Bacterial STDs Flashcards

1
Q

Bacteriological features of Neisseria (morphology, growth characteristics)

A

Morphology

  • Gram-negative diplococcus
  • Individual cocci are kidney-shaped, together look like a donut

Growth characteristics

  • Grow only on rich media in presence of 5% CO2
  • Sensitive to fatty acids and salts in growth medium
    • Chocolate agar
    • Thayer-Martin (VPN = Vanco, Polymyxin, Nystatin)
    • Transgrow bottle used in doc offices rurally –> provies CO2 in a bottle to send off to lab
  • Undergo rapid autolysis at 25C and at alkaline pH
  • Gonorrhoeae ferments only glucose, oxidase (+)
  • Meningitidis ferments both glucose and maltose
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2
Q

Diagnosis of gonorrhea

A
  • Gram-stained smears: urethral, endocervical, or conjunctival exudates
    • May be diplococci within PMNs
  • Cuture: on enriched selective medium at 37C in 5% CO2 atmosphere for 48 hours
    • Thayer Martin
    • Chocolate agar
  • Nucleic acid amplification tests (NAATS)
    • Preferred testing method to distinguish N. gonorrhoeae and C. trachomatis infection
    • Closest test to > 90% sensitivity and 99% specificity
  • Oxidase production and oxidative utilization of carbohydrates used for identification and differentiation between Neisseria spp.
    • Also between Neisseria and Moraxella
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3
Q

Most effective diagnostic procedures for Neisseria/Moraxella

A
  • Gram stained smears
    • Sensitivity: 90% for men, 50% for women
    • Specificity: 99% for men, 90% for women
  • True ONLY of urogenital infection with N. gonorrhoeae
  • Lower for women because they are more likely to be infected with other organisms (e.g. Moraxella) that would make diagnosis less clear (both are gram (-) diplococci)
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4
Q

Asymptomatic carriers of N. gonorrhoeae: men or women?

A
  • Both men and women can be asymptomatic carriers
  • Prevalence is higher among women
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5
Q

Epidemiological significance of asymptomatic carriers of gonorrhea

A
  • Major problem in control of gonorrhea
  • Asymptomatic infection can lead to more serious infections like PID, especially in women
  • “Toilet seat” theory unlikely as it doesn’t survive well
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6
Q

Clinical manifestations of gonorrhea

A
  • Range from asymptomatic to disseminated infection
  • Depend on site and type of infection
  • Lower tract infection:
    • Cervicitis
    • Abscess formation in glands adjacent to vagina
    • Urethritis
  • Upper tract infection
    • Endometritis
    • PID
    • Epididymitis
  • Other sites:
    • Proctitis: homosexual men
    • Pharyngitis
    • Ophthalmia neonatorum - bilateral conjunctivitis in infants born to infected mothers
    • Peritonitis
    • Perihepatitis
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7
Q

Disseminated gonococcal infection (DGI)

A
  • Dermatitis-arthritis-tenosynovitis syndrome
    • Reiter’s syndrome/reactive arthritis
    • “can’t see, can’t pee, can’t climb a tree”
      • also found post-chlamydial infection
  • Monoarticular septic arthritis
  • Endocarditis (rare)
  • Meningitis (rare)
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8
Q

Importance of antigenic heterogeneity in pathogenesis of gonorrhea

A
  • Means that N. gonorrhoeae is antigenically very heterogeneous
    • Capable of changing surface structures to avoid host defenses
  • So much antigenic variation –> single person can be infected with N. gonorrhoeae many times in the lifetime
  • Several types of pili: cause inability of vaccinations to gonorrhea
    • One person can be infected, treated, then reinfected due to Ab specificity to one single pili
    • Bug can synthesize a new and different type of pili for survival advantage
    • Bug can also turn pili on and off for attachment and detachment from host (phase variation)
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9
Q

