MMI 133 Four.five

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MMI 133 Four.five
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2013-03-31 01:23:25
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Lecture 10
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  1. Classification of UTIs
    • Urethritis (lower UTI)
    • Cystitis
    • Ureteritis
    • Pyelonephritis
    • (Ascending route)
  2. UTI symptoms
    • Lower UTI:
    • Urethritis: Dysuria, urgency/frequency, pyuria, bacteriuria
    • Upper UTI: Same as lower UTI PLUS
    • -Fever, + lower back pain
    • Cystitis
    • Male vs female
    • E. coli, S. saprophyticus
    • Other G-, Enterococcus Sp, Streptococcus sp., S. aureus
    • Complications: bladder, prostate damage
    • Ureteritis
    • Transient
    • Pyelonephritis
    • Fever, flank/back pain
    • E. coli
    • Complication: kidney damage, bacteremia, sepsis
  3. Asymptomatic UTI
    • Bacteriuria, no symptoms
    • Can cause complications scarring) in kidneys of young children and in pregnant women
  4. Significant Bacteriuria
    • 100 x 106 cfu/ml midstream urine, normally only of one species
    • "Contaminate urine" has often several species growing
  5. UTI in children
    • Reflux
    • Scarring
    • Supra-pubi aspiration
    • UTI often caused by other types of bacteria than normally found in adult UTI
    • Eg. Streptococcus Group A, Haemophilus influenza, Streptococcus pneumoniae
  6. Organisms common in UTI
    • E. coli
    • Staphylococcus saphrophyticus
    • Streptococcus agalactiae (Group B)
    • Enterococcus faecalis/faecium
  7. E. coli
    • Gram negative bacilli, motile + capsule
    • Has O (somatic), H (flagellar), K (capsular), F (fimbrial) antigens
    • Adhesion: p-fimbriae
    • Usually susceptible to wide variety of antibiotics
  8. Staphylococcus saphrophyticus
    • Gram positive cocci, coagulase negative, novobiocin resistant
    • Infections in healthy young women
  9. Streptococcus agalactiae (Group B)
    • Gram positive cocci in chains
    • Beta-hemolytic blood agar but very small "zones"
    • Important if the patient is pregnant
    • Neonatal meningitis, sepsis and respiratory failure for the infected neonate
  10. Enterococcus faecalis/faecium
    • Gram positive cocci, often short chains or pairs
    • May produce alpha, beta or no (gamma) hemolysis on BAP
    • Common in UTI
    • Bile and salt resistant
    • VRE = problem!
  11. Specimens
    • Collection and transportation to lab important due to quantitative nature of cultures
    • Mid-stream sampe (MSU) when possible to sterile container
    • Incubation in bladder 4 hr best, note other
    • Babies: bag urine often contaminated Suprapubic aspiration recommended
    • Catheterized patients: withdraw from tube wit syringe
    • M. tuberculosis: special case, morning urine on several consecutive days
    • Urine esterase can be measured by dip-stick, pos means presence of WBC (infection)
  12. Diseases of the reproductive tract attributable to STD:
    • PID - pelvic inflammatory disease
    • Cervicitis, vaginitis, urethritis
    • Viral lesions due to HSV
    • Genital warts
    • Vaginosis
    • NGU = nongonococcal urethritis
    • Arthropod manifestations
  13. STD = STI
    • "Sexually transmitted disease or infection"
    • No vaccines commonly available (except Gardasil)
    • Characteristics of these infections
  14. PID
    • Extensive infection in the female
    • Cervix, uterus, fallopian tubes, ovaries
    • Can spread to peritoneal cavity and cause liver damage (hepatitis)
    • Over 50% of women with PID asymptomatic but have sequalae
    • Symptoms: lower abdominal pain radiating to back, discharge from vagina
    • C. trachomatis and N. gonorrhoeae most common causative agents
  15. Gonorrhea
    • Gram negative, diplococci
    • Pathogenesis of GC
    • mucous membranes of vagina/cervix/urethra/rectum/throat
    • Pili: attachment, evade immune resonse
    • Spread up reproductive tract
    • Endotoxin
    • GC produced IgA protease
    • Opa proteins on cell surface vary
  16. Gonorrhea
