Micro Flashcards
Low risk condylomas are?
HPV 6+11
High risk HPV 16 + 18 have what two proteins that play in the pg of cervical cancer?
E6 + E7–> bind and inactivate two tumor suppressor proteins p53 and Rb
Where does HPV remain over time?
Basal cell layer
What is the anti-cancer HPV vaccine available?
Subunit vaccine consisting of L1 capsid
What is the genome/makeup of HPV?
Small DS DNA virus
Non enveloped capsid
What is the difference btwn virus in permissive and non permissive cells?
Permissive for virus growth= replicates and assembles in nucleus
non-permissive= late gene expression does NOT occur–> TRANSFORMS the cell= produce tumor
Genomic location differences btwn benign and malignant tumors?
Benign= extrachromosomal Malignant= genome integrated into host chromosome
What are the features of a transformed cell?
immortal
no longer contact inhibited
no longer require serum-derived GF in cell culture
no longer anchorage dependent for growth
Can lead to tumor formation in syngeneic animals
What are the late and early genes in HPV used for?
Late (L1+L2)= capsid proteins
Early= replication proteins and transformation
What is the function of E6 and E7 proteins?
E6= binds and degrades p53 E7= binds and inactivates Rb
What is the initial infection of HPV?
infect Germinal cells= non-permissive cells–> virus particles not produced but cells transform
What happens to the Germinal cells after infection?
mature + migrate to surface + keratinize + become Permissive + shed virus
Why do warts return after treatment?
because destroying the wart does not Eliminate the genome in the non-permissive Germinal cells
Describe HPV?
circular DS DNA
NON enveloped icosahedral capsid (L1+L2)
Rep + assembly in nucleus of permissive cells
NO virus production in non-permissive cells, but virus genome maintained and cells transform
E6 degrades p53 + E7 inactivates Rb
over-expression of E6 + E7= malignant
Differentiated keratinocytes are permissive=wart
Virus maintained in Germinal cells
What are the disease caused by HPV?
verruca vulgairs= common/ plantar warts
Conyloma acuminata/plana= Anogenital warts 6+11
Subclinical papilloma inf= HPV 16, 18, 31
Cervical penile, anal, oral, neck cancer= 16, 18,31
Infantile laryngeal papillomas: 6+11
Which HPV cause Anogenital warts?
HPV 6 + 11
Which HPV cause sub-clinical papilloma infections (SPI)?
HPV 16, 18, 31
Which HPV cause cervical, penile, anal, oral, neck cancer?
HPV 16, 18, 31
Which HPV cause infantile laryngeal papillomas?
HPV 6 + 11
What is laryngeal papillomas associated with?
Respiratory distress and 3% die annually
How can SPI be detected?
Brushing infected area with 5% acetic acid which turns the area WHITE
What would a positive pap smear show?
Koliocytes (vacuolated cytoplasm) Squamous epithelial cells
What is does HPV cause in the cervix?
Causes 90% of cervical dysplasias= lead to invasive cancer
What is the range of HPV in women in US?
15-60%
What are some other cofactors of Cervical cancer along with HPV (16,18,31)?
Smoking
Herpes Simplex
Which type of papillomas are acquired at birth?
Laryngeal –> HPV 6+11
What is necessary for Dx of HPV?
Clinical presentation
Pap smear
Colppscopy
FDA approved HPV DNA detection test
What is Gardasil?
Recombinant capsid protein (L1) from 6,11, 16,18
What are the methods for removing Warts?
Bichloroacetic acid
Trichloroacetic acid
Cryotherapy
LEEP (loop electrosurgical excision procedure)
Podofilox (anti mitotic)
Imiquimod ( stimulates IFN and cytokine product)
What accounts for 60-70% of STIs with dysuria and penile and vaginal exudation?
Chlamydia trochamatis
Neisseria gonorrhoeae
What is the most serious sequela for both Ct and GC (gonococcus)?
lower genital tract infection spreading up and causing PID = sterility and ectopic pregnancy
What are the complications associated with new borns of Ct and GC infected mothers?
Ct= Conjunctivitis + Pneumonia GC= Conjunctivitis
What are the chances that someone with GC has Ct?
50%
Chlamydia trachomatis description?
Obligate intracellular parasite
G- but deficient in peptidoglycans
replication via EB and RB
Isosmotic intracellular environment-> Beta lactams DO NOT work for Tx
What are the two main VFs of Ct?
Intracellular growth
Ability to cause inflammation (heat shock protein or LPS induced)
What are EB and RB?
EB= metabolically inert but infectious elementary body RB= Larger, grows within membrane bound vacuole in cytoplasm of mucosal epithelial cells
What happens during lysis of cell during Ct infection?
EBs released infect nearby cells or sexually transmitted to new host
Describe GC?
