ICL 2.15: Chlamydia

Question 1

what is the microbiology of chlamydiaceae?

Answer 1

gram (-) with unique lPS but no PG

possess inner and outer membranes

contain both DNA and RNA and prokaryotic ribosomes

they synthesize their own proteins, nucleic acids, and lipids –> obligate intracellular parasites; they’re ATP parasites!!

Question 2

what are the general characteristics of chalmydiaceae?

Answer 2

direct destruction of host cells after replication

pretty nontoxic, highly invasive and causes damage from immune system

Question 3

what’s the developmental cycle of chlamydiaceae?

Answer 3

elementary bodies (EB) = infectious forms that are metabolically inactive

reticulate bodies (RB) = noninfectious forms that are metabolically active

Question 4

which disease syndromes is chlamydia trachomatis responsible for?

Answer 4

trachoma biovariant
1. trachoma

2. conjunctivitis

urogenital biovariant

1. STDS = urethritis, epididymitis,
prostatitis, proctitis, cervicitis,
endometritis, salpingitis, PID,
ectopic pregnancy, infertility
arthritis, infant conjunctivitis,
and pneumonia 

LGV biovariant
1. lymphogranuloma venereum

Question 5

which disease syndromes is chlamydophila pneumoniae responsible for?

Answer 5

1. Pneumonia
2. upper respiratory
   disease
3. cardiovascular disease
4. arthritis

Question 6

which disease syndromes is chlamydophila psittaci responsible for?

Answer 6

1. psittacosis
2. abortion
3. heart tissue damage
4. arthritis

Question 7

what two genera has Chalmydia been split into?

Answer 7

1. chlamydia
   ex. chlamydia trachomatis
2. chlamydophila

Question 8

what is the cell wall of chlamydiaceae like?

Answer 8

their cell wall resembles the cell wall of Gram (-) bacteria with a relatively high lipid content so the gram stain isn’t useful for identifying this organism

instead use Giemsa stain or immunofluorescence

also the cell wall does NOT contain PG but does have penicillin binding proteins (PBP) – this means that cell wall formation is inhibited by penicillins and related B-lactams

however, B-lactam antibiotics are NOT a suitable treatment for Chlamydial infections

Question 9

why don’t B lactams work as treatment for Chlamydia?

Answer 9

chlamydia is an obligate parasite and beta lactams can’t enter our cells, so that would be completely ineffective

chlamydiae are intracellular and neither penicillins nor cephalosporins penetrate human cells adequately

also chlamydia doesn’t have peptidoglycan and beta lactams stop transpeptidase from cross linking peptidoglycan so no peptidoglycan means beta lactams can’t do anything!!

Question 10

which disease is often present at the same time as chlamydia?

Answer 10

about 45% of the cases of gonorrhea have coexisting chlamydial infections

so the recommended treatment of uncomplicated gonorrhea is the administration of both a cephalosporin for the gonococcus and a tetracycline for the chlamydiae

Question 11

which chlamydia disease is a major cause of urogenital disease?

Answer 11

chlamydia trachomatis

Question 12

what does untreated chlamydia lead to?

Answer 12

if left untreated, infection can ascend the endometrial epithelium to the fallopian tubes

severe reproductive complications:

1. PID

PID can cause scarring of the fallopian tubes, sterility, infertility, ectopic pregnancy, or chronic pelvic pain

2. 70% of tubal-factor infertility
3. 35% of cases of ectopic pregnancy

it can also have adverse outcomes during pregnancy like conjunctivitis or passing the infection to the infant

Question 13

what part of the US most prevlalent?

Answer 13

the south = louisiana, georgia, alabama, etc.

Question 14

are men or women more likely to have chlamydia?

Answer 14

black women

Question 15

what does the prevalence of chlamydia depend on?

Answer 15

prevalence is probably actually declining

the actual prevalence of chlamydia depends on the characteristics of the population studied

young age is the factor that is most strongly associated with infection

Question 16

what are the risk factors for chlamydia?

Answer 16

1. multiple sexual partners
2. new sexual partner
3. unmarried
4. black race
5. history of or coexistent sexually transmitted infection
6. cervical ectopy
7. inconsistent use of barrier contraceptive methods

Question 17

what is cervical ectopy?

Answer 17

Cervical ectopywhen the columnar cells of the endocervix extend beyond the external os onto the vaginal surface, the cervix has a red velvety appearance

as the endocervical epithelium is thinner than squamous epithelium, the more vascular endocervical stroma is seen in the underlying stroma

this is called an ectopy or often referred to incorrectly as erosion

Question 18

how is chlamydia transmitted?

