Chlamydiaceae family Lecture 26 Flashcards
Chlamydiaceae family
two genera: chlamydia (C. Trachomatis) and chlamydophilia (c. pneumoniae, and C. psittaci)
obligate intracellular pathogens
originally considered viruses due to small size
reclassified as bacteria. Possess inner and outer membranes similar to gram negative bacteria (but lack peptidoglycan layer). Contain both DNA and RNA. Possess prokaryotic ribosomes. Synthesize own proteins, nucleic acids, and lipids. Susceptible to antibacterial antibiotics.
Chlamydia: development cycle
exist in two forms. IN active infectious form (elementary bodies) and metabolically active non-infectious forms (reticulate bodies)
- EBs infect host cell and convert to RBs.
- RBs replicate using host cell’s ATP for energy and form inclusion (phagosome with replicating RBs)
- Reticulate bodies reorganize into EBs
- EB’s released by reverse endocytosis
Chlamydia trachomatis
Divided into two biovars: trachoma and LGV
major outer membrane protein (MOMP) important structural component
variable regions in gene encoding momp results in 18 serologic variants or serovars
trachoma: serovars A, B, Ba, C
Urogenital tract disease: serovars D-K
Lymphogranuloma venerum: Li, L2, L2a, L2b, L3
pathogenesis and immunity: chlamydia trachomatis
limited range of cells that can infect
receptors for EBs restricted to nonciliated columnar, cuboidal and transitional epithelial cells
Found on mucous membranes of urethra, endocervix, endometrium, falopian tubes, anorectum, respiratory tract, conjunctivae
LGV serovars more invasive due to replication within mononuclear phagocytes
Pathogenesis and immunity: chlamydia trachomatis 2 Chlamydia
Clinical manifestation caused by: direct destruction of cells during replication. Proinflammatory cytokine response they stimulate
entry via minute abrasions or lacerations
severe inflammatory response with neutrophils, lymphocytes, and plasma cells
LGV serovars form lesions in lymph nodes with resulting granuloma formation
infection does not result in immunity
reinfection results in vigorous inflammatory response and tissue damage
results in scarring (ocular and UG), blindness, sterility and sexual dysfunction
Epidemiology: trachoma Chlamydia
leading cause of preventable blindness worldwide
WHO estimates: 6 million blind due to trachoma. 150 million in need of treatment.
endemic in NOrth and sub-Sahara Africa, Middle east, Asia, and South America
Infections predominantly in chidlren and are chief reservoir for endemic disease
trasmitted eye to eye via droplet, hand, clothing, and eye seeking flies
Epidemiology: Urogenital disease Chlamydia
Most common bacterial STI in US
2006 reported 1 million infections
underestimate many patiients do not seek medical care, asymptomatic disease
estimated 2.8 million new infections each year in the US
50 million new infections each year worldwide.
Epidemiology: LGV Chlamydia
occurs only sporadically in US.
Highly prevalent in Africa, Asia, and South America
Seen more frequently in men (women with more asymptomatic disease)
recent outbreaks reported in Europe and NOrth America in MSM
HIV coinfection common
Clinical diseases: Trachoma Chlamydia
Two phases of infection
Active Trachoma: initial infetion causes mild self limited follicular conjunctivitis. Characeristic follice on superior tarsal conjunctiva. Often Asymptomatic.
Cicatricial disease: Severity and duration of active trachoma predicts progression to cicatricial disease. Repeated episodes infection -> conjunctiva inflammation and eyelid scarring. Scarring leads to corneal abrasion and scarring and blindness.
Trachoma Chlamydia
WHO grade TF (trachomatous inflammation, folicular). To make a diagnosis of WHO grade TF, five or more white or yellow follicles > 0.5 mm must be visualized on the upper tarsal conjunctiva
Herbert’s pits are shallow pits in the cornea that form as a result of follicle rupture. They are pathogenomonic for trachoma but are not assessed in the current grading scheme.
