1
Q
UTIs in children
A
UTIs in children: more common in those under the age of 2
2
Q
Proteus mirabilis
Virulence factors
A
- Proteases
- Haemolysins
- Biofilm formation
- Urease production
Increase in alkalization will cause stones to form
3
Q
Lactobacilli characteristics
A
- Gram + rods, non-spore forming
- Facultative or strict anaerobes, produce lactic acid
- Rarely cause UTIs do not grow in urine well
4
Q
Psuedomonas biofilm development
A
4
Q
Diagnosis of UTIs
A
- Clean catch urine specimen (unspun, midstream)
- White and red blood cells, bacteria
- Culture and sensitivity tests
- ~20% of patients w/UTIs do not have pyuria
- No simple test to distinguish between upper from lower UTIs
5
Q
Urine -> smells like ammonia, toxic to kidneys (alkaline -> urine struvite crystals)
A
Proteus mirabilis
6
Q
Serotypes of E. coli in UTI
A
~85% of community- acquired, ~50% of hospital acquired UTIs
7
Q
Uncomplicated vs Complicated UTIs
A
• Uncomplicated UTI
– no specific pre-disposing factors
– no structural abnormalities, etc.
• predisposing anatomic, functional, or metabolic abnormalities -> Complicated UTI
– requires more aggressive evaluation and follow- up
– definition is often imprecise
7
Q
Pathogenesis of UTI pic
A
8
Q
Clinical Outcomes of UTIs
A
• Prostatitis: spectrum of disorders, some infections (E. coli most common)
– acute bacterial prostatitis is most serious but least common (chronic more common)
– reflux of urine from urethra into prostate ducts
• Epididymitis: microorganisms can enter from prostate via ejaculatory duct
– pathogens vary in younger men vs older
– predisposing factors include prostatitis, indwelling urinary catheters, urologic surgery
9
Q
Chronic UTI associated with which bacteria
A
E. coli
10
Q
Sx and location of infection of UGT
A
10
Q
Virulence factors contributing to UTIs
A
– Adhesins (pili, fimbriae, etc.)
– Ig proteases
– Hemolysins (get cytokine release, inflammation) – Ureases (i.e. P. mirabilis)
– Siderophore expression
– Factors promoting colonization and movement
10
Q
Tamm-Horsfall Protein
A
Bladder host defense
- binds specifically to type 1 fimbriated E. coli
- key urinary anti-adherence factor serving to prevent type 1 fimbriated E. coli from binding to the urothelial receptors
10
Q
UTI Treatment
A
- Usually antibiotics
- Drug and length depends on patient’s history and infecting microbe
- Sensitivity tests useful in selecting most effective drug
11
Q
Protective components of UGT
A
– Antimicrobial properties of urine (high urea conc., immunoglobulins, etc.) – Presence of normal microflora
12
Q
most common site of healthcare-associated infection, accounting for more than 40% of the total # reported
A
UT infections due to catheterization
13
Q
Asymptomatic Bacteriuria
A
Relatively common finding
- Present in ~5% of unselected medical outpatients, 10% pregnant patients at term, also in hypertensive and diabetic patients
- Anatomic obstruction increases incidence
- Nearly all patients with indwelling catheter w/open drainage for more than 48 hrs
15
Q
Recurrent UTIs
A
- 3 or more UTIs within a 12-month period
- Relapse
- Re-infection
- New infection
- Predisposing factors
- 20 - 25% women w/acute uncomplicated cystitis have 2 or more infections/yr
16
Q
UTI vs. STI
A
Juxtaposition of urinary and genital tracts in
vertebrates is a source of confusion
- UTI = Urinary tract infection. May or may not be transmitted by sexual activity – the more general term
- STI = Sexually transmitted infection –more narrowly specific
- Not all UTIs are sexually transmitted, and not all STIs manifest their symptoms and/or pathology
in the urogenital tract
17
Q
Normal microflora of vagina
A
– More diverse, influenced by hormones
