Urogenital Tract Infections Lecture Notes

Urogenital Tract Infections

Lecture Aims

  • Describe the anatomy of the urogenital tract.
  • Describe innate immunity mechanisms of the urogenital tract.
  • Describe different infections of the urinary tract.
    • Causative organisms, epidemiology, risk factors.
  • Describe a number of genital tract infections including:
    • Causative organisms, epidemiology, risk factors.
    • Bacteria, viruses, fungi, protozoa.

Why People Get Infectious Diseases

  • Factors include physical, social, behavioral, cultural, political, and economic factors.

Urinary Tract Anatomy

  • Upper urinary tract:
    • Ureters and kidneys
    • Ureters drain urine through vesicoureteral valves to the bladder.
  • Lower urinary tract:
    • Bladder and urethra
    • Urine is voided through the urethra via the urethrovesical valve.
    • The urethra is colonized by a range of organisms.

Is Urine Sterile?

  • Historically thought of as sterile.
  • Now known to have its own microbiome based on 16s sequencing data.

Infections of the Urinary Tract

  • Infection can occur at several sites within the urinary tract:
    • Urinary tract infection (UTI) or cystitis: Bladder (common); ascending or descending; complicated or uncomplicated
    • Pyelonephritis: Kidney; acute or chronic
    • Prostatitis (enlarged prostate): Prostate; can cause chronic intermittent UTI in males
    • Urethritis: Urethra; not really a UTI; normally associated with STIs (e.g., gonorrhoea)

Ascending UTI

  • Colonization: Pathogen colonizes the periurethral area and ascends through the urethra upwards towards the bladder.
  • Uroepithelium penetration:
    • Fimbriae allow bladder epithelial cell attachment and penetration.
    • Following penetration, bacteria continue to replicate and may form biofilms.
  • Ascension:
    • Once sufficient bacterial colonization occurs, bacteria may ascend on the ureter towards the kidney.
    • Fimbriae may aid in the ascension process.
    • Bacterial toxins may also play a role by inhibiting peristalsis (reducing the flow of urine).
  • Pyelonephritis: Infection of the renal parenchyma causes an inflammatory response called pyelonephritis.
    • While infection of the renal parenchyma is usually the result of bacterial ascension, it can also occur from hematogenous spread.
  • If the inflammatory cascade continues, tubular obstruction and damage occur, leading to interstitial edema.
  • This may lead to interstitial nephritis, causing acute kidney injury (AKI).

Ascending UTI - Causes

  • Bacteria in urethral opening ascend urethra, leading to bladder infection.
  • Can result from:
    • Fecal soiling or contamination (more common in children and incontinent adults).
    • Incomplete emptying of the bladder:
      • Bacteria in bladder are normally voided in urine or removed by the immune system.
      • Incomplete emptying may leave a "reservoir" of organisms.
    • Urethrovesical reflux: Reflux of urine (from urethra to bladder).
    • Prostatic seeding: Chronic prostate infection; intermittent UTIs in males.
    • Instrumentation: Urethral organisms enter bladder via instruments (catheterization).

UTI - Causes

  • Descending UTI:
    • Pathogen travels via blood (hematogenous spread) or lymph from a source elsewhere in the body.
    • Organisms enter the bladder via the kidney.
    • Main organisms:
      • S. aureus
      • Candida albicans
      • Mycobacterium tuberculosis
      • Uncommon.

UTI - Risk Factors

  • Uncomplicated UTI:
    • No urinary tract defects, renal impairment, or comorbidities.
    • Afebrile, non-pregnant, immunocompetent.
    • Risk factors:
      • Female gender (comparatively short urethra increases risk).
      • Sexual activity increases risk.
      • Menopause (linked to decline in estrogen).
  • Complicated UTI:
    • Patients not described above.
    • Risk factors:
      • Altered immune status: diabetes or pregnancy.
      • Calculi within the urinary tract.
      • Urinary tract abnormality (congenital or acquired).
      • Urinary catheterization.

