Uploaded by b7840302

Urogenital Tract Infections Micro

advertisement
Urogenital Tract Infections
Medical Microbiology
By: Clark McLaughlin
Powerpoint adapted from Nikhil Shah
November 2017
• Urinary Tract Infections
• Vaginitis
• Cervicitis
• Pelvic Inflammatory Disease
• Urethritis
• Genital ulcers
• Prostatitis
Risk Factors for Infection
• Pregnancy
• Diabetes (elevated glucose)
• Urethra length (higher incidence in females)
• Obstruction or decreased clearance (stone formation)
• Catheterization
• Frequent or recent intercourse
• Antibiotics
• Previous UTIs and Retrovesicular movement
Upper vs. Lower UTIs
• Cystitis (Lower)
• Frequency
• Urgency
• Burning
• Dysuria
• Suprapubic pain
• Pyelonephritis (Upper)
• Cystitis Symptoms +
• Fever
• Chills
• Nausea / Vomiting
• Hypotension
• Costovertebral angle pain
UPEC vs. Klebsiella vs. Proteus(All gram neg)
• UPEC
• Non-encapsulated
• IBCforming(biofilm)
• Lactose fermenting
• Glucosefermenting
• Catalase (+)
• Klebsiella
• Encapsulated
• Carbapenemresistance
• Lactose
fermentation
• Proteus vulgaris
• Phenylalanine
deaminase
• Swarming motility
(concentric circles
when plated)
• H2S production
• Urease (+)
• Alkanization of
urine 
Struvite(MgNH4PO
4) formation
Pathogenesis of E. Coli in Cystitis and Pyelonephritis
• 1) Contamination of peri-urethral area with UPEC from gut
• 2) Colonization of urethra and bladder: pili & adhesins
• Type 1 Fimbrae: mannose-sensitive  can’t ascend  cystitis
• P-Fimbrae: not weakened by mannose exposure  can ascend  Pyelonephritis
•
•
•
•
•
•
•
•
3) Migration to bladder: motility
4) Colonization of bladder intracellular biofilm communities
5) Inflammation: LPS  immune system proliferation
6) Biofilm Formation(with use of Quorum Sensing)
7) Epithelial Damage: via bacterial toxins and proteases
8) Ascend to kidneys(P-Fimbrae)
9) Colonization of kidneys
10) Bacteremia
Struvite Stone Formation in Proteus spp.
• 1) Bacterial adhesion in kidney
• 2) Urease  ammonia  increased pH
• 3) Multiple micro-colony formation
• 4) Secretion of polysaccharide
• 5) Crystal formation within polysaccharide
• 6) Micro-colonies adhere to each other via crystals
• 7) Cycle repeats to form ‘staghorn’ stone
Staphylococcus saprophyticus
• Young Sexually active females (BUT REMEMBER E. COLI is more
common! You must have labs saying Gram + cocci is found)
• Gram (+) cocci
• Non-hemolytic on blood agar
• Coagulase (-) Catalase (+)
• Negative nitrates
• Resistant to novobiocin
Interpretation of Urinalysis
Component
Normal Range
Indicator of infection
Leukocyte esterase
0
Positive = pyuria  presence of WBCs
Nitrite
0
Positive = presence of bacteria that reduce
nitrate (except S. Saprophyticus)
WBC
<5
WBC>10 = pyuria
RBC
<5
RBC>5 = Hematuria
Epithelial Cells
<5
Indicated a good sample
pH
4.5 – 8
Elevated if urea-splitting bacteria present
Infections of the Pelvic Area
Syndrome
Main Pathogens
Less Common
Vaginitis
Mixed bacterial
Candida
T. vaginalis
Cervicitis
C. trachomatis
N. gonorrhea
Pelvic Inflammatory Disease
Polymicrobial
N. gonorrhea
C. trachomatis
Urethritis
N. gonorrhea
C. trachomatis
M. genitalium
T. vaginalis
Genital Ulcers
HSV-2
T. pallidum
H. ducreyi
C. trachomatis
K. granulomatis
Prostatitis
Gram (-) rods
N. gonorrhea
C. trachomatis
HSV
T. vaginalis
• Urinary Tract Infections
• Vaginitis
• Cervicitis
• Pelvic Inflammatory Disease
• Urethritis
• Genital ulcers
• Prostatitis
Polymicrobial (Bacterial) Vaginitis
• ETIOLOGY: endogenous bacterial overgrowth
•
•
•
•
Haemophilus spp.
Gardnerella vaginalis
Bacteroides spp.
