B2 G&D Lec:1 Genital ulcers and warts Flashcards
What is a genital ulcer disease?
a breach in the skin or mucosa of the genitalia
• Usually is sexually transmitted
Which organism cause syphilis?
Treponema pallidum
What is the reservoir of T.pallidum?
Human only
Describe the property of T.pallidum ?
• Belong to genera of spirochetes which are flexible, spiral rods
• They are motile through the undulation of axial filaments that lie under the outer sheath
• Treponemes are so thin that they are detected only by dark field microscopy, silver staining or immunofluorescence
• Has not been grown on bacteriologic media or in cell culture
• They grows very slowly, so antibiotics must be present at an effective level for several weeks to kill the organisms and cure the disease
What are the antigens of T.pallidum used as serologic diagnosis of syphilis?
- Specific antibodies
- Nonspecific antibodies (reagin), which can be detected by the flocculation
How is the specific antibodies detected in T.pallidum?
by immunofluorescence or hemagglutination tests in the clinical laboratory
What is flocculation ?
flocculation (agglutination of antibodies) of lipids (cardiolipin) extracted from normal mammalian tissues (e.g., beef heart)
How is T.pallidum transmitted?
—-> transmitted from spirochete-containing lesions in skin or mucous membranes (e.g., genitalia, mouth, and rectum) of an infected person to other persons by intimate contact mainly sexual.
• It can also be transmitted from pregnant women to their fetuses
• Rarely, by blood transfusion
What is endarteritis?
Infection in the endothelium of small blood vessels by T.pallidum
When endarteritis occur?
This occurs during all stages of syphilis but is particularly important in the pathogenesis of the brain and cardiovascular lesions seen in tertiary syphilis
What happens in primary syphilis?
The spirochetes multiply at the site of inoculation, and a local, non painful, non tender ulcer (chancre) usually forms in 2 to 10 weeks.
The ulcer heals spontaneously, but spirochetes spread widely via the bloodstream (bacteremia) to many organs.
What happens in secondary syphilis ?
• The lesions appear as a maculopapular rash, notably on the palms and soles, or as moist papules on skin and mucous membranes (mucous patches).
•Moist papules on the genitals are called condylomata lata.
• These lesions are rich in spirochetes and are highly infectious, but they also heal spontaneously
What is condylomata lata?
Moist papules on the genitals
When 2ndry syphilis occur?
one to 3 months later
What are the constitutional symptoms in 2ndry syphilis?
- low grade fever
- malaise
- anorexia
- weight loss
- headache
- myalgias
- generalized lymphadenopathy
How is syphilis usually treated?
• About one-third of these early (primary and secondary) syphilis cases will “cure” themselves, without treatment.
• Another third remain latent (i.e., no lesions appear, but positive serologic tests indicate continuing infection).
• The latent period can be divided into early and late stages.
What occurs in the early latent period?
can last for 1 or 2 years symptoms of secondary syphilis can reappear and patients can infect others
What occurs in the late latent period ?
can last for many years, no symptoms occur and patients are not infectious.
What does the remaining 1/3 represent?
the disease progresses to the tertiary stage. Tertiary syphilis usually occurs decades after infection with T. pallidum, but immunocompromised patients (e.g., HIV) may develop more rapidly.
Describe tertiary syphilis manifestation
may show granulomas (gummas), especially of skin, bones, cardiovascular (aortitic aneurysm) and central nervous system involvement known as neurosyphilis (e.g. tabes, paresis)
What does it mean that syphilis has incomplete immunity ?
Antibodies to the organism are produced but do not stop the progression of the disease.
Patients with early syphilis who have been treated can contract syphilis again. Patients with late syphilis are relatively resistant to reinfection.
When do the early onset of Congenital syphilis occur?
•Fetal infection can result in stillbirth.
•Early (onset < 2 years of age)
Describe the appearance of early congenital syphilis
macular, copper-colored rash on the palms and soles and papular lesions around the nose and mouth and in the diaper area.
Characteristic mucopurulent or blood-stained nasal discharge causing snuffles.
The infant may fail to thrive
Describe the appearance of late congenital syphilis
bone lesions, such as Hutchinson’s teeth, saddle nose, saber shins and frontal bossing.
•Other findings, such as lymphadenopathy,
hepatosplenomegaly, interstitial keratitis, and eighth nerve deafness, also occur.
