SpirochetesSpirochetes

Thin-walled

Spiral rods

Flexible

Motile

Having an axial filament under the outer memberane

MotilityMotility Spirochetes are motile through the undulation

of an axial filament that lies under the outer sheath.

Treponema - Seen only by darkfield microscopy, silver impregnation, or

immunofluorescence. - No growth in bacteriologic media or in cell culture except

nonpathogenic treponems which are part of the normal flora of human mucous membranes.

Leptospira Seen only by darkfield microscopy, silver impregnation, or

immunofluorescence. Growth in bacteriologic media

Borrelia - Larger than two others Seen by Giemsa’s and other blood stains Seen in the standard light microscope Growth in bacteriologic media

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Treponema1

Leptospira2

Borrelia3

Treponema pallidumTreponema pallidum

Causes syphilis

Treponema pallidum pallidumTreponema pallidum pallidum(The bacterial agent of syphilis)(The bacterial agent of syphilis)

Subspecies pallidum

(not bejel, pinta, yaws).

A worldwide STD

The incidence is increasing

TransmissionTransmission

From spirochete-containing lesions of the skin or mucous membranes

From pregnant women to their fetuses

Blood transfusion during early syphilis.

AntibodiesAntibodies

The antigenes of T. pallidum induce specific antibodies, which can be detected by immunofluorescence tests.

They also induce nonspecific antibodies (reagin), which can be detected by the flocculation of lipids (cardiolipin) extracted from normal mammalian tissues, eg. Beef heart.

PathogenesisPathogenesis

No important toxins or enzymes.

Clinical findingClinical finding

Primary stagePrimary stage Secondary stageSecondary stage Tertiary stageTertiary stage

Primary stagePrimary stage

ChancreChancre in 2 – 10 weeks (average 21 days) after exposure.

A single firm, painless, non itchy skin ulceration with a clean base and sharp borders between 0.3 and 3 cm in size.

The ulcer heals spontaneously after 3 to 6 weeks without treatment, but spirochetes spread widely in tissues.

Secondary stageSecondary stage

Secondary syphilis occurs approximately 4 to

10 weeks after the primary infection.

Lesions as maculopapular rash or moist papules on

skin and mucous membranes. Or organ involvement

(meningitis, nephritis, hepatitis….).

Secondary lesions are rich in spirochetes rich in spirochetes and highly

infectious but heal spontaneously.

Tertiary stageTertiary stage

One-third of early syphilis cases progress to cure without treatment.

Another third remain latent; i.e. no lesions appear, but positive serologic tests indicating continuing infections (Asymptomatic).

In the remainder, the disease progresses to the late, tertiary stage.

Tertiary stageTertiary stage

- Granulomas (gummas) ( Gummas in skin, bones, central nervous

system, cardiovascular lesions, e.g. aortitis, aneurysm).

- Paralysis (also tabes and paresis), Blindness, Insanity, Death

- In tertiary stage, the treponemes are very rare.

Congenital syphilisCongenital syphilis

Fetus infection through transplacental passage after the third month of pregnancy.

Unless treated promptly, multiple fetal abnormalities.

Congenital syphilisCongenital syphilis

Early congenital syphilis

Occurs in children between 0 and 2 years old Late congenital syphilis

Starts to occurs after 2 years old

Congenital syphilisCongenital syphilis

Early congenital syphilis

- - Born premature

- Active mucocutaneous syphilis

- Enlargement of the liver, spleen

- Skeletal abnormalities

- Pneumonia

Symptoms can develop two weeks to three Symptoms can develop two weeks to three months after birth:months after birth:

anemiaanemia feverfever rashesrashes skin soresskin sores weak/hoarse crying soundsweak/hoarse crying sounds yellowish skin (jaundice)yellowish skin (jaundice)

Late congenital syphilis

Malformations and damage to:

BonesBones

Brain Brain (neurologic changes)

EyesEyes

EarsEars

Teeth Teeth (Hutchinson's teeth)

ImmunityImmunity

ImmunityImmunity to syphilis is incompleteincomplete:

Antibodies are produced but not stop the progression of the disease.

Patients with early syphilis early syphilis treated can contract can contract syphilis againsyphilis again.

Patients with late syphilis late syphilis are relatively resistantresistant to reinfection.

Laboratory diagnosisLaboratory diagnosis

- MicroscopyMicroscopy

Demonstrating spirochetes by darkfielddarkfield or immunofluorescenceimmunofluorescence microscopy.

