Urogenital Tract Infections

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Pres: sexually active female, burning pain during urination, increased frequency, urgency x1d. Blood stained debris at end of urination.

Back 1

UTI

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Most common cause of UTI (uncomplicated cystitis) in women

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E. coli

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Culture medium for E. coli

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MacConkey agar
Form large, gray colonies

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E. coli microbial properties

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Family: Enterobacteriaceae
Gram neg rod
Facultative anaerobe
Glucose and Lactose fermenting
Oxidase neg

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E. coli antigens

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1. Somatic O antigen (carrying LPS)
2. H antigen (flagellum)
3. K antigen (polysaccharide capsule; a major virulence factor)

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What constitutes pyuria?

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>10 WBCs/hpf of unspun, voided midstream urine
(this amount of WBCs will turn leukocyte esterase dipstick positive)

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What allows E. coli to adhere to the uroepithelium?

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P-fimbriae and type-1 fimbriae (virulence factors)

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E. coli fimbriae cause these inflammatory responses

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Secretion of IL-6 and IL-8 (PMN recruitment)
Apoptosis and epithelial desquamation

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How do bacteria move against urinary flow to ascend urinary tract?

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Flagella

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E. coli virulence factors

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Fimbriae
Capsule (K antigen)
Flagella
LPS endotoxin
Hemolysin

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Factors causing high fever, shaking chills and localized flank/LBP in severe pyogenic infection

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IL-1 and TNF

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UA finding representing pyelonephritis (complicated UTI)

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White cell casts

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Siderophore used by bacteria in kidney to overcome iron limitations

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Aerobactin (increases iron uptake by bacteria)

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Tx for uncomplicated UTI

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TMP/SMX (Bactrim, Septra) x3d

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Contraceptive assoc. w/ higher rates of UTI

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Spermicide

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Alternative tx for UTI

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Beta-lactam (amox/cephalosporins)
Fluoroquinolone (cipro/levo)

Front 17

Pres: low-grade fever, malaise, rash on palms and soles, painless ulcers on genitals, multiple sexual partners, inguinal lymphadenopathy

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Syphilis (treponema pallidum)

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Distinctive feature of syphilis

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Febrile episode with generalized rash postprimary genital lesion

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Cytologic examination to detect HSV-infected cells

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Tzanck smear

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Syphilis screening test

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RPR (rapid plasma reagin) titer

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Treponema pallidum (syphilis) microbial properties

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Spirochete
Thin-walled, flexible rods (invisible on LM)

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Characteristic treponeme motility

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Corkscrew motility (endoflagella, seen on darkfield microscopy)

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Culture of treponema pallidum

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Treponemes do not grow in bacteriologic media or cell culture

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Basis for nontreponemal screening (RPR, VDRL)

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Treponemal membrane lipids (cardiolipin) induce nonspecific Abs that cross-react with beef heart cardiolipin (reactivity in early disease; titers wane with successful treatment)

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Diseases causing false-positive nontreponemal tests

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Autoimmune disease, SLE

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Specific, confirmatory test for T. pallidum

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Fluorescence treponemal antibody-absorption (FTA-Abs) or microhemaggluitinin-T. pallidum (MHA-TP)
(both detect T. pallidum-specific Abs; tests become positive later in disease and remain elevated for life)

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T. pallidum transmission

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Obligate human pathogen, transmitted by intimate contact with infected lesions or transplacentally from mother to fetus

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Proinflammatory mediators of syphilis

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Constituent membrane lipoproteins

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Primary syphilis

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Single lesion; indurated painless ulcer (chancre) at site of initial invasion

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T. pallidum virulence

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Evade immune recognition and elimination by antibodies, maintaining an outer membrane rich in lipid
Invasion of epithelial cell layers, entry into lymphatics and blood

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Secondary syphilis

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Maculopapular rash on skin/mucous membranes (palms and soles), may involve lymph nodes
Usually appears 6-8 weeks after healing of the chancre

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Tx for T. pallidum (primary, secondary and latent)

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Benzathine penicillin G (IM, weekly x3wks)

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Alt tx for penicillin-allergic pts with T. pallidum

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Doxycycline (adults only)
Ceftriaxone (congenital)

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Alt tx for penicillin-allergic pregnant women with T. palldium

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Erythromycin

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Tx for neurosyphilis

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High-dose IV penicillin G x10-14d

Front 36

Pres: painful, itchy vesicular lesions on genitals; low-grade fever, malaise, headache, unprotected sex, tender inguinal lymphadenopathy

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HSV-2

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Microbiologic properties of herpesviruses

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Large virions w/ icosahedral nucleocapsid
Linear dsDNA
Lipoprotein envelope

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Positive Tzanck smear for herpes shows

