Bacterial STDs Flashcards
Bacteriological features of Neisseria (morphology, growth characteristics)
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
Diagnosis of gonorrhea
- 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
Most effective diagnostic procedures for Neisseria/Moraxella
- 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)
Asymptomatic carriers of N. gonorrhoeae: men or women?
- Both men and women can be asymptomatic carriers
- Prevalence is higher among women
Epidemiological significance of asymptomatic carriers of gonorrhea
- 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
Clinical manifestations of gonorrhea
- 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
Disseminated gonococcal infection (DGI)
- 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)

Importance of antigenic heterogeneity in pathogenesis of gonorrhea
- 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)
Bacterial structures undergoing antigenic variation/phase variation in gonorrhea
- 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
Guidelines for treatment of gonorrhea
- 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
Relationship of gonorrhea treatment to other STD treatment
- 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)
Major characteristics of spirochetes & differences from other bacteria
- 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
Primary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness
- 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
Secondary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness
- 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
Latent syphilis: manifestations, diagnostic tests, infectiousness
- Manifestations:
- Asymptomatic
- Can relapse to stage 2
- Diagnostic test:
- Serologic testing, FTA
- Infectiousness
- Noninfectious except in pregnant women transmitting it to their fetuses
Tertiary syphilis: pathogenesis, manifestations, diagnostic tests, infectiousness
- 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
Tertiary syphilis complications
- 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
Diagnosis of syphilis: primary or secondary
- 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
Diagnosis of syphilis: latent or tertiary
- 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
Serologic testing for diagnosis of syphilis
- Not very suitable for primary stage - takes 2 weeks to develop antibodies to a given antigen
Diseases caused by Treponema spp.
- 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)
Epidemiology of Treponema spp.
- 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
Treatment of syphilis
- 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
Abx resistance in Treponema and alternative treatment if allergic
- No antibiotic resistance developed yet
- If allergic to penicillin - tx with doxycycline or tetracycline
Prevention of syphilis
- Prompt and adequate treatment
- Follow up on sources of infection and contacts
- Use of condoms
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
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
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
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
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
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
- All act at ribosomal subunits inhibiting protein synthesis
- Can’t use penicillins or cephalosporins due to atypical cell wall
Major diseases caused by C. trachomatis
- Trachoma
- Inclusion conjunctivitis
- Urogenital tract infections
- Lymphogranuloma venereum
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
Inclusion conjunctivitis
- Caused by C. trachomatis
- Mucopurulent conjunctivitis 7-12 days post-delivery
- Can disseminate and cause pneumonia
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
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
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
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
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
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
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
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
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
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
Chlamydial infection predominant in developing countries
- C. trachomatis
- Trachoma - leading cause of preventable blindness worldwide