Treponema pallidum: Introduction, Pathogenicity, Lab Diagnosis, Treatment and Prevention

Treponema pallidum: Introduction, Pathogenicity, Lab Diagnosis, Treatment and Prevention

Introduction of Treponema pallidum

Fritz Schaudinn (1871-1906) and Paul E. Hoffmann (1868-1959) discovered T.  pallidum in serum in 1905 and 93 years later, in 1998 scientists sequenced the genome of the Treponema Pallidum.

Trepo = turm, nema= thread

Commensals treponemes

T. microdentium  is found in the mouth as a part of normal flora

T. mucosum is found in genitalia as a part of normal flora.

Pathogenic treponemas:

Venereal syphilis and endemic syphilis are caused by T. pallidum

Yaws are caused by T. pertenue.

Pinta is caused by T. carateum.

Scientific Classification of Treponema

Domain: Bacteria

Phylum: Spirochaetes

Order:   Spirochaetales

Family:  Spirochaetaceae

Genus: Treponema

Species: T. pallidum

Binomial name: Treponema pallidum

Treponema pallidum

4-14×0.1-0.2 µm, thin delicate with tapering end with 10 even coils.

Coil to coil distance = 1 µm

Actively motile: back and forward movement and flexion of the whole body.

Demonstration  of Treponema

  • Reiter’s strain – nonpathogenic Treponema related to T. pallidum is cultivable.
  • Culture media is Thioglycolate media with 10% serum.
  • Nichol’s strain of T. pallidum which is pathogenic, non-cultivable, and maintained into Rabbit tests by several passages since 1912.

Resistance

  • Sensitive to heat and cold
  • Delicate and killed by antiseptic and disinfectant
  • Killed at 41°C in 1 hour, which is a basis of fever therapy.
  • Killed in 1-3 days at 0-4°C

The antigenic structure of T. pallidum  is complex.

  • Treponemal infection induces at least 3  types of antibodies.

Reagin antibodies that react with standard or non-specific serological test for syphilis ( antibodies that react with non -treponemal antigen).

  • Wasserman reaction
  • Kahn test
  • VDRL

Antigen: Combination Cardiolipin lecithin and cholesterol non-treponemal antigen have been used to detect antibodies pallidum. However, we have questions.

Is it the antigen of T. pallidum?

Is it the hapten released from tissue damage?

The above test can also be positive in other pathological conditions. e.g. acute febrile illness, immunization, pregnancy, connective tissue disease, leprosy, polyarteritis nodosa, malaria, etc.

2- Protein antigen: (Group Ag.)

This antigen is present in both pathogenic and non-pathogenic strains of T. pallidum.

eg. Reiter’s protein  CFT

3. Polysaccharide antigen ( specific)

Antibodies to this antigen react only with a pathogenic strain of T. pallidum ( including Treponema causing Pinta and Yaws)

  • Treponema Pallidum Immobilization Test

Syphilis

Syphilis is a venereal disease caused by T. pallidum leading to many structural and cutaneous lesions transmitted by direct sexual contact or in utero.

Incubation period: 10-90 days

Stage of syphilis:

Primary syphilis: 10-40 days

Stage of local ulceration and local draining leading to Lymph adenopathy.

” Hard chancre” around the genital area.

Chancres are filled with exudates and contain plenty of Spirochetes.

Secondary syphilis: (2-6 months)

Stage of generalized lymphadenopathy and hypersensitivity, characterized by rashes over skin and mucus membrane.

Tertiary syphilis:

Stage of involvement of internal organs with development of complications.

e.g. Syphilitic myocarditis

Cerebral thrombosis

Retinal thrombosis

Pathogenicity of Treponema

Venereal syphilis is acquired by sexual contact. The spirochete enters to the body through minute abrasion on the skin and mucosa. It multiplies of entry.

Diagnosis of syphilis

Primary syphilis:

Specimen/s:

Exudate from:

Hard chancre

Lymph node

Lab Diagnosis of Treponema

Darkfield microscopy for 3 days ( Sensitivity: there are 10 thousand spirochetes per ml of exudates)

TPI

FTA-ABS: Fluorescent Treponemal Antibody Absorption test

DEA-TP: Direct Fluorescent Antibody Treponema pallidum test ( in tissue and exudates)

Silver impregnation method: in biopsy

VDRL Test

TPHA

Secondary and Tertiary syphilis:

With the use of nontreponemal Antigen

Antigen: Alcoholised, Cholesterolised, Lecithinised beef heart extra cardiolipin.

It reacts with a reagin type of antibody primarily composed of IgG and IgM.