Answer 18

mainly during vaginal or anal sex

also possible through oral sex

Question 19

which cells does chlamydia infect?

Answer 19

it initially infects the single-cell columnar epithelial layers of the endocervix of women and the urethra for men

then it multiplies and spreads to surrounding tissues which leads to inflammation, redness, oedema and discharge

Question 20

what are the symptoms of chlamydia?

Answer 20

1. inflammation
2. redness
3. edema
4. discharge
5. mucopurulent cervicitis
6. non-gonococcal urethritis

however these conditions are often subclinical

infections may also be asymptomatic with burning during urination or an unusual discharge being the only symptom – this is super dangerous!!

Question 21

what % of chlamydia infections are asymptomatic?

Answer 21

≥75% of infected women

25%-50% of men

infected men are more likely to (at least) experience burning during urination

Question 22

how does chalmydia trachomatis infect the female genital tract?

Answer 22

Chlamydia trachomatis elementary bodies infect the columnar epithelial cells of the cervix, which often causes few or no clinical symptoms

but the bacteria can ascend to infect the endometrium and the fallopian tubes, causing pelvic inflammatory disease, tubal inflammation (also known as salpingitis), scarring and occlusion, which can lead to infertility or ectopic pregnancy

the inflammatory reaction is characterized by an influx of macrophages and neutrophils and the formation of immune inductive sites in the submucosa

Question 23

when does PID happen during a chlamydia infection?

Answer 23

PID is initiated when bacteria migrate from the vagina or cervix into the reproductive organs

many different organisms can cause PID, but most cases are associated with gonorrhea and chlamydia

up to 30-40% of acute PID cases are polymicrobial –> infection by N. gonorrhoeae or C. trachomatis may compromise mucosa or spread to parametrial structures, allowing bowel and/or normal flora to invade tissues

Question 24

how do you treat PID?

Answer 24

usually treated with at least two antibiotics that are effective against a wide range of infectious agents

must be effective against C. trachomatis and N. gonorrhoeae, as well as against gram-negative facultative organisms, anaerobes, and streptococci

Question 25

what is Reiter's syndrome?

Answer 25

peripheral arthritis lasting longer than 1 month seen with chlamydia infections strongest correlation is with C. trachomatis infection and/or seroreactivity inflammatory arthritis of *large* joints, inflammation of the eyes --> reactive arthritis = triggered following enteric or urogenital infections initial symptom is often painful urination or increased urination frequency also associated with urethritis in men and cervicitis in women sometimes you'll see mucocutaneous and penile lesions a small % of patients will also develop small hard nodules on the soles of their feed or hands symptoms usually resolve after eradicate the infection, but can become chronic "can't see, can't pee, can't blimb a tree"

Question 26

what is LGV caused by?

Answer 26

LGV is caused by serovars L1, L2, and L3 of C. trachomatis

Question 27

what is LGV?

Answer 27

LGV is caused by serovars L1, L2, and L3 of C. trachomatis it enters through skin breaks or crosses epithelial cells of mucous membranes primary stage is marked by the formation of a painless herpetiform ulceration at the site of inoculation = often unnoticed then the organism travels via the lymphatics to multiply within mononuclear phagocytes in regional lymph nodes --> this is characterized by painful inguinal lymphadenitis and associated constitutional symptoms there's also a tertiary stage of LGV that can occur years after the initial infection = anogenitorectal syndrome may occur with resultant rectal stricture or elephantiasis of the genitalia

Question 28

where in the world is LGV most common?

Answer 28

highly prevalent in Africa, Asia and South America mostly in homosexual men

Question 29

what is the EB form of chlamydia?

Answer 29

EB = elementary body this is the infectious environmentall stable particle that's analogous to a spore the highly disulfide crosslinked protein (EnvB) makes the EB resistant to environmental challenges glycosaminoglycan is found on the surface and is required for attachment to host cells (C. trachomatis) elementary bodies bind receptors on cells and are endocytosed they then reside in a host cell surface-derived membrane vacuole = endosome then EB then reorganizes to become the reticulate body! (RB)

Question 30

what is the RB form of chlamydia?

Answer 30

also known as the Initial Body not stable outside host cell and is fragile because it lacks extensive cross-linked outer membrane proteins it's metabolically active but not infectious it dives by binary fission --> reticulate bodies forms new EB by binary fission until the entire vacuole is filled by EB forming an inclusion the developmental cycle takes 24-48 hours

Question 31

what is the developmental lifecycle of C. trachomatis?