Bacterial structures undergoing antigenic variation/phase variation in gonorrhea

A
  • Pili
    • Important for attachment to mucosal epithelium
      • Phase variation –> bacteria capable of switching on/off the expression of pili
      • Hundreds of antigenic types of pili
  • Opa proteins
    • Outer membrane proteins
    • N. gonorrhoeae either transparent, opaque, or mixed depending on presence of Opa proteins at bacterial surface
    • Important for attachment and may influence site and type of infection
    • Hundreds of antigenic types of Opa proteins
  • LOS
    • Equivalent of LPS of gram-negative bacteria, but without long O-side chains
    • 8+ types of LOS
    • Toxic for ciliated cells in tissue culture
    • Responsible for many of inflammatory processes during infection
  • IgA protease
    • Cleaves Fc portion of IgA –> prevents opsonized bacteria from being phagocytosed
    • 2 types
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10
Q

Guidelines for treatment of gonorrhea

A
  • No quinolones in US because of widespread resistance
  • Treatment of choice:
    • Third-generation cephalosporins: cefixime (oral, single dose); ceftriaxone (IM, single dose)
    • Also treat concurrently for Chlamydia (travel together)
  • Ophthalmia neonatorum - preventable by administration of drops/ointment into eyes at birth
    • Silver nitrate (2%) or
    • Antibiotics - erythromycin or tetracyline ointment
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11
Q

Relationship of gonorrhea treatment to other STD treatment

A
  • Dual therapy recommended for chlamydial and gonococcal urogenital infections because:
    • Patients infected with one are often infected with the other
    • Cost of treating for both is less than cost of testing
  • Therapy for N. gonorrhoeae
    • Third generation cephalosporin - cefixime, ceftriaxone
    • do NOT use quinolones - too much resistance in US
  • Therapy for C. trachomatis
    • Macrolides (azithromycin - oral, single dose) OR
    • Tetracycline (doxycycline - oral, 7 days)
  • Ocular infection with N. gonorrhoeae
    • Ceftriaxone (IV or IM, single dose)
    • Topical abx alone are inadequate
  • Ocular infection with C. trachomatis
    • Erythromycin (oral, 10-14 days)
    • Topical abx alone are inadequate
  • Treatment of infected pregnant women
    • N. gonorrhoeae - 3rd generation cephalosporin or spectinomycin
    • C. trachomatis - erythromycin (oral, 7 days) or amoxicillin (oral, 7 days)
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12
Q

Major characteristics of spirochetes & differences from other bacteria

A
  • Large, heterogeneous group of spiral, motile bacteria
  • Gram negative
  • LPS not exposed due to outer phospholipid rich membrane with few exposed proteins
  • Endoflagella between cell wall and outer membrane
  • Reproduce by transverse fission
  • Grown only in broth with 1-4% O2 at 25C
  • Other bacteria have variety of other shapes, metabolism, growing conditions, reproduction, motility, other characteristics
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13
Q

Primary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness

A
  • Pathogenesis:
    • Enter body through mucous membranes, epithelial abrasions, or skin contact with ulcer
  • Manifestations:
    • One or more painless chancres
    • Regional nontender lymph node enlargement
  • Diagnosis:
    • Specimens in darkfield microscopy or direct fluorescence Ab (DFA-TP)
  • Infectiousness:
    • Very! Wear gloves to touch a chancre.
    • Blood transmissible
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14
Q

Secondary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness

A
  • Pathogenesis:
    • Secondary syphilis is systemic
  • Manifestations
    • 6 weeks after initial chancre heals
    • Localized or diffuse mucocutaneous lesions
    • Rash, lymphadenopathy, condyloma lata, bacteremia, alopecia
    • 30% untreated develop tertiary syphilis
  • Diagnostic tests
    • Specimens in darkfield microscopy or direct fluorescence Ab (DFA-TP)
  • Infectiousness
    • Organisms can be located in condylomata
    • Also transmissible by blood
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15
Q

Latent syphilis: manifestations, diagnostic tests, infectiousness

A
  • Manifestations:
    • Asymptomatic
    • Can relapse to stage 2
  • Diagnostic test:
    • Serologic testing, FTA
  • Infectiousness
    • Noninfectious except in pregnant women transmitting it to their fetuses
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16
Q

