SPIROCHETES

Introduction to Spirochetes

• Long, slender, helically tightly coiled bacteria

• Gram-negative
• Aerobic, microaerophilic or anaerobic .
• Corkscrew motility
• Can be free living or parasitic
• Best-known are those which cause disease: Syphilis
and Lyme’s disease

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Morphology

• Have axial filaments, which are otherwise similar to bacterial flagella

• Filaments enable movement of bacterium by rotating in place

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 Spirochaetales Associated Human Diseases

Genus Species Disease

Treponema pallidum ssp. pallidum Syphilis
pallidum ssp. endemicum Bejel
pallidum ssp. pertenue Yaws
carateum Pinta
Borrelia burgdorferi Lyme disease (borreliosis)
recurrentis Epidemic relapsing fever
Many species e.g duttonii Endemic relapsing fever
Leptospira interrogans Leptospirosis
(Weil’s Disease)

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GENUS TREPONEMA
• Regularly coiled with longer a wavelength than Leptospira.
Several species and subspecies are important human
pathogens, others are members of normal flora especially in
the mouth.
• T.pallidum and its subspecies pertunue and T.caratenum are
most important species.

CHARACTERISTICS OF TREPONEMA
• Individual cell are too small to visualize by direct light
microscopy, can be seen with darkfield illumination or silver
impregnation or immunofluorescent .
• staining cells are actively motile by means of flagella
contained within the periplasmic. 5
TRANSMISION
• Very susceptible to heat and drying, so successful transmission
depends upon very close contact. T.pallidum is spread by close sexual
contact and may also be vertically transmitted in utero.
• Yaws and pinta spread by direct contact from infected skin lesions.
No animal reservoir.

PATHOGENESIS
-Study of virulence factors hampered by the inability to grow
T.pallidum in artificial culture media

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Stages of Syphilis
• Primary
• Secondary
• Latent
• Tertiary
• Congenital Syphilis

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Primary - Chancre
• Chancre is most frequently seen on the external
genitalia
• In women the lesions may form in the vagina or on the
cervix.
• In men it may be inside the urethra, resulting in a serous
discharge.
• The lesion heals spontaneously after 1-5 weeks.
• Swab of chancre smeared on slide, examined under
dark-field microscope, spirochetes will be present.
• Thirty percent become serologically positive one week
after appearance of chancre, 90% positive after three
weeks.
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Primary Syphilis - Chancre

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Primary Syphilis - Chancre

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Differences between chancre and
chancroid
• This a chancroid caused by
Haemophilus ducreyi or
Streptobacillus
• Unlike chancre it’s painful and
soft.

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Darkfield Microscopy

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Fluid From Chancre

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Secondary Syphilis
• Occurs 6-8 weeks after initial chancre, becomes systemic, patient
highly infectious.
• Characterized by localized or diffuse mucocutaneous lesions, often
with generalized lymphadenopathy.
• Primary chancre may still be present.
• Secondary lesions subside in about 2-6 weeks.
• Serology tests nearly 100% positive.

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Secondary Syphilis
• A widespread eruption resembling psoriasis or pityriasis rosea which
prominently involves the hands should always include the differential
diagnosis of secondary syphilis.

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Secondary Syphilis
• Secondary syphilis lesions on back

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Latent Syphilis
• Stage of infection in which organisms persist in the body of the
infected person without causing symptoms or signs (asymptomatic).
• This stage may last for years.
• One-third of untreated latent stage individuals develop signs of
tertiary syphilis.
• After four years it is rarely communicable sexually but can be passed
from mother to fetus.

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Latent Syphilis
• This stage may be further subdivided.
• Early latent, initial infection occurred within previous 12 months.
• Late latent, initial infection occurred greater than 12 months.

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Tertiary Syphilis
• Divided into three manifestations:
• Gummatous syphilis
• Cardiovascular syphilis
• Neurosyphilis

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Tertiary Syphilis - Gummatous
• Gummas are localized areas of granulomatous inflammation found on
bones, skin and subcutaneous tissue.
• Cutaneous gummas may be single or multiple, generally asymmetric
and grouped together.
• Visceral lesions often cause local destruction of the affected organ.
• Contain lymphocytes, plasma cells and perivascular inflammation.

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Tertiary Syphilis Buboe of Neck

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Tertiary Syphilis

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Tertiary Syphilis - Gumma

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Tertiary - Cardiovascular
• This condition appears 20 or more years post-infection.
• Usually involves the aorta.
• Invading treponemes cause scarring of the tunica media.
• Over many years, the inflammatory scarring weakens the aortic wall,
leading to aneurysm (weakness or thinness in the blood vessel wall
formation) which causes incompetence of the aortic valve and
narrowing of the coronary ostia

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Tertiary - Cardiovascular
• Antibiotic treatment cures the syphilis infection and stops the
progress of cardiovascular syphilis.
• The damage that has already occurred may not be reversed.

