LECTURE 12 (Chlamydia) Flashcards
What are the different types of Chlamydia?
- Genital Chlamydia
- Ocular Chlamydia
- Laryngeal Chlamydia
Describe Chlamydia Trachomatis
- Gram-negative
- Round
- Outer membrane contains lipopolysaccharide and proteins + has a major outer membrane protein (MOMP) which is immunogenic
- Envelope has no peptidoglycan layer between membranes
- Obligate intracellular growth requires metabolites from host cell
Describe the Chlamydia life cycle
1) Elementary bodies are smaller, have rigid cell walls, can survive outside cells and are infectious
2) EBs attach to cell membranes of susceptible cells they enter + enter cell by endocytosis + transform into larger, fragile Reticulate bodies (RBs)
3) RBs multiply by binary fission and form more EBs that are released by exocytosis or cell rupture to infect adjacent cells + begin a new cycle
What is Chlamydia Trachomatis?
A gram-negative bacteria that leads to the infection “Chlamydia”
EPIDEMIOLOGY:
- Have tropism for (capability of infecting) columnar epithelial cells of endocervix, upper GI tract of women and urethra, rectum and conjunctiva of both sexes
- Endothelium, smooth muscle, lymphocytes and macrophages can also be infected
- Neonatal conjunctivitis contracted from maternal genital infection
- Fomites, fingers and flies involved in transmission of trachoma
- High rate of sexual transmission
SYMPTOMS:
- In men: painful ejaculation, penile discharge, testicular swelling
- In women: painful intercourse, vaginal discharge, bleeding between periods [most women initially have no signs or symptoms]
- Trachoma = chronic inflammation of eyelids + increased vascularisation of corneal conjunctiva + corneal scarring -> visual loss
- Inclusion conjunctivitis = usually presents as acute, watery mucopurulent eye discharge in neonates -> develops into INFANT PNEUMONIA SYNDROME
COMPLICATIONS:
- In men: epididymitis, reactive arthritis, proctitis and proctocolitis
- In women: cervicitis, urethritis, pelvic inflammatory disease (PID), perihepatitis, endometritis, salpingitis or reactive arthritis
DIAGNOSIS:
- Smear/culture from collection of epithelial cells from site of infection (conjunctiva, urethra, cervix) -> detected by immunofluorescence
- Direct fluorescent antibody (DFA) + immunoassay
- Nucleic acid amplification (NAA) tests
- Serodiagnosis (only for genital infections)
TREATMENT:
- Azithromycin, doxycycline and erythromycin
- Prophylaxis for infants using erythromycin or silver nitrate
[not that effective since 15-25% still develop inclusion conjunctivitis]
What is Lymphogranuloma Venereum (LGV)?
A sexually transmitted infection caused by Chlamydia Trachomatis strains L1, L2 or L3
What is Chlamydia Psittaci?
Human Psittacosis is a zoonotic pneumonia contracted through inhalation of respiratory secretions or dust from droppings of infected birds. It leads to an acute infection of the lower respiratory tract.
EPIDEMIOLOGY:
- associated with poultry processing and many birds
- occupational hazard for poultry workers and bird keepers (especially owners of Psittacine birds)
INCUBATION PERIOD:
5-10 days
SYMPTOMS:
- fever + headache
- malaise
- muscle aches
- dry hacking cough
- bilateral interstitial pneumonia
- hepatosplenomegaly
DIAGNOSIS:
fourfold rise in titer of microimmunofluorescence antibody or a single IgM titer of higher than 1:16
[can be isolated from blood/sputum early in disease -> methods attempted in special labs since risk of infection]
TREATMENT:
- doxycycline (preferred)
- tetracycline
- azithromycin
- erythromycin
What is Chlamydophila Pneumoniae?