– Newborn girls colonized w/ Lactobacilli, vaginal flora becomes more diverse over time
– Lactobacilli become more prominent at puberty
19
Q
Epidemiology of UTIs
A
2nd most common type of infection in the body*
Women: especially prone to UTIs (20-40% develops a UTI during her lifetime)
- Men: not as common as in women but can be very serious when they do occur
- US women that develop a UTI: 20% will have a recurrence
- Women who experience three or more UTIs are likely to continue experiencing them
20
Q
Acute uncomplicated cystitis, Recurrent cystitis in young women, Acute cystitis in young men, Acute uncomplicated pyelonephritis, Asymptomatic bacteriuria in pregnancy
What bacteria
A
- Escherichia coli • Klebsiella pneumoniae
- S. saprophyticus • Proteus mirabilis
21
Q
Complicated urinary tract infection bacteria
A
- E. coli
- Enterococcus species
- K. pneumoniae
- Pseudomonas aeruginosa
- P. mirabilis
22
Normal Microflora
• Urethra
– Lactobacilli
– Streptococci
– Coagulase-negative Staphlococci
24
Staphylococcus saprophyticus seasonality
Summer
(summer time sex)
26
Ascending vs Descending UTIs
* Descending is far less common
* Ascending – microorganisms may travel from urethra bladder kidney
27
What allows for organisms to stick to catheters
Biofilms
28
UPEC serotypes
29
Pregnant women w/UTIs
untreated - increased risk of delivering low birth weight / premature infants
– Smooth muscle relaxation
– Urethral dilation
– Greater chance to progress to pyelonephritis
30
UPEC (Uropathogenic E. coli)
Characteristics
primary cause of UTIs
## Footnote
Gram – rods, normal habitat is gastrointestinal
tract of humans and animals
distinguished by acquired genes (iron acquisition, siderophores) virulence-
distinct UPEC associated biosynthetic pathways
31
UTI Risk Factors
* being female
* recent sexual intercourse
– abrasions, etc.
* recent use of a diaphragm with spermicide • history of recurrent infection
* urinary catheter
32
Abbreviated work-ups for UTIs
* Leukocyte-esterase test
* Nitrates → nitrites: what does this mean?
* UTI symptoms in the presence of leukocytes are considered adequate to make a diagnosis of UTI
Urine cultures w/ 105 CFUs have defined infection
33
Catheterization predisposes you to
– obstruction -\> bacterial glycocalyx
– encourages formation of encrustations and infection
stones consisting of urea, other complex substances
– local infections (urethritis, periurethral abscess, epididymitis, and prostatitis)
34
Organisms predominately responsible for remaining UTIs (~15% community- acquired, ~50% of hospital-acquired)
– Staphylococcus saprophyticus
– Proteus mirabilis
– Klebsiella species
– Mycoplasma and Ureaplasma
– Candida
35
Primary cause of UTIs pathogen
UPEC (Uropathogenic E. coli)
36
* Cause of UTIs (usually young, sexually active women)
* Infrequent asymptomatic colonizer of UT
* Infections have been on the increase
Staphylococcus saprophyticus
37
Adhesion support for differnt types of organisms
39
Uropathogenic E. coli (UPEC)
Key virulence features
* Type I (cystitis)
* P pili (pyelonephritis)
Additional:
* α-hemolysin
* Siderophore
* Pathogenicity islands
40
Biofilms
are groups of microorganisms, often many species, growing on surfaces encased in “slime”
* Inert and living substances can be destroyed
* Multi-step process involving communication
41
Lactobacilli
• In addition to genitourinary tract also found in
– mouth, intestines, stomach
42
uropathogenicity of Staphylococcus saprophyticus
– novel cell wall-anchored adhesin
– redundant uro-adaptive transport systems
– urease
43
Summary 1 of STDs
44
STD summary 2
45
STI epi
• Affect both sexes, all socio-economic groups; Disproportionately affect:
– women, infants of infected mothers
– adolescents and young adults
– communities of color