Organisms Responsible for UTI

  • Uncomplicated UTI:
    • UPEC (Uropathogenic E. coli): 75 \%
    • K. pneumoniae: 6 \%
    • S. saprophyticus: 6 \%
    • Enterococcus spp.: 3 \%
    • GBS: 3 \%
    • P. mirabilis: 2 \%
    • P. aeruginosa: 1 \%
    • S. aureus: 1 \%
    • Risk factors:
      • Female gender
      • Older age
      • Younger age
  • Complicated UTI:
    • UPEC: 65 \%
    • K. pneumoniae: 11 \%
    • Enterococcus spp.: 7 \%
    • Candida spp.: 8 \%
    • P. aeruginosa: 2 \%
    • P. mirabilis: 2 \%
    • S. aureus: 2 \%
    • GBS: 1 \%
    • Risk factors:
      • Indwelling catheters
      • Immunosuppression
      • Urinary tract abnormalities
      • Antibiotic exposure

Genital Tract Infections

  • Affect any gender.
  • May or may not be sexually transmitted.
    • Sexually transmitted infection (STI) includes both:
      • Asymptomatic infection
      • Symptomatic disease
  • Female genital tract microbiome is protective:
    • Dominated by Lactobacillus species.
      • Create mildly acidic environment (pH < 4.5).
      • Produce hydrogen peroxide, lactic acid, bacteriocins.
      • Activates complement.

Overview of Genital Tract Infections - Bacterial

  • Syphilis:
    • Organism: Treponema pallidum
  • Gonorrhoea:
    • Organism: Neisseria gonorrhoeae
  • Chlamydia:
    • Organism: Chlamydia trachomatis
  • Bacterial vaginosis:
    • Organisms: Gardnerella vaginalis, anaerobes
  • MG:
    • Organism: Mycoplasma genitalum
  • Donovanosis:
    • Organism: Klebsiella granulomatis
  • Chancroid:
    • Organism: Haemophilus ducreyi
  • Puerpural sepsis:
    • Organisms: Various (e.g., Streptococcus pyogenes)
  • Septic abortion:
    • Organisms: Various (e.g., Clostridium)

Overview of Genital Tract Infections - Viral, Fungal, Protozoal

  • Viral
    • Genital herpes:
      • Organism: Herpes simplex virus
    • Human papilloma virus:
      • Organism: Human papilloma virus
  • Fungal
    • Candidiasis/Thrush:
      • Organism: Candida spp.
  • Protozoal
    • Trichomoniasis:
      • Organism: Trichomonas vaginalis
  • HIV is sexually transmitted, but does not actually cause a genital tract infection (covered in a later lecture).

Burden of Disease (USA)

  • 2018: in USA estimated 26 million new STIs.
  • Almost 16 billion in costs.
  • Syphilis in newborns still increasing compared to previous years.
  • Not all STIs are reportable – many are under-reported.

Gonorrhoea

  • Infection caused by Neisseria gonorrhoeae
    • Gram-negative; fastidious.
    • Obligate human pathogen.
    • Facultative intracellular pathogen.
  • Transmitted sexually or during childbirth (vertical transmission).
    • Gonococcal ophthalmia an issue in developing countries.
  • Organism infects mucous membranes
    • Range of symptoms or asymptomatic.
    • May clinically resemble Chlamydia infection.
  • Diagnosed by nucleic acid amplification test (NAAT) +/- culture.
  • Infection still relatively common due to two important factors:
    • Large reservoir of asymptomatic carriers, particularly females.
    • Increasing (and alarming) resistance to antibiotics.

Gonorrhoea Symptoms

  • Males: asymptomatic or mild symptoms
    • Most common symptom is acute urethritis.
    • Second common symptom is urethral discharge / pus.
    • Symptoms appear one week after infection.
    • If untreated: epididymitis, infertility (rare).
  • Females: most remain asymptomatic
    • Primary site of infection is the endocervix.
    • If untreated: may spread to uterus or fallopian tubes.
      • Leads to pelvic inflammatory disease.
      • Complication: scarring of fallopian tubes; infertility.
  • Rectal and oropharyngeal gonorrhoea can occur
    • Most common in men who have sex with men (MSM).

