Lecture_23_MICHUM2_lectureppt_ch23_V2.pptx

CHAPTER 23 Infections of the Urinary and Reproductive Tracts Copyright © 2021 W. W. Norton & Company Infections of the Urinary and Reproductive Tracts Chapter Objectives  Describe similarities and differences between sexually transmitted and non–sexually transmitted infections of the genitourina...

CHAPTER 23 Infections of the Urinary and Reproductive Tracts Copyright © 2021 W. W. Norton & Company Infections of the Urinary and Reproductive Tracts Chapter Objectives  Describe similarities and differences between sexually transmitted and non–sexually transmitted infections of the genitourinary system.  Explain effective prevention and treatment methods for infectious diseases affecting the urinary and reproductive tractsCorrelate the anatomy and physiology of the urinary and reproductive tracts with the infectious diseases affecting them.  Identify different genitourinary infections by their presenting signs and symptoms. 2  . 23.3 Anatomy of the Reproductive Tract ‒ 1 Section Objectives  List the structural components of the male and female reproductive tracts.  Explain the function of each component of the male and female reproductive tracts.  Discuss the significance of structural differences between the male and female reproductive tracts as they relate to infections. 3 23.3 Anatomy of the Reproductive Tract ‒ 2 4 23.3 Anatomy of the Reproductive Tract ‒ 3 5 23.4 Sexually Transmitted Infections of the Reproductive Tract ‒ 1 Section Objectives  Relate the signs and symptoms of sexually transmitted infections to their microbial etiology.  Distinguish complications of each sexually transmitted infection according to the disease progression.  Describe how infectious diseases present differently in biologically male and female individuals and how those differences impact communicability.  List prevention and treatment options available for sexually transmitted infections. 6 23.4 Sexually Transmitted Infections of the Reproductive Tract ‒ 2  Sexually transmitted infections (STIs) • Infections transmitted through sexual activity – Genital, oral-genital, or anal-genital contact • Some infections of the reproductive tract are not exclusively sexually transmitted. • Some STIs cause symptoms but others are asymptomatic. 7 Case History: Freeze What? ‒ 1  Jamie, a 20-year-old college student from New Mexico, was in the clinic complaining of a “growth” around her “private area.” She said she had no other symptoms and denied any itching or discomfort in the affected area. Her medical history was benign. She said she liked to drink a lot and admitted to having unprotected sex with multiple partners. Physical examination showed warts near the vaginal introitus (vaginal opening) but no edema (swelling) or erythema (reddening). 8 Case History: Freeze What? ‒ 2  The doctor diagnosed genital warts and discussed different treatment options, including cryotherapy, which freezes the warts. Jamie was shocked but picked cryotherapy anyway, even though the procedure had to be repeated every 1–2 weeks. Her warts disappeared after the third session, but she was told to come back to the clinic every 3 months for 1 year to check for recurrence. She followed up as directed and was lucky enough to be free of any genital warts 1 year later. 9 Viral Infections of the Reproductive System –2 Genital warts  Most common sexually transmitted viral infection • Subtypes 6 and 11 – Low risk – Responsible for nearly 90% of all cases • Subtypes 16 and 18 – High risk – Linked to cervical, penile, anal, and throat cancers Condylomata acuminata Cauliflower -shaped, soft, fleshcolored lesions on an infected patient’s genitals or rectum • Recombinant HPV vaccine Gardasil offers protection against types 6, 11, 16, and 18 – In 2013 there was a remarkable 50% decrease in the rate of cervical cancer in vaccinated individuals. 10 Viral Infections of the Reproductive System –3  Genital herpes • Herpes simplex viruses 1 and 2 • Primary infection: may be asymptomatic – Erythematous papules, progress to vesicles and pustules, burning pain, muscle ache, fever • Latent period: no symptoms; virus moves to nerves • Recurrent episode – Milder than primary infection – Herpes encephalitis  Neonatal herpes • Pregnant mothers with genital herpes can transmit the virus to their baby before (transplacental), during, or after delivery. • The virus can also spread through the infant and affect many parts of the infant’s body, including the brain, liver, lungs, and kidneys. 11 Viral Infections of the Reproductive System –5 Human Immunodeficiency Virus (HIV)  Classification: Lentivirus in the Retroviridae family with an RNA genome.  