– 15-24-year-olds represent ~ 1⁄4 of the sexually active population nearly 1⁄2 of all new STDs
46
“New” STIs
– Giardia lamblia - Protozoan
– Amoeba sp. - Protozoan
– Shigella sp., E. coli – True Bacteria
47
Vaginal discharge seen in
VAGINITIS:
– Trichomoniasis
– Candidiasis
CERVICITIS:
– Gonorrhoea
– Chlamydia
48
Urethral discharge seen in
Gonorrhoea
Chlamydia
49
Genital ulcer caues
Syphilis
Chancroid
Genital herpes
50
Lower abdominal pain seen in what STI
Gonorrhoea
Chlamydia
Mixed anaerobes
51
Scrotal swelling seen in which STDs
Gonorrhoea
Chlamydia
52
Inguinal bubo what is it/ seen in what stds
what is it:
Painful enlarged
inguinal lymph nodes
seen in:
LGV
Chancroid
53
Neonatal conjunctivitis in what stds
Gonorrhoea
Chlamydia
54
Anaerobic Gram negative bacteria and GYN Infections includes what organisms
Prevotella bivia and disiens,
Bacteriodes fragilis (common in abscesses)
• Virulence factors: capsules, etc. (adherence)
55
Gonorrhea: Epidemiology
* occurs only in humans (no other known reservoir)
* transmittedprimarilybysexualcontact,veryrare fomite transmission
* major reservoir is the asymptomatically infected individual
* infectionincreaseslikelihoodofHIVinfection
56
Gonhrea age relation
57
* Men (~95% have symptoms): generally restricted to the urethra – purulent urethral discharge, dysuria
* Women: site of infection is cervix – vaginal discharge, dysuria and abdominal pain
Gonorrhea
58
Neisseria gonorrhoeae: Characteristics
* Neisseria gonorrhoeae: Gram – diplococci
* non-motile, non-spore forming
* Fastidious
* oxidase +
* outer surface w/ multiple antigens
59
Neisseria gonorrhoeae: Pathogensis
• Attachment to columnar epithelium of
distal urethra or cervix
– Pili – unusual, specialized mechanism of antigenic variation by DNA rearrangement
– Opa
– por protein
– Lipooligosaccharide – induces TNF-alpha in some cells
– iron-binding proteins
60
Neisseria gonorrhoeae microbe movement
• Gonococci spread into the urethra or cervix (as far as the fallopian tubes, usually limited to urethra in males)
– Not motile (no flagella)
– urethral or uterine contractions may contribute to the ascending infection
* Bloodstream can be seeded (most commonly in individuals with defects in Complement System)
* Chronic infection can produce scarring and stricture of fallopian tubes or urethra
61
Gonorrhea: Diagnosis
* 1) Microscopic examination of smears for intracellular Gram – diplococci
* 2) Non-culture lab test
* 3) Isolation on appropriate media for confirmation
– 24 hrs: Thayer Martin (VCN agar, Chocolate II Agar w/ vancomycin, colistin, nystatin)
– oxidase + colonies
Thayer used for neisseria only
62
Three Paths of Neisseria gonorrhoea Infections
63
Gonorrhea: Prevention, Control and Treatment
• Recommended treatments are limited to a single class of antibiotics, cephalosporins (– Lactamase resistant)
since resistance is prominent
64
Resistance of N. Gonorrhoeae
65
Chlamydia: Epidemiology
* Most commonly reported STI in the US
* 1,244,180 diagnoses in 2009 (majority in women 15-24 yrs old)
* Most cases still go undiagnosed
* Presence may increase HIV transmission
* Severe impact on women, especially young and minority women
66
Chlamydia sex/age rates
67
Chlamydia trachomatis: Divided into 3 biovars (biological variants), then subdivided into serovars
68
Chlamydia complications for women
– Infertility
– ectopic pregnancy
– chronic pelvic pain
69
Chlamydia: Characteristics
Atypical bacterium, \*\*Gram - \*\*(Chlamydia trachomatis) - unique developmental cycle
* infectious form elementary bodies (EB)
* noninfectious form reticulate bodies
(RB)
* small obligate intracellular parasites
* gain entry through abrasions/lacerations
70
Chlamydia trachomatis is not visible w/
Gram stain!