Tests:

  • VDRL test
  • Kahn test
  • Wasserman CFT
  • Rapid Plasma Reagin test

It can also be positive other than syphilis:

  • LL type Leprosy
  • Malaria
  • Infection mononucleosis
  • Hepatitis
  • Tropical eosinophilia
  • SLE
  • Rheumatoid arthritis

With Treponemal antigen:

  • Protein Antigen of Reiter’s stain
  • Carbohydrate Antigen of Nichol’s strain

FTA: Fluorescent Treponemal Antibody test

TPI

Immobilization

If the Spirochetes show loss of mobility after treatment with patient sera in the following rage, The test should be interpreted as follows

More than 50% = Positive

20-50% = Doubtful

Less than 50%= Negative

  • Treponemal protein CFT
  • TPHA: Ag. From Nichol’s strain is coated on RBC
  • Test using killed Treponema pallidum

Nichol’s strain OD Tp ( Formalin Killed)

Serum——– Agglutination—— Positive

(Look under Microscope)

  • Treponema Immune adherence test:

(Von Rickenberg Phenomenon)

Table:28 Suspensions of Treponemes + Test Serum + Complement+ Fresh heparinized whole blood from a normal person

Incubate

Treponemes adhere to the surface of RBC

Phagocyte by WBC

Disappearance    → Positive

Secondary and Tertiary syphilis:

  • VDRL test
  • Kahn test
  • Wasserman CFT
  • Rapid Plasma Reagin test
  • FTA: Fluorescent Treponemal Antibody test
  • TPI
  • Treponema protein CFT
  • TPHA: RBC coated with Nichol’s strain

Frequency of Reactive Serological test in untreated syphilis (%)

Stage                       VDRL                           TPHA             FTA-ABS

Primary                     70                                85                              55

Secondary               100                          100                              100

Latent or Late         70                             98                            98

Treatment of Syphilis

Treatment of T. pallidum, a causative agent of syphilis is included in the following guidelines:

early latent syphilis

late latent syphilis and

congenital syphilis.

Following antibiotics are useful to treat this STI –

  1. benzathine penicillin G,
  2. procaine penicillin,
  3. ceftriaxone,
  4. azithromycin and
  5. doxycycline

Prevention of Syphilis

It cab be prevented by following ways-

  1. Providing education about Syphilis.
  2.  Abstinence
  3. Using condoms during sexual intercourse
  4. Abstain from risky sexual behavior.

Keynotes on Treponema pallidum

  • More than a million Sexually transmitted infections (STIs)  are acquired every day.
  • In 2012, an estimated 357 million new cases of curable STIs may be either gonorrhea, chlamydia, syphilis, or trichomoniasis.
  • It occurred among 15- to 49-year-olds worldwide, including 5.6 million cases of syphilis. There are an estimated 18 million prevalent cases of syphilis.
  • Serologic tests for syphilis may not be positive during early primary syphilis.
  • Doxycycline is strictly prohibited in pregnant women since syphilis during pregnancy can lead to severe adverse complications to the fetus or newborn, stock-outs of benzathine penicillin for use in antenatal care should be avoided.
  • Although erythromycin and azithromycin treat pregnant women, these antibiotics do not cross the placental barrier completely and as a result, the fetus is not treated. It is thus necessary to treat the newborn infant soon after delivery.

Abbreviations and Acronyms

PMTCT: Prevention of Mother-to-Child Transmission

RDT:  Rapid Diagnostic Tests

RPR:  Rapid Plasma Reagin

TPHA:  Treponema pallidum Haemagglutination Assay

TPPA:  Treponema pallidum Particle Agglutination Assay

TRUST:  Toluidine Red Unheated Serum Test

VDRL:  Venereal Diseases Research Laboratory

Further Reading

  1. https://www.ncbi.nlm.nih.gov/books/NBK7716/
  2. http://apps.who.int/iris/bitstream/handle/10665/249572/9789241549806-eng.pdf;jsessionid=106E5A4280411DB19A577E2C12038FD6?sequence=1
  3. https://www.aiims.edu/en/mic_education.html?id=996
  4. Bailey & Scott’s Diagnostic Microbiology. Editors: Bettey A. Forbes, Daniel F. Sahm & Alice S. Weissfeld, 12th ed 2007, Publisher Elsevier
  5. Colour Atlas and Textbook of Diagnostic Microbiology. Editors: Koneman E.W., Allen D.D., Dowell V.R. Jr, and Sommers H.M.
  6. Topley and Wilson’s microbiology and microbial infection – Bacteriology-2-10th Edn

 

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