Trachoma 2 Chlmydia
- Trichiasis occurs when eyelid conjunctiva scar tissue contracts, distorting the lid margin and causing the eylashes to rub on the cornea.
- Pannus is the growth of vascular tissue over the cornea as a result of edema and ulceration due to eyelash abrasion on the cornea
- evidence of corneal opacity blurring part of the pupil margin.
Clinical disease: Urogenital disease in Women Chlamydia
Asymptomatic disease common in women (up to 80%)
clinical manifestations in women include bartholinitis, cervicitis, endometritis, perihepatitis, salpingitis, and urethrtis
cervicitis most common presentation in women
mucopurulent discharge, friable cervix, and cervica edema see
urethritis often accompanies cervicitis and presents with UTI like symptoms
Tishugh-curtis syndrome: perihepatitis with inflammation of liver capsule
if untreated may develop PID
Chlamydia Cervicitis
mucopurulent discharge is visible coming from the OS in a patient with chlamydia cervicitis. The cervix is erythematous and friable.
Clinical diseases: Urogenitcal disease in Men Chlamydia
Most infections 75% in men symptomatic.
urethral discharge and/or dysuria
Causes 35-50% of cases of NGU (non gonococcal urethritis)
Incubation period longer than N. Gonorrhoeae so consider diagnosis in patients treated for GC who present with new symptoms
Clinical disease: Oculogentical syndromes Chlamydia
Newborn inclusion conjunctivits: acquired during passage of infant through infected birth canal. Develops in 25% of infants whose mothers have active genital infections. After incubation of 5-12 days develop swollen eyelids, hyperemia and purulent discharge
Adult inclusion conjunctivitis: Afflicts 18-20 year olds. Genital infection precedes eye involvement. Transmitted via autoinoculation or oral genital contact. Mucopurulent discharge, keratitis, corneal infiltrates and scarring.
Clinical diseases: Reiter syndrome and infant pneumonia Chlamydia
Reiter syndrome: Uretrhtis conjunctivitis, polyarthritis, and mucocutaneous lesions. Initiated by genital infection with C. Trachomatis. Typically occurs in young men.
Infant pneumonia: Occurs 2-3 weeks after birth. Rhinitis initially hten staccato cough and tachypnea. Typically afebrile. Chest X ray shows bilateral interstitial infiltrates.
Clinical syndromes: LGV
Primary lesion (papule or ulcer) at site of infection develops after incubation period of 1-4 weeks
lesion non painful
may be accompanied by systemic symptoms
second stage of infection with inflammation and swelling of lymph nodes that drain the site of initial infection
inguinal nodes most commonly involved become painful, fluctuant buboes that can rupture
proctitis common in women with LGV due to lymphatic spread from cervix or vagina
utreated may resolve or become chronic with fistulas, strictures, and genital elephantiasis
Clinical syndromes: LGV parinaud oculoglandular syndrome
Caused by LGV serotypes
conjunctival inflammation with preauricular, submandibular, and cervical lymphadenopathy
Laboratory diagnosis Chlamydia
Symptomatic easier than asymptomatic
do not culture pus: need epi cells
do culture: urethra, cervix, rectum, oropharynx, conjunctiva
do not culture vagina
cytology for inclusions, pap smears: insensitive
cultured in cell culture: process quickly, only acceptable test in criminal cases, less sensitive than nucleic acid based tests but more specific
Laboratory diagnosis 2 Chlamydia
antigen detection: direct immunofluorescence, enzyme linked immunoassay, utilizes antibodies directed at MOMP or LPS, may cross react to LPS of other bacteria
Nucleic acid assay (NAAT): best test today. Nucleic acid probe (16s rRNA). PCR, Ligase chain rxn (LCX). Preformed on first voided urine or urethralcervical discharge
serology: limited value except in neonatal disease.