Answer 31

EBs attach to epithelial cells and are internalized via receptor mediated endocytosis then the endosome matures into phagosome -- however, the intact EB prevents vesicle fusion to lysosome the EB will convert to RB and the RB will replicate by binary fission to form a mature inclusion that contains like 3000 RB persistence can occur at this stage then the RBs convert to EBs (the inclusion contains both!) after 48-72 hours the EBs are released

Question 32

when should you screen for chlamydia?

Answer 32

screening for C. trachomatis is indicated in sexually active women with risk factors for this infection, including: 1. < 25 years old 2. inconsistent use of barrier contraceptives 3. a new sexual partner 4. more than one sexual partner 5. cervical ectopy 6. history of or coexisting STD annual screening would be recommended if any of these are met

Question 33

how do you detect chlamydia?

Answer 33

chlamydiaceae are obligate intracellular parasites so they can't be grown on any known media source so instead to detect C. trachomatis you have to isolate it in tissue culture; specifically human epithelial cell lines. 1. direct immunofluorescence staining (IFA) 2. ELISA (Ab for both of above assay are against MOMP & LPS) 3. PCR is best ****appropriate sample collection is critical; you have to get into appropriate epithelial layers to get intracellular organisms

Question 34

how do you treat chlamydia?

Answer 34

DOC = tetracycline derivatives ex. Doxycycline for 7 days or single dose of azithromycin topical application can be used for trachoma for STDs, both (all) sexual partners need to be treated to prevent reinfection antibiotics are only effective against the reticulate bodies! and you must take the entire antibiotics course....noncompliance is a big problem

Question 35

how do you treat LGV?

Answer 35

doxycycline twice a day for 21 days

Question 36

what is trachoma?

Answer 36

an infectious disease caused by bacterium Chlamydia trachomatis gradual manifestation of the infection causes a roughening of the inner surface of the eyelids this roughening can lead to pain in the eyes, breakdown of the outer surface or cornea of the eyes, and eventual blindness chronic conjunctivitis is what can lead to blindness caused by eyeshadow......

Question 37

how is trachoma transmitted?

Answer 37

highly infectious through personal contact 1. contact with an infected person’s hands or clothing 2. carried by flies that have come in contact with discharge from the eyes or nose of an infected person (droplet) 3. vaginal delivery of child from infected mother because transmission is through close personal contact, it tends to occur in clusters, often infecting entire families and communities

Question 38

where is trachoma common in the world?

Answer 38

africa is the most affected continent almost half of trachoma burden is concentrated in 5 countries = Ethiopia, India, Nigeria, Sudan, and Guinea but honestly it's all over the world

Question 39

who is susceptible to trachoma?

Answer 39

children are most susceptible to infection, but initial symptoms not too severe they're susceptible because they have a poor protective immune response women are also three times more likely than men to be blinded by the disease which is bad because they're usually the caretakers in the house! it's also a disease of poverty....was used at Ellis Island to turn people away

Question 40

what is the manifestation of trachoma?

Answer 40

initial symptoms aren't severe but repeated infections over 15-20 years lead to scarring it causes the eyelashes to turn inward (trichiasis) and scratch the cornea this leads slowly and painfully to complete blindness... clindness from trachoma usually strikes adults in their prime years which hinders their ability to care for themselves and their families by the end their cornea is literally totally opaque and cloudy....

Question 41

which bacteria causes trachoma?

Answer 41

chlamydia trachomatis

Question 42

how is trachoma a disease of poverty?

Answer 42

women are three times more likely than men to be blinded by the disease and they are traditionally the caretakers of the home when a woman can no longer perform vital activities for her household, an older daughter is often removed from school to fulfill her mother’s role losing her opportunity for a formal education without intervention, trachoma keeps families shackled within a cycle of poverty

Question 43

FLASHCARD: microbiology, pathology, epidemiology, clinical, diagnosis and treatment for chlamydia trachomatis