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Neurosyphilis
• Caused by invasion of organisms into the CNS.
• Manifests as an insidious but progressive loss of mental and physical
functions and is accompanied by mood alterations.
• General paresis of the insane:
• forgetful,
• personality change,
• psychiatric symptoms.
• Onset usually 10-20 years after primary infection.
• Treatment may not improve symptoms.

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Neurosyphilis
• Neurological complications at this stage include generalized paresis of
the insane which results in personality changes, changes in emotional
affect, hyperactive reflexes.
• Tabes dorsalis, degeneration of lower spinal cord, general paresis and
chronic progressive in a state of mind which prevents normal
perception, behaviour, or social interaction; seriously often results in a
characteristic shuffling gait.
• Can only be diagnosed serologically by VDRL.

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Neurosyphilis
• Cerebral atrophy, most prominent in frontal lobes
seen in general paresis.

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Congenital Syphilis
• Transmitted from mother to fetus.
• Fetus affected during second or third trimester.
• Forty percent result in syphilitic stillbirth-fetal death that occurs after
a 20 week gestation and the mother had untreated or inadequately
treated syphilis at delivery.

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Congenital Syphilis…
• According to the CDC, 40% of births to syphilitic mothers are stillborn.
• 40-70% of the survivors will be infected, and 12% of these will
subsequently die prematurely
• Death from congenital syphilis is usually through pulmonary
hemorrhage.

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Congenital Syphilis…
• Bone deformities
• Blindness
• Deafness
• Deformed faces
• Dental deformities
• Skin rashes
• Neonatal death

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Congenital Syphilis..
• Live-born infants show no signs during first few weeks.
• Sixty to 90 % develop clear or hemorrhagic rhinitis.
• skin eruptions (rash) especially around mouth, palms of hands and soles of
feet.

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Congenital Syphilis
• Early onset syphilis manifests at birth or months after, exhibiting a diffuse
infiltration, scabs and fissuring along the periphery of the mouth, which
leave sulci in a radiated pattern or rhagades

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Congenital Syphilis
• clear or hemorrhagic rhinitis

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Congenital Syphilis
• Skin eruptions (rash) especially around mouth, palms of hands and soles
of feet

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Congenital Syphilis
• Hutchinson’s incisors.

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Diagnosis of Syphilis
• Evaluation based on three factors:
• Clinical findings.
• Demonstration of spirochetes in clinical specimen.
• Present of antibodies in blood or cerebrospinal fluid.
• More than one test should be performed.
• No serological test can distinguish between other
treponemal infections.

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LABORATORY IDENTIFICATION
• T.pallidum and closely related species cannot be
grown in artificial media; diagnosis of infections
depends upon microscopic examination of fluid from
primary lesions and serology

• Direct examination of clinical specimen by dark-field

microscopy or fluorescent antibody testing of sample.
• Non-specific or non-treponemal serological test to
detect reagin, utilized as screening test only

• Specific Treponemal antibody tests are used as a

confirmatory test for a positive reagin test.
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Nontreponemal Reagin Tests
• Non-specific or non-treponemal serological test to
detect reagin, utilized as screening test only.
• Reagin is an antibody formed against cardiolipin.
• Found in sera of patients with syphilis as well as other
diseases.
• This type of reagin not to be confused with same word
originally used to describe IgE.
• Non treponemal tests become positive 1 to 4 weeks after
appearance of primary chancre.
• in secondary stage may have false negative due to
Prozone, in tertiary 25% are negative, after successful
treatment will become nonreactive after 1 to 2 years.

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Nontreponemal Reagin Tests
• VDRL
• RPR
• USR-unheated serum reagin test
• RST-reagin screen test
• ELISA

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TREATMENT AND PREVENTION
• Penicillin is the treatment of choice of Syphilis.
• Tetracycline may be given to penicillin allergic patients.

PREVENTION
• Depends upon detection and treatment of cases, contact
tracing and serological testing of pregnant women.
• Possible cross reaction between T.pallidum and the
species causing yaws and pinta must be noted

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GENUS BORRELIA
• Two species of Borrelia are important in humans
B.burgorferia cause Lyme disease; B.recurrentis
causes relapsing fever.

