Infectious Diseases Affecting the Urinary and Reproductive Systems

Urinary and Reproductive Systems: Infectious Diseases

Urinary Tract Defenses

  • Physical Flushing: Urine flow helps to remove microbes from the urinary tract.

  • Low pH: The acidity of urine inhibits the growth of many bacteria.

  • High Urea Content: Urea is toxic to some bacteria.

  • Antimicrobial Proteins:

    • Defensins: Antimicrobial peptides that disrupt bacterial membranes.

    • Secretory IgA: An antibody that neutralizes pathogens.

    • Small amounts of IgG and IgM: Antibodies that provide immune protection.

  • Prostate Secretion (Males): Contains zinc, which has antimicrobial properties.

  • Epithelial Cell Shedding: Removes attached bacteria.

  • Mucus Secretions and Ciliary Clearance: Trap and remove pathogens.

Indigenous Microbiota of the Urinary Tract

  • Kidneys, Ureters, and Bladder: Normally sterile.

  • Urethra: Often colonized near the terminus, with approximately 10-1000 cells/mL of urine.

  • Midstream Samples: Important for accurate infection diagnosis by avoiding normal microbiota contamination.

  • Transmission: Microbes can be transmitted to partners during sexual intercourse, especially from male to female.

Reproductive System Defenses

  • Males

    • Prostate Secretion: Contains zinc.

    • Localized Immune Responses: Antibodies along the urethra and in seminal fluid.

  • Females

    • Acidic vaginal pH encourages the growth of Lactobacillus which in turn lowers the pH.

    • Mucosa of the vagina and cervix.

    • Mucociliary Escalator: Transports mucus and trapped pathogens.

    • Antimicrobial Chemicals in Mucus:

      • Lysozyme: Antibacterial enzyme (Less friendly to sperm).

      • Lactoferrin: Iron-binding protein with antibacterial properties (High at day 7, low at day 21 of the menstrual cycle).

    • Antibacterial Peptides:

      • Defensins

      • IgA

      • IgG

  • Note: Lactoferrin, Definsins, IgA and IgG fluctuate oppositely during the menstrual cycle

Indigenous Microbiota of the Reproductive System

  • Males

    • Semen: Sterile.

    • Urethra: Accumulates indigenous microbiota as it travels along. The end of the urethra is naturally colonized.

  • Females

    • Acidic pH in vagina: Encourages growth of Lactobacillus, which lowers the pH.

    • Vulva and Cervix: Also colonized by various microbes.

Common Sexually Transmitted Diseases (STDs)

  • Chlamydia

  • Gonorrhea

  • Syphilis

  • Herpes Simplex Viruses

  • Human Papilloma Viruses

  • Trichomoniasis

  • Human Immunodeficiency Virus

STD Trends

  • Chlamydia and Gonorrhea Rates Among Females Aged 15-54

    • Chlamydia rates are significantly higher than gonorrhea rates across all age groups.
      *Rate comparisons for Chlamydia and gonnorehea from the United Kingdom from 2009 to 2011

Chlamydia trachomatis

  • Characteristics

    • Ovoid-shaped with cellular and outer membranes, but no peptidoglycan.

    • Size: 0.35μm0.35 \,\mu m

    • Obligate intracellular pathogen.

    • Very small chromosome.

    • Unique biphasic life cycle.

Developmental Cycle of C. trachomatis

  • Elementary Body (EB): The infectious form that attaches to epithelial cells.

  • Reticulate Body (RB): The replicative form that multiplies within the host cell.

  • Process: EB attaches to the cell, transforms into RB, replicates, and then transforms back into EB to infect other cells.

  • Timescale: The cycle takes approximately 48-72 hours.

Chlamydia trachomatis

  • Epidemiology

    • Reservoir: Humans.

    • Transmission: Vertically (mother to child) or during sexual intercourse.

    • Chlamydial pharyngitis or proctitis may result from oral or anal intercourse.

  • Pathogenesis

    • Incubation period: 1-3 weeks.