No capsule
LPS= shed, invokes inflammatory response
Antigenic variation (pili + outer membrane surface proteins for attachments)
Extracellular= phagocytosed by PMNs
secrete IgA1
Ct strains that causes urethritis and cervicitis are restricted to what?
mucosal epithelia and DO NOT disseminate into Blood or lymph
Some strains of GC can do what that Ct doesnt?
Disseminate= septicemia + Rash
Ureaplasma is a significant cause of what?
UTIs
What organisms cause Cervicitis and urethritis?
Ct + GC
What bacterial organism causes Prostatitis/ pharyngitis?
GC
What bacterial organism causes Infant pneumonia and conjunctivitis?
Ct
What bacterial organism often Disseminates causing sepsis, Rash, Aseptic arthritis, Meningitis?
GC
Urethritis with Purulent penile discharge + dysuria?
GC
Urethritis with penile milky discharge + dysuria?
Ct
Dull to severe lower abdominal pain, cervicitis, adnexal tenderness, Cervical motion tenderness, Fever?
PID–> Ct, GC, Mycoplasma, anaerobes
Serious infection often requiring hospitalization, Tubo-ovarian abscesses, sterility, ectopic pregnancy, Chronic pelvic pain results from?
PID
Fever, Rash (fingers, toes, and feet), septic arthritis?
GC
1-4 months postpartum, afebrile, repetitive staccato cough with tachypnea, hyperinflated chest of CXR?
Infant pneumonia–> Ct only
Gram stain of penile exudate shows G- cocci and PMN infiltration?
GC
** without PMNs= non-gonorrheal urethritis (Ct)
What can GC colonies be grown on?
Thayer Martin medium
What is Thayer Martin medium?
Chocolate blood agar
With antibiotics (vanco, nystatin, colistin)
Only GC growth
Organism that is G- diplococcus, Oxidase positive?
GC
MC Dx tool for Ct infections?
NAAT on urine and cervical/urethral exudates
What is the DOC for GC infections?
IM Ceftriaxone
**Fluoroquinolones–> Organism now resistant
DOC for Ct infections?
Azithromycin
2nd–> Doxycyline
Urethritis/ cervicitis with Swollen lymph nodes, Suppuration of lymph nodes, ulceration at site of entry?
Lymphogranuloma venereum
Potentially blinding disease, high prevalence in Asia, Middle East, Africa?
Trachoma (non STD Ct infection)
HSV structure?
Large
DS DNA
Capsid + lipid Envelope
HSV replication?
Attachment + pH dependent fusion nucleocapsid migrates to nucleus Translation of immediate early genes (replication proteins) Late protein translation Viral assembly in nucleus FORM SYNCYTIAs
What are the prominent early proteins translated by HSV?
Thymidine kinase
DNA polymerase
What are the diagnostic tests for HSV infections?
Tzanck smear–> look for Multinucleated cells
What is the function of the only gene expressed during latency?
LAT–> prevent apoptosis of infected neuron
NO virus particles are produced
Causes Fever blisters, herpetic whitlow, Keratitis, Conjunctivitis, Encephalitis?
HSV 1 –> ABOVE BELT
Causes cervicitis, Vulvular/ penile vesicles, MENINGITIS?
HSV 2
What limits the duration of HSV lesions?
Neutralizing Antibodies
What are prodrome symptoms of HSV primary or recurrent genital infections?
Flu like
Itching or burning skin
Muscle aches
What are the ocular complications of HSV?
Blepharitis and conjunctivitis
What are the indications of neonatal infection?
95% transfered during delivery
primary= 30% risk of transmission
Recurring= 2-3% risk of transmission
Herpetic lesions at deliver= MUST DO C-section
What are the typical diagnostic tools for HSV?
culture showing Cytopathic effect (CPE) Fluorescent antibody screening PCR Serology to distinguish serotypes of past infections TZANCK SMEAR
Patient with neck stiffness and CSF is cultured to differentiate btwn what?
Bacterial or HSV (showing CPE)
What diagnostic test can rule out herpes encephalitis?
normal EEG and confirmation by PCR from CSF
What diagnostic tests should be performed for Neonatal or congenital HSV infection?
Skin, eye, mouth, or CNS samples
LIVER enzymes for signs of Dissemination
What is the DOC for HSV?
Acyclovir
What is the MOA of acyclovir?
Inhibits Viral DNA polymerase
Requires phosphorylation by Viral Thymadine kinase
What are the AE of Acyclovir?
Nausea Rash Diarrhea Renal Failure (high does causes precipitation) SEIZURES
MAO of Foscarnet?
Pyrophosphate analog blocks viral DNA pol.
MOA of Docosanol?
Over the counter medication for cold sores:
Modifies host cell membrane to inhibit viral fusion to limit spread
What is the MC way to Dx infectious agents of Vaginitis and vaginosis?
Microscopically
Rapid examination of Discharge
What are the factors that allow for overgrowth of Candidia and other agents of bacterial vaginitis?
Disturbance of Normal flora (esp G+ Lactobacilli)
Other organisms tat Maintain LOW pH and produce Hydrogen Peroxide
SIngle cell protozoan that is considered the pathogen causing sexually transmitted Trichomoniasis?