- Nonspecific serologic tests Nonspecific serologic tests

- Specific serologic tests- Specific serologic tests

Antibodies agains Treponema palidum:Antibodies agains Treponema palidum:- Nonspecific reaginNonspecific reagin- Specific antitreponemal antibodySpecific antitreponemal antibody

Nonspecific serologic tests- Nontreponemal antigens Nontreponemal antigens (extracts of Cardiolipin

from beef heart) react with “reagin” antibodies in serum samples from patients with syphilis. These antibodies are a mixture of IgG and IgM.

- VDRL (Venereal Disease Research Laboratory)/RPR (Rapid plasma reagin) (a simplified version of VDRL test)

- The reagin antibody binds with the antigen (Antigen is composed of a complex of cardiolipin, lecithin and cholesterol particles with activated charcoal).

- FlocculationFlocculation or or clumpingclumping of the particles is read as a positive test. The test can be quantitated by examining serial dilutions of serum.

The ASI RPR test is in an 8-minute

Nonspecific antibodies (cont.)Nonspecific antibodies (cont.)

Detectable in the majority of patients at the time the primary syphilis and are always present in secondary syphilis.

False-positive reactions may occur (in hepatitis and infectious mononucleosis and autoimmune diseases).

So, positive results have to be confirmed by specific tests.

Specific serologic testsSpecific serologic tests

Using treponemal antigenstreponemal antigens T. pallidum extracted from experimentally infected

rabbits. Reacts in FTA-ABS (fluorescent treponemal

antibody absorbed) test or TPHA (treponema pallidum hemagglutination)

Specific antitreponemal antibodies arise within 2-3 weeks of syphilitic infection.

Specific serologic testsSpecific serologic tests

Treponemal antibody tests are specific for treponematoses but:

- expensive

- remain positive after treatment

TreatmentTreatment

Penicillin G

(A single injection of benzathin penicillin G) can eradicate T pallidum and cure early syphilis.

PreventionPrevention

Administration of antibiotic after suspected

exposure.

The presence of any sexually transmitted disease

makes testing for syphilis mandatory.

No vaccine is available.

BorreliaBorrelia

Borrelia species are irregular, loosly coiled spirochetes which stain with Giemsa’s and other stains.

Culturable in bacteriologic media containing serum or tissue extracts.

Transmitted by arthropods. Cause 2 major disease: relapsing fever and

lyme disease.

Borrelia recurrentisBorrelia recurrentis

Causing relapsing fever During infection, the antigens of these organisms

undergo variation. As antibodies develop against one antigen, variants

emerge and produce relapses of the illness repeating 3-10 times.

Transmission from person to person by human body louse.

Humans are the only hosts

Clinical findingClinical finding

Cyclic Fever, chills, headaches Multiple organ dysfunction

Lab DiagnosisLab Diagnosis

- Microscopy (large spirochetes in stained smears of peripheral blood)

- Culture in special media- Serological tests

Treatment & PreventionTreatment & Prevention

Tetracycline may be beneficial early in the illness and may prevent relapses.

Avoidance of arthropod vectors

Borrelia burgdorferiBorrelia burgdorferi

Causes Lyme disease Transmission by tick bite (genus Ixodes) The main reservoirs: Mice and deer

Incidence of Lyme Disease in the United States, 1991-2006. Lyme

disease is the most prevalent tick-borne illness in the United States.

Clinical findingClinical finding

Early in diseaseEarly in disease:

Fever, severe headache, myalgia, fatigue, depression, stiff neck, and a typical skin rash called ‘erythema chronicum migranserythema chronicum migrans [ECM]’

If untreated, neurologic and cardiac abnormalities ensue weeks later and arthritis follows months to years later. Immune complexes are found in the affected joints.

Erythema migrans

Lab diagnosisLab diagnosis

Serology:

Detecting IgM antibodies by immunofluorescence tests or ELISA

Culture are not typically done.

Treatment & PreventionTreatment & Prevention

Penicillin or Tetracycline

Prevention includes avoiding tick bites.

LeptospiraLeptospira Tightly coiled, fine spirochetes that are not stained

with dyes.

They are seen by darkfield microscopy.

They grow in bacteriologic media containing serum.