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Presence of multinucleated giant cells in virus-infected host cells

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How Tzanck smear sample is prepared

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Scraping the floor of a herpetic vesicle

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How HSV-2 is distinguished from HSV-1

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Antigenicity (MAbs labeled with fluorescein stain specific proteins)

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Transmission of HSV-2

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Sexual contact (with person actively shedding virus), vertical transmission

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Cause of primary HSV-2 lesions

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Cytopathic effect of virus on mucocutaneous epithelium

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Where HSV-2 multiplication occurs

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Sensory neurons (Cell-mediated immunity causes virus become quiescent and remain latent until reactivation)

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Things that cause HSV-2 reactivation

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Transient suppression of cellular immunity (physical/emotional stress, fever, UV light, tissue damage)

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Tx for HSV-2

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Acyclovir (oral x10d)
Topical acyclovir may be helpful in first episode but not recurrences; tx has no effect on latency

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Tx in acyclovir-resistant HSV-2

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Foscarnet

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Pregnancy risks with first-episode HSV-2 infection w/o seroconversion

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Spontaneous abortion
Prematurity
Congenital/neonatal herpes (recommend C-section in women with active infection)

Front 48

Pres: Multiple sexual partners; early onset sexual activity; small, raised lesions on friable, erythematous cervix; condylomata acuminata on labia

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HPV

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Pap smear findings in HPV

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Squamous cells show binucleation with enlarged, hyperchromatic nuclei

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HPV microbiologic properties

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Nonenveloped viruses
Icosahedral symmetry
dsDNA (circular)
>100 types

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HPVs causing genital warts in women

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HPV-6 and HPV-11

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HPV transmission

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Genital contact

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HPV infections are usually..

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Asymptomatic; Infected persons are unaware they are infected and able to transmit the virus

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Risk factors (8) for HPV infection leading to cervical carcinoma

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Sexual activity before age 15
Multiple sexual partners
Exposure to STD
Familial cervical cancer
Smoking
Immunosuppression
HIV/AIDS
Chronic corticosteroid use

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Cells infected by HPV

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Squamous epithelial cells of basal layer of skin/mucous membrane (enter through disturbed epithelial barrier)

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HPV multiplies only in the

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Nucleus
(infected cells exhibit a high degree of nuclear atypia)

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Pap smear abnormalities caused by HPV

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Koilocytosis (intracellular changes with perinuclear clearing [halo] and shrunken nucleus)

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HPV causes warts because of

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Proliferation and thickening of the basal layer (virus infected cells)

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Tx for HPV

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Wart removal (cautery, cryotherapy, laser therapy, 10-20% podophyllin solution, or 80-90% trichloroacetic acid)

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HPV types assoc with cervical cancer

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HPV 16 and HPV 18

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Hallmark of malignant transformation in HPV 16 and 18

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Integration of viral genome into host cell genome

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How HPV 16 and 18 cause malignancy

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Proteins E6 and E7 inactivate host tumor suppressors p53 and Rb, allowing unregulated epithelial growth

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Pres: 48h hx of painful urination with purulent yellowish penile discharge, sexual promiscuity; no lymphadenopathy or skin lesions

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Neisseria gonorrhoeae (gonorrhea)

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Neisseria microbiologic properties

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Gram-neg diplococci
Oxidase +
Glucose fermenter

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Dx finding for gonorrhea

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Multiple pairs of bean-shaped, Gram-neg diplococci within a neutrophil in a Gram smear of urethral discharge

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N. gonorrhoeae virulence factors

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Pili
Cell-wall LOS
Outer membrane proteins (OMPs/protein I)
IgA protease
[DO NOT have capsule]

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N. gonorrhoeae culture medium

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Thayer Martin medium

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N. gonorrhoeae initiates infection by

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Binding to columnar epithelial cells (using pili and OMPs), colonizing mucosa

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Ability of gonococcus to control presence or absence of pili and OMPs, making host antibodies to these component ineffective

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Phase variation

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How IgA protease protects Neisseria

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Hydrolyzes IgA1 mucosal antibodies, inhibits opsonization

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How OMP/protein I protects Neisseria

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Protects against phagocytosis, interferes with neutrophil degranulation

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Tx for N. gonorrhoeae

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Ceftriaxone (single injection)

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Pts tx for gonorrhea should be treated simultaneously for

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Chlamydia (with doxycycline or azithromycin, x10d)

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Complications of gonococcal infection in women

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PID/salpingitis
(chronic pelvic pain, infertility, ectopic pregnancy)

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Complications of gonococcal infection in men

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Epididymitis (infertility if untreated)

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Complications of gonococcal infection in newborns

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Gonococcal conjunctivitis, formerly a major cause of blindness (now tx w/ silver nitrate, tetracyclin or erythromycin)

