
Stages of herpes infection:
Primary infections
Latency
Reactivation

6. Primary infections: (Herpes genitalis): usually asymptomatic
Primary infections: (Herpes genitalis): usually asymptomatic Symptomatic manifestations: Fever, painful bilateral vesicles and ulcers on the penis, vulva, vagina or cervix. Extensive infection: fever, dysuria and inguinal lymphadenopathy.
Latency: in sacral ganglia.
Reactivation: often asymptomatic.
Manifest at the sites innervated by the affected neurons.
Transmitted during sexual intercourse.

8. HSV-2 Diseases:
Genital herpes.
Neonatal herpes:
The most serious consequence of genital herpes. It is acquired during birth.
Aseptic meningitis.

10. Laboratory Diagnosis:
Very important to prevent neonatal and CNS herpes.
Specimen: vesicle swab, serum for serology.
Direct:
Detection of the viral antigens by: electron or immunofluorescent microscopy.
Detection of viral DNA by PCR.
Isolation of the virus on tissue culture: Cellular ballooning cytopathic-effect
Indirect (serology): to detect IgM & IgG anti-herpese antibodies.

11. Diagnosis of HSV-2:
HSV in cell culture

12. Human Papillomavirus (HPV):
Family: Papovaviridae.
Non enveloped, icosahedral, epitheliotropic supercoiled Ds DNA virus.
75% of the adult population will have at least one HPV infection during their lifetime.
The genome encodes for 7 early proteins (E1 to E7), and 2 late proteins (L1 and L2).
Based on L1 gene, there are over 100 types of HPV; 40 can cause anogenital infection.
Epitheliotropic: having an affinity for epithelium

13. Low-risk HPV types: cause anogenital warts and other benign lesions
Low-risk HPV types: cause anogenital warts and other benign lesions. Viral genome is not integrated with the cell DNA.
High-risk HPV types: are associated with malignant carcinomas (mainly of the cervix). Viral genome is integrated with the cell DNA.
A vaccine is available for both high and low risk types or for high risk alone.
Transmission:
Direct contact including sexual contact.
Contaminated surfaces and fomites.

14. HPV genital tract diseases:
genital warts: cauliflower-like growth in men & women, caused by HPV-6 and HPV-11. On the vulva, vagina, cervix, penis…. (highly contagious)
Low-grade cervical dysplasia: caused by oncogenic and non-oncogenic types.
High grade cervical dysplasia: caused by oncogenic types (pre-malignant).
Cervical cancer: oncogenic viruses: caused by HPV-16 and HPV-18.

15. Pathogenesis:
Primary infection: basal cell layer of stratified squamous epithelium.
High risk types:
high grade-dysplasia due to integration of viral genome within cell chromosome; Expression of E6, and E7 protein.
E6 and E7 interact with P53 and retinoblastoma protein (Rb) respectively and inactivate them. (P53 and RB are tumor suppressor proteins that play a central role in DNA repair and control of division).
Cervical carcinoma, penis, anus and other genital cancers.

19. HPV Perianal Wart: HPV Penile Warts:

21. Cancer of the genital tissues:
In women, pre-cancerous cells can be detected in the cervix by a Papanicolaou (Pap) test.
It is the only way to detect abnormal cells in the cervix that could potentially develop into cancer cell line later in life.
A girl should have her first Pap test within 3 years of becoming sexually active.
It is unlikely that a young girl will be diagnosed with cervical cancer as it takes many years for a cancer to develop.

22. Laboratory Diagnosis in early stage:
Specimens: Cervical swabs or biopsy.
Direct detection of abnormal cells:
Cytology (Pap smear)
Immunohistochemistry: detect E6 and E7 in the smear by specific antibodies.
Direct detection of viral genes by: PCR or DNA sequence methods for L1 genes.

23. Pap test showing
a low-grade
intraepithelial lesion
and benign endocervical
mucosa

24. Congenital viral infections
Most common congenital viral infections:
CMV,
parvovirus B 19,
rubella virus.
Diagnosis of congenital infectious diseases detection:
specific IgM or increasing IgG titer in the mother serum by the TORCH test: Toxoplasma, other (syphilis) rubella, CMV, Herpes simplex
Amniotic fluid or fetal blood test (intrauterine).

25. Human Cytomegalovirus (HCMV):
Belong to the beta herpesviruses subfamily.
Cytomegalo: The infected cells are enlarged and multinucleated.
Transmission:
direct contact with infected body fluids such as breast milk, saliva, blood, urine, semen, and vaginal fluids.
Sexual intercourse.
Transplacental.

26. Pathogenesis:
Primary infection:
CMV replicates in the epithelial cells of respiratory and gastrointestinal tracts then invade the blood (viremia) and infect all organs of the body.
Latency: in monocytes and macrophages.
Reactivation: common in immunocompromised and immunocompetent persons.
Active infection: in the fetus.

27. Clinical Features:
In fetus and neonates: “cytomegalic inclusion disease” Congenital CMV syndrome: in 20% with microcephaly, mental retardation, hepatosplenomegaly and jaundice, blindness and growth retardation.
Infections of immunocompromised patients: such as transplant recipients and AIDS patients; Severe organ disease retinitis, encephalopathy, colitis, and lung pneumonitis.

28. Congenital Cytomegalovirus Disease:
Growth retardation
purpuric skin lesions and
hepatosplenomegaly.

29. Twins with congenital CMV

30. Laboratory Diagnosis:
Specimens: throat washings, urine, exudate
Detection of viral antigens in urine or saliva.
Isolation of the virus on tissue culture.
Detection of viral DNA by PCR.
Serodiagnosis: Detection of CMV specific IgM or rising titer of IgG by ELISA.
Typical owl-eye
inclusions

31. Parvovirus B19: (Erythrovirus B19):
-Classification: Parvoviridae Family. Non-enveloped, icosahedral, Ss linear DNA.
-Transmission: Blood-borne; transfusion, transplacental, or airborne; respiratory inf.
-It infects red blood cell precursors in the bone marrow.
-Congenital infection:
Miscarriage: before week 20 of the pregnancy.
Hydrops fetalis; due to severe fetal anemia;
-No vaccine, No effective treatment. Pregnant women should avoid contact with infected children. n

32. Rubella virus infection:
Classification: Togavirus. Enveloped Ss RNA.
Transmission: Respiratory airborne in children and adults, transplacental for fetus.
Disease: Congenital rubella syndrome (CRS): teratogenic virus: infects fetal cells & stops cellular development and destroy the cells. Cardiac, ophthalmic, cerebral defects: ductus arteriosus, cataracts, blindness or deafness.
Vaccination for children, adolescent girls and seronegative pregnant ladies. n

33. Hydrops fetalis
Congenital rubella; cataract