MICR 201 Microbiology for Health Related Sciences

1. MICR 201 Microbiology for Health Related Sciences Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 23: Infections of the genitourinary system

2. Why is this chapter important? • The urogenital tract is directly exposed to the outer environment and many pathogens use this portal of entry. • As a health care professional you will see many infections here. • Major complications of STDs are infertility and ectopic pregnancies. • STDs can infect the fetus and the newborn.

3. Map for chapter 23

4. Anatomy of the urinary system

5. Urinary flow Some organism can move retrograde causing an ascending UTI using pili and adhesins Obstructions in urinary system associated with increased incidence of infections

6. Gender distribution of UTI Blue: male Orange: female Prostate enlargement

7. General information urinary tract infections (UTI) • Urine is essentially sterile. • When passing through urethral opening urine becomes contaminated with normal microbiota and some epithelial cells. • Refrigerate urine after collection! • Presence of one type of microbe at > 105 CFU/mLindicates UTI. • Presence inflammatory cells and erythrocytes indicates UTI. • UTIs are typically caused by bacteria, less often yeasts. • UTIs are more common in women due to the ureter anatomy, closeness of the anus and contaminating fecal normal microbiota.

8. NosocomialUTIs • UTIs are serious problems in hospitals. • Usually associated with indwelling catheters • Bacteria or yeast ascend the outside of the catheter and reach the bladder. • Complicated by high antibiotic resistance among nosocomial strains.

9. Types of UTIs • Urethritis – in the urethra • Cystitis – in the bladder • Pyelonephritis – in the kidneys • Prostatitis – in the prostate

10. Key symptoms of UTIs • Prostatitis • Pain in the lower back, perirectal area, and testicles • Can be high fever, chills, and symptoms similar to bacterial cystitis • Inflammatory swelling can lead to obstruction of the urethra. • Retention of urine can cause abscess formation, epididymitis, and seminal vesiculitis. • Urethritis and cystitis • Dysuria with painful, frequent and urgent urination • Low back pain, abdominal pain, and tenderness over bladder • Urine will be cloudy. • Pyelonephritis • Pain in the flanks • Fever above 38.3˚C • Severe cases can cause septic shock. • Usually no damage to kidney function • Can further ascend and develop into sepsis: iv antibiotics.

11. UTI diagnostic • Detection of nitrate and leukocytes in urine • > 10 leukocytes/mL urine • Bacteria urine culture with > 105 CFU (colony forming unit)/mL in clean catch urine

12. Pyelonephritis Diseased kidney Normal kidney

13. Most frequent bacterial causes of UTI Kidney stones Nosocomial

14. Bacterial UTI therapy • Trimethoprim: uncomplicated outpatient UTI • Cephalexin • Amoxycillin: Enterococcus infection • Ciprofloxacin, gentamicin, : complicated UTI

15. Fungal infections of the urinary tract • Primarily Candidainfections • Descending UTI with yeasts more often in diabetic patients • Indwelling catheters • Therapy mainly removal of catheter and azoles • Fluconazole

16. Bacterial infections of the reproductive system • Major infections in the reproductive system are sexually transmitted. • Sexual promiscuity more likely to contract STD • Concurrent STDs increase risk for HIV infection • Many infected individuals do not seek medical help, because asymptomatic • Infertility and ectopic pregnancies are major complications of even asymptomatic STDs. • The term sexually transmitted infections (STI) includes infections that are transmitted via intercourse but manifest elsewhere.

17. Anatomy of the reproductive system

18. Bacterial infections of the reproductive system • Urethritis • Vaginitis • Cervicitis • Lymphadenitis • Pelvic Inflammatory Disease (PID) • Prostatitis, epididymis • Pharyngitis

19. Bacterial infections of the reproductive system • STDs have been around for hundreds of years. • Affect all populations and social strata • Most common pathogens: • Chlamydia trachomatis • Neisseria gonorrhoeae • Also occurring • Papilloma virus, herpes simplex, and HIV virus • Less frequent but still around • Treponema pallidum • Sexually transmitted infections (STI) transmitted via intercourse but the disease manifests elsewhere • HIV, Hepatitis B