    • Complications:

      • In females, 40% of untreated infections progress to Pelvic Inflammatory Disease (PID), including salpingitis, leading to infertility due to scarring, and ectopic pregnancies.

      • A leading cause of first-trimester-related deaths in the U.S.

      • In males, inflammation of the epididymis may result in sterility.

      • Neonatal conjunctivitis in newborns.

  • Symptoms

    • Asymptomatic in 80-90% of infected individuals.

    • Related to the inflammatory response of the immune system.

    • Discharge (difficult to distinguish in females).

    • Inflammation of the cervix.

    • Tingling in the penis.

    • Painful urination.

  • Treatment

    • 95% cure rate with one dose of azithromycin or seven days of doxycycline.

    • Pregnant women cannot use doxycycline due to its effect on bone development in infants.

    • Neonatal conjunctivitis can be treated with oral antibiotics.

  • Prevention

    • Self-screening.

    • Safe sex practices.

    • Treatment of pregnant mothers before delivery.

Treponema pallidum

  • Characteristics

    • Spirochete with a flexible cell wall.

    • Motility: Moves using endoflagella (axial filaments) that rotate, causing the spirochete to corkscrew and move forward.

    • Structure: Outer membrane, cell membrane, and axial filaments.

Syphilis

  • Epidemiology

    • Reservoir: Humans.

    • Approximately 44,000 cases annually (85% males) in the U.S.

    • 12 million cases worldwide.

  • Pathogenesis

    • Penetrates the epithelial surface of mucosal membranes of genitalia, wounds, hair follicles, or abrasions.

    • Penetrates the placental barrier after the third or fourth month of pregnancy, causing congenital syphilis.

    • Congenital Syphilis: Hutchinson’s triad includes deafness, impaired vision, and notched, peg-shaped teeth.

Stages of Syphilis

  • Primary

    • Chancre (painless ulcer) lasting 10-90 days.

    • Enlarged lymph nodes in the groin.

  • Secondary

    • Occurs in 30% of untreated primary cases.

    • Skin rash on palms and soles (3-12 weeks).

    • Flu-like symptoms.

    • Hair and weight loss.

    • May last for years or resolve without treatment.

  • Latent

    • Untreated during primary and secondary stages.

    • Non-contagious.

    • Asymptomatic.

    • Lasts 1-30 years.

  • Tertiary

    • Occurs in 40% of latent cases.

    • Lasts from 1 year to decades.

    • Causes severe damage to the body and pronounced symptoms, often resulting in death.

    • Symptoms include blindness, paralysis, numbness, uncoordinated muscle movements, heart problems, neurological problems, dementia, other mental disorders, and lesions on various parts of the body.

Syphilis

  • Treatment

    • Detection of infection:

      • Using fluorescence or dark-field microscopy from chancre sample.

      • Serological exams for antibodies in the serum.

    • Identification and treatment of sexual contacts of patients.

    • Penicillin: Usually a single dose for primary and secondary syphilis.

  • Prevention

    • Safe sex practices.

    • Treatment of pregnant mothers.

Trichomonas vaginalis

  • Characteristics

    • Anaerobic eukaryotic parasite.

    • Only has the trophozoite stage.

    • Most common protozoan infection in humans in industrialized countries.

Trichomonas vaginalis

  • Epidemiology

    • Reservoir: Humans.

    • 160 million cases per year worldwide.

  • Pathogenesis

    • Transmitted sexually, most commonly through vaginal intercourse.

    • Specializes in attachment to vaginal epithelial cells.

    • Sensitive to time, temperature, and pH.

    • Attachment damages epithelial cells causing inflammation, and RBCs released will also lyse.

    • Predisposes tissue to other infections, making complications common.

  • Symptoms

    • Women:

      • Strawberry cervix (punctate hemorrhages).

      • Vaginalis characterized by frothy, green secretions with a bad odor.

      • Itching around the vagina or on the thighs.

    • Men (varies):

      • Urethritis.

      • Small gray/white vesicles on the exterior.

    • Infected individuals may be asymptomatic and still infectious.

