Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 23: Infections of the genitourinary system 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. Some organism can move retrograde causing an ascending UTI using pili and adhesins Obstructions in urinary system associated with increased incidence of infections Blue: male Orange: female Prostate enlargement 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/mL indicates 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. 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. Urethritis – in the urethra Cystitis – in the bladder Pyelonephritis – in the kidneys Prostatitis – in the prostate Urethritis and cystitis Pyelonephritis ◦ Dysuria with painful, frequent and urgent urination ◦ Low back pain, abdominal pain, and tenderness over bladder ◦ Urine will be cloudy. ◦ 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. 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. 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 Diseased kidney Normal kidney Kidney stones Nosocomial Trimethoprim: uncomplicated outpatient UTI Cephalexin Amoxycillin: Enterococcus infection Ciprofloxacin, gentamicin, : complicated UTI Primarily Candida infections Descending UTI with yeasts more often in diabetic patients Indwelling catheters Therapy mainly removal of catheter and azoles ◦ Fluconazole 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. Urethritis Vaginitis Cervicitis Lymphadenitis Pelvic Inflammatory Disease (PID) Prostatitis, epididymis Pharyngitis 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 Ulcers (Haemphilus dycrei, Treponema pallidum, Herpes simplex) Vesicles (Herpes simplex ) Warts (Human papillomavirus) Discharge (Neisseria gonrrohoeae, Chlamydia trachomatis) Unpleasant smell (fishy in bacterial vaginosis and foul smelling in trichonomiasis) Pruritus (Candida infections) Pain Fever (PID) Presents as dysuria and/or urethral discharge. Caused by Neisseria gonorrhoeae and Chlamydia trachomatis pus watery Diagnosis typically based on molecular genetic methods (nucleic acid amplification tests) 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 Etiology can vary. May involve mucopurulent vaginal discharge. ◦ Usually caused by Neisseria gonorrhoeae and Chlamydia trachomatis ◦ Inflammation of the cervix ◦ Leukocytes found in discharge. 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. Usually presents with abdominal pain. Neisseria gonorrhoeae Chlamydia trachomatis Scarring can block uterine tubes Chronic abdominal pain Infertility and ectopic pregnancies Three of the most common bacterial sexually transmitted infections causing disease in the genital tract: CDC 2010 data Chlamydia Gonorrhea Syphilis Cases reported 1,307,893 309,341 13774 Rates per 100,000 426.0 100.8 4,5 Originally called non-gonococcal urethritis (NGU) Caused by Chlamydia – a unique form of bacteria ◦ ◦ ◦ ◦ Obligate intracellular Chlamydia trachomatis most common species One of the smallest genomes of all the prokaryotes Life cycle- elementary body (EB) and reticulate body (RB) EB RB 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 Initiates its own uptake Prevents fusion of lysosomes with endosome Blocks inflammatory responses of the cell Diagnosis Treatment ◦ Nuclei acid amplification assay for detection ◦ doxycycline (7 days), azithromycin (single dose), and some fluoroquinolones. Treat partner too. No vaccines available 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 Neisseria has 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 Often asymptomatic (~ 50%) ◦ Newborn conjunctivitis ◦ Transmission rate ~ 20 – 50% 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) 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 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 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 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 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. 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 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 Hutchinson’s teeth Perforated palate Diagnosis Treatment ◦ Darkfield micoscopy ◦ Extensive serological testing with multiple assays primarily looking for antibodies ◦ Penicillin Single dose in early stages Later on several doses ◦ Patients allergic to penicillin are treated with tetracycline, azithromycin, or cephalosporin. Most important viral infection is HIV. Two other prominent viruses: ◦ Herpes simplex type 2 ◦ Human papillomavirus 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 HSV-2 Painful burning recurrent multiple ulcerations ◦ Double stranded DNA, icosahedral enveloped virus ◦ 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 “Unlike love herpes is forever” 48 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% 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 Double stranded DNA, icosahedral nonenveloped virus Cause papillomas (benign tumors) or warts Wide genetic diversity among human papillomaviruses. ◦ Indicated by using numbers to identify different genotypes. ◦ More than 70 genotypes of HPB have been identified. ◦ Some are associated with specific lesions. HPVs identified cause genital hyperplastic epithelial lesions. ◦ Cervical, vulvar, and penile warts HPVs are also associated with premalignant and malignant cervical cancer. In particular HPV 16 causes cervical cancer and cancer of the penis DNA test to detect cancer-causing strains Only treatments are surgical, cytotoxic drugs, and cryotherapy. ◦ Recurrence is common after cessation of treatment. A vaccine has recently become available. Most prominent fungal infection is vaginal candidiasis caused by Candida albicans Infections are normally endogenous. Infections are usually opportunistic ◦ Except in direct mucosal contact e.g. sexual intercourse. ◦ Increased after antibiotic therapy, in pregnancy and diabetes Main symptoms are itching and a thick white cheesy discharge. Therapy topical antifungal creme ◦ Clotrimazole, miconazole, nystatin Hyphae excrete proteases and phospholipases. ◦ Digest epithelial cells. ◦ Facilitate tissue invasion. Trichomonas vaginalis Protozoan Found in semen or urine of male carriers Vaginal infection causes irritation and profuse discharge (foul smelling, frothy) Diagnosis: “strawberry cervix”, microscopic identification of protozoan Therapy: metronidazole PMN Epithelial cell The presence of pathogens or inflammatory cells in urine is an indication of a urinary tract infection. Urinary tract infections that occur in hospitals are usually related to indwelling catheters. Infections of the urethra are called urethritis; infections of the bladder are called cystitis; and infections of the kidneys are referred to as pyelonephritis. Urinary tract infections are seen in women more than men because of the difference in the lengths of the urethra. The majority of bacterial infections seen in the reproductive system are STDs. STDs can be caused by bacteria, viruses, fungi, and protozoan parasites. The most common STDs are non-gonococcal urethritis, which is caused by Chlamydia trachomatis and gonorrhea, caused by Neisseria gonorrhoeae. There are several viral STIs, including those caused by HIV and herpes simplex virus type 2. Humans are the only reservoir for herpes simplex virus type 2, and many people infected with this virus are asymptomatic. The most common form of genital fungal infection is candidiasis. 10:45am – 1:15pm Lecture, Chapter End Self Study Questions 100 Multiple Choice Questions: 2 points each x 100 = 200 points ~65%: Chapters 14-26 ~35%: Chapters 1-13 Please bring Scantron and No. 2 pencil