Chlamydia

  • Infection caused by Chlamydia trachomatis
    • Gram negative-like, coccoid bacteria.
    • Obligately intracellular (can't synthesize ATP).
  • Infection also known as non-gonococcal urethritis (NGU) or non-specific urethritis (NSU).
  • Most common STI in many countries.
    • In Australia in 2021:
      • 86,916 chlamydia notifications compared to
      • 26,577 gonorrhoea notifications
      • Most cases remain undiagnosed and untreated.
  • Diagnosed by NAAT or antigen testing.

Chlamydia Symptoms

  • Males: asymptomatic (\sim 50 \%. or mild symptoms
    • Pain on urination, discharge
  • Females: asymptomatic (\sim 70 \%.)
    • Often NGU is untreated
    • Chronic infection may lead to
      • Pelvic inflammatory disease
      • Scarring and infertility
      • Increased risk of ectopic pregnancy
    • May increase risk of cervical cancer
      • Possibly in association with human papillomavirus
  • Vertical transmission:
    • Can cause pneumonia in infants born to infected mothers

Syphilis

  • Infection caused by Treponema pallidum
    • Spirochaete (bacterium)
  • Transmitted sexually or vertically
    • Sexually transmitted only ~20 \%. of the time (inefficient)
  • Organism historically could not be cultured (until 2018)
    • Diagnosis is largely by serology
    • Culture now possible but growth is extremely slow
  • Three disease stages: primary, secondary, latent, tertiary

Syphilis - Stages

  • Primary stage syphilis
    • Initial sign is small, hard-based chancre (sore)
      • Painless ulcer
      • Appears at infection site
      • Lesions are highly infectious
      • Lesions disappear after two weeks
    • Bacteria enter bloodstream and lymphatic system:
      • Distributes organisms throughout body (systemic infection)
  • Secondary stage syphilis
    • Skin rashes, caused by circulating immune complexes
      • Rash also present in mucous membranes of mouth, throat, cervix
      • Lesions also present, patient highly infectious
  • Latent syphilis
    • No symptoms, stage may last for years
  • Tertiary stage syphilis
    • Occurs in 15-30 \%. of untreated people
    • Most symptoms due to immune reaction to surviving spirochaetes
      • Cell mediated immunity
    • Neurosyphilis may occur
      • Occurs in 10 \%. patients if untreated
      • Personality changes, dementia (paresis), seizures, paralysis, loss of sight, hearing

Syphilis - Congenital & Outbreaks

  • Congenital syphilis
    • Organism transmitted across placenta
    • Range of outcomes depending on how long mother has had syphilis
      • Pregnancy in primary or secondary stage likely to result in stillbirth
    • Still a major global issue
  • Ongoing syphilis outbreak in Australia
    • Started in 2011 in QLD
    • 2013 started in NT, 2014 WA, 2016 SA
    • 2016-2022: 69 cases of congenital syphilis
      • 18 resulted in death of the infant

Bacterial Vaginosis

  • Most common cause of vaginitis symptoms
    • Vaginitis: inflammation, itching, pain
  • Symptoms:
    • Loose, fishy-odour discharge
    • Irritation
  • Not sexually transmitted
  • Characterized by:
    • Substantial depletion of commensal Lactobacillus population
    • Increased mix of anaerobic bacteria
      • Commensal bacteria that are normally present at low levels
      • Includes Gardnerella vaginalis
        • Gram-variable coccobacillus

BV Diagnosis

  • Diagnosis is by microscopy
    • Wet mount: look for characteristic clue cells
      • Epithelial cells studded with tiny cocco-bacilli
    • Routine culture not valuable
  • Other diagnostic features
    • High vaginal pH (>4.5)
    • Positive Amines test
      • In contrast with Candida infection