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Pres: Lower abd pain (adnexal/cervical motion tenderness), reddened cervical os, vaginal discharge, dysuria x1wk; fevers, chills x2d; unprotected sex with multiple partners

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Chlamydia trachomatis

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Infection assoc with IUDs

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Actinomyces israelii

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Analysis of endocervix for chlamydia

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Giemsa or direct fluorescent antibody stain of cytobrush specimen

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C. trachomatis microbiologic properties

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Obligate intracellular bacteria
Energy dependent on host cells
Serotypes D-K are most common STDs in the world

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Risk factors for C. trachomatis infection

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Young age at first intercourse
Multiple sexual partners
IUDs
Smoking

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C. trachomatis infection

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Elementary bodies (EBs) enter columnar epithelial cells of cervix
Within host-derived vacuole (cytoplasmic inclusion, seen on Giemsa/fluorescence) differentiate into reticulate bodies (RB)
RBs multiply by binary fission, reorganize to EBs and are released from host cell to initiate another cycle of infection

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Symptoms of chlamydia are caused by

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Columnar epithelial cell destruction during acute disease process, causing release of proinflammatory cytokines which recruit PMNs and mononuclear cells

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Tx of C. trachomatis

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Doxycycline x14d

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Alt tx for chlamydia in non-compliant pts

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Azithromycin (single dose)

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Tx of PID assoc with chlamydia

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Cefoxitin

Front 87

Reiter syndrome

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Triad of urethritis, arthritis, and conjunctivitis (and anterior uveitis) within 6 mos of chlamydia infection

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Reiter syndrom HLA association

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HLA-B27

Front 89

Pres: profuse yellow, foamy vaginal discharge with foul odor, vulvular irritation/itiching, dyspareunia, strawberry cervix, multiple sex partners

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Trichomonas vaginalis (trichomoniasis)

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C. trachomatis microbiologic properties

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Obligate intracellular bacteria
Energy dependent on host cells
Serotypes D-K are most common STDs in the world

Front 91

Risk factors for C. trachomatis infection

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Young age at first intercourse
Multiple sexual partners
IUDs
Smoking

Front 92

C. trachomatis infection

Back 92

Elementary bodies (EBs) enter columnar epithelial cells of cervix
Within host-derived vacuole (cytoplasmic inclusion, seen on Giemsa/fluorescence) differentiate into reticulate bodies (RB)
RBs multiply by binary fission, reorganize to EBs and are released from host cell to initiate another cycle of infection

Front 93

Symptoms of chlamydia are caused by

Back 93

Columnar epithelial cell destruction during acute disease process, causing release of proinflammatory cytokines which recruit PMNs and mononuclear cells

Front 94

Tx of C. trachomatis

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Doxycycline x14d

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Alt tx for chlamydia in non-compliant pts

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Azithromycin (single dose)

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Tx of PID assoc with chlamydia

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Cefoxitin

Front 97

Reiter syndrome

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Triad of urethritis, arthritis, and conjunctivitis (and anterior uveitis) within 6 mos of chlamydia infection

Front 98

Reiter syndrom HLA association

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HLA-B27

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Pres: profuse yellow, foamy vaginal discharge with foul odor, vulvular irritation/itiching, dyspareunia, strawberry cervix, multiple sex partners

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Trichomonas vaginalis (trichomoniasis)

Front 100

Diffuse macular erythematous lesion of cervix associated with trichomoniasis

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Strawberry cervix

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Positive (fishy odor produced) 10% KOH amine/whiff test suggests

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Trichomoniasis or bacterial vaginosis

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Microbes assoc with bacterial vaginosis

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Gardnerella vaginalis
Mobiluncus

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Dx finding for bacterial vaginosis

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Clue cells (vaginal epithelial cells with stippled appearance due to attached microorganisms)

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T. vaginalis microbiologic properties

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Motile (visible flagella)
Pear-shaped protozoa
Replicates by binary fission in lower genital tract
Do not have a cyst form
Transmission by direct contact

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Examination of vaginal secretion in trichomoniasis reveals

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Pus cells interspersed with nucleated, flagellated trichomonads (slightly larger than PMNs, ameboid motility)

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In women, T. vaginalis is found in

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Vagina
Urethra
Bladder
Bartholin/Skene glands

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In men, T. vaginalis is found in

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Anterior urethra
External genitalia
Prostate
Epididymis
Semen

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T. vaginalis infections in men are

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Asymptomatic
(all partners of infected persons must be treated because men harbor infection)

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Incubation period and symptoms in women with T. vaginalis

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4-28 d; inflammatory reaction (vaginitis) w/ neutrophilia, vaginal pH >4.5

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Tx for T. vaginalis

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Metronidazole