T vaginalis
What are the agents of Bacterial Vaginosis?
Gardnerella vaginalis
Mobiluncus
Anaerobes
Agents of Candidiasis?
Candidia albicans
C glabrata
Fungi
A protozoan species causes what Female infection?
Trichomoniasis
Pt with Abnormal scant, White, Clumped vaginal discharge, external dysuria, vulvar itching, pain and irritation?
Vulvovaginal Candidiasis
Microscopy shows: Leukocytes, epithelial cells, mycelia, or pseudo mycelia?
Vulvovaginal Candidiasis
Profuse Yellow frothy vaginal discharge, dysuria, vulvar itching, erythema, colipitis macularis, and Amine odor with KOH?
Trichomonal Vaginitis
Amine= Fishy
Loss of normal vaginal Lactobacilli, associated with Gardnerella vaginalis; increased anaerobic bacteria and mycoplasmas?
Bacterial Vaginosis
Increased White/gray, Malodorous discharge that is Adherent uniformly to vagina, and has Amine odor with KOH?
Bacterial Vaginosis
Dysuria, Suprapubic pain, Polys in urine, SIgnificant # of bacteria in urine is characteristic of?
Cystitis
Cystitis, Significant fever, Flank pain and WBC/RBC casts in urine?
Pyelonephritis
Dysuria, Mucopurulent discharge, pruritis, lower abdominal pain, fever?
Cervicitis
How is trichomoniasis transmitted?
Sexually
Foul odor (KOH whiff test) Dirty white Discharge pH above 4.5 Presence of CLUE cells (vaginal epi with adherent bacteria in wet mounts or gram stains) NO DYSURIA no inflammation?
Bacterial Vaginosis
Vaginal itching Patchy white adherent clumpy discharge (cottage cheese exudate) Discharge w/ foul smell pH 4.5 or less Branching hyphae seen in wet mount?
Candidiasis
Yellow homogenous Frothy discharge Whiff test Positive pH above 4.5 Dysuria Wet mount shows twitching motility and PMNs?
Tichomonas
DOC for Trichomonasis?
Metronidazole
DOC for candidiasis?
Azoles
Which STI organism cannot be grown in lab but can be propagated in rabbit testes?
Syphilis (T. pallidum)
What is the Hallmark of Primary syphilis?
NON PAINFUL ulcer= CHANCRE
Hallmark of Secondary syphilis?
Systemic infection Fever Swollen Lymph nodes Mucous membrane lesions Rash on PALMS & SOLES maybe warts in perineum or anal region
Hallmarks of Congenital syphilis?
Saddle nose
Sabre shins
bifid Incisor teeth
MC Tx of Syphilis?
Penicillin G
What are the characteristics of T. palladium?
Helical bacterium= Spirochete
Too thin to be seen on Gram stain or microscopy
USE DARKFIELD microscopy
What method can be used to Dx early syphilis disease process?
Darkfield microscopy
What are the inner and outer membranes of T. palladium made of?
Inner= periplasm with peptidyglycan + flagella outer= lipoproteins and lipids
What is responsible for controlling syphilis infections and contributes to its pathology?
Cellular immune response
**Spirochetes have LATENT phase
Pt with painless ulcer and non tender inguinal LAD?
Primary Syphilis
Pt with Hyperpigmented rash over entire body that extends into his hands and feet, Snail track lesions in mucous membranes, and condylomata lata, NON tender LAD, mild Meningeal symptoms?
Secondary Syphilis
DDx for Rash on Palms and Soles?
Secondary syphilis
RMSF
Hand foot and mouth disease (CMV)
What is tertiary Syphilis considered?
Endarteritis
Pt with characteristic skin and bone granulomatous lessons, aortic regurgitation, meningeal signs (Tabes dorsalis) ?
Tertiary syphilis
Causes still births or abortions, often transmitted across placenta in 1st trimester hematogenously. Infant with Snuffles, Bulllous rash, enlarged liver and spleen?
Early Congenital syphilis
How does late Congenital syphilis present?
Bone abnormalities
Frontal bossing + sabre shins
Vision defects
what is Hutchinson’s triad and what disease is it seen in?
Triad: Notched incisors, keratitis, Deafness
Congenital syphilis
What are the Dx tests for Syphilis?
Non-treponemal serology= RPR and VDRL
Treponemal= FTA-ABS
What are the non-Treponemal serological tests?
Using beef heart mito cardiolipin
Rapid Plasma Reagin (RPR)
Venereal Disease Research Lab test (VDRL)
RPR and VDRL tests are Cheap and sensitive but have many False positive because of the Cardiolipin including with?
Viral Hepatitis
Mono
Lupus
rarely Pregnancy
What is the Treponemal specific tests?
Fluorescent Treponemal Antigen-Absorbed test
FTA-ABS
- Cumbersome + expensive + but cured slides last for years