    Clinical symptoms
    • Damage to tissues results from the inflammation that the gonococcus elicits (no exotoxin)
    • Infection usually localized but some strains, which are resistant to the bactericidal effects of serum, can spread systemically
    • Clinical Symptoms:
    • incubation period 2-7 days
    • male: urethral discharge and dysuria
    • female: vaginal discharge, 50% asymptomatic
  17. Systemic disease in both males and females
    Gonorrhea
    • Can result in endocarditis, meningitis, monoarticular arthritis with tendinitis, skin lesions
    • Pharyngeal gonorrhoea: Sore throat
    • Rectal gonorrhoea: itching, or painful inflammation
  18. Laboratory Diagnosis Gonorrhea
    • Gram negative diplococcic in WBC in urethral discharge (men)
    • Culture, DNA probes, PCR
    • Antibiotic susceptibility tests as there is increasing resistance to many antibiotics
  19. Treatment Gonorrhoea
    • Ciprofloxacin, spectinomycin, ceftriamxone
    • Penicillin was drug of choice, but many strains now produce beta-lactamase
    • Partner tracing and treatment important
    • MHO can order arrest of non-compliant individual
    • No vaccine available
  20. Chlamydia trachomatis
    • Most common bacterial STD:>500,000 in USA Jan-Sept 2002
    • Gram negative type (LPS in cell wall)
    • Unique developmental cycle with an infectious form (EB) and a metabolically active form (RB), obligate intracellular parasites
  21. 3 species of Chlamydia infect humans
    • C. trachomatis
    • -serotypes A-C cause trachoma
    • -serotypes D-K cause genital infection
    • -serotypes L1, L2, L3, cause LGV
    • C. psittaci: zoonosis from birds, respiratory infection
    • C. pneumonia: respiratory infection, associated with cardiovascular disease
  22. Pathogenesis of Chlamydia
    • Elementary bodies (EBs) enter-mucosal membrane
    • Bind host cell receptors, internalized in a vacuole
    • Chlamydia vacuole is not fused with the host lysosome
    • Site of infection determines the disease
    • Disease effects due to inflammation
    • Serotypes D-K infect only columnar and transitional epithelial cells including neonates eyes (inclusion conjunctivitis as opposed to "trachoma")
    • LGV (lymphogranuloma venereum) are invasive and cause systemic disease
  23. Genital infection with C trachomatis D-K
    • Endemic
    • Highest frequency in 15-25 year olds
    • 50% asymptomatic in women
    • PID (pelvic inflammatory disease) (50% asymptomatic): result: ectopic pregnancy, scarring of fallopian tubes, infertility, peritonitis
    • Causes NGU (non-gonococcal urethritis in men)
  24. Laboratory Diagnosis and treatment of C. trachomatis
    • Lab
    • Culture, DNA probes, PCR (urine and secretions)
    • Serology not helpful in uncomplicated genital infections
    • Treatment
    • Tetracycline or macrolides (eg. axithromycin)
    • Partner tracing
    • No VACCINE
  25. LGV (Lymphogranuloma venereum)
    • C. trachomatis (L-1, L-2, L-3)
    • Characterized by supperative inguinal adenitis
    • More common in tropics
    • Lesion forms on genitals, infects nearby lymph glands
    • Untreated can result in tissue damage, fibrosis, elephantiasis
  26. Laboratory Diagnosis and treatment for LGV
    • Lab
    • Culture, DNA probes, PCR (urine and secretions)
    • Serology not helpful in uncomplicated genital infections
    • Treatment
    • Tetracycline or macrolides (eg. azithromycin)
    • Partner tracing
    • No VACCINE
  27. Syphilis
    • Treponema pallidum
    • Spirochaete, Gram-negative helix (not visible in Gram stain)
    • Cannot be cultured in vitro
    • Known for hundreds of ears - reports since 1500's in Europe
    • Prevalence low, often found with other STD
    • Risk population: homosexuals, drug users
    • Closely related to other Treponema species causing tropical disease
    • eg. T. pertenue - yaws
    • T. carateum - pinta
  28. Syphilis, 3 stages
    • Incubation period usually 3 weeks (10-90 days)
    • 3 stages:
    • Primary: initial sign is chancre (painless) - highly infectious (hard chancre)    bacteria enter blood and lymph
