Lecture 8: Microbial Diseases of the Urinary & Reproductive System PDF

7/15/2024 Lecture 8 Microbial Diseases of the Urinary & Reproductive System General Microbiology MW 211...

7/15/2024 Lecture 8 Microbial Diseases of the Urinary & Reproductive System General Microbiology MW 211 2023-2024 Instructor: Dr. Roba Bdeir Dr. Roba Bdeir 1 Normal flora of the urinary system All parts of urinary system except the portion of urethra closest to urethral opening are sterile. Escherichia coli & lactobacillus are the most common m.o colonizing the outer portion of the urethra (100,000 bacteria /ml). That’s why it is important to provide “clean catch” mid stream urine sample for lab culturing. In males, other than the last third of the urethra, the genital tract does not have a normal microflora and is sterile. Dr. Roba Bdeir 2 1  7/15/2024 Normal flora of the urinary system In females: During the child-bearing years, lactobacilli are dominant in vagina feeding on glycogen present in vaginal cells. Vaginal pH of about 4.4 (innate defense, as most microbes other than lactobacilli cannot survive in this acidic environment) During childhood and after menopause, glycogen is absent from vaginal cells, and streptotocci and staphylococci rather than lactobacilli are the dominant organisms in those alkaline conditions. Dr. Roba Bdeir 3 Urogenital Diseases Usually Not Transmitted Sexually Bacterial Urogenital Diseases Urinary tract infections (UTI) The 2nd most common infection after respiratory infections. UTI causes urethritis (inflammation of urethra) & cystitis (inflammation of bladder) Urethritis characterized by dysuria (pain & burning on urination) Cystitis characterized by dysuria, frequent & urgent urination, sometimes Pyuria; pus in urine. Dr. Roba Bdeir 4 2  7/15/2024 Causes of UTI Incomplete emptying of bladder during urination (retained urine allows microbial growth) Factors that interfere with flow of urine or bladder emptying e.g pregnancy (expansion & compression of uterus), prostate enlargement in elderly, people with paralysis & behavioral factors (not visiting the bathroom enough) Focal infections: Descending UTIs are usually focal infections that release m.o into blood stream (abscessed tooth), m.o filtered by kidney & cause single or chronic infection. Dr. Roba Bdeir 5 Upper UTIs : the renal parenchyma (pyelonephritis) or the ureters (ureteritis). Lower UTIs : the bladder (cystitis), the urethra (urethritis) and, in males, the prostate (prostatitis). Dr. Roba Bdeir 6 3  7/15/2024 clinical schemas for classifying UTIs 1. Single episode versus recurrent 2. Complicated versus uncomplicated. A single-episode UTI occurs once and does not recur. Patients with chronic or recurrent UTIs have repeated episodes of bacteriuria with or without clinical manifestations. These episodes are divided into: 1- relapse (the same organism and implies a focus of infection in the renal or prostatic parenchyma) 2- reinfection (implies a different organism and usually is limited to the bladder). Dr. Roba Bdeir 7 Upper vs. Lower UTI  (U-UTI)  A genitourinary tract infection that is limited to the renal parenchyma (pyelonephritis) or the ureters (ureteritis).  It is often accompanied by lower urinary tract (L-UTI) symptoms in addition to costovertebral (CV) flank pain and fever.  (L-UTI)  A GU tract infection that is limited to the urethra (urethritis), bladder (cystitis), and, in males, the prostate (prostatitis).  These infections generally appear in adults with dysuria (painful or difficult urination), polyuria (increased frequency), urgency, and occasionally suprapubic tenderness. Dr. Roba Bdeir 8 4  7/15/2024  Acute urethral syndrome  Includes dysuria and pyuria.  Bacteriuria  The presence of detectable bacteria in the urine. Patients may be symptomatic or asymptomatic (e.g., geriatric or pregnant patients).  Cystitis  Inflammation of the bladder, presenting as dysuria, urinary frequency, and urgency.  It is often due to gram-negative bacilli, such as E. coli, Proteus, and Klebsiella.  It occurs more frequently in women than men. Dr. Roba Bdeir 9  Prostatitis  A GU infection in males that involves the prostate; fever often is present.  The symptoms of prostatitis are urgent and frequent urination, low fever, back pain, and sometimes muscle and joint pain.  E. coli is the cause of 80% of the cases, but it is still uncertain how the bacteria reach the prostate.  Although uncommon, chronic prostatitis is a major cause of persistent UTIs in males, and it can cause infertility. Dr. Roba Bdeir 10 5  7/15/2024  Cervicitis  Inflammation of the cervix; it may occur as an acute or a chronic presentation.  