Genito — Urinary

Urinary — strictly excretory system:
kidneys
ureters normally sterile
bladder
urethra–tip has flora from skin
flushing action of urine
– pH
– relative lack of nutrients
– final apurature of urethra — sphincter muscle closes it
Urinary tract
inf. very common in clinical practice
increased risk for infection because of proximity to anus
in men urethra ~8 inches [20cm]
in women it is shorter: 1.5inches [4cm] long RESULT–higher risk for women
Genitalia
intercourse from a pathogen’s viewpoint=moist sexual organs
Sexually Transmitted Disease [STD]
ORGANS: vagina, cervix, uterus
accessible to outside world.
esp. moist in female during menstrual shedding — raw surface
– blood is nutrient rich
-Hormonal changes — microenvironment changes drastically every few days =difficult for normal non-pathogenic bacteria to establish themselves
Countering Risk:
flushing action of urine
uninterrupted flow of menstrual blood
Vagina
normal flora = lactobacilli => acid pH inhibits other bacteria
glycogen (estrogen-stimulated) stored in cells of

vaginal lining (shed during menstration)
Lactobacilli die in post-menopausal women
– increases risk of vaginal infections
– infections of urinary tract
KIDNEY INFECTIONS
Ascending infections most common from peri-anal region
Descending infections — blood born seeding
– kidney
slow circulation: kidney, lung, liver
Inf. Ascending to kidney
nephritis-
site of the major infection is in the urine collecting area

[called the calysis] and

the pelvis of the kidney [its waist]

infection in urine collecting parts rather than in the filtration units

“Honeymoon” cystitis–caused by bacteria common in the perianal region
urinary infections:

90% infections come from a person’s own gut flora
E. coli, enterobacteria
Proteus
Enterobacter
Pseudomonus aeruginasa — antibiotic resistant
A case
19 yr female
previous UTI, amp treated
5d nausea, 4 d pain in left flank, fever, chills, freq. urination
current 38.8 C,

tender costo-vertebral angle [last ribs join vertebrae
Lab work
clean catch urine shows
– >50 wbc/hpf
– 6 rbc
– >100,000 on sheep bc agar [b-hemo] and MacConkey agar

diagnosis:
UTI
pyuria = >10wbc/hpf
hematuria [rbc in urine]
visible bacteria in urine
lots of bac. on culture
Pyelonephritis
kidney inf.
Cystitis
bladder inf.
E. coli virulence factors
adhesion: fimbriae bind epithelial cells

types:

P causes 80% of E. coli pyelonephritis found also on the P blood group antigen
type 1 …….causes cystitis, rbc adh,

mannose blocks
hemolysis
– 55% of the E. coli in pyelonephritis do this
kills not just rbc,kills renal tubular cells = direct kidney damage
aerobactin– a siderophore [ iron chelators] growth advantage
Genital Tract Infections
Neisseria gonorrhoeae —smear from urethral pus,

EM showing pili

map of distribution

Nov 2015 update
G – round bac
naming the disease:

(genital) gono + rrhea (discharge)
ONLY a human reservoir, sexual transmitted disease [STD]
mechanism:
pili attach urethra, vagina, fallopian tubes
evade the immune system by several mechanisms

including shuffle of DNA that codes for pili
opA also
generates antigenic variations
porins [por]
1. PMNs & Mac kill by free radicals, these are inhibited by N. gonorrhea
2. induce local release of TNF-alpha

Pillins:
1. phase variation
2. vary from one copy of the gene to another
mc2 is the most variable
the regions between the mc [microcassettes]are highly homologous & genetic recombination can occur in these regions
– pil S silent pili gene
– pil E expressed pili gene

3. pilC and opa showing slip-stranded synthesis, alternate products or phase variation results

another virulence factor IgA-ase

pdf primer virulence factors

pus, inflammation, swelling
scarring

WOMEN
urethra –> preventing urine flow
cervix:
uterus –>pelvic inflammatory disease
BABIES
eyes & mouth; ophthalmia neonatorum
MEN
prostrate
testes

