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Chlamydia Classification

- order
- family
- genera containing pathogens x2
- Chlamydiales

- Chlamydiaceae

- Chlamydia
- Chlamydophila
Chlamydia

O - Alice
F - See A
G - Fella
What is the pathogenic species from the genera Chlamydia?
Chlamydia Trachomatis
"Chlamy...T...a"
What is the pathogenic species from the genera Chlamydiaphila? x2
Chlamydophila

- Psittaci

- Pneumoniae
chlamydo....P....hila
The term "Chlamys" comes from the histological appearance meaning what?
"draped around the shoulder"
Chlamydia is what Type of parasite depending on its growth/replication location & O2 requirement?
Obligate Intracellular Parasite
Chlamydia pathogen

- Size?
- Clinical relevance
- Small

- Passes through Filtration method even with a 45 micrometer filter
Chlamydia stains how?
Gram NEGATIVE
Chlamydia has what 2 types of morphological forms?
- EB (Elementary body)

- RB (Reticulate body)
Chlamydia's morphological form can be determined at the ER

"Chlamydia is SIMPLE, yet MESHY"
Which morphological form is the infectious one, & what is the clinical relevance?
EB only

EB is the type of FORM that lives OUTSIDE the cell to infect another cell. Then replicate inside
Elementary body (EB)

- size comparison to RB?
- durability to environmental factors?
- Small : ~300nm - ~400nm

(RB is ~800nm - 1000nm in size)

- EB is VERY RESISTANT to harsh environmental factors

(much like a spore)
Compared to most bacteria, EB's outer membrane is unique because it....

- NOT have what?
- Has what to compensate?

- how does it help it survive?
NO Peptidoglycan layer

Extensive
DISULFIDE CROSSLINKING
btw cysteine residues

Disulfide Crosslinks = Protection from osmotic pressure, so don't need PG
EB outer membrane has an extensive disulfide crosslink. What is the name of the protein that forms this crosslink?
Outer membrane protein 2
If EB is the infectious form, then the RB (or Initial Body - IB) is?
- Replicative form
Differences btw EB vs. RB

- function in lifecycle
- metabolic activity
EB
- infectious form
- metabolically INERT (spore-like)

RB
- replicative form (intracellularly)
- metabolically ACTIVE
Discuss the outer membrane of the RB in comparison to EB.

This implies what about its status?
Reduction of Disulfide bonds

(membrane proteins are NO longer crosslinked)

Osmotically FRAGILE
Which Chlamydia form is called the Energy Parasite and why?
RB

b/c Requires Host-Derived ATP (energy)
Describe the Growth cycle of Chlamydia.

- 8 steps
1. EB enters cell via ENDOCYTOSIS

2. After EB internalizes, it PERSISTS inside endosome
(aka-Cytoplasmic PHAGOSOMES)

3. While in the Endosome, EB will INHIBIT Phago-Lysosomal Fusion

4. EB will CHANGE in to RB (after 8 hrs) while still in the endosome/phagosome

5. RB REPLICATES by binary fission

6. Replication causes ASSEMBLY & ACCUMULATION of many INCLUSION BODIES inside the phagosome

7. Once persistent infection established, RB will STOP Replicating & CHANGE Back into EB (18-24 hrs later)

8. Cell EXOCYTOSIS/RUPTURE, thus releasing 100 - 1000 EB units
(48 - 72 hrs)
EPIC

RACE
In order to stop the digestion of itself, Chlamydia Trachoma....

- does what?
- where?
- then what?
Inhibit Phago-Lysosomal Fusion

Inside the Phagosome/Endosome

Changes to RB for replication
While inside the phagosome/endosome, C. trachoma will at what time....