A disease that is a common cause of “walking pneumonia”
EPIDEMIOLOGY:
- occurs throughout the year
- spreads between person-to-person contact
SYMPTOMS:
- pharyngitis or lowers respiratory infection or both
- pharyngitis/laryngitis may occur 1-3 weeks before bronchitis/pneumonia + cough may persist for weeks
DIAGNOSIS:
- serologic testing (microimmunofluorescence)
- culture
- NAA methods
TREATMENT:
- erythromycin
- clarithromycin
- azithromycin
- doxycycline
- fluoroquinoloones
Describe Rickettsiae
- Pleomorphic coccobacilli -> appear as short rods/cocci
- Structurally Gram -ve, but stain poorly with gram stain
[stained with Giemsa stain, Gimenez stain, Acridine orange] - Cell wall contains lipopolysaccharide, 2 large outer membrane proteins, peptidoglycan
- Obligate intracellular bacteria
- Enter cells by induced phagocytosis + escape cytoplasm by phospholipase
- Outside host cell -> leak protein, nucleic acids and other small molecules
What is Rickettsiae?
Rickettsia is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci, bacilli, or threads
EPIDEMIOLOGY:
- mostly animal reservoirs + spread by ticks, fleas, mites or lice
- global distribution determined by climate, reservoir, vector and human interactions
- quickly destroyed by heat, drying and bactericidal chemicals
PATHOGENESIS:
- tropism for vascular endothelium -> vasculitis -> increased vascular permeability, hypovalemia and hypotension
- focal areas of endothelial proliferation + perivascular infiltration -> thrombosis + leakage of RBCs into surrounding tissues -> rash + petechial lesions
- vascular lesions occur throughout body + produce systemic manifestations
- endotoxins (NO EXOTOXINS!)
DISEASES:
- Rocky Mountain spotted fever
[caused by Rickettsia Rickettsii]
- Epidemic typhus
[caused by Rickettsia Prowazekii + occurs mainly in crowded, unsanitary living conditions during wartime]
- Endemic + Scrub typhus
[occur in developing countries]
- Rickettsialpox
[caused by Rickettsia akari + found in densely populated cities]
What is Rocky Mountain Spotted Fever?
An acute febrile illness that occurs in association with residential and recreational exposure to wooded areas where infected ticks exist. Disease mortality rate is 25% if left untreated.
INCUBATION PERIOD:
6-7 days
EPIDEMIOLOGY:
- caused by Rickettsia Rickettsi
- “wood tick” is the primary vector + “dog tick” is the natural carrier and vector of the disease
- does not kill host -> passed through by transovarial spread
- humans are “accidental hosts” -> no person-to-person transmission
- found in north, central and South America + seen generally between April-September
SYMPTOMS:
- fever
- headache
- petechial rash [diagnositic feature -> rash on palms and soles]
- toxicity
- mental confusion
- myalgia
DIAGNOSIS:
- indirect immune-fluorescence
- ELISA (enzyme immunoassays)
[serologic tests]
TREATMENT:
- Doxycycline [antibiotic of choice]
- Appropriate antibiotic therapy is highly effective on 1st week of illness -> if delayed, therapy is futile
What is Rickettsialpox?
A disease caused by Rickettsia akari and is transmitted by a rodent mice
EPIDEMIOLOGY:
- house mouse + other rodents are primary reservoirs
- humans acquire infection when mite seeks an alternative host
MANIFESTATIONS:
2 PHASES
1) local lesion at bite -> starts as papulovesicle + develops into black eschar in 3-5 days -> fever + other symptoms appear as organism disseminates
2) diffuse rash distributed randomly in body -> becomes vesicular + develops into eschars [IMPORTANT!!!]
RASH DOES NOT APPEAR IN PALMS OR SOLES
TREATMENT:
- self limiting after 1 week
- doxycycline therapy shortens course to 1-2 days
What is Epidemic Louse-borne typhus fever?