Causative agents include sexually transmitted organisms, such as Neisseria gonorrhoeae and Chlamydia trachomatis.  Symptoms include dysuria, urgency, vaginal discharge, and low back pain.  Urethritis  Inflammation of the urethra, presenting as dysuria and discharge.  Causative agents include Neisseria gonorrhoeae, andChlamydia trachomatis, Other causes include trauma, allergic, or chemical. Dr. Roba Bdeir 11  Pyelonephritis  Infection in the kidney.  This is often due to infection in the lower tract ascending to the kidney.  Symptoms include fever, chills, nausea, vomiting, and lower back tenderness, dysuria, frequent urination & nocturia are common (urination at nighttime).  It can be accompanied by bacteremia.  Caused by kidney stones, or back up of urine (due to lower UT blockage or anatomical defect) & ascent of m.o. Young children have imperfect UT valves to prevent urine from backing up  Causative agent: Most common E.coli & occasionally Candida.  Pyelonephritis more difficult to treat than UTI Dr. Roba Bdeir 12 6  7/15/2024 Causative agents:  Escherichia coli (80% of UTI)  enteric bact from feces (Proteus mirabilis, Klebsiella pneumoniae) hygiene & toilet habits (female children)!  Staphylococcus spp affects people using catheters. Between 35 and 40% of all nosocomial infections are UTIs. Outpatients have a 1% chance of developing a UTI following a single catheterization, whereas hospitalized patients have a 10% chance. Dr. Roba Bdeir 13 UTIs are diagnosed by identifying organisms in urine cultures. Normal urine in the bladder is sterile, but urine is inevitably contaminated by bacteria as it passes through the lower part of the urethra. Even a clean-catch, midstream urine specimen will contain 10,000 to 100,000 organisms /ml. Low numbers of organisms do not necessarily rule out infection; in pyelonephritis and acute prostatitis, organisms sometimes enter the urine only in small numbers. Treatment: Amoxicillin, sulfonamides-trimethoprim, quinolones according to susceptibility Prevention: good hygiene & frequent complete emptying of the bladder Dr. Roba Bdeir 14 7  7/15/2024 ESBL producing microorganisms Extended-spectrum beta-lactamases are enzymes that confer resistance to most beta- lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. ESBLs have been found exclusively in gram-negative organisms, e.g E. coli, Pseudomonas, Salmonella, Serratia, and Neisseria gonorrhoeae. Most ESBL-producing E. coli are resistant to cephalosporins, penicillins, tetracycline and some other antibiotics, leaving very limited options for oral treatment in the community, usually only nitrofurantoin and fosfomycin (cell wall synthesis inhibitor). Treatment: The only current proven therapeutic option for severe infections caused by ESBL-producing organisms is the carbapenem family (imipenem-cilastatin, meropenem, doripenem, and ertapenem) Dr. Roba Bdeir 15 Vaginitis Vaginal infection is usually caused by opportunistic organisms from disturbance of normal flora by antibiotics or other factors. Predisposing conditions: pregnancy, diabetes, oral contraceptives, menopause, conditions that result in estrogen & progesterone imbalance will result in pH & sugar change. Causative agent: Gardnerella vaginalis in combination with anaerobic bacteria, Candida albicans (yeast), the protozoan Trichomonas vaginalis (sexually transmitted). Gardnerella vaginalis : G-ve bacillus or coccobacilli, present as normal vaginal flora in 20-40% of women. Dr. Roba Bdeir 16 8  7/15/2024 Vaginitis Normal pH 3.8-4.4 of reproductive age women & neutral in young girls & elderly women. To cause disease, G. vaginalis should interact with anaerobic bacteria like bacteroides or peptostreptococcus to cause vaginitis. Symptoms: frothy, fishy-smelling vaginal discharge, even discharge is small but contains millions of m.o. Treatment: Metronidazole (to kill the anaerobic bacteria needed for the association to produce disease), Ampicillin & tetracyclines may be used +live culture yogurt douche (to replace killed lactobacilli) Dr. Roba Bdeir 17 Parasitic urogenital disease Trichomoniasis  Primarily is STD, but can infect children from contaminated linen & toilet seats.  Caused by flagellated protozoan Trichomonas vaginalis, other Trichomonas are commensals in mouth or intestines.  Infects urogenital tract of males & females & feeds on Trichomonas vaginalis bacteria & cell secretion. It lives at pH 5.5-6 so vagina infected when its secretions are abnormal.  