CHARECTERISTICS
• Less finely coiled than the leptospires. Cell 0.2-
0.5macro meter in diameter; stain readily so are
visible by using light microscopy

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LABORATORY IDENTIFICATION
• Microaerophilic, complex nutritional requirements, long growth time
(weeks) thus culture is not routinely used for identification
B.recurrentis demonstrated in blood smear by staining Giemsa or
acridine orange.
• B.burgdorferi much more difficult to visualize culture from biopsy
material, possible but difficult diagnosis usually by serology.

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DISEASES
• In relapsing fever the relapsing element may be due
to antigen switching.
• Lyme disease slowly progressive rather than relapsing.
Characteristic ‘’bulls eyes’’ skin lesion (erythema
chronicum migrans) commonly occurs.
• Joint pains and fatigue common and latter in
untreated cases, neurologic and cardiac
manifestations.

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Erythema chronicum migrans
of Lyme Borreliosis

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TRANSMISSION
• B.recurrentis spread from person to person by Lice.
• Lyme is a zoonosis transmitted to human by hard ticks (lxodes spp).
• Ticks bite is often unnoticed but less than a minute is required for the
organism to enter the host.

PATHOGENESIS
-Little known about pathogenesis of either disease Antigen switching in
B.recurrentis presumably allows evasion of host’s antibody response.

TREATMENT AND PREVENTION

-Doxycycline, but erythromycin and penicillin have both been used
successfully.

PREVENTION
-Prevention depends upon avoiding contact with vectors. 46
BORRELIOSIS (LYME
DISEASE)
• Lyme disease is a zoonotic infection caused by the
corkscrew-shaped spirochaetes of the genus Borrelia
• The species known in causing the disease are:
• Borrelia burgdorferi senso stricto,
• B. recurrentis,
• B. garinii,
• B. afzelii.
• Borrelia burgdorferi senso stricto and B.
recurrentis are commom causes of Relapsing
fever

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BORRELIOSIS by Borrelia
bugdorferi sensu stricto
• Aetiology: Borrelia bugdorferi sensu stricto (zoonotic
to human)

• Distribution: World wide including Tanzania

• Host susceptibility: All age of both genders are equally

susceptible although children are more affected

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BORRELIOSIS by Borrelia bugdorferi sensu stricto

• Reservoirs: Small rodents especially white footed

mouse (Peromyscus leucopus), chipmunk, dusky
wood rat (pack rat) and Kangaroo rat serve as
reservoirs for vector soft ticks (Ixodes dammini)

• Deer and other wild ruminants serve as a mating

ground for adult ticks and provide adult female ticks
the blood meal required for egg production

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BORRELIOSIS by Borrelia bugdorferi sensu
stricto

• Dogs, horses, cattle and passerine birds are also more

susceptible to infection.

• Transmission: Bite by Ixodes dammini, I. recinus and

Dermacentor variabilis

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BORRELIOSIS by Borrelia bugdorferi sensu
stricto

Disease in humans:
Incubation period is 7-14 days

Three forms of the disease:

Skin rashes, stiffness of joints and neck, headaches, malaise
and swelling of lymph nodes.
Characteristic bull’s eye rash, erythema migrans and
fever

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BORRELIOSIS by Borrelia bugdorferi sensu
stricto

Multiple skin patches, arthritis, fatique,

intermittent swelling and pain of large
weight bearing joints like knee and nervous
signs
• Chronic arthritis, chronic neurological signs
and cardiac signs

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BORRELIOSIS by Borrelia bugdorferi sensu stricto

Diagnosis
History and clinical signs may be suggestive
Serological techniques (ELISA and IFA)
Laboratory isolation of the organism by culture
Molecular techniques

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BORRELIOSIS by Borrelia bugdorferi
sensu stricto

Prevention and control:

Avoid entering areas likely to be infested with soft
ticks
If you are in infested areas, wear a light coloured
clothings to easily spot out the ticks
Wear a long sleeved shirts and boots in infested areas
Frequent uses of insect repellent
Early diagnosis and treatment of borreliosis cases

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BORRELIOSIS (Relapsing
fever)

• Aetiology is B. recurrentis

• Vector: Louse, rodents, ornithodorus ticks

• Transmission: Rodent lice or tick when bites humans

may carry the infection from rodents.

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BORRELIOSIS (Relapsing
fever)
Distribution: Mostly in USA but there have been
some reports in Africa.

Disease in humans:
Characterized by on and off fever (3-10 days of
incubation period) followed by sudden onset of fever
lasting for four days

Later the fever declines till after again 3-10 days is

when it reoccurs.

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BORRELIOSIS (Relapsing
fever)
Diagnosis:
Microscopic examination of urine and blood during
febrile attack on dark field microscope
Serology
Animal inoculation

Treatment: Broad spectrum antibiotics

Control: Avoid bites from louse and Ornithodorus

ticks

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Genus: LEPTOSPIROSIS
• Is an acute infective illness affecting human and
animals caused by Spirochaetes of the genus
Leptospira

• Humans are an accidental host and infected through

contact with urine or tissue from the sick animals.