A disease caused by Rickettsia Prowazekii that is transmitted to humans by the body louse
INCUBATION PERIOD:
1-2 weeks
EPIDEMIOLOGY:
- only rickettsial disease that can occur as an epidemic
- persist in parts of Africa, Latin America and Asia
SYMPTOMS:
- first signs: fever, headache and rash
- malaise + myalgia
COMPLICATIONS:
- myocarditis
- central nervous sytem dysfunction
- if untreated, fatality rate increases to 60%
DIAGNOSIS:
serology
TREATMENT:
- therapy must be initiated immediately on clinical suspicion
- doxycycline
PREVENTION:
- louse control
- no effective vaccine available
What is Endemic (Murine) Typhus?
Endemic typhus fever is a disease caused by bacteria called Rickettsia typhi or Rickettsia felis
INCUBATION PERIOD:
6-14 days
EPIDEMIOLOGY:
- spread by fleas
SYMPTOMS:
- fever and headache
- rash (not as common)
- GI symptoms: nausea + vomiting + abdominal pain, diarrhoea
- jaundice
- cough
- confusion + seizures
DIAGNOSIS:
antigens shared by R typhi + R prowazekii -> tests may not separate the two diseases
TREATMENT:
typically self-limited disease
What is Scrub Typhus?
A disease caused by Orienta Tsutsugamushi
EPIDEMIOLOGY:
- found predominantly in South Asia, china and Indonesia
- reservoir = mites that infest rodents
- human pick up mites as they pass low trees or bush
SYMPTOMS:
- necrotic eschar at the site of bite
- fever increases slowly over the first week (can reach 40.5 degrees Celsius)
- headache, rash + generalised lymphadenopathy
- hepatosplenomegaly + conjunctivitis
DIAGNOSIS:
- IFA test or PCR test on blood or biopsy
TREATMENT:
doxycycline
[mortality rate of untreated patient is 30%]
Describe Spirochetes
- Large, heterogenous group of spiral, motile bacteria
- Treponemes + Leptospirae -> thin so are seen only by dark field microscopy, silver impregnation or immunofluorescence
- Borreliae -> larger + can be seen with light microscope
What are the three types of Spirochetes that cause human infection?
- Treponema = causes syphilis + non-venereal treponematoses
- Borrelia = causes Lyme disease + relapsing fever
- Leptospira = causes leptospirosis
What is Treponema?
Treponema Pallidum is a spiral-shaped bacteria which is an exclusively human pathogen that causes syphilis
EPIDEMIOLOGY:
- Infection acquired from direct sexual contact with someone who has an active primary or secondary syphilitic lesion
[can also be spread via lips + sharing of needles]
- Late disease is not infectious
- Can be transmitted from pregnant women to foetuses
PATHOGENESIS:
growth of organisms at site of infection, dissemination to various tissues including CNS
PRIMARY SYPHILIS:
spirochetes multiply at site of inoculation -> local, non-tender ulcer (Chancre) forms in 2-10 weeks -> lesion becomes indurated + ulcerates but remains painless + sensitive to touch -> ulcer heals spontaneously but spreads to many organs via bloodstream
SECONDARY SYPHILIS:
1-3 months later, maculopapular rash appear on palms and soles or moist papule on skin and mucous membranes [CONDYLOMATA LATA = moist lesions on genitals] -> lesions rich in spirochetes + highly infectious
LATENT SYPHILIS:
2 stages (early + late) -> early latent period (1-2 years after 2nd stage) symptoms can reappear + patients can infect others -> late latent period, no symptoms occur + patient not infectious
TERTIARY SYPHILIS:
develop from untreated syphilis + appear after 15-20 years -> lead to neurosyphilis
SYMPTOMS:
- Primary syphilis: local, non-tender ulcer
- Secondary syphilis: low-grade fever, malaise, anorexia, weight loss, headache, myalgias, generalised lymphadenopathy, pharyngitis, meningitis, nephritis + hepatitis
- Tertiary syphilis: chronic meningitis with fever, headache, focal neurologic findings, increased cells + protein in CSF, cortical degeneration of brain -> decreased memory, frank psychosis
LAB DIAGNOSIS:
- Microscopy
[lesions of primary and secondary syphilis have chancres -> dark field microscopy + direct fluorescent antibody (DFA) test]
- Serologic tests
[Treponemal tests measure antibodies against T palladium antigens]
TREATMENT:
- Benzathine Penicillin G
[effective for all stages of syphilis + released very slowly so can be present for weeks since T palladium grows slowly]
- If allergic, doxycycline for prolonged periods
What is cardiovascular syphilis?
