Spirochaetales

The Spirochetes

Spirochaetales

 Classification Spirochetes are members of the order Spirochaetales which contains 2 families  Spirochaetaceae – contains 2 medically important genera   

Borrelia

Leptospiraceae – 1 medically important genus 

Treponema Leptospira

 Morphology and general characteristics  Is composed of:  A helical protplasmic cylinder with a peptidoglycan layer similar to G-B, cytoplasmic membrane, and cytoplasm

Spirochaetales

 A multilayered outer membrane that surrounds the cylinder  Periplasmic flagella which are attached to each end of the protoplasmic cylinder and extend toward the opposite end.  Are not typical flagella and are often called axial filaments

Spirochaetales

 None of the pathogenic

Treponemes

have been successfully cultured on artificial media 

T. pallidum

is usually cultured in the testes of rabbits, although it has been grown in tissue culture for short periods of time.



T. pallidum

host.

does not survive for long outside the  Visualized by darkfield microscopy or iron staining

T. pallidum

Spirochaetales

 Borrelia may be grown on a complex media called Kelly’s media, but this is not usually done in diagnostic labs.

 Borrelia may be observed with darkfield microscopy or be stained in a blood sample with a Giemsa stain or Wright stain.

Borrelia sp.

in blood smear

Spirochaetales

 Leptospira can be grown on semi-solid media containing peptone, beef extract supplemented with rabbit serum or bovine serum albumin and tween 80.  Incubation may be for as long as 28 days.

 Visualize using darkfield microscopy  Identification  Treponema  Observation of organisms in lesions  Detection of antibodies made in the host.  Two types of tests may be used:

Spirochaetales

 Nonspecific, nontreponemal tests – used for screening purposes   Very sensitive, but not specific Many diseases give positive results    Is inexpensive and easy to do Detects non-treponemal antibodies, called reagenic or Wasserman antibodies, that react with a phospholipid (cardiolipin-lecithin) that is a normal tissue constituent Tests include: VDRL test, rapid plasma reagin card tests (RPR), and automated reagin test (ART)

Spirochaetales

   Specific, treponemal tests – used to confirm positive nontreponemal results   Very specific, expensive, and more difficult to perform Include T. pallidum immobilization tests, Fluorescent Treponemal antibody absorption test, indirect Treponemal hemagglutination test Borrelia  Demonstration of Spirochetes in the blood Leptospira   Isolate and culture Specific agglutination test or C’ fixation test – look for 4 fold rise in titer in patient’s antibodies against the organism

Spirochaetales



Virulence factors

 Treponema  Molecular mimicry – the outer sheath contains molecules that resemble the molecules commonly found on the surface of human cells.

 This allows the organism to resist host defenses.

 Hyaluronidase  Borrelia  Antigenic variation

Spirochaetales

 Leptospira  Unknown  Clinical significance  Treponema 

T. pallidum

causes venereal (transmitted by sexual contact) and non-venereal (transmitted by directly by non sexual contact, and indirectly by common usage of eating and drinking utensils) syphilis.    In venereal syphilis the primary lesion is on the genitals In non-venereal syphilis it is on oral mucous membranes. The normal untreated course of the disease occurs in several stages:

Spirochaetales

 Primary stage – following penetration of the skin or mucous membranes, a characteristic, painless hard chancre develops at the site of entry within 3 weeks.

  The chancre is highly contagious and filled with Treponemes. Simultaneously the organism enters the lymphatics and becomes disseminated.  The chancre heals without treatment in a few weeks due to local immunity, but by that time the organism has already disseminated.

Primary syphilis

Spirochaetales

 Secondary stage – 4-8 weeks after the primary stage, the secondary stage develops.   Typically there are lesions (filled with treponemes) throughout the body including the skin, mucous membranes, organs, and eyes.

Most lesions are on the skin and mucous membranes.   The patient may also have a loss of hair, a mild fever, and the development of malaise. This also heals without treatment and the patient may either spontaneously get well or develop a latent infection

Secondary syphilis

Secondary syphilis

Spirochaetales

  Latent infection – during this stage there are no symptoms, but specific anti-treponemal antibodies are found.  This stage may last 3-10 years.   During this time these is a biological balance between the organism and the host. 1/3 to ½ may eventually progress to the next stage.

Tertiary syphilis – this stage is characterized by granulomatous lesions, called gummas, of the skin, internal organs, CNS, bones, eyes, and cardiovascular system.  They are cause by the body’s hyperimmune reaction to remaining spirochetes.    When lesions develop in the CNS it is called neurosyphilis and it can lead to paralysis. In the eyes it can lead to blindness In the heart it can lead to aortic damage or aneurisms.

Tertiary syphilis - gummas

Spirochaetales

 Congenital syphilis – occurs when the treponemes cross the placenta during the fifth month to infect the unborn fetus (occurs usually when mom is in the latent stage).

  This can result in damage to mental development or other neurological symptoms or the child may be born with generalized syphilis. In a pregnant woman who has a primary or secondary stage of the disease, this usually results in stillbirth.

 

T. pertenue

- causes Yaws or tropical syphilis which transmitted by non-venereal direct contact.

T. carateum – causes Pinta, a skin disease with hyperpigmentation in patches.

Spirochaetales

 Borrelia – are arthropod transmitted Spirochetes and they cause:  Relapsing fever – two types:  Epidemic – is caused by

B. recurrentis

human lice. and is transmitted by    This is a more severe form of the disease than the endemic form.

Endemic – is caused by many

Borrelia species

transmitted by ticks and is Both types of relapsing fever follow the same clinical pattern.    12-15 days after infection there is an abrupt onset of fever, headache, and myalgia for 4-10 days.

Antibodies are formed and the number of organisms decrease. This leads to an afebrile period for a few days to several weeks

Spirochaetales

   The fever then relapses because the organism has undergone antigenic variation. The antibodies are no longer effective and the organism numbers increase.  Several relapses may occur with each one being less severe than the previous one.

Lyme disease – caused by

Borrelia burgdorferi

and transmitted by ticks.

   This is a systemic illness that may begin with the appearance of a red skin lesion called erythema chronicum migrans (ECM) because the lesion expands in a circular manner. The patient may also have a fever, headache, nausea, vomiting, myalgia, and fatigue. If untreated, the patient may develop arthritis (acute or chronic), and cardiac or neurologic complications weeks or months later due to immune complexes .

Lyme disease

ECM – from Lyme disease

Spirochaetales

 Leptospira –

L. interrogans

disease or leptospirosis causes Weil’s  This disease is acquired by contact with the urine of an infected animal or ingestion of contaminated food or water.  It is more a disease of animals other than man.

 Infection can vary from asymptomatic to fulminant.

 The CNS, liver, and kidneys are most commonly infected.

Spirochaetales

  In most cases the incubation is 2-20 days followed by fever, chills, severe headache, myalgia, malaise, nausea and vomiting.

  Jaundice occurs in severe cases Death may occur due to renal failure.

Antibiotic therapy/treatment  Treponema – penicillin, tetracycline, or erythromycin   Borrelia - for relapsing fever use tetracycline or erythromycin; for Lyme disease use amoxicillin or doxycycline  Use protective clothing and repellents to prevent infection Leptospirosis provide supportive care; antibiotics (penicillin or erythromycin) are only effective if given during the first 2-4 days of illness