Decrease in lactobacilli (increased pH)
• PATHOGENESIS:
•
•
•
•
•
Mucin/cell-degrading enzymes (collagenase, sialidase, fibrinolysins)
Hemolysins  release nutrients
IgA protease  reduces host immunity
Urease  cytotoxicity of ammonia
Amines  increase pH
• DIAGNOSIS: Nugent Score (wet mount and gram stain) or Amsel Criteria (¾ of the following…)
•
•
•
•
(1) pH >4.5
(2) >20%/HPF of clue cells (epithelial cells covered with bacteria)
(3) positive whiff test (sniff sniff…. Mmmmm)
(4) homogenous, non-viscous, milky white discharge
• SYMPTOMS: mostly asymptomatic
• Malodorous (fishy smelling) discharge (more commonly after intercourse or menses)
Vulvovaginal Candidiasis
• PATHOGENESIS:
•
•
•
•
•
Adhesins (Als3)
Directional hyphal growth (contact sensing)
Dimorphism
Biofilm formation
Iron acquisition (siderophore)
• SYMPTOMS: vulvar pruritis
• Thick, white, curdy vaginal discharge (cottage-cheese like)
• Erythematous ‘satellite’ lesion
• DIAGNOSIS: 10% KOH to find pseudohyphae w/ budding, Germ tubes
• pH should be normal
Sexually Transmitted Diseases
Trichomonas Vaginalis
• ETIOLOGY: only protozoan parasite that infects the genital tract
• MORPHOLOGY: 4 flagella + undulating membrane trophozoite(the
only form this has), no mitochondria
• SYMPTOMS: frothy gray/yellow-green vaginal discharge
• Pruritis
• Cervical petechia (strawberry cervix)
• May infect Skene’s glands
• DIAGNOSIS: modified Diamond’s Media (gold standard)
• Increased vaginal pH
• Whiff test (+)
• Urinary Tract Infections
• Vaginitis
• Cervicitis
• Pelvic Inflammatory Disease
• Urethritis
• Genital ulcers
• Prostatitis
Neisseria
gonorrhea
Neisseria gonorrhea
• CLASS: Gram (-) diplococci, intracellular, no capsule, oxidase (+)
• PATHOGENESIS:
•
•
•
•
Type IV Pili (pilE): adhesion
IgA1 protease: inactivation of IgA
Opa, Opc, porin: adhesion, invasion, iron uptake
LOS (instead of LPS): absence of O-antigen, triggers cytokine production
• SYMPTOMS:
•
•
•
•
Male: white, yellow/green discharge, painful urination, testicular swelling
Women: vaginal discharge, painful urination, painful intercourse, metrorrhagia
Neonatal: conjunctivitis
Disseminated: dermatitis, endocarditis, meningitis, tenosynovitis
• DIAGNOSIS: Thayer-Martin agar(Which is just chocolate agar with antibiotics selective
for N. gonorrhea) in 10% CO2
• Gram smear sufficient for men
• Culture required for women (N.gonorrhea as normal vaginal flora)
• Urinary Tract Infections
• Vaginitis
• Cervicitis
• Pelvic Inflammatory Disease
• Urethritis
• Genital ulcers
• Prostatitis
Chlamydia
trachomatis
Chlamydia trachomatis
• LIFE CYCLE: infectious Elementary Bodies  mitotic Reticulate
Bodies  EB  exocytosis
• SYMPTOMS:
• Males: penile discharge, burning urination, itching of tip of penis
• Females: abnormal discharge, dyspareunia, burning urination
• Complications: endometritis, salpingitis, abscess, peritonitis, reactive arthritis
• Fitz-Hugh-Curtis Syndrome (perihepatitis)
• DIAGNOSIS: collection of columnar or cuboidal epithelial cells via
urethral or cervical swabs (cell culture = gold standard)
• Nucleic Acid Amplification Tests (NAATs)
Lymphogranuloma venereum (LGV)
• ETIOLOGY: invasive C. trachomatis strains L1,2,3 infection
• SYMPTOMS: painful buboes in inguinal lymph nodes with systemic
symptoms
• Males: lesions at site of infection, fever/malaise/nausea, enlarged tender
lymph nodes
• Females: lesions at site of infection, rectal infection
• Diagnosis: Collect epithelial cells, PCR
• Urinary Tract Infections
• Vaginitis
• Cervicitis
• Pelvic Inflammatory Disease
• Urethritis
• Genital ulcers
• Prostatitis
Herpes Simplex 2 Virus
• ETIOLOGY: life-long chronic infection
• Dormant in sacral ganglia (S2-S4): circularized genome  latency transcript
• Neurovirulence (HSV2)
• Reactivation: fever, menstruation, sunlight, stress
• PATHOGENESIS:
•
•
•
•
•
Glycoprotein-mediated binding to epithelial cells and keratinocytes
Membrane fusion
Early and late genes expressed
Production of viral proteins and copies of genome
Assembly and budding from cell  cytolysis due to disruption of cytoskeleton
• MORPHOLOGY: Cowdry type A intranuclear inclusions
• Syncytia formation(Merging), Molding(nuclei condensed around circular circumference), Molding (nuclei form
together)
• SYMPTOMS: up to 80% asymptomatic
• Primary: HSV1/2, tender painful vesicular ulcerative lesions, fever, headache, malaise, itching, dysuria, discharge,
lymphadenopathy
• Recurrent: HSV2 more common
• CNS Complications: aseptic meningitis, HSV1 necrotizing encephalitis
• DIAGNOSIS: microscopic examination  Tzanck smear, Immunofluorescence or PCR
Treponema Pallidum
• CLASS: spirochete, no gram staining, burrowing motility, lacks TCA cycle, can
grow in Armadillo feet
• PATHOGENESIS:
• Entry via minute lesions on skin and mucous membranes
• Minimal species-specific antigens on surface (reduces immune efficacy)
• Attaches to fibronectin and changes lipid membrane antigens daily=evasion!