Syphilis: Treponema pallidum
spirochete
only a HUMAN reservoir, sexually transmitted [STD]

1st stage of syphilis

discrete area on skin or [rarely] urethra
local ulcer — a chancre
epithelial cell attachment, ICAM-1 induced
walls itself in by immune respose
2nd stage of syphilus
skin rashes
3rd stage of syphilus
joint pain & loss of function
nervous system damage
varied presentation
– 1. stroke
– 2. insanity
mothers –> in utero
syphilytic faeces
1. tooth malformation
2. skeletal abnormalities
Chlamydia trachonmatis
– intracellular inf.

The “strawberry cervix” is a coined term for the inflamed cervix that is infected with Trichomonas
fallopian tubes: sterility or ecotopic pregnancy

map Chlamydial disease
5% of people –normal flora –not pathogenic
acute inflammation, pus & pain
characterized by intracellular colonization
damage to urethral lining — path like gonorrhea

Koalas have it worse

Mycoplasma genitalium

estimated that 1% of people between 16 and 44 years old in the US and the UK are infected.

Organism is flask shaped with a narrow neck and a wide base.

Mechanism of Pathogenesis: Protein M–binds to all antibodies

from the CDC site on emerging infectious diseases:

Mycoplasma genitalium

M. genitalium was first identified in the early 1980s (249) and has become recognized as a cause of male urethritis, responsible for approximately 15%–20% of nongonococcal urethritis (NGU) cases, 20%–25% of nonchlamydial NGU, and approximately 30% of persistent or recurrent urethritis (250). In most settings, it is more common than N. gonorrhoeae but less common than C. trachomatis. While M. genitalium is often the sole pathogen detected, coinfection with C. trachomatis is not uncommon in selected areas (251-253).

Although strong and consistent evidence has linked M. genitalium to urethritis in men, it remains unknown whether this infection can cause male infertility or other male anogenital tract disease syndromes. The organism has been detected in men with epididymitis in a limited number of cases, but this has not been extensively investigated. Similarly, M. genitalium has been found in the rectum, but detection is infrequently accompanied by rectal symptoms, and its presence does not appear to cause a syndrome of clinical proctitis.

The pathogenic role of M. genitalium is less definitive in women than it is in men. M. genitalium can be found in the vagina, cervix, and endometrium and, like chlamydial and gonococcal infections, M. genitalium infections in women are commonly asymptomatic. M. genitalium can be detected in 10%–30% of women with clinical cervicitis, and most (253-259) studies have found that this organism is more common among women with cervicitis than those without this syndrome (251,260,261).

M. genitalium is found in the cervix and/or endometrium of women with PID more often than in women without PID (262-271), and endosalpingitis develops in nonhuman primates after inoculation with M. genitalium, suggesting that this organism can cause PID. M. genitalium has been detected in 2%–22% of PID cases (median: 10%) depending on the setting, but the frequency with which M. genitalium-infected women experience PID has been under studied. Although one study in Sweden reported a substantial increase in risk for postabortal PID among women with M. genitalium (262 ), the proportion of M. genitalium-positive women who subsequently experienced PID in two other studies was relatively low (<5%) (272,273), and evidence from serologic studies assessing the association of PID with antibody to M. genitalium is inconsistent. Overall, evidence suggests that M. genitalium can cause PID, but that this occurs less frequently than it does with C. trachomatis (271, 273).

A few seroepidemologic studies have found that women with tubal factor infertility are more likely to have antibodies to M. genitalium than fertile women, suggesting that this organism might cause female infertility. However, more research is needed. On the basis of certain reports, M. genitalium was uncommonly identified in women who experience adverse pregnancy outcomes, but was associated with increased risk for preterm delivery in one U.S. and another Peruvian study (274,275). Data are scarce regarding M. genitalium and ectopic pregnancy.