- Change into RB
- Change back in to EB
- Exocytose/rupture out of the cell releasing 100 - 1000 infectious EB units.
- 8 hours

- 18 - 24 hours

- 48 - 72 hours
Trachoma has 8 letters

3 events so just multiple previous hr by 3
What is a BIOVAR?
Prokaryotic strain with different BCHM and/or Physiological characteristic

yet are of the SAME SPECIES
What are the 2 HUMAN Biovars for C. Trachomatis?
1. Trachoma

2. LGV
(LymphoGranuloma Venereum)
C. Trachomatis biovar, Trachoma

- infects what cell types?
- infecting what type of tissues?
- infecting what type of areas? x6
- NON-ciliated Epithelial cells
on
- Mucous membranes
of the
- Urethra (not uterus!!!!)
- Fallopian tubes
- Cervix
- AnoRectum
- Respiratory Tract
- Conjunctiva
Infection areas are a NE-Mesis to the UFC ARC
C. Trachomatis biovar, LGV

- stands for?
- can also replicate inside what cells
- ... of what body system?
- LymphoGranuloma Venereum

- Mononuclear Phagocytes

- Lymphatic system
C. trachomatis causes what generalized symptoms?
- Ocular / Eye infections
- Genitals / Sex organ infections
- Pneumonia (Lungs infections)
- LGV
ESL

LGV
Describe the Pathogenesis options the C. trichomatis has after internalizing inside the host cell.

(also include whether it is in EB or RB form)
1. DIRECT destruction of host cell during replication & lyse. (RB)

2. Establishment of persistent/LATENT infection (EB)
For C. trachomatis, what would be the cause for the organism going into latent stage?
Unfavorable conditions cause development of EB form (non-replicating form)

- Antibody presence
- IFN-gamma
- Deprivation Nutrient
For C. trichomatis, describe the duration of infection
Can last many months and spontaneously clear

or Direct destruction
For C. trichomatis, describe the host's inflammatory immune response with infection, including the consequences.
NO long lasting immunity or partial immunological protection
allows for
RE-Infection AND Chronic inflammation
For C. trichomatis, Reinfection will induce the host's inflammatory immune system to do what?

What is the end result of this response?
VIGOROUS inflammatory response
(potent inducer of IFN-gamma & IL-1)

subsequent TISSUE DAMAGE
(SCARRING)
T/F : Chlamydia has a vaccine
False
Trachoma Biovar

- # of serotypes
- epidemiology x3
Leading cause of

- BLINDNESS in developing nations
- Clamydial GENITAL infections
- STD in western world
bcs
LGV Biovar

- # of serotypes
FIVE

- L1, L2, L2a, L2b, L3
Why is it so challenging to ID & Tx infected individuals before irreversible tissue damage occurs?
B/c patients are ASYMPTOMATIC
Chlamydia Epidemiology

- Highest infection rate in US?
- Louisiana?
- Alaska
(Mississippi is #2)

- #7
Chlamydia Epidemiology

- Highest incidence rate for gender
- for age group?
- women

- 15 - 24
List the clinical Dz caused by Trachoma biovar. x5
4. Trachoma
5. Adult Inclusion Conjunctivitis
2. Neonatal Conjunctivitis

3. Infant Pneumonia
1. Urogenital infections
TAN UP

Adult I(c)
Neonatal C
Infant P
List the clinical Dz caused by LGV biovar.
LGV
Trachoma Biovar of Serotype A - C

- causes what Dz?
- Dz aka?
- Epidemiology for blindness
- Predominantly occurs in?
Trachoma

Chronic Keratoconjunctivitis

Leading cause of PREVENTABLE blindness
#2 Cause of Blindness (behind cataracts)

Children in Endemic areas
(reduced in older kids, but increases again as Dz progresses)
Trachoma Dz

- Transmitted how? x6
- what promotes transmission?
- hand
- eye to eye droplets
- respiratory droplets
- fecal contamination
- fomites
- flies

Poor sanitation, hygeine, & crowded conditions
her fff
Trachoma Dz Progression

- What happens initially x2
- leading to?

- Then what follows?
- leading to?

- Overtime, what leads to blindness? x3
1. Chronic Follicular Conjunctivitis
2. Diffuse inflammation involving the ENTIRE conjunctiva

- Scarring of conjunctiva

1. Eyelids turn inward (TRICHIASIS)

- Corneal abrasion

Corneal scarring
Ulceration
Pannus formation
Adult inclusion conjunctivitis

- serotypes?
- transmission how?
- transmission vehicles?