Tertiary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness

A
  • Pathogenesis:
    • Lesions caused by immune mediated destruction of tissues
  • Manifestations
    • Develops over 6-40 years
    • Neurologic, gummatous, or cardiovascular
    • 25% die
  • Diagnostic tests:
    • Serologic testing, FTA
  • Infectiousness:
    • Non-infectious
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17
Q

Tertiary syphilis complications

A
  • Neurologic syphilis:
    • Common
    • Can be asymptomatic
    • Subacute meningitis with predominance of lymphocytes
    • Meningovascular syphilis
    • Tabes dorsalis
    • General paresis of insane
    • Associated with Argyll Robertson pupil - reactive to accomodation but not to light
  • Gummatous syphilis:
    • Rare
    • Granulomatous lesions that eventually fibrose
    • Often located in skin and bone
  • Cardiovascular syphilis
    • Rare
    • Aortic aneurysm
    • Aortic insufficiency
    • CAD
    • Dissection
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18
Q

Diagnosis of syphilis: primary or secondary

A
  • Darkfield examination: drop of tissue fluid or exudate placed on slide –> examined with light
    • Still used for diagnosis of primary syphilis because Ab-based tests may not yet be positive (takes about 2 weeks for person to develop Abs against Ag)
  • Immunofluorescence: detection of T. pallidum from specimens using fluorescein-labeled anti-treponema serum
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19
Q

Diagnosis of syphilis: latent or tertiary

A
  • Serological tests: antibodies found in serum of patients after 2-3 weeks of untreated syphilis infection and in spinal fluid after 4-8 weeks of infection
    • VDRL (nonspecific): Abs made against T. pallidum (agent of syphilis) cross-react with antigens that are used
      • Detection of IgM and IgA Abs reactive to “reagin” - mixture of cardiolipin, lecithin, and cholesterol
      • Many biologic false positives, including viral infection (mono, hepatitis), some drugs, rheumatic fever, SLE, and leprosy
    • Agglutination reaction
  • Fluorescent treponemal antibody (FTA) (specific): detection of specific Abs in serum of patients, using killed organisms as Ag to generate Abs for the test
    • Specific Abs detected by addition of fluorescein-labeled anti-human IgG or IgM
20
Q

Serologic testing for diagnosis of syphilis

A
  • Not very suitable for primary stage - takes 2 weeks to develop antibodies to a given antigen
21
Q

Diseases caused by Treponema spp.

A
  • T. pallidum subsp pallidum –> syphilis
  • T. pallidum subsp pertenue –> yaws
  • T. pallidum subsp endemicum –> endemic syphilis or bejel
  • T. carateum –> pinta (red –> blue –> white lesions, limited to Latin American)
22
Q

Epidemiology of Treponema spp.

A
  • Treponema very susceptible to environmental conditions of heat, drying, and sunlight
    • Will remain viable in blood stored at 4C for only 24 hours
  • Transmission of T. pallidum by direct personal among humans
  • Infected person may remain contagious for 3-5 years during early syphilis
  • Increases in incidence in gay communities over last several years
  • 36,000 new cases/year in US
  • Often contracted at same time as other STIs like HIV
  • In 2006: half of all primary and secondary syphilis were reported from 20 counties and 2 cities
    • Most P&S syphilis cases occurred in persons 20-39 years of age
    • Highest in women 20-24 years, men 30-35 years
23
Q

Treatment of syphilis

A
  • Shot of penicillin G in buttocks
  • Jarisch-Herxheimer reaction:
    • Malaise, fever, HA, sweating, rigors, temporary exacerbation of syphilitic lesions
    • Occurs a few hours after onset of treatment, only in spirochetes
    • Thought that spirochetes lyse and release all toxins
    • Happens in Lyme disease too
    • Warn patients in advance that it might happen
24
Q

Abx resistance in Treponema and alternative treatment if allergic

A
  • No antibiotic resistance developed yet
  • If allergic to penicillin - tx with doxycycline or tetracycline
25
Q

Prevention of syphilis

A
  • Prompt and adequate treatment
  • Follow up on sources of infection and contacts
  • Use of condoms
26
Q