The usual result is dilation of aorta and aortic valve ring which leads to aneurysms of amending and transverse segments of aorta
What is congenital syphilis?
Syphilis that can be transmitted from mother to foetus through the placenta beginning in the 10th-15th week of gestation
MANIFESTATIONS:
- Foetus death
- Interstitial keratitis
- Hutchinson’s teeth
- Saddle nose
- Periostitis
- Variety of CNS abnormalities
TREATMENT:
adequate treatment of mother during pregnancy
Describe Borrelia
- Irregular, loosely coiled spirochetes
- Stain readily with Giemsa + visualised by dark field microscopy
- Cultured in bacteriologic media containing serum or tissue extracts
- “Borrelia burgdorferi” causes Lyme disease/Lyme borreliosis
What is Borrelia?
Borrelia burgdorferi is a pathogenic spirochete responsible for Lyme disease via a tick vector
INCUBATION PERIOD:
7 days
EPIDEMIOLOGY:
- main reservoir are small mammals (e.g mouse)
- tick must feed for 24-48 hrs to transmit an infectious dose -> inspecting skin after exposure can prevent disease
- no human-to-human spread
- after injection, organism migrates out from site producing skin lesion -> dissemination occurs by lymphatics/blood to other skin and musculoskeletal sites
PATHOGENESIS:
- no exotoxins, enzymes or other virulence factors
- spread of organism from bite site + dissemination through blood to heart, joints and CNS
MANIFESTATIONS:
- After 7 days, SPIROCHETEMIA develops with high fever, rigours, severe headache, muscle pains, weakness -> terminates after 1 week when adequate immune response develops -> disease relapses 2-4 days later
- COMPLICATIONS: myocarditis, cerebral haemorrhage and hepatic failure
LAB DIAGNOSIS:
- Serologic tests from CSF or joint fluid
- Smears (not recommended as not sensitive)
- Culture (not performed since 6-8 weeks + lacks sensitivity)
- Nucleic acid amplification methods + Serology
TREATMENT:
- doxycycline
- amoxicillin
- cefuroxime axetil
[for 14-21 days]
PREVENTION:
- wearing protective clothing
- using insect repellents
What are the symptoms of Lyme disease?
- Headache
- Hearing loss/Paralysis of face
- Muscle soreness
- Erythema migrant
- Fever, chills, fatigue, weakness
- Heart complications
- Nausea + vomiting
Describe Leptospira and Leptospirosis
- Tightly coiled, thin, flexible spirochetes
- One end is often bent, forming a hook
- Actively motile + best seen using a dark-field microscope
- Grow best under aerobic conditions at 28-30 degree Celsius in semi-solid medium
- After 1-2 weeks, produce “diffuse zone”
What is Leptospirosis?
An infection that accidentally infects humans after contact with water or other materials contaminated with excretes of animal hosts
EPIDEMIOLOGY:
- principal sources of human infection = rats, mice, wild rodents, dogs, swine and cattle
- remain viable in stagnant water for several weeks
PATHOGENESIS:
Spread when leptospiras are ingested/pass through mucous membranes or skin -> circulate in blood + multiply in various organs -> produce fever + dysfunction of liver, kidneys, lungs and CNS
SYMPTOMS:
- high fever + headache
- chills + muscle aches
- vomiting
- jaundice
- red eyes
- abdominal pain + diarrhoea
- rash
LAB DIAGNOSIS:
serologic testing
TREATMENT:
- mild cases = oral doxycycline, ampicillin or amoxicillin
- moderate/severe = intravenous penicillin or ampicillin