- Associated with what symptoms?
- A,B, D - K

- STD
- Autoinnoculation w/ genital secretions
OR Direct inoculation by infected partner

- Genital infection that PRECEDE eye involvement
Adult inclusion conjunctivitis symptoms? x4
- Mucopurulent discharge
- Occasional corneal vascularization
- Corneal infiltrates
- Keratitis
MOCK
Adult inclusion conjunctivitis prognosis?
Corneal scarring may occur in chronic infections

BUT infections usually resolve without complications
Urogenital Infections

- serotypes?
- occurs mostly in?
- symptoms?
- severity of consequences?
- Trachoma Biovar D - K

- Women

- Asymptomatic

- Serious consequences
What is Trichiasis?

What Dz is it associated with?
Eyelids turn inward

Trachoma
Trac-tion of eye turns it inward in Trach-oma
Urogenital Infections in women

- Risks x3
- sexual intercourse 30% higher than men

- younger age increase risk
(cervix not fully mature?)

- chlamydia infected women are 5x's more likely to be infected with HIV if exposed
Urogenital Infections in women

- Infections usually begin where?

- spread to where?
Cervix and/or Urethra

ASCENDS to: (if untreated)

- Fallopian tubes
- Uterus
Urogenital Infections in women

- Symptomatic infection characterized by? x2

- occurs when?

- resulting Sx? x3
- Mucopurulent discharge
- Hypertrophic ectopy

- 1 to 3 wks after infection

- Post-Coital bleed
- Abnormal menstrual bleed
- Dysuria
HE MD

PAD
Urogenital Infections in women

- Untreated/Undertreated infections progressing to where?

- resulting Dz

- why bad?

- Sx x3
- uterus/fallopian tubes lead to?

- PID

- Irreversible tissue/organ damage

- Infertility
- Chronic pelvic pain
- Ectopic pregnancy
ICE needed for the Pelvis In Disease
Urogenital Infections in women

- Ectopic pregnancy occurs b/c of?

- what % of ectopic pregnancies are due to C. trachomatis?
Salpingitis
(inflammation of fallopian tubes)

1/3
Urogenital Infections in women

- infection during pregnancy can result in? x5
- preterm labor
- premature rupture of membranes
- post-partum endometriosis

- Low birth weight
- Neonatal Death
Urogenital Infections in women

- C. trachomatis EB's prefer to infect what cells in the cervix?

- problem with this?
Columnar epithelial cells of cervix

causes little to no clinical symptoms
Neonatal conjunctivitis

- serotype?
- aka
- acquired how?
- Trachoma Biovar D - K

- (ophthalmia neonatorum )

- passage thru birth canal thats infected
Neonatal conjunctivitis

- what % of exposed newborns develop conjunctivitis?

- Eye infection develops when?

- Prognosis?

- Untreated INFANTS are at increased risk of?
25% to 50%

5 to 12 days after birth

Self-Limiting
Spontaneous resolution in 3 - 12 mo.

Pneumonia
Infant Pneumonia

- 10 to 20% of exposed newborns will develop what type of pneumonia?

- Onset when usually?

- Characterized by?
- Diffuse Interstitial Pneumonia

- 2 to 3 weeks after birth

- Afeb &
- Rhinitis
- Staccato cough
Urogenital infections in Men

- What % is Asymptomatic?
- Responsible for what % of nongonococcal urethritis?

- Symptoms?
- Sx develops when?
- Dual infection with what is common?
- 25 - 50% asymptomatic
- 35 - 50% of nongonococcal urethritis

- Less purulent (almost clear) Discharge
- Dysuria
- Pyuria

- 1 to 3 wks post infection

- N. gonorrohoeae
Urogenital infections in Men

- infected men have what attached to sperm?

- associated with what syndrome?
EB

Reiters
Reiter's syndrome has what hereditary factor associated?

What % of patients has it?

What % of patients has chlamydial infection?
HLA - B27

80%

50 - 60%
Urogenital infections in Men

- progression associated Dz? X3
- Proctitis (usually symptomatic)
- Urethritis (Non-gonococcal)
- Reiter's
- Epididymitis
MEN get it PURE
Urogenital infections in Women

- progression associated Dz? X3
- PID

- Infertility

- Ectopic pregnancy
Women's PIE hole progressive worse.
LGV

- transmitted how?
- Acute form affects which gender
- why so?
STD

Men

Symptomatic infection LESS in Women
LGV

- Reservoir in the US?

