Treponema pallidum causes syphilis in humans. It has a long incubation period and can progress through primary, secondary, latent, and tertiary stages if left untreated. Borrelia recurrentis causes epidemic relapsing fever which is transmitted between humans by body lice. Borrelia burgdorferi causes Lyme disease transmitted by certain ticks and causes a characteristic bullseye rash. Leptospira interrogans causes leptospirosis, a zoonotic disease transmitted by contact with infected animal urine, which can range from mild to severe with jaundice and organ failure.

1. Spirochaetales
~~~~~~~~~~~~~~~~~~
Treponema
Borrelia e
Leptospira

2. Ordem: Spirochaetales
Família: Spirochaetaceae
Genêro: Treponema
Borrelia
Família: Leptospiraceae
Gênero: Leptospira
Taxonomia

3. Características Gerais das Espiroquetas
 Gram-negativas
• Espiroqueta vem do grego “cabelo encaracolado”
 Células extremamente finas e podem ser longas
 Células helicoidais com extremidades cônicas
 Móveis através de flagelos periplásmicos
• Diferente número de flagelos e diferentes inserções em
Treponema, Borrelia e Leptospira

4. Flagelos Periplásmicos

5. Espiroqueta helicoidal
AF
OS = bainha externa
AF = Fibrilas axiais
Leptospira interrogans

6. Corte de
espiroqueta
com flagelo
periplásmico
(Outer sheath)
Corte de Borrelia
burgdorferi

7. Gênero Espécie Doença
Treponema pallidum ssp. pallidum
pallidum ssp.endemicum
pallidum ssp. pertenue
carateum
Sífilis
Bejel
Bouba (Yaws)
Pinta
Borrelia burgdorferi
recurrentis
Muitas espécies
Doença de Lyme (borreliose)
Febre recorrente epidêmica
Febre recorrente epidêmica
Leptospira interrogans Leptospirose
(Doença de Weil)
Doenças associadas à ordem
Spirochaetales

9. Treponema spp.

10. Doenças Treponêmicas
não DST
 Bejel, Yaws e Pinta
 Regiões tropicais e subtropicais
 Principalmente crianças pobres

11. Treponema pallidum ssp. endemicum
Bejel (sífilis endêmica)
• Initial lesions: nondescript oral lesions
• Secondary lesions: oral papules and mucosal patches
• Late: gummas (granulomas) of skin, bones &
nasopharynx
 Transmitted person-to-person by contaminated
eating utensils
 Tropical/subtropical areas (Africa, Asia & Australia)

12. Treponema pallidum ssp. pertenue
Papillomatous Lesions of
Yaws: painless nodules widely
distributed over body with
abundant contagious
spirochetes.
Bouba (Yaws): doença granulomatosa
• Early: skin lesions (see below)
• Late: destructive lesions of skin, lymph nodes & bones
 Transmitted by direct contact with lesions
containing abundant spirochetes
 Primitive tropical areas (S. America, Central Africa, SE Asia)

13. Treponema carateum
Pinta: Primariamente restrita à pele
• 1-3 week incubation period
• Initial lesions: small pruritic papules
• Secondary: enlarged plaques persist for
months to years
• Late: disseminated, recurrent
hypopigmentation or depigmentation of
skin lesions; scarring & disfigurement
Transmitted by direct contact with skin
lesions
Primitive tropical areas
(Mexico, Central & South America)
Hypopigmented Skin Lesions
of Pinta: depigmentation is
commonly seen as a late sequel with
all treponemal diseases

15. Treponema pallidum
ssp. pallidum

16. Sífilis
 DST
 Pode ser transmitida congenitamente

17. Microscopia de Campo escuro
Treponema pallidum

18. Muito finos para serem vistos pela microscopia
óptica, apesar de serem corados pelo Gram
• Espiroquetas móveis pela microscopia de campo
escuro
• Imunofluorescência direta ou impregnação pela prata
Patógeno intra-celular
Não crescem in vitro
Não sobrevivem fora do hospedeiro
Características do Treponema
pallidum

19. Epidemiologia do T. pallidum
 Transmitidos por contato sexual direto ou
transmissão materno fetal
 Não são altamente contagiosos (~30% de chance
de adquirir doença após exposição única a parceiro
infectado). Taxa de transmissão depende do estágio
da doença
 Longo período de incubação durante o qual o
hospedeiro não transmite a doença
• Epidemiologia útil para rastrear contatos e
administrar tratamento preventivo
 Prostituição permanece aspecto epidemiológico
central na transmissão

20. Patogênese do T. pallidum
 Destruição de tecidos e lesões são primariamente