When does the late onset of congenital syphilis take place?
onset > 2 years of age
Mention how T.pallidum is diagnosed ?
- Microscopy
- Non spesific serologic tests
- Specific Serologic Tests
- The laboratory diagnosis of congenital syphilis
How is Spirochetes of primary & secondary syphilis demonstrated in microscopy ?
by dark field microscopy or by direct fluorescent antibody (DFA) test. They are not seen on a Gram-stained smear
How microscopy approach is done in tertiary syphilis?
• In biopsy specimens, such as those obtained from the gummas seen in tertiary syphilis
• Histologic stains such as silver stain or fluorescent antibody can be used.
What is gummas?
Gummas are granulomatous lesions with central area of necrosis due to obliterating endarteritis
Which test is inexpensive and easy to perform and therefore are used as a method of screening the population for infection?
Non spesific serologic tests
What does non specific serologic test use as an antigen?
- nontreponemal antigens ( Extracts of normal mammalian tissues (e.g., cardiolipin from beef heart) react with antibodies in serum samples from patients with syphilis)
- reagin antibodies (are a mixture of IgG and IgM)
Which test detect the non specific antibodies in T.pallidum?
Flocculation tests e.g.:
- Venereal Disease Research Laboratory [VDRL]
- and rapid plasma reagin [RPR] tests
The titer of these nonspecific antibodies ________ with effective treatment, in contrast to the specific antibodies, which are_______ for life.
Decrease; positive
When does false positive reaction occur in non specific test in syphilis?
- Infections: such as leprosy (Mycobacterium lepra), hepatitis B, and infectious mononucleosis (Epstein-Barr virus)
- Various autoimmune diseases. Therefore, positive results have to be confirmed by specific tests
Which test involve the use of treponemal antigens and therefore are more specific?
Specific Serologic Tests
When does the specific treponemal antibodies arise?
within 2 to 3 weeks of infection
Can specific serological tests be used for reinfection?
No , cannot be used to determine the response to treatment or reinfection but they remain positive for life even after effective treatment
What is the difference between specific from the non specific test?
Specific test are more expensive and more difficult to perform than the nonspecific tests and therefore are not used as screening procedures.
What are the antibodies in specific serological tests?
Fluorescent (treponemal) antibody- Absorbed test (FTA-ABS) or T. pallidum hemagglutination assay (TPHA)
What is the determinant of diagnosing congenital syphilis?
based on the finding that the infant has a higher titer of antibody in the VDRL test than has the mother
What happens in false positive VDRL test?
result in the infant because maternal antibody has crossed the placenta, the titer will decline with time. If the infant is truly infected, the titer will remain high.
• However, irrespective of the VDRL test results, any infant whose mother has syphilis should be treated
What does the presences of syphilis mean to other STIs?
The presence of syphilis means high risk of other STIs (Chlamydia trachomatis & Neisseria gonorrhea) and screening is therefore indicated
What does the organism Haemophilus ducreyi cause?
sexually transmitted disease “chancroid (soft chancre)”.
Describe the property of H.ducreyi
small gram-negative rod
requires heated (chocolate) blood agar supplemented with X factor (Heme) but, unlike H. influenzae, does not require V factor (NAD)
Where does H.ducreyi begin?
The disease begins with penile lesions, which are painful; non indurated (soft) ulcers; and local lymphadenitis (bubo)
How is Haemophilus ducreyi diagnosed ?
made by isolating H. ducreyi from the ulcer or from pus aspirated from a lymph node
Describe papillomas
Caused by Human papillomavirus , which are benign tumors of squamous cells (e.g., warts on the skin).
Which type of HPV cause carcinoma of the cervix, penis, and anus.?
Type 16 and 18
Enumerate the important properties of Papillomaviruses
• are non enveloped viruses with double-stranded circular DNA and an icosahedral nucleocapsid.
• There are at least 100 types of papillomaviruses with a pronounced predilection of certain types to infect certain tissues.
• Approximately 30 types of HPV can infect the genital tract.
Which type of HPV cause skin warts?
primarily by HPV-1 through HPV-4
Which type of HPV cause genital warts?
HPV-6 and HPV-11
How many early and late genes does HOV genome contain?