- emerging dz has led to new dz variant where?
- Homo dudes

- Amsterdam (L2b)
LGV

- systemic Sx
- Fever , HA , Malaise
- Arthralgia , Myalgia,
- Anorexia , Meningismus,
T/F : LGV more invasive than Dz caused by urogenital serovars (D-K)
True
LGV manifests as? x2 syndromes

- include associated symptoms
Anogenitorectal syndrome

- Protocolitis
- Intestinal hyperplasia
- Perirectal lymphatic hyperplasia


Inguinal syndrome

- Buboes (inguinal lymphadenopathy)
- Ulcerations of genitals
- Supparation
LGV --> A PIP , IN BUS
Which LGV associated Syndrome is common in women?

- spread how? x2
Anogenitorectal Syndrome

- anal intercourse
- lymphatic spread from urethra
LGV stages x3
1. PAINLESS primary lesion of sexual organs/area
(1-4 wks after infection)

2. Inflammation / swelling of Lymph nodes draining site of infection

3. Chronic Ulcerative phase
LGV 's 3 stages

- if left UNtreated, what stage occurs?

- in stage 2, lymph nodes become?
- what can happen from this?

- in stage 2, which lymph node most affected?
stage 3

PAINFUL Buboes
- can rupture into draining fistulas

Inguinal lymph node
LGV camera at the big stage took good PICs

Pain-LESS
Inflammation --> Pain-FULL Buboes
Chronic ulceration
What is a Buboes?

In LGV, seen in what stage usually?

Pain?
Inguinal Lymphadenopathy

Stage 2

YES!!!!!!!!!
LGV Stage 3 involves development of?
Genital
- Fistulas
- Ulcers
- Strictures
- Elephantitis
FUSE
LGV can occur where besides the genital area?

- indicated in what Dz
- Sx?
Ocular LGV

Perinaud's oculogranuloma conjunctivitis

Conjunctival inflammation
- with nearby swollen lymph nodes
LAB DIAGNOSIS

- specimen from? & NOT from?

- specimen cell type should be

- specimen is INADEQUATE if from?
- tissue specimen from EndoCervix
- Vagina

- Columnar epithelium cells

- Pus or Exudate

-
LAB DIAGNOSIS

- what are the methods? x5
Cytology

Serology

Culture

Antigenic detection

Nucleic acid based test
SCAN CYTe (site)
LAB DIAGNOSIS : Cytology

- examine what?

- look for what?

- PROBLEM? x2
- Giemsa stained cell scrapings

- Look for INCLUSIONS

PROBLEMS:
- Insensitive
- NOT recommended
LAB DIAGNOSIS

What is the GOLD standard?
Nucleic acid based Test
- molecular probes
LAB DIAGNOSIS : Culture

- advantage?

- disadvantage?

- problem is that detection compromised during?
- MOST SPECIFIC

- only 70% Sensitive

- specimen manipulation / transport
LAB DIAGNOSIS : Culture

- looks for what?
Inclusion bodies
- Iodine stained

MOMP or LPS
- Fluorescent
LAB DIAGNOSIS : Antigen Detection

- technique? x2
- look for what?

- Problem?
- Direct immunofluorescence
- ELISA

- Antibody to detect LPS or MOMP

- Low bacterial load in male urethral samples & asymptomatics
- LPS may be shared with other bacteria
LAB DIAGNOSIS : Serology

- value?

- why or why not? x2
LIMITED

- Antibody titers do NOT distinguish current or past infections.

- IgM often are NOT produced
LAB DIAGNOSIS: Serology

- is there any exception to a good serology test being worthwhile?

- explain

- THUS, Serology is helpful in?
- why?
Yes

Most patients do NOT produce IgM antibodies, EXCEPT for ...
- INFANTS with Chlamydial Pneumonia

LGV diagnosis in INFANTS
- Infants produce vigorous Ab response