20. Typical Manifestations of STDs • Ulcers (Haemphilusdycrei, Treponemapallidum, Herpes simplex) • Vesicles (Herpes simplex ) • Warts (Human papillomavirus) • Discharge (Neisseriagonrrohoeae, Chlamydia trachomatis) • Unpleasant smell (fishy in bacterial vaginosis and foul smelling in trichonomiasis) • Pruritus (Candida infections) • Pain • Fever (PID)

21. Genital ulcers

22. Sexually transmitted urethritis • Presents as dysuria and/or urethral discharge. • Caused by Neisseria gonorrhoeaeandChlamydia trachomatis • Diagnosis typically based on molecular genetic methods (nucleic acid amplification tests) pus watery

23. Vaginitis • Bacterial is the most common type of vaginitis. • Associated with overgrowth of vaginal anaerobic flora • Can be homogeneous yellowish discharge • Stays adhered to vaginal wall • Clue cells found in discharge covered with bacteria. • Also caused by Trichomonas vaginalis • Abundant foul smelling frothy discharge

24. Cervicitis • Etiology can vary. • Usually caused by Neisseria gonorrhoeaeandChlamydia trachomatis • May involve mucopurulent vaginal discharge. • Inflammation of the cervix • Leukocytes found in discharge.

25. Lymphadenitis • Inflammation of lymph nodes. • Seen in several sexually transmitted infections • Especially in lymphogranuloma venereum • Caused by a certain serotypes of Chlamydia trachomatis • Usually begins as a small genital ulcer that is frequently unnoticed. • First evidence is usually a tender swollen lymph node in groin.

26. Pelvic inflammatory disease (PID) • Usually presents with abdominal pain. • Neisseria gonorrhoeae • Chlamydia trachomatis • Scarring can block uterine tubes • Chronic abdominal pain • Infertility and ectopic pregnancies

27. Common STDs • Three of the most common bacterial sexually transmitted infections causing disease in the genital tract:

28. Chlamydia trachomatisurethritis and cervicitis • Originally called non-gonococcal urethritis (NGU) • Caused by Chlamydia– a unique form of bacteria • Obligate intracellular • Chlamydia trachomatismost common species • One of the smallest genomes of all the prokaryotes • Life cycle- elementary body (EB) and reticulate body (RB) EB RB

29. Life cylce of Chlamydia • Unique replication cycle involving two forms • Small, hardy, infectious form • Elementary body (EB) • Larger, more fragile, replicative form • Reticulate body (RB) • Full cycle takes about 48 - 72h

30. Pathogenic factors of Chlamydia trachomatis • Initiates its own uptake • Prevents fusion of lysosomes with endosome • Blocks inflammatory responses of the cell

31. Chlamydia trachomatis diagnosisandtreatment • Diagnosis • Nuclei acid amplification assay for detection • Treatment • doxycycline (7 days), azithromycin (single dose), and some fluoroquinolones. • Treat partner too. • No vaccines available

32. Neisseriagonorrhoeae: Gonorrhea • Gram-negative diplococcus • Fastidious • Requires transport medium, avoid cooling • Numerous pili which are essential pathogenicity factors • High antigenic variability • No vaccine • Typically causes urethritis and cervicitis • Adheres with pili to epithelial cells, transcytoses, and sets an subepithelial infection • Attracts large numbers of neutrophils Pili

33. Neisseriagonorrhoeae: Gonorrhea • Neisseriahas a variety of mechanisms to evade neutrophil killing • Blocks the deposition of C3 and shuts down complement • Surface proteins bind to antibodies and inhibit their bacteriocidal response. • Produces excess catalase and neutralizes phagocytic oxidative killing • May spread to nearby genital tissue • May spread systemically and cause joint infections (knee) • Can cause PID • Mothers can infect newborns during birth • Newborn conjunctivitis • Often asymptomatic (~ 50%) • Transmission rate ~ 20 – 50%

34. Gonococcal arthritis

35. Diagnosis and treatment of gonorrhea • Diagnosis • Nucleic acid amplification assay and culture on chocolate agar for diagnosis • Treatment • Many patients are co-infected with Chlamydia trachomatis, hence dual therapy. • To prevent that patients stop treatment early because of clinical improvement give single doses • Cephalosporine (ceftriaxone, i.m. ) PLUS azithromycin (orally)