Diagnostic Considerations

M. genitalium is a slow-growing organism. Culture can take up to 6 months, and only a few laboratories in the world are able to recover clinical isolates. Therefore, NAAT is the preferred method for M. genitalium detection. In research settings, M. genitalium is diagnosed by NAAT testing of urine, urethral, vaginal, and cervical swabs and through endometrial biopsies, typically using in-house PCR or assays intended for research use only. NAAT tests (polymerase chain reaction or transcription mediated amplification) for M. genitalium are available in some large medical centers and commercial laboratories, but there is no diagnostic test for M. genitalium that is cleared by the FDA for use in the United States. In the absence of validated tests, M. genitalium should be suspected in cases of persistent or recurrent urethritis and may be considered in persistent or recurrent cases of cervicitis and PID.

Treatment

M. genitalium lacks a cell wall, and thus antibiotics targeting cell-wall biosynthesis (e.g., beta-lactams including penicillins and cephalosporins) are ineffective against this organism. Given the diagnostic challenges, treatment of most M. genitalium infections will occur in the context of syndromic management for urethritis, cervicitis, and PID.

Urethritis and cervicitis

The 7-day doxycycline regimen recommended for treatment of urethritis is largely ineffective against M. genitalium with a median cure rate of approximately 31% (276-278). The 1-g single dose of azithromycin was significantly more effective against M. genitalium than doxycycline in two randomized urethritis treatment trials (276,277) and is preferred over doxycycline. However, resistance to azithromycin appears to be rapidly emerging. The median cure rate for both men and women is approximately 85%, but was only 40% in the most recent trial (278). Persons with treatment failures after the 1-g azithromycin regimen frequently have macrolide-resistant strains, suggesting that single-dose azithromycin therapy might select for resistance. A longer course of azithromycin (an initial 500-mg dose followed by 250 mg daily for 4 days) might be marginally superior to the single dose regimen (279-281). However, in some settings, approximately 50% of all M. genitalium infections are caused by organisms that are already resistant to azithromycin (282), and persons who do not respond to the 1-g azithromycin regimen generally do not benefit from retreatment with the extended dose regimen.

Moxifloxacin (400 mg daily x 7, 10 or 14 days) has been successfully used to treat M. genitalium in men and women with previous treatment failures, with cure rates of 100% in initial reports (280, 283). However, moxifloxacin has been used in only a few cases, and the drug has not been tested in clinical trials. Although generally considered effective, studies in Japan, Australia, and the United States have reported moxifloxacin treatment failures after the 7 day regimen (284-287).

PID

Recommended PID treatment regimens are based on antibiotics that are not effective against M. genitalium. Therefore, clinicians might consider M. genitalium in cases that do not respond to therapy within 7–10 days. Where validated M. genitalium testing is available, clinicians might test women with PID for M. genitalium. When M. genitalium is detected, a regimen of moxifloxacin 400 mg/day for 14 days has been effective in eradicating the organism (288). Nevertheless, no data have been published that assess the benefits of testing women with PID for M. genitalium, and the importance of directing treatment against this organism is currently unknown.

Follow-up

In settings where validated M. genitalium testing is available, persons with persistent urethritis, cervicitis, or PID accompanied by persistent detection of M. genitalium might be treated with moxifloxacin. However, routine tests-of-cure in asymptomatic persons are not recommended.

Management of Sex Partners

Sex partners should be managed according to guidelines for patients with nongonococcal urethritis (NGU), cervicitis, and PID. In settings with access to validated M. genitalium tests, partner testing and treatment of identified infections might be considered.

Special considerations

HIV infection

Persons who have an M. genitalium infection and HIV infection should receive the same treatment regimen as those who are HIV negative. Treatment of most M. genitalium infections will occur in the context of syndromic management for urethritis, cervicitis, and PID (See Mycoplasma genitalium , Treatment).
Haemophiliis ducreyi — chancroid lesion, G – rod
– exquisitely painful

Viral genital diseases:
Herpes Simplex type 2

life cycle
Papillomaviruses
– HPV16 — genital warts and worse: cervical cancer

PAP smear