  • Complications

    • Pregnancy: Pre-term delivery, low birth weight, and increased mortality.

    • Increased risk for HIV (men and women).

    • Cervical cancer.

  • Treatment

    • Single dose of metronidazole or tinidazole.

    • Increasing to 500mg metronidazole twice daily for seven days if initial treatment unsuccessful.

    • Contact and treatment of previous sexual partners, even if asymptomatic.

  • Prevention

    • Safe sex practices.

      • Parasite can infect areas not covered by a condom, so not 100% effective.

    • Treatment of pregnant mother with a single dose of metronidazole (NOT tinidazole).

Human Immunodeficiency Virus (HIV)

  • Characteristics

    • Retroviridae family.

    • Two copies of ss +RNA packed with reverse transcriptase enzymes.

    • Icosahedral capsid with envelope.

    • Two spikes: gp120 (attachment) and gp41 (fusion with host plasma membrane).

    • Two types:

    • HIV-1

    • HIV-2 (Develops slowly, Less infectious during early stages.)

  • History

    • Most likely jumped from chimpanzees to humans via bush meat in west-central Africa.

    • 1981: First U.S. report of a syndrome involving opportunistic infections related to immune deficiency.

    • Blood samples taken in 1959 from a man from the Congo showed that he was infected by HIV.

    • Scientists suspect that the disease actually emerged in the 1930s.

Transmission of HIV

  • Does not occur through sharing utensils, plates, or cups.

  • Saliva has natural inhibitors of the virus, though there is one documented case of transmission through deep kissing (French kissing).

  • Most Common Modes of Transmission:

    • Male-male sexual contact.

    • Male-female sexual contact.

  • Blood Transmission:

    • Historically a major problem. Now, all donations are tested.

    • Can be prevented with antiviral drugs early in pregnancy.

    • Associated with helper T-cells, macrophages, and dendritic cells.

  • Sexual transmission: CD4 T-cells associated with the mucosa of the genital tract.

Pathogenesis

  • The CD4 surface antigen allows communication with antigen-presenting cells.

  • CD4 (helper) T-cells are targeted by HIV.

Stages of AIDS

  • Stage 1: Acute

    • Incubation: 1-3 months.

    • Symptoms: Asymptomatic to acute flu-like illness (~3 days).

    • Seroconversion occurs (anti-HIV antibodies detectable in the blood).

    • Virus count in the blood is very high, and individuals are very infectious.

  • Stage II: Asymptomatic

    • Asymptomatic.

    • T-cell count is high.

    • May last 2-12 years.

    • Can transfer the virus to other individuals during this time.

  • Stage III: Chronic Disease

    • The number of viruses rises rapidly.

    • Increased antibody production against the virus.

    • T-cell count begins to plummet.

    • Antibody production decreases.

    • Symptoms include fatigue, weight loss, weakness, and opportunistic infections.

  • Stage IV: Full-blown AIDS

    • Persistent opportunistic infections.

    • Extreme weight loss and weakness.

    • T-cell count VERY low.

    • Extreme immunocompromised state causes death from usually harmless microorganisms.

    • HIV also causes a rare form of skin cancer called Kaposi’s sarcoma and produces a substance that may cause deterioration of brain function.

Treatment

  • Antiretroviral Therapy (ART)

    • Ideally, a combination of three different drugs.

    • Expensive.

    • Active treatment campaigns in many African nations (charity or governments).

  • In developed countries, the most common causes of AIDS-related deaths are now lifestyle-related, such as suicide, drug overdose, and liver disease.

Preventing the Spread of AIDS

  • Screening donated blood, tissue, and organs.

  • Administration of AZT to pregnant women prevents transmission of the virus to the fetus.

    • Delivering the baby via cesarean section lowers the risk of transmission through blood contact during birth.

  • Providing clean needles to drug addicts in big cities has helped reduce the spread of the virus among these populations.

  • Circumcision of males significantly reduces the risk of infection.

  • Safe sex education and practices:

    • Abstinence.

    • Limit the number of partners.

    • Use condoms (only 80% effective!!!!).