Symptoms: intense itching & copious white discharge especially in females (egg white consistency).  Treatment: Metronidazole + vinegar douche. Dr. Roba Bdeir 18 9  7/15/2024 Sexually transmitted diseases STD Gonorrhea Caused by Neisseria gonorrhea, G-ve diplococci. It has pili (fimbriae) that attaches it to the UT epithelia so it is not flushed with urine, also they attach to sperm & cause infection to upper part of female reproductive tract. Gonococci produce endotoxin that destroys mucosa in fallopian tubes & produce proteases that cleaves IgA present in secretions. It is killed by phagocytes but some bacteria can survive inside the leukocytes It is transmitted by carriers who may be asymptomatic, few number of m.o cause infection. symptoms:  many patients are asymptomatic & act as carriers for 5-15yrs  men: dripping of yellow discharge from urethra, pain during urination  Women: itching & burning of vagina, yellow-green discharge, frequent urination Dr. Roba Bdeir 19 Complications: anorectal infection in women, infection of the cervix (neck of uterus), urethra & 50% suffer from pelvic inflammatory disease (uterus, fallopian tubes & or ovaries) which results in sterility. Some patients will have bacteremia, fever, endocarditis, joint pain & skin lesion. When organisms reach the joints, they can cause arthritis. Contaminated hands or towels may cause eye infections. Newborns (ophthalmia neonatorum) during passage thru birth canal Treatment: Most frequently used is Cephalosporin e.g Ceftriaxone plus Azithromycin. The reason of dual treatment is that people with N. gonnorhea are most of the time coinfected with Chlamydia trachomatis (& azithromycin is effective against it). If allergic to cephalosporin use spectinomycin Dr. Roba Bdeir 20 10  7/15/2024 Syphilis (great pox) Caused by the spirochete Treponema pallidum, transmitted sexually & through saliva (hazard for dentists). The disease can be transmitted to fetus through placenta (congenital syphilis: arched leg, notched teeth, saddle nose: snuffling breathing) Symptoms:  Incubation stage: Over a period of 2 to 6 weeks after entering the body, the organisms multiply and spread throughout the body.  After incubation period the disease enters into stages: Primary stage: inflammatory response forms a chancre (one or more hard, painless non discharging lesion) on genitals & may be on lips or hands. Symptoms disappears after sometime. Dr. Roba Bdeir 21 Primary latent period: All external signs of the disease disappear, but blood tests diagnostic for syphilis are positive, and the spirochete is spreading through the circulation. Secondary stage: Symptoms appear & disappear for up to 5 yrs. The patient is highly contagious. Copper-colored rash on palms of hands & feet appear followed by various pustular rashes and skin eruptions. Painful whitish mucous patches with spirochetes appear on the tongue, cheeks & gums (spreads by kissing too). Symptoms disappear. Secondary latent stage: Again all symptoms disappear, and blood tests can be negative. This stage can persist for life or for a highly variable period, or it may never occur. Symptoms can reoccur at any time during latency. In some patients syphilis does not progress beyond this stage, but in many patients it progresses to the tertiary stage. Transmission across the placenta to a fetus can also occur. Dr. Roba Bdeir 22 11  7/15/2024 Tertiary stage: In some people disease progress to damage other organs, like cardiovascular (Ca deposits in heart valves & the bl vessels are damaged), nervous system (neurosyphilis) (thickening of meninges, ataxia, paralysis & insanity) Syphilis called “great imitator” as signs & symptoms mimic other diseases Treatment: Benzathine penicillin G Dr. Roba Bdeir 23 Nongonococcal urethritis NGU Chlamydial infection A gonorrhea-like STD not caused by gonococci. Most cases caused by Chlamydia trachomatis. C. trachomatis causes also conjunctivitis in new born Symptoms: Most chlamydial NGU are asymptomatic. Males: Symptoms are similar to gonorrhea with watery urethral discharge, sometimes inflammation of epididymis (tube through which sperms pass from testes) leads to sterility. Complications in women: Pelvic inflammatory disease may result & lead to sterility & ectopic pregnancy. Infants are infected during birth. Self inoculation by hand or towels transfer the m.o to the eyes causing conjunctivitis (before chlorine use it causes swimming pool conjunctivitis). Treatment: tetracyclines & sulfa drugs. Chlamydia not susceptible to penicillin Dr. Roba Bdeir 24 12  7/15/2024 Nongonococcal urethritis