Treatment Chlamydia
LGV: doxycycline for 21 days
erythromycin for neonatal disease.
ocular/genital disease: azithromycin or doxycycline
preventions: increased sanitation, safe sex practices
control: treatment of contacts
FAMILY MYCOPLASMATACEAE
five species associated with human disease
most important species mycoplasma pneumoniae: important cause of respiratory disease
additional pathogens cause GU disease: mycoplasma genitalium, mycoplasma hominis, Ureaplasma urelyticum
Mycoplasma pneumoniae: physiology and structure
smallest free living bacteria
unique because do not have a cell wall and cell membrane contains sterols
because lack cell wall are pleomorphic and cannot be classified as rods or cocci.
sterols may provide added strength/stability to membrane
unable to syntehsis sterol ring so require external source of cholesterol from serum or supplemented media
facultative anaerobes except M. Pneumoniae which is a strict aerobe
Pathogenesis and immunity of mycoplasma pneumoniae
extracellular pathogen that adheres to respiratory epithelium via adhesion proteins
terminal adhesion protein (P1): binds glycoprotein receptors of base of cilia of epithelial cells
results in cilistastasis and then destruction of ciliated epithelial cells.
Pathogenesis and immunity of mycoplasma pneumoniae
loss of ciliated cells interfers with clearnace of upper airways and lower respiratory tract becomes contaminated and irritated
caues the chronic cough seen in M pneumoniae infections
M pneumoniae acts as super antigen
stimulates inflammatory cells to site of infection
cytokine release of TNF alpha, IL1, and IL6
Epidemiology of mycoplasma pneumoniae
strict human pathogen
respiratory disease due to m pneumoniae occurs worldwide throughout the year
proportionally more common during summer and fall
epidemic disease occurs every 4-8 years: usually start in the fall and persist for 12-30 motnhs
most common in 5-15 year olds
not a reportable disease so true incidence is unknown
colonizes airway and transmited vial respiratory droplets during coughing episodes.
Clinical syndromes of Mycoplasma
Mild URTI: most common manifestation
Otitis media; can develop bullous hemorrhaic myringitis
tracheobronchitis: low grade fever, malaise, HA, and dry nonproductive cough. Symptoms develop 2-3 weeks after exposure and can persist for weeks
Pneumonia can develop in some patients. A typical pneumonia (often referred to as walking pneumonia). Patchy bronchopneumonia on chest x ray
compicatios include pericarditis, hemolytic anemia, neurologic abnormalities, encephalitis, arthritis, erythema multiforme and stevens johnson syndrome.
Laboratory diagnosis Mycoplasma
microscopy limited value since no cell wall
culture: relatively insensitive.
Special media with serum (for cholesterol), yeast extract (nucleic acid precursors), glucose, pH indicator, penicillin
gowth indicated by metabolism of glucose and pH change
colonies with homogenous granular appearance
difficult to grow; most labs do not perform cultures
Laboratory diagnosis mycoplasma 2
serology: enzyme immunoassays for IgM and IgG. Four fold rise in titers suggestive of infection. Commonly single serum IgM used for diagnosis results in voer diagnosis due to low specficity. Specific antibody responses may last for months so single serum sample may be misleading. Paired sera should be used to confirm diagnosis
PCR: very sensitive. variable specficity due to cross reaction with non pathogenic mycoplasma
Tx, prevention, and control mycoplasma
sensitive to macrolides, tetracylcines, and fluoroquinolones
avoid tetracyclines and flouroquinolones in children
treatment should be reserved for more serious disease (pneumonia, steves johnson syndrome, neurologic disease.
steroids may be of benefit in servere pulmonary disase, stevens johnson syndrome, encephalitis and hemolytic anemia.
treatment, prevention, and control mycoplasma 2
patients contagious as long as cough persists even with antibiotic therapy
isolation of hospitalized patients
no vaccine available
antibiotic prophylaxis to close contacts who are at high risk (sickle cell disase, immunosupressed) may be of some benefit.