71
Chlamydia should be suspected with cervicitis when
should be suspected in absence of clue cells, yeasts and trichomonads
72
Chlamydia: Pathogenesis
Receptors for EBs: restricted to certain epithelial cells
– mucous membranes of the urethra
– endocervix, endometrium, fallopian tubes
– anorectum
– respiratory tract and conjunctivae
73
Chlamydia: Diagnosis
Appropriate specimens intracellular parasites, swabs, not exudate, must be submitted for analysis
74
Chlamydia: Prevention, Control and Treatment
* STI prevention
* Can be cured w/antibiotics
– Azithromycin 1 g orally in a single dose
– Doxycycline 100 mg orally twice a day for 7 days
* Data suggests screening and treatment can reduce PID by over 50%
* Reducing the impact of Chlamydia
requires reducing/treating it in males
75
Syphilis: Epidemiology
Generally a highly infectious (transmission via direct contact with 10 or 20 lesions), genital, ulcerative disease that is easily curable in its early Primary&Secondary stages
• Increased likelihood of HIV transmission
76
hard, painless but sensitive ulcer develops 9-90 days post-infection (pi)
– Disappears w/in 1 week after proper treatment
– Disappears spontaneously w/out treatment after 4 to 12 weeks
– 75% of all untreated cases resolve here and do not progress past this stage
– Easy, definitive diagnosis by Darkfield
Microscopy: examine exudate from the lesion
Primary Syphilis
77
most common STds
78
* Lesionsoftenhavethin, greyish crust (easily removed crater w/ viscous fluid containing living T. pallidum cells
* Multiple lesions are quite common
Hard painless chancre
Primary syphilis
79
Wet, mucous patches are contagious
The inflammatory reaction is similar to but less intense
than that of the primary chancre
Condylomata Lata of Secondary Syphilis
80
generalized maculopapular rash + multiple symptoms indicative of systemic infection
– flulike syndrome, 2-8 weeks after ulcer
– rarely concurrent with chancre
– 80% show the maculopapular rash (rash may extend over face, palms and soles)
– lesions are “swarming” with the organism
Secondary syph
81
Primary/ secondary syph epi
82
Where in the US has the highest syph incidence
South
West
83
Primary and Secondary Syphilis—Rates by Age and Sex, United States, 2012
84
– diffuse chronic inflammation
– neurosyphilis (damage to CNS including progressive dementia, meningitis, hallucinations, etc.)
– cardiovascular effects such as aortic aneurysm
– “Gummatous” - A hypersensitive granulomatous reaction - Can be destructive to viscera or mucocutaneous areas
Tertiary syph
85
INfective organism for congenital syph
T. pallidum
86
Effects of Tertiary syph
Most cases spontaneous, septic abortion
• Occasionally a live birth takes place; infants
are actively infected with the organism
• Teratogenic effects usually seen
87
Stromal haze syphilitic interstitial keratitis
due to late-staged congenital syph
88
saddle nose
Congenital syph
89
Hutchinson’s teeth
Congenital syph
90
Treponema pallidum: Characteristics
* Thin, tightly coiled spirochetes w/pointed straight ends
* 3 flagella @ each end: MOTILE
* Replication slow – no in vitro culture
* Obligate human pathogen
* Unusual outer membrane
(no LPS, no porins)
91
Treponema pallidum: Pathogenesis
• Tissue destruction and lesions patient’s
immune response to infection
* Outer membrane proteins promote adherence
* Hyaluronidase may facilitate perivascular infiltration: “spreading factor”
* Coating of fibronectin may protect against phagocytosis
92
Syphilis: Pathogenesis primary
1 – enters subepithelial tissues via skin breach
* Slow replication, not a wide range of environmental conditions tolerated: Fastidious
* Endarteritis and granulomas
* Lesion heals but bacteria disseminate via lymph nodes and blood stream (latency poorly understood)
93
Syphilis: Pathogenesis secondary
2 – evasion of the immune system poorly understood
• Inflammatory response may be responsible for some symptoms
94
Syphilis: Pathogenesis tertiary
diffuse chronic inflammation, damage to CNS
95
Syphilis: Diagnosis
Rapid with dark-field examination of exudate from skin lesions (however, organism HIGHLY SENSITIVE)
* Definitive for diagnosing early syphilis
* Direct fluorescent antibody test
96
A presumptive diagnosis of syphilis is possible with the use of two types of serologic tests:
– 1) nontreponemal tests (e.g., Venereal Disease Research Laboratory [VDRL] and RPR)
– 2) treponemal tests (e.g., fluorescent treponemal antibody absorbed [FTA-ABS] tests, the T. pallidum passive particle agglutination [TP-PA] assay, various EIAs, and chemiluminescence immunoassays)
97
Syphilis: Prevention, Control and Treatment
* STI prevention