NGU Mycoplasmal infections Mycoplasma hominis & Ureaplasma: cause NGU also they may cause spontaneous abortion. Treatment: (not susceptible to penicillin), Tetracyclines, if resistant strains to tetracycline, erythromycin & spectinomycin are used. Dr. Roba Bdeir 25 Viral sexually transmitted diseases Herpesvirus infections Two closely related viruses: HSV-1 (typically causes cold sores) & HSV-2 (typically causes genital herpes) cause same kind of lesions on mucous membrane of mouth & genitals. Genital herpes is most severe of herpes simplex viral infections. Most adults have Ab against herpes but 15% experienced symptoms. In HSV1 & 2 infections, vesicles form under keratinized cells & filled with fluid from virus damaged cells & inflammatory cells. They are painful &heal within 2-3wks without scaring. Herpesvirus is a latent virus, within 2wks of active infection, viruses travel via sensory neuron to ganglia where they replicate slowly or not at all. They can reactivate spontaneously or be activated by fever, stress, hormone imbalance, change in immune system or trauma. Dr. Roba Bdeir 26 13  7/15/2024 After reactivation, the virus moves along the nerve axon to the epithelial cells. There it replicates, causing recurrent lesions. These lesions, always recur in the same place as the original infection and heal more rapidly than primary lesions. Recurrences can be limited to one or two episodes or can appear periodically for the life of the patient but typically occur five to seven times. While the virus is in a neuron, neither humoral nor cellular immunity can combat it. Once the virus reaches target epithelial cells and starts to replicate, antibodies can neutralize the viruses, and T cells can eliminate virus-infected cells. This will reduce the severity & duration of recurrent infections No vaccine available. The infection can spread to and kill cells in the adrenal glands, liver, spleen, and lungs. In fatal herpes encephalitis, soft, discolored lesions appear in the brain Dr. Roba Bdeir 27 Genital herpes: causes vesicles in genitals of both males & females which are severely painful &itchy. Lesions shed viruses which are very contagious. Women infected with genital herpes may be subject to other serious problems. 1. the incidence of miscarriages among women with genital herpes is higher than that for uninfected women. 2. when infected women become pregnant, the infant must be delivered by Caesarean section. 3. infected women have an increased risk of becoming infected with the AIDS virus, as lesions provide open pathways of entrance for the virus Dr. Roba Bdeir 28 14  7/15/2024 Neonatal herpes Can appear at birth or up to 3 weeks after birth. Babies most often become infected by delivery through a birth canal contaminated with HSV-2, but they can also become infected through contaminated equipment and hospital procedures. In rare instances, infants are infected in utero. Neonates are highly susceptible to HSV infections, therefore, their infected mothers must follow strict sanitary procedures. At diagnosis, two-thirds of infected infants have skin vesicles; the others already have disseminated infection with neural or visceral lesions. Infants with disseminated infections display poor appetite, vomiting, diarrhea, respiratory difficulties, and hypoactivity. Some also have neurological symptoms, jaundice, and eye disorders. Neonates with disseminated infections deteriorate rapidly and usually die within 10 days. The few that survive usually have central nervous system and eye damage. Dr. Roba Bdeir 29 Genital warts (Condylomas) Caused by Human papilloma virus (HPV) several strains are known. Genital warts cause irritation & itching. In males appear on penis, anus; in female appear on vagina, cervix& anus. They persist or regress spontaneously, but are prone to secondary bacterial infections. Those persisting for long time can become malignant. HPV responsible for 99% of cervical cancer Vaccine is available against strains that cause 70% of cervical cancer. Dr. Roba Bdeir 30 15  7/15/2024 Laryngeal Papillomas Are benign growths that can be dangerous if they block the airway. Hoarseness, voice changes, and respiratory distress occur when the airway becomes obstructed. Children are more likely to have laryngeal papillomas than adults. Surgical removal, sometimes every 2 to 4 weeks, is the only treatment for these obstructive growths. There is danger of spreading the virus to the lungs during surgery. Laryngeal papillomas are usually caused by HPV-6 and HPV-11, which are thought to infect infants