Behavior associated with small epidemics of syphilis

A
  • Outbreaks most frequently associated with increased illicit drug (e.g. crack cocaine) use and exchange of money or drugs for sex
  • ~36,000 new reported cases of syphilis in US every year
27
Q

Pathogenesis and clinical manifestations of leptospirosis

A
  • Fever due to bacteremia
  • Infect liver and kidney –> hemorrhage and necrosis of tissue causing dysfunction of organs –> jaundice, hemorrhage, nitrogen retention
  • Second phase develops when IgM antibody titer rises - often manifests as aseptic meningitis
  • Carried in rodents, dogs, fish, birds –> shed in animal urine –> transmitted to humans via contaminated water or soil –> leptospires enter mucosal abrasions –> system spread:
    • Phase I: host immune response
    • Phase II: immune response and rise in anti-leptospirosis IgM associated with mild or severe damage
28
Q

Epidemiology of leptospirosis

A
  • Human infections usually result from ingestion of contaminated water or food
  • More rarely - organisms may enter through mucous memrbanes or breaks in skin
  • CKI in many animal species results in shedding of organism in urine
    • Probably main source of contamination and infection of humans
  • Leptospira remains viable in stagnant water for several weeks
  • Incubation period of 1-2 weeks
29
Q

Characteristics differentiating Chlamydia from other bacteria

A
  • Obligate intracellular, biphasic life cycle
  • Cocci or coccobacilli
  • Gram-negative
    • Cell wall doesn’t have N-acetymuramic acid
  • Very small genome (~1mb)
  • Can’t synthesize ATP or oxidize NADP - obligate inracellular
  • Multiply in specialized endosome
30
Q

Life cycle of Chlamydia

A
  • Replicate by binary fission
  • Infectious form:
    • Elementary bodies (EBs)
    • Have condensed chromosome
    • Enter cell by endocytosis
  • Intracellular replicative form:
    • Reticular bodies (RBs)
    • Vegetative form
    • Reorganize and condense inside cell to form new EBs, which rupture out of host cell and infect other cells
31
Q

Effect of Chlamydial life cycle on treatment

A
  • Reticulate bodies synthesize own DNA, RNA, and proteins, but require ATP from host
  • Protein products used to replicate and form more elementary bodies from growing reticulate bodies
  • Elementary bodies inhibit phagosome-lysosome fusion, probably from carried protein
    • Treatment easy with inhibiting bacterial protein synthesis
    • Options are macrolides (usually first line), doxycycline, or fluoroquinolone (but lots of ADRs)
  • Treat with Macrolides –> azithromycin, erythromycin, or doxycycline
    • All act at ribosomal subunits inhibiting protein synthesis
      • Azithro, erythro at 50S
      • Doxy at 30S
  • Can’t use penicillins or cephalosporins due to atypical cell wall
32
Q

Major diseases caused by C. trachomatis

A
  • Trachoma
  • Inclusion conjunctivitis
  • Urogenital tract infections
  • Lymphogranuloma venereum
33
Q

Trachoma

A
  • Caused by C. trachomatis
  • Conjunctivitis and follicular hypertrophy, corneal scarring and conjunctival deformity
  • Scarring causes eyelids to turn inwards (trichiasis) allowing eyelashes to continually abrade the cornea
34
Q

Inclusion conjunctivitis

A
  • Caused by C. trachomatis
  • Mucopurulent conjunctivitis 7-12 days post-delivery
  • Can disseminate and cause pneumonia
35
Q

Urogenital tract infections (from Chlamydia)

A
  • Caused by Chlamydia trachomatis
  • Men: 50% have no symptoms
    • Urethritis, similar to gonorrhea
    • Dysuria and purulent urethral discharge
    • PMNs under microscope but no bacteria
  • Persistence of symptoms with disappearance of gonococci from gram-stained smear after anti-gonococcal therapy
    • Indicative of concomitant urethritis from C. trachomatis
  • Women: 75% have no symptoms
    • Mucopurulent urethritis, cervicitis, salpingitis
36
Q

Lymphogranuloma venereum

A
  • Caused by C. trachomatis
  • Small ulcer on genitalia
  • Inguinal lymph node swelling
  • 2-6 weeks later: may suppurate and form draining sinuses
  • Can disseminate to peritoneum (especially in women) or lower bladder
  • Can cause ulcerative colitis especially in MSM
37
Q