uma consequência da resposta imune dos
pacientes
 Sífilis é uma doença dos vasos sanguíneos e das
áreas perivasculares
 Apesar de uma vigorosa resposta imune do
hospedeiro o microorganismo é capaz de persistir
por décadas
• Infecção não é completamente controlada ou
erradicada
• Nos estágios iniciais, há inibição da imunidade celular
• Nos estágios tardios da doença, as lesões tendem a ser
localizadas

21. Fatores de Virulência -T. pallidum
 Outer membrane proteins promote adherence
 Hyaluronidase may facilitate perivascular
infiltration
 Antiphagocytic coating of fibronectin
 Tissue destruction and lesions are primarily
result of host’s immune response
(immunopathology)

22. Doença primária envolve a invasão das membranas
mucosas, multiplicação rápida e ampla
disseminação através dos vasos linfáticos e
circulação sistêmica
Ocorre antes do desenvolvimento da lesão primária
10-90 dias (usualmente 3-4 semanas) após contato
inicial o hospedeiro apresenta uma resposta
inflamatória no sítio da inoculação resultando na
lesão sifilítica, chamada de cancro (não dolorosa)
• Cancro muda de duro a ulcerativo com abundante
disseminação de espiroquetas
• Edema das paredes capilares e linfonodos regionais
• Lesão Primária cicatriza espontaneamente em dois meses,
levando a falsa sensação de alívio
Patogênese do T. pallidum (cont.)
Sífilis Primária

23.  Doença secundária aparece 2-10 semanas após
lesão primária
 Rash mucocutâneo amplamente disseminado
 Lesões secundárias da pele e membranas
mucosas são altamente contagiosas
 Resposta imunológica generalizada
Patogênese do T. pallidum (cont.)
Sífilis secundária

24. Generalized
Mucocutaneous
Rash of
Secondary
Syphilis

25. Após estágio secundário da doença, hospedeiro
entra em período latente
•Primeiros 4 anos = latente precoce
•Período subsequente = latente tardio
Cerca de 40% dos pacientes em estágio latente
progridem para doença sifilítica tardia latente
terciária (estágio terciário)
Patogênese do T. pallidum (cont.)
Estágio Latente da Sífilis

26.  Sífilis Terciária caracterizada por lesões cutâneas
granulomatosas localizadas (gomas) nas quais
poucos organismos estão presentes
 Neurosífilis tardia se desenvolve em cerca de 1/6
dos casos não tratados, usualmente mais de 5 anos
após infecção inicial
• Demência, convulsões, etc.
 Involvimento cardiovascular aparece 10-40 anos
após infecção inicial resultando em insuficiência
cardíaca e morte
Patogênese do T. pallidum (cont.)
Sífilis Terciária

27. Progressão da Sífilis Não Tratada
Tertiary Stage
Late benign Gomas na pele e partes moles

28.  Congenital syphilis results from transplacental
infection
 T. pallidum septicemia in the developing fetus and
widespread dissemination
 Abortion, neonatal mortality, and late mental or
physical problems resulting from scars from the
active disease and progression of the active disease
state
Pathogenesis of T. pallidum (cont.)
Congenital Syphilis

29. Comparison of
Incidence of 1o
& 2o
Syphilis in
Women and
Congenital
Syphilis

30. Prevention & Treatment of Syphilis
 Penicillin remains drug of choice
• WHO monitors treatment recommendations
• 7-10 days continuously for early stage
• At least 21 days continuously beyond the early stage
 Prevention with barrier methods (e.g., condoms)
 Prophylactic treatment of contacts identified
through epidemiological tracing

31. Diagnostic Tests for Syphilis
NOTE: Treponemal antigen tests indicate experience with a treponemal
infection, but cross-react with antigens other than T. pallidum ssp.
pallidum. Since pinta and yaws are rare in USA, positive treponemal
antigen tests are usually indicative of syphilitic infection.
(Original Wasserman Test)

32. Sensitivity & Specificity of
Serologic Tests for Syphillis

33. Review Handout on
Sensitivity & Specificity
of Diagnostic Tests

34. Conditions Associated with False
Positive Serological Tests for Syphillis

35. Effect of
Treatment for
Syphillis on
Rapid Plasma
Reagin Test
Reactivity

37. Borrelia spp.

38. Giemsa Stain of
Borrelia recurrentis in Blood
Light Microscopy Phase Contrast Microscopy

39. Epidemiology of Borrelia Infections
Borrelia
recurrentis
Borrelia spp.