during birth to women with active genital warts. Dr. Roba Bdeir 31 Cytomegalovirus Infections The cytomegaloviruses (CMVs) constitute a widespread and diverse group of herpesviruses. Each strain of CMV is capable of infecting a single species. CMV is sexually transmitted. It can also be spread through transplanted organs and blood transfusions, thru placenta, thru mucous membrane (eyes, nose after touching the secretions of infected person) The majority of human CMV infections do not produce clinically apparent symptoms. Almost 80% of U.S. adults carry the virus. When there are symptoms, they include malaise, myalgia, protracted (long term) fever, abnormal liver function. Symptoms are more severe in patients with AIDS and other immunodeficiencies (will cause severe pneumonia, hepatitis, irreversible damage to eyes). In fetuses and infants, CMV infections can be life threatening because the virus disseminates widely to various organs. Dr. Roba Bdeir 32 16  7/15/2024 Fetuses become infected by viruses that cross the placenta from infected mothers. Maternal antibodies can cross the placenta but inactivate small quantities of virus. In severe CMV infections in which the fetus has been infected with large numbers of viruses intrauterine growth retardation and severe brain damage can occur, mortality reaches 30% Less severe infections, cause damage to certain brain areas and mild central nervous system disorders with or without damage to hearing or sight loss Treatment, and Prevention: No effective treatment for CMV infections in infants is available. The prognosis is poor. Interferon and hyperimmune gamma globulin given before and after organ transplantation reduce the incidence and severity of CMV infections in transplant patients. No effective vaccine exists. Dr. Roba Bdeir 33 AIDS Is a secondary or acquired immunodeficiency disease caused by 2 different types of HIV, HIV-1 & HIV-2. HIV-2 is very closely related to the simian (monkey) immunodeficiency virus (SIV). It is a mutated version of this virus, while HIV-1 is believed to evolve from chimpanzee version of the SIV The virus gradually destroys the immune system HIV targets & damages TH cells, macrophages, dendritic cells & Langerhans cells which have a CD4 molecule on their surface. Macrophages that phagocytized HIV from dead tissue are impaired & become reservoir of HIV & deliver HIV to various organs in the body including brain & lungs. (only 4% of the virus in blood, 96% in lymph nodes, intestines & brain). After a person is infected, a battle starts between HIV & immune system, large amounts of virus are produced (fatigue, fever, body aches occur) Dr. Roba Bdeir 34 17  7/15/2024 As immune cells are activated, antibodies & Tc cells destroy large no. of HIV, but immune cells are also destroyed (2x more than killed virus) & replaced. The virus wins the war!! As years pass, it becomes difficult to replace TH cells & other immune cells. Since TH are reduced, B cells are not stimulated to form plasma cells (produce Ab), also cytokine production is not enough to activate the macrophages & Tc cells, thus the person is prone to infections & malignancies Dr. Roba Bdeir 35 The progression of disease depends on frequency of exposure to the virus & amount of virus. WHO classification into stages1-4. Stages1-3: have HIV, Stage 4 AIDS patient. Stage 1: HIV infection (flu like symptoms), Stage 2: mildly symptomatic stage (unexplained weight loss of 10%, diarrhea >1month, mild anemia, mild leukopenia, some decrease in Tcell, shingles, symptoms advance to moderate anemia, thrush, TB, severe bacterial infections (pneumonia, pyelonephritis, joint & bone infections), recurrent shingles Stage 4: AIDS, severe immune dysfunction, opportunistic infections (Fungi, bacteria, toxoplasma), malignancies eg Kaposi’s sarcoma caused by herpes virus 8: blood vessels grow in tangled masses filled with blood & easily ruptured in skin & viscera (GI, lungs, liver, spleen & lymph nodes). Dr. Roba Bdeir 36 18  7/15/2024 within 15 years 90% of HIV-infected patients will develop AIDS. Some of the drugs currently being used are capable of prolonging the life of AIDS patients, and so the death rate, but not the number of infected persons, is dropping. (modern drugs extend life for several yrs), >88% die from infections. Transmission: sexual contact, sharing unsterilized needles, contaminated blood transfusion or blood products, passage from infected mother to an infant (in uterus, during delivery, breast feeding), health care workers with abrasions through dire Dr. Roba Bdeir 37 19