    • Secondary: occurs weeks after the chancre disappears
    • -characterized by rash on skin and mucous membranes
    • -very infectious
    • -Latent period: may last months - years
    • Tertiary stage: 50% of patients, chronic stage
  29. Pathogenesis of syphilis
    • Portal of entry: breaks in skin or mucous membranes
    • Local lesion leads to inflammation, recruitment of macrophages
    • Poorly antigenic due to lipid layer, only dead Treponema can activate immune system and induce antibody formation
    • Inflammatory responses cause "gumma" formation
  30. Diagnosis Syphilis
    Complications and Treatment
    • Serology
    • Wet mount direct microscopy
    • Complications:
    • Aortic aneurysm
    • CNS damage (paresis), blindness, seizures, dementia
    • Congenital syphilis
    • Treatment: penicillin is drug of choice (no resistant!)
    • No immunity, no vaccine
  31. Haemophilus ducrey
    • Gram negative bacillus
    • Causes chancroid
    • Soft chancre, painful
    • No permanent immunity
    • Treated with ceftriaxone
  32. Vaginosis
    • Most common bacterial infection of fertile women
    • No inflammation involved, multiple types of bacteria are involved, many anaerobic
    • Characterized by a thin, froth vaginal discharge that smells "fishy"
    • Often asymptomatic
    • Diagnosed by smear and finding of "clue" cell or epithelial cells with bacteria attached
  33. Viruses cause STI as well
    • Herpes simplex
    • Papilloma virus
    • Both viruses can have serious consequences for the individual
  34. HSV 1/2
    • Incubation 1 week, primary lesions = vesicles
    • -break down to form shallow ulcers (=pain)
    • Chronic infection, latent infection
    • Most infectious when vesicles are apparent
    • Complications: encephalitis or disseminated herpes in fetus
    • Treated with acyclovir or other acyclovir derivatives
    • Primary infection with HEV 2 often causes an aseptic meningitis
    • Pregnant women with a primary infection may pass the virus to the fetus resulting in fetal loss or damage
    • Many with chronic infections and reoccurrences self-medicate
    • Both HSV 1 and HSV 2 can cause genital Herpes but more common with HSV 2
  35. HPV (Genital Warts)
    • Papillomavirus, > 60 types
    • Certain serotypes are associated with cervical cancer and cancer of the penic (eg. types 16, 18)
    • Warts of the genital tract may be either flat or raised ("candylomata accuminata")
    • Cervical (usually flat) warts removed by laser or podophyllin, visualized by acetic acid
  36. New Vaccine for HPV
    • New vaccine for HPV 16, 18 (cx & penile cancer) & 6, 11 (genital warts) - Gardasil (subunit vaccine based on capsids)
    • Only will be effective if children can be vaccinated before sexual debut
  37. Perinatal or neonatal infections: during or immediately before parturation
    • HIV 1 and 2
    • Hepatitis B and C
    • Varicella zoster virus
    • Herpes simplex
    • Group B streptococci
    • Listeria monocytogenes
    • Chlamydia trachomatis
    • Neisseria gonorrhoeae
    • Papilomavirus
  38. Perinatal or Neonatal infections
    • Infection in first 4 weeks of life
    • Usually acquire pathogens during birth
    • Host Factors: immature immunity
    • Breached skin barrier
    • Severity depends on infectious agent
  39. Neonatal Herpes
    • Pregnant women with a primary infection often have spontaneous abortions
    • Caesarians sometimes used to prevent infection during birth, otherwise antivirals used
    • Risk to infant: disseminated Herpes infection, encephalitis
    • Can be due to either HSV 1 or HSV 2
  40. Streptococcus agalactiae (group B)
    • Leading cause of neonatal meningitis and sepsis
    • Infection can be early onset (2-7 days) or late onset (between 7 and 12 days)
    • Early onset more common: risk factors: prematurity and prolonged rupture of membranes
    • Portal of entry: respiratory tract
    • Late onset infection usually acquired at birth, but in the hospital by mother/nurses/visitors
    • Mortality of infection due to meningitis is 50%!!!!!!