Transmission: Via sexual contact, direct exposure to body fluids, and motherto-fetus transmission.  Infection and Progression: • Targets CD4+ T cells: Rapid replication with a concentration known as viral load. • Clinical Stages: Primary, Clinical Latency, Early Symptomatic Disease, and AIDS.  Clinical Manifestations: • Primary Infection: Often asymptomatic, with some experiencing nonspecific symptoms lasting 1–2 weeks. • Early Symptomatic Stage: Decrease in CD4+ T cells, unusual infections, persistent fever, diarrhea, and susceptibility to secondary infections.  AIDS Diagnosis: CD4+ T cell count less than 200 cells/µl, with opportunistic infections and unusual cancers. 12 Case History: The Great Imitator  Odonna came to the Nassau County, New York, urgent care clinic with a low-grade fever, malaise, and headache. She was sent home with a diagnosis of influenza.  She again sought treatment 7 days later after she discovered a macular rash (flat, red) developing on her trunk, arms, palms, and soles of her feet. She thought maybe she was allergic to the new soap she was using, but the rash was not itchy or painful.  Further questioning of the patient revealed that 1 year ago, she had a painless ulcer on her vagina that healed spontaneously. She was diagnosed with secondary syphilis. She was given a single intramuscular injection of penicillin and told that her sexual partners had to be treated as well. 13 Bacterial and Protozoan Infections of the Reproductive Tract – 1  Syphilis • Treponema pallidum • Spirochete • “Great imitator”  Primary syphilis Treponema pallidum Macular rash of secondary syph – Chancre: painless inflammatory reaction – Latency  Secondary syphilis • Years after exposure • Rash  Tertiary syphilis • Cardiovascular or nervous system involvement • Gummas: necrotic tissue – Found in liver, mouth, bone, brain, hearts, and skin Gumma Chancre of primary syphilis. 14 Bacterial and Protozoan Infections of the Reproductive Tract – 3  Syphilis • Congenital syphilis – Organism crosses placenta • Infected newborns may have – Notched teeth – Perforated palates • Treatment – Penicillin G – Jarisch Herxheimer reaction: after treatment begins, the dying treponemes release inflammatory molecules, triggering a cytokine cascade leading to symptoms that include myalgias, fever, headache, and tachycardia for 24 hours. 15 Bacterial and Protozoan Infections of the Reproductive Tract – 6  Chlamydia trachomatis • Gram-negative-like • Obligate intracellular pathogen • Most frequently reported sexually transmitted infectious disease • 75% of infected women have no symptoms. Most men are also asymptomatic. • Chlamydia is the major cause of nongonococcal Replication Cycle of Chlamydia 16 Case History: Symptom: Urethral Discharge ‒1  Rick saw his family doctor for treatment of painful urination and urethral discharge. His medical history was unremarkable. Rick was sexually active.  Physical examination was benign except for a prevalent urethral discharge. The discharge was Gramstained and sent for culture. The Gram stain revealed many pus cells, some of which contained many phagocytosed Gram-negative diplococci, a finding consistent with Neisseria gonorrhoeae infection. 17 Case History: Symptom: Urethral Discharge ‒2  The organism produced characteristic colonies on chocolate agar and was identified as Neisseria gonorrhoeae. Chocolate agar plates contain heat-lysed red blood cells that turn the medium chocolate brown. The case was subsequently reported to the state public health department. Upon his return visit, Rick’s symptoms had resolved, and a repeat culture was negative. 18 Bacterial and Protozoan Infections of the Reproductive Tract – 4  Gonorrhea (“the clap”) • Neisseria gonorrhoeae (gonococcus) • Gram-negative diplococcus • Symptoms occur 2–7 days after infection but can take as long as 30 days to develop. • Men (85–90%) exhibit symptoms such as painful urination, yellowish white discharge from the penis, and swelling of the testicles and penis. • Women (80%) do not exhibit symptoms. exists as diplococcus – When symptoms are present, they are usually mild, such as painful, burning sensation when urinating, and vaginal discharge that is yellowish-white and sometimes bloody. 19 Bacterial and Protozoan Infections of the Reproductive Tract – 5  Gonorrhea complications • Pelvic inflammatory disease – Infection spreads to uterus and fallopian tubes • Opthalmia neonatorum – Antimicrobial eyedrops Normal cervix. Gonococcal cervicitis. 20 Gonorrhoea Transmission  Gonorrhea is transmitted through sexual contact with the penis, vagina, mouth, or anus of an infected partner.  