Answer 43

MICROBIOLOGY: Gram – cocci, will not Gram-stain, no peptidoglycan, obligate intracellular parasite. Has two-phase life cycle. Elementary body (EB) is infectious, non-metabolically active stable particle. Reticulate body (RB) not stable outside host cell, but replicate intracellular in vacuole until form EB. Are 3 biovars: Urogenital (venereal infect), LGV (Lymphogranuloma venereum), Trachoma (eye) PATHOLOGY: EBs attach to epithelial cells and enter endosome. Convert to vacuole, where EBs RBs and replicate to large numbers. Eventually convert to EBs and leave host cells after lysis. EBs introduced via sexual contact or contact (Trachoma). UTI: Preferentially infect columnar epithelial layers (cervix in women, urethra in men) to cause persistent infection. Cause cell death and moderate/light discharge. Women often asymptomatic, men usually symptomatic, particularly when urinating. If untreated, infection in women ascend to damage the fallopian tubes and tissues/organs. LGV: Same as UTI, but migrate to draining lymphatic within macrophages to cause LGV. Trachoma: Infect eye via droplet/contact. Get repeated infection of conjunctiva, leading to scarring & blindness. EPIDEMIOLOGY: Vast majority of the cases in the US are acquired via sexual contact (include oral & anal). Most common in ages 15-25 for both men & women. Also predisposed to lack of barrier contraception, new or multiple sexual partners, African heritage, & living in the South/Midwest US. CLINICAL: Women are often subclinical; discharge only apparent during exam. Men develop urethritis that causes painful urination and strangury, along with discharge. Discharge is usually lighter compared to gonorrhea. Untreated women often develop PID, similar to gonorrhea, leading to infertility and/or ectopic pregnancy. DIAGNOSIS: Cannot culture. Test cervical scrapings or urethral swabs using either fluorescent antibodies (IFA) or via PCR for Chlamydia DNA. TREATMENT: Doxycycline or azithromycin. If UTI, then add Cefixime to treat potential gonorrhea infect

Question 44

how do you treat trachoma?

Answer 44

doxycycline or azithromycin if UTI, then add Cefixime to treat potential gonorrhea infect

Question 45

how do you diagnose trachoma?

Answer 45

cannot culture instead, test cervical scrapings or urethral swabs using either fluorescent antibodies (IFA) or via PCR for Chlamydia DNA

Question 46

C. psittaci vingette

Answer 46

a cough of 3 weeks’ duration fever, chills, shortness of breath, headache, diarrhea, and increasing confusion CXR showed interstitial pneumonia; prominent in lower lobe of left lung family had several parrots in the home that were purchased from a roadside stand near the Texas-Mexico border lab test revealed complement fixation titer for C. psittaci = 1:128 this is a C. psittaci pneumonia infection that is causing psittacosis!

Question 47

what is psittacosis?

Answer 47

an acute infection of lower respiratory tract by Chlamydophila psittaci

Question 48

how do you get psittacosis?

Answer 48

it's contracted by inhaling bird feces, urine, or droplets so people who are at risk are parakeet owners, poultry workers or many other people because any bird can be a reservoir

Question 49

what are the symptoms of psittacosis?

Answer 49

initial infection occurs via respiratory tract you'll see symptoms at 1-2 weeks which can be mild or asymptomatic like a non-productive cough, CNS involvement or headache it can also spread to the liver and spleen and produce focal necrosis there can also be hematogenous spread to other organs..

Question 50

what are the symptoms of severe psittacosis?

Answer 50

1. chills 2. high fever 3. cough 4. confusion 5. dyspnea 6. cyanosis 7. jaundice 8. interstitial pneumonitis

Question 51

what bacteria causes TWAR?

Answer 51

chlamydophila pneumoniae

Question 52

what is TWAR?

Answer 52

chlamydophila pneumoniae infection that produces unique pear-shaped EBs with large periplasmic space it can cause acute respiratory disease but most cases are asymptomatic this is what causes walking pneumonia in young adults!

Question 53

how is C. pneumoniae transmitted?

Answer 53

respiratory secretions humans are only known reservoir, so is considered a human pathogen

Question 54

where in the body can C. pneumonia grow?

Answer 54

1. smooth muscle cells 2. endothelial cells of coronary arteries 3. macrophages

Question 55

which other diseases is C. pneumoniae possibly linked to?

Answer 55

1. heart disease 2. strokes 3. Alzheimers 4. atherosclerosis still hotly debated though if it's actually related to any of these...none of it has actually been proven

Question 56

what is the theoretical mechanims behind how C. pneumoniae would cause atherosclerosis?

Answer 56

atherosclerosis = a disease of the arteries characterized by the deposition of plaques of fatty material on their inner walls infected monocytes adhere and migrate into intima = he innermost coating or membrane of a part or organ, especially of a vein or artery RB --> EB allow infection of other cells infected macrophage start LDL uptake and oxidation infected smooth muscle cells proliferate & secrete cytokines and infected endothelial cells secrete inflammatory mediators further macrophage activation via cytokines elicit tissue factor and metalloproteinases which leads to plaque destabilation and thrombus formation all of this causes an MI....

Question 57

how does the chlamydiae family cause damage in the body?

Answer 57

cause damage by evoking both a cellular and humoral immune response! but they are treatable with antibiotics that can permeate the host cell (aka NOT B-lactams)