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 LEPTOSPIROSIS…

• Aetiology:
• Leptospira interrogans

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LEPTOSPIROSIS…

• Leptospira spp. are:

• Obligate aerobic spirochetes
• Visualization with dark-field or phase contrast microscopy
• >14 named species
• More than 250 pathogenic serovars grouped into
serogroups

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LEPTOSPIROSIS…

• Most mammal species are susceptible to infection

with Leptospira spp.

• Infection can lead to colonisation of kidneys with

leptospira organisms -> shedding of infectious
organisms in the urine

• Distribution: Worldwide; but very prevalent in

tropical countries with heavy rainfall and neutral or
alkaline soils

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 LEPTOSPIROSIS…
• Environmental conditions favourable for leptospira to
survive include:
• High humidity,
• Neutral or slightly alkaline PH
• Favorable temperature.

• The disease is the occupational hazards in some

countries.
• Workers in slaughterhouses, fish centers, miners, farmers,
swimmers, sewer workers are at high risk especially in the
endemic areas.

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 Transmission Risks

• Livestock and occupational risks

• Problem of expanding urban informal settlements
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LEPTOSPIROSIS…
• Transmission
• Direct contact with infected animal urine or milk
• Chronic renal colonization of animal carriers
• Environmental contamination – leptospires survive for days to
months in soil, mud or freshwater
• Indirect through environmental contamination
• Leptospires may enter through breaks in skin
(scratches/scrapes), mucous membranes or conjunctiva
• Transplacental infection has also been reported

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LEPTOSPIROSIS……….
Disease in humans
• Clinical manifestations range from asymptomatic,
self-resolving febrile illness to severe, fatal disease
• Common symptoms include rigors, headache, myalgias
• More specific, but less common, symptoms include
conjunctival suffusion (<50% cases) and calf
pain/tenderness
• Severe disease in ~5-10% of known cases
• Weil’s syndrome
• Pulmonary hemorrhage syndrome
• Mortality estimates for severe disease 5-40%
• Weil’s syndrome is used to describe the severe form of
leptospirosis, characterized by liver damage, jaundice
and renal failure
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LEPTOSPIROSIS diagnosis
• Direct microscopy of blood and urine possible, but difficult
to interpret Leptospira can be grown, with difficulty in
special serum containing media.
• Serological test is usual
• Most commonly diagnosed by serology- Microscopic
Agglutination Test (MAT)
• Culture
• Insensitive, brief period of leptospiremia
• Prolonged culture time
• Special culture techniques
• Rapid tests, IgM ELISA
• Performance characteristics poor for acute dx
• RT PCR
• Important to know the circulating Leptospira spp 66
LEPTOSPIROSIS……….

• During the first week of infection; leptospira can be

isolated from the blood stream or urine and can be
directly viewed on darkfield microscope.
• Urine can be the source of the organism for culture or
hamster inoculation.

• In all species: Diagnosis is through dark field

examination of urine, serological tests like
Fluorescent Antibody Tests (FAT), Microscopic
Agglutination Test (MAT) and ELISA

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Silver Stain of Leptospira interrogans
serotype icterohaemorrhagiae

 Obligate aerobes
 Characteristic hooked ends (like a
question mark, thus the species epithet –
interrogans) 68
LEPTOSPIROSIS……….

Prevention:
• Personal hygiene
• Use of protective clothing
• Drainage of low-lying grounds
• Food protection and proper disposal of wastes.
• Avoid swimming in fresh stagnant water.
• Vaccination to most susceptible groups
• Eradication of rats in man habitats.
• Immunizations of farm animals.

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 Treatment

• Penicillin, doxycycline in penicillin-allergic patients.

• Disease may be prevented after exposure by doxy cycling.

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Leptospirosis in Kibera slum, Nairobi
(Halliday et al, in preparation)

• Urban slum setting

• Cross-sectional
trapping survey of
rodents
• PCR testing of kidneys
– 18.4% overall positive
– Predominantly Mus spp.
• ELISA testing of serum
– No correlation with PCR
status in individuals

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LABORATORY IDENTIFICATION
• Direct microscopy of blood and urine possible, but
difficult to interpret Leptospira can be grown, with
difficulty in special serum containing media.
• Serological test is usual

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 TREATMENT AND
PREVENTION
• Penicillin, doxycycline in penicillin-allergic patients.
• Disease may be prevented after exposure by doxy cycling.

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• Self study: Providencia, Legionella, , Francicella, Brucella.

THANKS

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