Easily transmitted from men to partners through ejaculates • N. gonorrhoeae attaches to sperm in high numbers.  The efficiency of transmission from women to their partners is not fully understood. • May require cooperation of female vaginal microbiota: bacterial sialidases secreted by cervicovaginal microbiota desialylate N. gonorrhoeae lipooligosaccharide (LOS) • Only desialylated N. gonorrhoeae surface glyconjugates can successfully bind and enter urethral epithelial cells of men  Gonorrhea can also be spread perinatally from mother to baby during childbirth. Gonococcus attached to sperm People who have had gonorrhea and received treatment may be reinfected if they have sexual contact with a person infected with gonorrhea Gonorrhoea Steps of Neisseria gonorrhoeae infection 1. During initial infection, Neisseria gonorrhoeae adheres to host epithelial cells through type IV pili  Type IV pili then retract and enable epithelial interactions with other prominent surface structures (e.g. Opa protein). 2. After initial adherence, N. gonorrhoeae replicates and forms microcolonies and possibly biofilms  likely competes with the resident microbiota.  N. gonorrhoeae becomes capable of invasion and transcytosis. 3. During these initial stages of infection, N. gonorrhoeae releases fragments of peptidoglycan, lipooligosaccharide (LOS) and outer membrane vesicles (OMVs)  activates TLR and NOD signalling in epithelial cells, macrophages and dendritic cells (DCs). 4. NOD and TLR signalling from these cells Gonorrhoea Steps of Neisseria gonorrhoeae infection (cont’d) 5. N. gonorrhoeae also releases heptose-1,7-bisphosphate (HBP), which activates TIFA-dependent innate immunity  Next slide gives brief primer on this novel pathway 6. Cytokine and chemokine gradients generated by innate signaling  recruitment of many neutrophils which interact with and phagocytose N. gonorrhoeae. 7. The influx of neutrophils makes up a purulent exudate which facilitates transmission. Gonorrhoea TIFA-dependent immunity and Gonococcus Basic Pathway LPS structureLPS biosynthetic intermediates  ADP-d/l-glycero-b-d-manno-heptose (ADP-Hep) is a Gram-ve PAMP • Intermediate in LPS biosynthetic pathways • Translocated into host cytosol via T3SS-dependent and independent strategies  Translocated ADP-Hep is sensed by the HPB PRR Alphakinase 1 (ALPK1) to trigger TIFA-TRAF6- mediated activation of NFkB  inflammation.  The pathway can also be triggered by HBP; • HBP is metabolized by host adenylyltransferase enzymes into ADP-Hep 7-P  ALPK1 TIFA NF-kB  TIFA = TRAF-interacting protein with forkhead-associated inflammation domain heptose 1,7 bisphosphate (HBP) • N. gonorrhoeae produces HPB Gonorrhoea N. gonorrhoeae uses its surface structures in myriad ways to evade complement and promote serum resistance and invasion:  binds complement proteins to prevent opsonization and killing by membrane attack complexes  sialylates lipooligosaccharide (LOS) to hide from the complement system.  binds host factor H to present as “self” • Factor H prevents complement activation on host cells  Binds C4b-binding protein (C4BP), to shield itself from complement recognition • C4BP negative regulates the complement cascade by inhibiting C3 convertase (C4b2a) and faciliting factor I activity.  binds and inactivates C3b through lipid A on its LOS via factor I-induced conversion to iC3b. • Factor I is a plasma protease that regulates the complement cascade  binds to the alternative complement pathway receptor CR3 (complement receptor 3)  epithelial cell invasion Gonorrhoea Interactions of N. gonorrhoeae with other immune cells  N. gonorrhoeae is able to survive in and around macrophages and neutrophils during infection and modulate the immune-activating properties of dendritic cells (DCs).  In macrophages, N. gonorrhoeae is able to survive inside the phagosome and modulate apoptosis and production of inflammatory cytokines.  The interactions of N. gonorrhoeae and neutrophils are complex • Stimulate NETs, which kill other bacteria besides N. gonorrhoeae – mechanism for enhancing competitive edge in vaginal microbiome ? • Can suppress oxidative burst, promoting pathogen survival • Can survive in phagosome • Promote cell death to release pathogen IL-10, interleukin-10; NETosis, cell death caused by neutrophil extracellular traps (NETs); PDL1, programmed cell death 1 ligand 1; TGFβ, transforming growth factor-β; TLR, Toll-like receptor. Gonorrhoea N. gonorrhoeae infection does not generate immunological memory. Why not?  It can antigenically and phase vary its surface structures • type IV pili • opacity (Opa) protein • LOS  modulates the adaptive immune responses • suppresses T helper 1 (TH1) and TH2 cell proliferation and subsequent activation by influencing cytokine production.  