• TIMELINE:
• Primary: 10-90 days, Secondary 14-30 days, Tertiary: years
• DIAGNOSIS:
• Darkfield and Fluorescent Treponemal Antibody (FTA-ABS)
• VDRL (microscopic) and RPR (naked eye), cardiolipin-cholesterol lecithin antigen
• Doesn’t grow an artificial media
• SYMPTOMS:
• Primary: painless hard chancre at site of infection
• Secondary: rash (centrifugal including palms/soles), generalized lymphadenopathy,
condylomata lata, alopecia
• Late/Tertiary: 10-20 years after initial infection, (1) Gummatous lesions, (2) CV syphilis
with aortic regurgitation (tree bark appearance due to endarteritis), (3) neurosyphilis
• Latent: Early (initial infection <1 year ago) or Late (initial infection >1 year ago)
• If untreated  transmission to fetus up to 4 years after primary infection
Hemophilus ducreyi
• Organisms: Gram (-), pleomorphic coccobacillus aligned in chains
• SYMPTOMS: ragged, painful soft chancroid (ulcer)(Because you “Do Cry “(Ducreyi)
• Has CYTOLETHAL DISTENDING TOXIN and HEMOLYSIN
• Tender regional lymphadenopathy
• DIAGNOSIS: culture requires chocolate agar or blood agar with Factor X (hemin)
•
•
•
•
•
Gonococcal Agar base + 2% bovine hemoglobin + 5% fetal calf serum
Mueller-Hinton agar with 5% heated horse blood
Diagnosis based on ulcer appearance
Rule out T. pallidum (darkfield microscopy)
Rule out HSV (PCR negative)
Mycoplasma genitalium
• ETIOLOGY: triple layer external membrane contains sterol
 cholesterol(or serum) must be added to growth
media(organisms do not grow on conventional agar!)
• Free living
• Self-replicating
• PATHOGENESIS:
•
•
•
•
•
Adhesion via MgPa tip adhesins
Evasion of host defenses via variable surface lipoproteins
H2O2 and superoxides
Inflammatory cytokines, immune cell stimulation/suppression
Tissue damage
Klebsiella granulomatis
• CLASS: gram (-) enterobacteriacea, encapsulated
• ETIOLOGY: Granuloma inguinale
• MORPHOLOGY: safety pin appearance
• Intracellular inclusions in macrophages  Donovan bodies
• SYMPTOMS: painless, expanding, suppurative ulcers
• ”Beefy-red”  tend to bleed easily
Human Papilloma Virus (HPV)
• PATHOGENESIS OF WART:
•
•
•
•
•
•
Infection of basal layer, cell growth stimulation by early genes
Prickle cells in stratum spinosum increases
Differentiation of basal cells results in transcription of viral genes
Skin becomes thicker (hyperkeratosis)
Epithelial spikes (papillomatosis)
Late gene expressed
• SYMPTOMS:
•
•
•
•
Non-genital skin warts
Non-melanoma skin cancers: Basal Cell carcinoma, Squamous Cell carcinoma
Benign laryngeal tumor
Condylomata accuminata: external warts on perineum, anus, penis (HPV11)
• VIRULENCE:
• E6 + E7: bind p53 and Rb (high-risk strains HPV16/18)
• Types 16 + 18 + 31 + 33= Cervical cancer
• Types 6 + 11= Condyloma acuminatum (NOT LATA!! That is syphilis!)
• Vaccines= Bivalent, Quadrivalent(Gardasil), Enneavalent (Gardasil-9)
Thanks for watching! Don’t forget to subscribe!
Download