Leptospira interrogansLeptospira interrogans

The causative of leptospirosis Divided into serogroups (occurring in different

animals and geographic locations) Each serogroup is subdivided into serovars by

response to agglutination tests. Leptospira infects various animals including rats

and other rodents, domestic livestock and household pets.

TransmissionTransmission Animals excrete leptospiras in urine, which

contaminates water and soil. Swimming in contaminated water or consuming food

or drink results human infection. Miners, farmers and people who work in sewers are at

high risk. Person-to-person transmission is rare.

PathogenesisPathogenesis

Leptospira are ingested or pass through mucous membranes or skin.

They circulate in the blood and multiply in various organs.

Clinical findingClinical finding

Fever Dysfunction of the liver (jundice, hemmorrhage),

kidneys (uremia), and central nervous system (aseptic meningitis)

Subclinical infection is common.

Serovar-specific immunity develops with infection.

Lab DiagnosisLab Diagnosis

Clinical Diagnosis is based on history of exposure.

Serology:

Marked rise in agglutinating antibodies.

Occasionally leptospira is isolated from blood and urine cultures.

Treatment & PreventionTreatment & Prevention

Tetracycline

Prevention:

- Avoiding contact with the contaminated environment.

- Doxycycline in exposed persons.

RickettsiaeRickettsiae

Very short rods and barely visible in the light microscope

Gram-negative but poorly stain with gram stain

RickettsiaeRickettsiae

Non-motile coccobacillus Obligate intracellular parasites, so normally

must be grown in cell culture.

Against chlamydiae divide by binary division not by a distinctive intracellular cycle.

TransmissionTransmission

They maintained in nature in certain arthropods: ticks, lice, fleas and mites

The exception to arthropod transmission is C. burnetii, transmitted by aerosol and inhaled into the lungs.

All rickettsial diseases are zoonoses with the exception of epidemic typhus epidemic typhus which occurs only in only in humanshumans.

Coxiella burnetiiCoxiella burnetii

Q fever (inhalation, contact with the milk, urine, feces, vaginal mucus, or semen of infected animals

R. prowazekii R. prowazekii Epidemic Typhus Epidemic Typhus (by lice)(by lice)

R. typhi Murine or endemic typhus (by fleas, commonly rat flea)

Orientia (formerly Rickettsia) tsutsugamushi Scrub typhus (by mite)

Rickettsia rickettsii Rocky mountain spotted fever (by ticks)

R. prowazekiiR. prowazekii

Growth in the louse's gut Excretion in its feces. Transmition to an uninfected human who

scratches the louse bite (which itches) and rubs the feces into the wound.

R. prowazekiiR. prowazekii

The incubation period: 1-2 weeks.

R. prowazekii can remain viable and virulent in the dried louse feces for many days.

Typhus will eventually kill the louse, though the disease will remain viable for many weeks in the dead louse.

Clinical findingsClinical findings

Severe headache, a sustained high fever (39 °C , common to all forms of typhus), cough, rash, severe muscle pain, chills, falling blood pressure, stupor, sensitivity to light, and delirium.

A rash begins on the chest about five days after the fever appears, and spreads to the trunk and extremities.

Brill-Zinsser diseaseBrill-Zinsser disease

A mild form of epidemic typhus

It occurs when the disease re-activates in a person who was previously infected.

More common in the elderly

R. typhi R. typhi (Murine/Endemic typhus)(Murine/Endemic typhus)

• By bite of certain fleas• Rash and other manifestations are similar to epidemic

typhus:• High fever, severe headaches, a red rash, chills,

myalgia, nausea, vomiting, and cough.

Typhus rashesTyphus rashes

Laboratory diagnosis Laboratory diagnosis of rickettsial infectionsof rickettsial infections

A complete blood count (CBC) may show anemia and low platelets.

Other tests: High level of typhus antibodies Low level of albumin Low sodium level Mild kidney failure Mildly high liver enzymes

Laboratory diagnosis Laboratory diagnosis of rickettsial infectionsof rickettsial infections

Weil-Felix test:

(based on a cross-reaction of proteus vulgaris with R. prowazekii, R. tsutsugamushi, R. ricketsii, …)

Detection of antirickettsial antibodies by agglutination of the antigenes of OX strain of proteus vulgaris

TreatmentTreatment

Mortality rate 10% to 60% in untreated cases Close to zero if intracellular antibiotics, such as

tetracycline.

Can prevented by vaccination.

Intravenous fluids Intravenous fluids and oxygen may be needed to stabilize the patient.