* CDC recommends sexually active men having sex with men be tested annually
* Pregnant women should be screened at first prenatal visit
* Penicillin (generally used for all stages, is only treatment for neurosyphilis)
* All persons who have syphilis should be
tested for HIV infection
98
Chancroid: Epidemiology
Predominant in the tropics (commonly in Africa, Asia and Latin America (accounting for 20% to 60% of genital ulcer disease infections)
* Sporadic in North America
* Infection increases likelihood of HIV transmission
99
pathogen for Chancroid
Obligate human pathogen Haemophilus ducreyi
• Chancroid (ulcer of the genital region)
100
* Soft chancre or chancroid
* Painful genital ulcer (5-10 days incubation period)
* spontaneously rupturing buboes occur in approximately 25% of cases
Chancroid
101
Unilateral Painful Inguinal lymph- adenopathy (50% of infected)
Inguinal bubo along w/ penile ulceration
Chancroid
102
Chancroid ulcer where on vagina
posterior wall
103
Haemophilus ducreyi: Characteristics
* Fastidious
* Gram – anaerobic rods (sometimes called “coccobacilli”)
* Pleomorphic
* Related to H. influenzae
104
Haemophilus ducreyi stain
Gentian Violet Simple Stain
105
Haemophilus ducreyi: Pathogenesis
extracellular pathogen that
resists phagocytosis
• Virulence factors include:
– an outer membrane serum resistance protein
– two toxins: cytolethal distending toxin (CDT) and hemolysin, both of which contribute to tissue destruction
106
Chancroid: Diagnosis
requires the identification of H. ducreyi on special culture media that is not widely available from commercial sources; even when these media are used, sensitivity is \<80%
* Antigen detection, serology and genetic amplification methods: reported for H. ducreyi, but are not easily available
* Accuracy of clinical diagnosis for chancroid ranges from 30% to 80%
* Exclude T. pallidum and HHV-1 & -2
107
Chancroid: Prevention, Control and Treatment
Antibiotics used for treatment
– Azithromycin 1 g orally in a single dose
– Ceftriaxone 250 mg intramuscularly (IM) in a single dose
– Ciprofloxacin 500 mg orally twice a day for 3 days
– Erythromycin base 500 mg orally three times a day for 7 days
108
Chancroid vs Syphilis
109
Normal balance of bacteria in vagina is disrupted - replaced by certain overgrowth
– sometimes accompanied by discharge (unpleasant odor, may be thin, white or gray)
– pain, itching, or burning outside vagina
Bacterial Vaginosis/Vaginitis
110
most common vaginal infection in childbearing aged women (sexual activity?)
Bacterial Vaginosis/Vaginitis
111
Vaginal infection that can increase HIV transmission
Bacterial Vaginosis/Vaginitis
112
can help distinguish BV from Candidiasis and Trichomonas
Examining the vaginal discharge under the microscope can help distinguish BV from Candidiasis and Trichomonas
* A sign of BV: unusual vaginal cell called a clue cell
* Women with BV (polymicrobial) have fewer than normal vaginal lactobacilli
* Vaginal pH \> 4.5 can be suggestive of BV
113
Candida albicans: Characteristics
Oval, yeastlike forms
site of colonization is GI tract • Normal microflora
• Commensuals:
– vagina
– urethra
– skin, under the nails
114
Candidiasis: Source of infection patient
* ~ 75% of all adult women at least one genital "yeast infection" in lifetime (people w/ weakened immune systems, more frequent and severe)
* Rarely, men may also experience genital Candidiasis
* Other conditions that may put a woman at risk for genital Candidiasis:
– Pregnancy
– Diabetes mellitus
– Use of broad-spectrum antibiotics and / or corticosteroid medications
115
Clinical Manifestations of Candidiasis
Candidiasis of the fingernail
2ndary oral pseudomembraneous candidiasis infection,
116
Common curable STD in young, sexually active women
Trichomoniasis
117
Trichomoniasis most common site of infection in women/men
Vagina: most common site of infection in women, urethra: most common site in men
118
primary mode of transmission Trichomoniasis
Sexual intercourse is primary mode of transmission; fomite transmission possible
119
Trichomoniasis increases risk for
• Genital inflammation, risk of HIV transmission
120
Parasite with 4 flagella and short undulating
membrane responsible for motility
Trichomoniasis
121
Trichomoniasis: Clinical Presentation
Vulvovaginal trichomoniasis
Cervical trichomoniasis
Vaginal pH \> 4.5 can also be suggestive of Trich
122
Most genital herpes type
HHV-2
123
HHV-1 and -2 is transmitted by
by close and/or sexual contact through mucosal membranes, breaks in the skin
124
When are viruses released with ulcers
released from these ulcers, but they are also released between outbreaks from skin
HHV1/2
125
What is the sequence of tests you should do for syph?
