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
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
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)
4
Q
Asymptomatic carriers of N. gonorrhoeae: men or women?
A
- Both men and women can be asymptomatic carriers
- Prevalence is higher among women
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
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
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)
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)
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
- Important for attachment to mucosal epithelium
- 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
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
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)
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
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
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
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
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
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
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
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
- VDRL (nonspecific): Abs made against T. pallidum (agent of syphilis) cross-react with antigens that are used
- 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
Prevention of syphilis
* Prompt and adequate treatment
* Follow up on sources of infection and contacts
* Use of condoms
26
Behavior associated with small epidemics of syphilis
* 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
Pathogenesis and clinical manifestations of leptospirosis
* 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
Epidemiology of leptospirosis
* 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
Characteristics differentiating Chlamydia from other bacteria
* 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
Life cycle of Chlamydia
* 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
Effect of Chlamydial life cycle on treatment
* 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
Major diseases caused by C. trachomatis
* Trachoma
* Inclusion conjunctivitis
* Urogenital tract infections
* Lymphogranuloma venereum
33
Trachoma
* 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
Inclusion conjunctivitis
* Caused by C. trachomatis
* Mucopurulent conjunctivitis 7-12 days post-delivery
* Can disseminate and cause pneumonia
35
Urogenital tract infections (from Chlamydia)
* 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
Lymphogranuloma venereum
* 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
Disease caused by C. psittaci
* 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
Diseases caused by C. pneumoniae
* 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
Potential complications of sexually transmitted chlamydial infections for women
* 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
Epidemiological characteristics of C. trachomatis
* 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
Epidemiological characteristics of C. psittaci
* 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
Epidemiological characteristics of C. pneumoniae
* Most prevalent chlamydial pathogen in human population
* 50% have been infected by age 20
* Transmission: person to person, airborne
* No known animal reservoir
43
C. trachomatis diagnosis
* 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
Diagnosis of C. psittaci and C. pneumoniae
* 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
Chlamydial infection predominant in developing countries
* C. trachomatis
* Trachoma - leading cause of preventable blindness worldwide