The bacterium polarizes macrophages  macrophages that are less capable of T cell activation,  DCs exposed to N. gonorrhoeae are less capable of stimulating T cell proliferation. Trichomoniasis  Trichomoniasis is the most common, nonviral sexually transmitted infection worldwide, • ~270 million cases/year.  Clinically, it presents with the “4 D’s”: • Discharge • Dysuria (painful urination) • Dyspareunia (painful intercourse) • Disagreeable odor  usually in women age > 30.  Acquisition during pregnancy associated with poor birth outcomes • Risk for preterm rupture of membranes, • preterm delivery • low birth weight  Risk factor for HIV transmission, cervical cancer. Trichomoniasis  Trophozoites of Trichomonas vaginalis are pyriform (pearshaped) and 7-30 µm long.  extracellular protozoan parasite  Have five flagella: • four anteriorly directed flagella and one posteriorly along the outer membrane of the undulating membrane.  The large nucleus is usually located at the wider, anterior end  The cytoplasm also contains many granules. Trichomoniasis  colonizes the lower urogenital tract of humans : • the female vagina, cervix • the male urethra and prostate  replicates by binary fission .  does not to have a cyst form, • Sensitive to external environment.  humans are only known host; • Transmitted by sexual intercourse  often carries endosymbionts (Mycoplasma and Trichomonasvirus spp.) Trichomoniasis Disease Characteristics  Pathogenesis best characterized in the female genital tract  accompanied with vaginal dysbiotic microbiota containing mostly anaerobic bacteria. • Modulate immunopathogenesis  Major virulence traits • Host cell adhesion, • phagocytosis • lysis  5-nitroimidazoles remain the only treatment option. Trichomoniasis Disease Characteristics  Size-variable microcolonies dysregulate epithelium permeability or promote its destruction..  Parasite extracellular vesicles are immunomodulatory • ‘prime’ host cells and parasites for adherence.  T. vaginalis-induced immunomodulation contributes to pathology, HIV spread, and immune evasion.  Neutrophils kill the parasites by trogocytosis • Eats away at parasite  reinfections are common due to insufficient immunity. Frequent Urination ‒ 1 Scenario  Lois is an 87-year-old woman who lives by herself. She was losing sleep as she kept waking up to urinate.  Lois is diabetic, but her blood sugar the night before had been 120 mg/dl (normal is 100 mg/dl) and it measured 180 mg/dl in the morning.  After an uneventful morning she began to throw up repeatedly. 33 Frequent Urination ‒ 2 Signs and Symptoms  Her son and daughter-in-law took Lois to the ER. Her temperature measured below normal. Her heart rate was faster than normal and her blood pressure dangerously low. Lois was immediately given fluids, and blood and urine samples were taken for laboratory analysis. 34 Frequent Urination ‒ 3 Laboratory Results  Gram stain of Lois’s urine sample showed Gram-negative rods. She had a severe urinary tract infection, and the bacteria had spread to her bloodstream, causing sepsis (blood infection; see Chapter 21).  Lois was diagnosed with urosepsis. The organism in this case was found to be a uropathogenic strain of Escherichia coli. 35 Frequent Urination ‒ 4 Treatment  Lois was transferred to the intensive care unit (ICU), where she was treated with IV antibiotics, fluids, and her routine medications.  Lois fully recovered and was sent home with extensive patient education given to her, her son, and her daughter-in-law. 36 23.1 Anatomy of the Urinary Tract ‒ 1 Section Objectives  List the function of each structural component of the male and female urinary tracts.  Explain the relationship between the upper and lower urinary tract anatomy and physiology.  Discuss the significance of structural differences between the male and female urinary tract as they relate to infections. 37 23.1 Anatomy of the Urinary Tract ‒ 2  The urinary tract removes • Waste • Excess water • Electrolytes  Kidneys act as a filter to eliminate unwanted small molecules from the blood. 38 23.1 Anatomy of the Urinary Tract ‒ 3  Renal arteries bring unfiltered blood from the heart to each kidney via the aorta.  Renal veins return renal blood from each kidney to the heart via the inferior vena cava.  A ureter originates from each kidney and ends in the urinary bladder.  Urine collects in the bladder until it is full; the urine is expelled through the urethra. 39 23.1 Anatomy of the Urinary Tract ‒ 4  Nephrons = filtering units of the kidneys.  