- seven early genes (E1–E7)
- two late genes (L1 and L2)
What do the early genes encode in HPV?
early genes encode proteins involved in the synthesis of viral mRNA and in the replication of the progeny DNA genomes
What do the late genes encode in HPV?
encode the structural proteins of the progeny viruses
Where does the Two of the early genes, E6 and E7 implicate ?
carcinogenesis
Summarize the replicative cycle of early HPV
- After attachment and uncoating, the genome DNA moves to the nucleus. Messenger RNA is synthesized by host cell
- RNA polymerase with early viral protein E2 acting as a transcriptional activator
- Early viral protein E1 acts as a helicase that separates the DNA strands of the incoming viral genome.
- episomes in the nucleus
What is the role of E1 as a helicase helps with?
This allows the host cell DNA polymerase to synthesize the progeny DNA genomes.
The initial progeny genomes are maintained as_______ in the nucleus.
episomes
Summarize the replicative cycle of late HPV
- The late proteins L1 protein comprises the capsid of HPV virions. L1 has the ability to self assemble into capsids in vitro
- L2 protein aids in the packaging of genome DNA into the progeny virions as well as in uncoating the genome when they infect the next cell
Which form is the immunogen in the HPV vaccine?
Self assembled L1 into capsids in vitro
Where does the infectious virus particles are found in human tissue?
in the terminally differentiated squamous cells rather than in the basal cells
** Note: HPV initially infects the cells of the basal layer in the skin, but no virus is produced by the basal cells. Rather, infectious virions are produced by squamous cells on the surface, which enhances the likelihood that efficient transmission will occur.
What happens in malignant cells replication cycle?
viral DNA is integrated into host cell DNA in the vicinity of cellular proto-oncogenes, and E6 and E7 are over expressed
What happens with latent infection of non malignant cells?
the viral DNA is episomal, and E6 and E7 are not overexpressed. This difference occurs because another early gene (E2) controls E6 and E7 expression.
The E2 gene is functional when the viral DNA is_________ but is inactivated when it is__________ .
episomal ; integrated
How is Papillomaviruses transmitted?
By skin-to-skin contact and genital contact
How Papillomaviruses reach basal epithelial cells?
Micro-abrasions in the skin allow access to the basal epithelial cells where infection begins
Explain the manifestations of HPV transmitted from an infected mother to the neonate.
causes warts in the mouth and in the respiratory tract, especially on the larynx of the infant
What is koilocytes?
a characteristic cytoplasmic vacuole induced by Papillomaviruses that infect squamous epithelial cells and thus it’s considered a hallmark of infection
Are warts are benign or malignant?
Most are benign & do not progress to malignancy
But they are associated with carcinoma of the uterine cervix and penis.
Explain the pathogenesis that makes Papillomaviruses associated with malignancy
• The proteins encoded by viral genes E6 and E7 interfere with the growthinhibitory activity of the proteins encoded by the p53 and RB tumor suppressor genes and thereby contribute to oncogenesis by these viruses
• The E6 and E7 proteins of HPV-16 bind more strongly to p53 and RB proteins than the E6 and E7 proteins of HPV types not implicated in carcinomas—a finding that explains why HPV-16 causes carcinomas more frequently than the other types of HPV.
Who is involved in immunity leading to regression of warts?
Both cell-mediated immunity and antibody are induced by viral infection and are involved in the spontaneous regression of warts.
Who is at higher risk of HPV?
Immunosuppressed patients (e.g., patients with acquired immunodeficiency syndrome [AIDS] have more extensive warts
HIV infected women have a very high rate of carcinoma of the cervix.
What are the clinical findings of HPV?
• Skin papillary lesions (dry raised verrucous lesions “Verrucca vulgaris”)
• Genital warts (condylomata acuminata) are caused primarily by HPV-6 and HPV11.
• HPV-6 and HPV-11 also cause respiratory tract papillomas, especially laryngeal papillomas, in infants and young children.
Carcinoma of the cervix, the penis, and the anus, as well as premalignant lesions “intraepithelial neoplasia”, are associated with which type of HPV?
HPV-16 and HPV-18
What is the laboratory diagnosis of genital warts?
• The presence of koilocytes in the lesions indicates HPV infection
• A polymerase chain reaction (PCR)–based test can be used to detect the presence of the DNA of high-risk genotypes, including HPV-16 and HPV-18
