Transcript 5-viral infections of reproductive systemx

Viral Infections of
Reproductive
System
The most common viral causes are:
• Herpes simplex virus type 2 (HSV-2)
• Human papillomavirus (HPV).
Herpesviridae Family:
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Icosahedral, enveloped Ds DNA viruses.
Three subfamilies:
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Alpha herpes viruses: HSV-1 & 2, VZV
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Beta herpes viruses: CMV, HHV-6, HHV-7
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Gamma herpes viruses: EBV, HHV-8
Latent or persistent infection after primary
infection. Reactivations take place during periods of
immunosuppression.
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Herpes virus Particle
All herpes viruses have identical
morphology and cannot be
distinguished from each
other under electron microscopy
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
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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.
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Latency: in sacral ganglia.
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Reactivation: often asymptomatic.
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Manifest at the sites innervated by the affected
neurons.
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Transmitted during sexual intercourse.
HSV-2 Diseases:
 Genital herpes.
 Neonatal herpes:
The most serious consequence of genital
herpes. It is acquired during birth.
 Aseptic meningitis.
Laboratory Diagnosis:
Very important to prevent neonatal and CNS herpes.
Specimen: vesicle swab, serum for serology.
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Direct:
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Detection of the viral antigens by: electron or
immunofluorescent microscopy.
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Detection of viral DNA by PCR.
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Isolation of the virus on tissue culture: Cellular
ballooning cytopathic-effect
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Indirect (serology): to detect IgM & IgG antiherpese antibodies.
Diagnosis of HSV-2:
HSV in cell
culture
Human Papillomavirus (HPV):
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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.
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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.
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.
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.
HPV Perianal Wart:
HPV Penile Warts:
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.
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.
Pap test showing
a low-grade
intraepithelial lesion
and benign
endocervical
mucosa
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).
 Human Cytomegalovirus (HCMV):
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Belong to the beta herpesviruses subfamily.
Cytomegalo: The infected cells are enlarged
and multinucleated.
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Transmission:
direct contact with infected body fluids such
as breast milk, saliva, blood, urine, semen, and
vaginal fluids.
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Sexual intercourse.
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Transplacental.
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.
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.
Congenital Cytomegalovirus Disease:
Growth retardation
purpuric skin lesions and
hepatosplenomegaly.
Twins with congenital CMV
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
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 Parvovirus B19: (Erythrovirus B19):
-Classification: Parvoviridae Family. Nonenveloped, 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:
o Miscarriage: before week 20 of the pregnancy.
o Hydrops fetalis; due to severe fetal anemia;
-No vaccine, No effective treatment. Pregnant
women should avoid contact with infected children.
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 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.
Hydrops fetalis
Congenital rubella; cataract