Each nephron starts at the glomerular capsule (Bowman’s capsule) and continues as a long tube that ends in the collecting duct. afferent  glomerulus ( tuft of capillaries) is surrounded by the glomerular capsule.  afferent arteriole brings blood into the efferent glomerulus. Protein-free plasma passes through the capillary wall and into the glomerular capsule (filtration).  The remaining blood leaves the glomerulus via an efferent arteriole. 40 23.1 Anatomy of the Urinary Tract ‒ 5  Urinary bladder • Triangle-shaped muscular organ • Can collect and store 400‒600 ml of urine • Lined with transitional epithelium that can easily accommodate the changes in bladder volume required  Uropathogenic E. coli can invade and form a biofilm and serve as a source for recurrent bladder infections. 41 23.2 Urinary Tract Infections ‒ 1 Section Objectives  Discuss the role of physical and hormonal factors in the development of urinary tract infections in women.  Explain the relationships between lower and upper urinary tract infections.  Compare and contrast the signs and symptoms of common urinary tract infections.  List treatments for the most common etiologies of urinary tract infections. 42 23.2 Urinary Tract Infections ‒ 2  How big a problem are urinary tract infections?  Adult females suffer the most cases. • 50% chance of a adult females getting one in lifetime • 20–40% will have recurrent infections. • Why? Perineum is half as long in adult females vs males.  UTI is the most common nosocomial infection.  There are two types of urinary tract infections. • Bladder infections (cystitis) • Kidney infections (pyelonephritis) 43 Pathogenesis of Urinary Tract Infections – 1  Infection from the urethra to the bladder • Urogenital membranes ascend into the bladder. • More common in adult females  Ascending infection to the kidney • Organisms from an established infection in the bladder • Ascend along the ureter to infect the kidney  Descending infection from the kidney • Infected kidney sheds bacteria that descend into the bladder. • Kidney infections may arise when microbes are 44 Pathogenesis of Urinary Tract Infections – 2  Urine is collected in a sterile cup by the cleancatch technique.  A dry reagent strip (a dipstick) is then inserted into the patient’s urine, and color changes on the strip indicate the diagnosis. 45 Bacterial Infections of the Urinary Tract – 2  Cystitis (bladder) and pyelonephritis (kidney) infections  Urethritis • Signified by pain or burning upon urination • Urethral discharge • Typically contract the disease as a result of sexual intercourse  Asymptomatic bacteriuria • Bacteria in the urine (bacteriuria) – No signs or symptoms – Concern for pregnant woman and the elderly • Lack of symptoms may be due to – Changes in the pathogens – Less-responsive immune system – Combination of these factors 46 Bacterial Infections of the Urinary Tract – 3  Cystitis • Diagnosis when the number of bacteria sample is greater than 105/ml • Symptoms include – Sudden onset of dysuria (painful or difficult urination) – Increased frequency of urination – Nocturia (waking up at night to urinate) • Less common symptoms – Fever – Lower abdominal pain 47 Bacterial Infections of the Urinary Tract – 4  Urinary tract infections in children • Risk factors in children are – Incomplete emptying of the bladder – Postponing emptying of the bladder • Childhood urinary tract infections can lead to damage of the kidney if not treated. • Prevalence of UTI in children decreases with age. 48 Bacterial Infections of the Urinary Tract – 5  Recurrent urinary tract infections • Some adult females suffer from recurrent UTIs. – Two or more UTIs in 6 months – Three or more UTIs in 12 months • Causes – Incomplete emptying of the bladder – Sexual activity – Use of spermicides • Prophylactic (preventative) continuous antibiotic therapy • Postcoital antibiotic prophylaxis is an alternative to 49 continuous therapy for some. Bacterial Infections of the Urinary Tract – 6  Hospital-acquired urinary tract infections • Most common developed nosocomial infection – – – – – E. coli P. mirabilis P. aeruginosa E. faecalis S. epidermidis • Associated with urinary catheterization – Likely to be antibiotic resistant 50 Bacterial Infections of the Urinary Tract – 7  Pyelonephritis • More prevalent in adult females • Symptoms – High fever (38°C or 104°F, or higher) – Chills – Oliguria (producing less than normal urine) – Flank pain – Costovertebral tenderness – Nausea • Bacterial flagella and pili allow bacteria to access ureters. • Can be treated with antibiotics The point between the last rib and the lumbar vertebrae is called the costovertebral angle 51