    • No vaccine
  41. Neonatal gonorrhea and C. trachomatis
    • Chlamydia: usually begins as eye infections, progress to pneumonia/meningitis/sepsis
    • GC infection: ophthalmia neonatorum in newborns, newborns have erythromycin drops put in eyes to prevent!
  42. Congenital infections
    • Fetus is infected in utero or at birth
    • Often result of a primary infection of the mother during pregnancy
    • Fetus may die, spontaneously abort, or survive, often with abnormalities
    • Fetus cannot protect itself immunologically from infection
    • Striking feature of these infections is the lack of symptoms in the mother!
  43. When to suspect congenital infections
    • IUGR
    • Blueberry muffin rash
    • Jaundice
    • Hydrops
    • Presence of blisters
    • Thrombocytopenia
    • Intracranial calcifications
  44. Congenital CMV (cytomegalovirus)
    • Mother infected with a 1o infection during pregnancy
    • 40% of babies infected at birth, but effects may not become apparent until later in life
    • Clinical features: severe mental retardation; spasticity; eye abnormalities; hearing defects; hepatosplenomegaly; thrombocytopenic purpura; anaemia
  45. Congenital Hepatities B and C
    • Earlier in life the infection, the greater the chance to become chronic
    • Chronic infection = increased risk of liver cancer
    • 70-90% of neonates with HBV become chronic
    • 10% chronic if infected between birth and 6 years of age
    • Normal to both vaccinate newborns with Hep B vaccine and give them hepatitis immunoglobulin
    • Vaccination of newborns in undeveloped countries is a goal
  46. Congenital Rubella
    • Fetus is especially susceptible when mother in first trimester (heart, brain, eyes, ear formed)
    • 25% of children with congenital infections develop diabetes type 1 but causality not proven
    • Fetal death common when infection occurs in 1st month
    • -26% abnormalities if infected in 2nd month
    • -18% abnormalities if infected in 3rd month
    • -7% abnormalities if infected in 4th month
  47. Congenital Toxoplasmosis
    • Taxoplasma gondii
    • Infection in first trimester gives 14% fetal death or abnormality
    • Infection in third trimester gives 59% fetal death or abnormality
    • Clinical features: convulsions, microcephaly, chorioetinitis, hepatosplenomegaly, jaundice, hydrocephaly, mental retardation, defective vision
  48. Congenital HIV
    • Reduction in vertical transmission in western world due to treatment of mothers before birth! (<1%)
    • Elective Caesarians, no breast feeding unless necessary, who has recommended mothers in underdeveloped countries with poor hygienic conditions, lack of antivirals etc to breast feed for 6 mo
    • Poor weight gain, susceptibility to sepsis, developmental delays, lymphocytic pneumonitis, oral thrush, enlarged lymph nodes, hepatosplenomegaly, diarrhea, pneumonia
  49. Congenital Syphilis
    • Syphilis is transmitted to the fetus via the placenta
    • Sever damage to fetus: mental development, nerve system, abnormalities due to tissue damage (eg. perforation of hard palate) facial deformities, death
    • "Hutchinson's Teeth" - characteristic abnormality

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