Viral Infections of the Urogenital Tract

  • Genital herpes
    • Usually caused by Herpes simplex virus type 2 (HSV-2)
      • HSV-1 (usually causes cold sores or blisters) can also cause genital herpes
    • Symptoms:
      • Burning sensation, pain on urination
      • Lesions:
        • Appear after incubation period of 1 week
        • Fluid within vesicles contain virions:
          • Highly infectious
          • Virus is transmissible
        • Heal after about two weeks
    • Disease is also transmitted when no lesions or symptoms are apparent
      • Virus is shed through mucosa

Genital Herpes - Latency

  • Virus enters lifelong latent state in nerve cells
    • Like cold sores (HSV1) and chickenpox virus (Varicella; herpesvirus 3)
  • Recurs in >80 \%. of HSV2 cases
    • Recurs more in men than women
    • Various triggers such as stress, illness (with fever), scratching, menstruation
  • Neonatal herpes: virus can cross placenta
    • May cause abortion, developmental delay, deafness
    • Worse if mother acquires herpes (primary infection) during pregnancy
  • No cure: use suppression or management
    • Acyclovir alleviates symptoms of primary outbreak

Genital Warts

  • Caused by papillomaviruses
  • More than 60 serotypes of HPV
    • Specific types linked to genital warts (e.g. HPV16)
  • Symptoms:
    • Infection is usually asymptomatic; no symptoms in 9/10 cases
    • Symptoms (females and males) can include:
      • Warts/bumps on genitals, groin, anus
      • Genital pain, itching, discomfort
    • Incubation period is a few weeks to months
  • Diagnosed by:
    • Examination: appearance, biopsy or Pap test
    • DNA test: detects DNA from some of the more likely cancer-causing HPV

Genital Warts - Treatment and Prevention

  • Treat lesions topically with cryotherapy or gels
    • E.g. Imiquimod gel stimulates body to produce interferon
  • But link to cervical cancer is the greatest danger
    • Women: cervical cancer
    • Men: penile cancer
  • Vaccine (Gardasil) against strains associated with cancer
    • “Gardasil 9”, 2-3 doses
      • HPV types 6, 11, 16, 18, 31, 33, 45, 52 and 58
    • Cervarix
      • HPV types 16, 18

Fungal Infections

  • Candidiasis or Thrush
    • Second most common cause of vaginitis symptoms
      • First is bacterial vaginosis
    • Caused mainly by C. albicans but also other Candida species
    • Symptoms in females:
      • Pruritus (itching)
      • Discharge: may be slight but usually thick and ‘curd like’
    • Symptoms in males:
      • Balanitis: inflammation of the head of the penis
      • Pruritis, inflammation, swelling
    • Not sexually transmitted
      • Evidence does not support treating partner with antifungals
    • Candida: pH normal (4.5), discharge thick, Amines neg
    • BV: pH high (>4.5), discharge thin, Amines pos

Candidiasis - Risk Factors & Diagnosis

  • Risk factors for infection are:
    • Recent antibiotic use (disrupts bacterial microbiome)
    • High oestrogen levels
      • E.g. pregnancy, oral contraceptives, pre-menstrual
    • Uncontrolled diabetes
    • Immune system dysfunction
  • 20-30 \%. of women carry Candida in the genital tract
    • Usually in low numbers, asymptomatic
  • Diagnosis
    • Microscopy: examine vaginal swab by wet mount
    • Culture

Protozoan Diseases

  • Trichomoniasis
    • Caused by anaerobic protozoan Trichomonas vaginalis
    • Asymptomatic in ~50 \%. of women and ~80 \%. of men
    • Symptoms in females:
      • Discharge copious “yellow-green frothy”
      • Vaginal soreness
      • Pain on urination
    • Diagnosis
      • Wet mount: positive ~70 \%. of cases
      • Culture
      • Vaginal pH usually elevated