Disease caused by C. psittaci

A
  • Psittacosis
  • Acute pulmonary infection with:
    • Fever
    • Headache
    • Malaise
    • Myalgia
    • Nonproductive, hacking cough
  • Xray shows bilateral interstitial pneumonia
  • Resembles influenza or typhoid
  • Can be systemic
38
Q

Diseases caused by C. pneumoniae

A
  • Asymptomatic or mild URI (sinusitis)
  • Severe disease can cause atypical pneumonia
  • Chronic infections associated with progressive and detrimental diseases:
    • Asthma
    • COPD
    • CF
    • Lung cancer
39
Q

Potential complications of sexually transmitted chlamydial infections for women

A
  • Salpingitis
    • Pelvic inflammatory disease = PID
  • Painful inflammation of fallopian tubes
  • Can lead to scarring (–> infertility), ectopic pregnancy, chronic pelvic pain
  • 50% of women with PID have C. trachomatis
40
Q

Epidemiological characteristics of C. trachomatis

A
  • Trachoma: main cause of global blindness
    • 146 million have active infections
    • 6 million are blind
    • Africa, SE Asia, Western Pacific, E. Mediterranean
    • Hand-to-hand + eye secretions: mode of transmission
  • Inclusion conjunctivitis: baby gets while passing through birth canal from infected mom
    • Can be in adults who have genital infection
  • Urogenital tract infections
    • 1.2 million cases in US/year
    • Most frequently reported infectious disease in US
    • 10% of adolescent girls are infected
    • Infected women –> 3-5x risk of acquiring HIV if exposed
  • Lymphogranuloma venereum
    • Sexually transmitted
    • Africa and S. America
    • High in young adults and homosexual men
    • Swelling of lymph glands around GU tract
41
Q

Epidemiological characteristics of C. psittaci

A
  • Psittacosis
  • Found in wild and domestic birds
  • Usually latent but activated by stress of captivity/shipping
  • Humans get it from inhaling “dust” (fecal material)
  • Reduced frequency in US due to addition of antimicrobial agents to poultry feed and quarantine regulations for imported birds
42
Q

Epidemiological characteristics of C. pneumoniae

A
  • Most prevalent chlamydial pathogen in human population
  • 50% have been infected by age 20
  • Transmission: person to person, airborne
  • No known animal reservoir
43
Q

C. trachomatis diagnosis

A
  • Cell culture:
    • High specificity
    • Essential for medicolegal cases
    • Expertise essential
    • Expensive - method of choice for confirmation of other assays
  • Direct fluorescent antibody (DFA)
    • High sensitivity in experienced hands provided a cutoff of 2 elementary bodies is used
    • Labor-intensive, needs skilled personnel
    • Unsuitable for large numbers (> 30/day)
    • Can be used for confirmation of other assay
    • Will accomodate all specimen types
  • Enzyme immunoassays (EIA)
    • High specificity (assay dependent) when combined with confirmation assay
    • Variable sensitivity (assay dependent)
    • Inexpensive, suitable for large numbers
    • Automatable - can be used for hundreds of samples
  • Nucleic acid amplification techniques (NAAT)
    • High specificity (89-100%), high sensitivity (99-100%)
    • Inhibitors may be a problem, especially with urine specimens
    • Expensive in staff, space, and consumables
    • Can pool specimens to decrease costs and maintain sensitivity
    • Needs particular care in lab to avoid contamination
  • Ideal diagnostic test sensitivity >90% with specificity > 99%
    • NAATs most closely approach this ideal
44
Q

Diagnosis of C. psittaci and C. pneumoniae

A
  • C. psittaci
    • Psittacosis: 4-fold increase in complement fixing antibody to chlamydial antigen is confirmatory
  • C. pneumoniae
    • Microimmunofluorescence to detect species-specific IgM or IgG antibodies
45
Q

Chlamydial infection predominant in developing countries

A
  • C. trachomatis
  • Trachoma - leading cause of preventable blindness worldwide