Nontreponemal initially (this has a high false positive) treponemal is then used to confirm.
126
What do you test for in reinfection of syph
Nontreponemal RPR levels
127
Clinical Manifestations of HHV-2
Primary genital herpes of the vulva
vesiculopapular herpes genitalis lesions
128
HHV-1 and -2: Characteristics
share DNA homology, antigenic determinants, tissue tropism and disease symptoms
* Ubiquitous, large, ds DNA, enveloped icosahedral virus, can stay in the body indefinitely
* Encode enzymes that are good antiviral targets
129
HHV-1 and -2: Pathogenesis
initially infect and replicate in mucoepithelial cells – lytic (most cells: Cowdry type A inclusion bodies, syncytia)
– persistent (lymphocytes and macrophages)
– latent infections (neurons)
Virus blocks effects of interferon, prevents CD8 T-cell recognition of infected cells, escapes antibody neutralization and clearance by going into “hiding” during latent infection
• Recurrence occurs in response to various stimuli
130
HSV infection sites
131
HHV-1 and -2: Diagnosis
– visual inspection if the outbreak is typical
– test a sample from the ulcer(s)
– virologic (PCR, cell culture) and type-specific serologic tests (based on type-specific glycoprotein G) are available
– between outbreaks by the use of a blood test to detect antibodies (results are not always definitive)
132
HHV-1 and -2: Prevention, Control and Treatment
antiviral medications – 1st occurrence:
– Acyclovir 400 mg orally three times a day for 7–10 days or 200 mg orally five times a day for 7–10 days
– Famciclovir 250 mg orally three times a day for 7–10 days
– Valacyclovir 1 g orally twice a day for 7–10 days
– shorten and prevent outbreaks with medication
• Daily suppressive therapy for symptomatic herpes can reduce transmission
133
Human Papillomavirus (HPV): Epidemiology
cumulative risk of acquiring HPV in sexually active persons = 80%
134
Spectrum of HPV
* Condyloma Acuminata (low-risk HPVs)
* Cervical Dysplasia (high-risk HPVs)
* Cervical Cancer (high-risk HPVs)
135
Estimated Contribution of
HR-Mucosal HPVs to
Various Cancers
136
Human Papillomavirus—Prevalence of High-risk and Low-risk Types Among Females Aged 14–59 Years,
137
Cervical Cancer International Incidence Patterns
138
HPV: Clinical Presentation, Anogenital Warts
HPV infections are often asymptomatic (both low- and high-risk)
May take weeks, months, years for symptoms to appear
Untreated, genital warts (low-risk HPV infections) may regress or increase in size and/or #
139
responsible for \>90% of anogenital warts1
• Peakprevalence
– Women 20–24 years of age (6.2/1,000 person years)
– Men 25–29 years of age (5.0/1,000 person years)
• Clinically apparent in ~1% of sexually active US adult population3
HPV 6 and 11
140
HPV – Oral sex causes throat cancer
HPV16 present in the tumors of 72% of cancer patients
141
HPV: Pathogenesis
HPV lifecycle tightly coupled to differentiation process of the epithelium
142
Mechanisms of Human Papillomavirus-Associated Carcinogenesis
HPV genome integration during malignant progression
Integration terminates life cycle
No evidence for insertional mutagenesis Expression of E6 and E7 is retained
143
Mechanisms of HPV-Associated Carcinogenesis
144
HPV: Diagnosis
* Genital warts diagnosed by visual inspection
* Cervical cell changes: 1) routine Pap tests, 2) HPV testing / typing
145
HPV: Prevention, Control and Treatment
* Women 21 – 29: Pap test every 3 years
* Women 30 and 65: both Pap test and HPV test every 5 years (preferred), OR Pap test alone every 3 years
HPV Vaccine – Gardasil ®
– Active against 16, 18, 6, 11
– FDA approved in US for girls & boys ages 9-26 (Cervarix ® targets only HPV 16 and 18)
Micro
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