36. Syphilis • Earliest recorded sexually transmitted infection. • First described in 1600s • “The great imitator” • Caused by Treponema pallidum • Slim spirochete • Slow rotating motility • Cannot be grown on bacterial media • Can be grown in mammalian cell cultures • Exclusive human pathogen

37. Syphilis: Pathogenesis • Key virulence factors • Can penetrate tissue easily • Evade immune response by binging off complement factors and immunoglobulins • Several clinically defined stages: • Primary • Secondary • Latent • Tertiary • Congenital

38. Primary syphilis • Painless hard ulcer called chancre • Rubbery painless lymph node swelling • Appears 1 -3 weeks after infection • Highly infectious • Can be hidden • Self healing within several weeks • Treponema have already spread

39. Secondary Syphilis • Also known as disseminated syphilis • Develops 2-8 weeks after the chancre disappears. • Characterized by: • Generalized lymphadenopathy • Symmetric mucocutaneous maculopapular rash • On the face, trunk, and extremities including the palms of the hands and soles of feet • Infectious • Mucosal changes • Comdylomata lata • Also fever, malaise, and lymphadenitis. • Self healing

40. Latent syphilis • Can last for years • No clinical signs or symptoms but infection is continuing. • Serological tests are positive • Latency can be interrupted by less severe bouts of secondary syphilis. • Sexual transmission only possible during relapses. • Transmission from mother to fetus is possible throughout latent period.

41. Tertiary syphilis • Occurs in about 1/3 of untreated patients. • Takes years to develop. • Can be 5 years after the initial infection • Usually 15-20 years • Characterized by appearance of Gummas • Localized granulomatous lesions in skin, bones, joints, and internal organs • Clinical findings depend on where the infection spreads. • Cardiovascular system – cardiovascular syphilis • Nervous system – neurosyphilis

42. Congenital syphilis • Passed from mother to fetus during any stage but more frequently during primary and secondary syphilis • Can have devastating consequences • Miscarriage and still birth • Neonatal death and infant disorders such as deafness, neurologic impairment, and bone deformities • Anemia, thrombocytopenia, and liver failure

43. Congenital syphilis Hutchinson’s teeth Perforated palate

44. Diagnosis and treatment of syphiis • Diagnosis • Darkfield micoscopy • Extensive serological testing with multiple assays primarily looking for antibodies • Treatment • Penicillin • Single dose in early stages • Later on several doses • Patients allergic to penicillin are treated with tetracycline, azithromycin, or cephalosporin.

45. Viral infections of the genitourinary system • Most important viral infection is HIV. • Two other prominent viruses: • Herpes simplex type 2 • Human papillomavirus

46. Herpes simplex virus • Two distinct epidemiological and antigenic types of herpes simplex virus. • HSV-1 – above-the-waist • Causes cold sores • HSV-2 – below-the-waist • Causes genital herpes • Transmission is through direct contact with infected secretions. • Antibodies against HSV-1 found in large portion of the population. • Antibodies against HSV-2 are rarely seen before puberty. • Both viruses are able to undergo latent stage hiding in neurons • When exacerbate painful liquid filled vesicles that turn into ulcerations

47. Genital herpes • HSV-2 • Double stranded DNA, icosahedral enveloped virus • Painful burning recurrent multiple ulcerations • Triggered by UV, fever, stress. • 4 – 5 episodes per year • Liquid is infectious, contains many viruses • Latency in sacral ganglion • Primary infection often undetected • 90% of HSV2-antibody positive patients cannot recollect an acute infection

48. Genital herpes: recurrent, very painful vesicles and ulcerations “Unlike love herpes is forever”

49. HSV-2:Neonatal herpes infection • Infections in newborn infants results from transmission during delivery. • Most cases associated with maternal primary infection at or near the time of delivery. • Intense viral exposure to infant. • Very serious infection • Mortality rate of approximately 60%

50. HSV-2: Treatment • Most effective and most commonly used is the nucleoside analog acyclovir. • Decreases the duration of a primary infection • Can also suppress recurrent infections • Foscarnet is effective for resistant HSV virions. • Can be prevented by avoiding contact with infected individuals expressing lesions • Important to remember virus still being shed in asymptomatic individuals • Can also be transmitted via saliva