Borrelia
burgdorferi
Ixodes spp.
Ornithodoros spp.
Pediculus humanus

40. Borrelia recurrentis
& other Borrelia spp.

41.  Associated with poverty, crowding, and warfare
 Arthropod vectors
• Louse-borne borreliosis = Epidemic Relapsing Fever
 Transmitted person-to-person by human body lice
(vectors) from infected human reservoir
 Infect host only when louse is injured, e.g., during
scratching
 Therefore, a single louse can only infect a single person
 Lice leave host that develops a fever and seek normal
temperature host
• Tick-borne borreliosis = Endemic Relapsing Fever
 Sporadic cases
 Transmitted by soft body ticks (vectors) from small
mammal reservoir
 Ticks can multiply and infect new human hosts
Epidemiology of Relapsing Fever

42. Pathogenesis of Relapsing Fever
 Relapsing fever (a.k.a., tick fever, borreliosis, famine
fever)
• Acute infection with 2-14 day (~ 6 day) incubation period
• Followed by recurring febrile episodes
• Constant spirochaetemia that worsens during febrile
stages
 Epidemic Relapsing Fever = Louse-borne borreliosis
• Borrelia recurrentis
 Endemic Relapsing Fever = Tick-borne borreliosis
• Borrelia spp.

43. Clinical Progression of
Relapsing Fever

44. Borrelia burgdorferi

45. Pathogenesis of Lyme Borreliosis
 Lyme disease characterized by three stages:
i. Initially a unique skin lesion (erythema chronicum
migrans (ECM)) with general malaise
 ECM not seen in all infected hosts
 ECM often described as bullseye rash
 Lesions periodically reoccur
i. Subsequent stage seen in 5-15% of patients with
neurological or cardiac involvement
ii. Third stage involves migrating episodes of non-
destructive, but painful arthritis
 Acute illness treated with phenoxymethylpenicillin
or tetracycline

46. Erythema chronicum migrans of
Lyme Borreliosis
Bullseye rash

47. Diagnosis of Lyme Borreliosis

48. Bacteria and Syndromes that Cause
Cross-Reactions with Lyme
Borreliosis Serological Tests

49.  Lyme disease was recognized as a syndrome in
1975 with outbreak in Lyme, Connecticut
 Transmitted by hard body tick (Ixodes spp.)
vectors
• Nymph stage are usually more aggressive feeders
• Nymph stage generally too small to discern with
unaided eye
• For these reasons, nymph stage transmits more
pathogens
 White-footed deer mice and other rodents, deer,
domesticated pets and hard-shelled ticks are most
common reservoirs
Epidemiology of Lyme Borreliosis

50. Incidence of Lyme Borreliosis in USA

52. Leptospira interrogans

53. Silver Stain of Leptospira interrogans
serotype icterohaemorrhagiae
 Obligate aerobes
 Characteristic hooked ends
(like a question mark, thus the
species epithet – interrogans)

54. Leptospirosis Clinical Syndromes
 Mild virus-like syndrome
 (Anicteric leptospirosis) Systemic with aseptic
meningitis
 (Icteric leptospirosis) Overwhelming disease
(Weil’s disease)
Vascular collapse
Thrombocytopenia
Hemorrhage
Hepatic and renal dysfunction
NOTE: Icteric refers to jaundice (yellowing of skin and mucus
membranes by deposition of bile) and liver involvement

55.  Leptospirosis, also called Weil’s disease in humans
 Direct invasion and replication in tissues
 Characterized by an acute febrile jaundice &
immune complex glomerulonephritis
 Incubation period usually 10-12 days with flu-like
illness usually progressing through two clinical
stages:
i. Leptospiremia develops rapidly after infection (usually
lasts about 7 days) without local lesion
ii. Infects the kidneys and organisms are shed in the urine
(leptospiruria) with renal failure and death not
uncommon
 Hepatic injury & meningeal irritation is common
Pathogenesis of Icteric Leptospirosis

56. Clinical Progression of Icteric (Weil’s
Disease) and Anicteric Leptospirosis
(pigmented
part of eye)

57. Epidemiology of Leptospirosis
 Mainly a zoonotic disease
• Transmitted to humans from a variety of wild and
domesticated animal hosts
• In USA most common reservoirs rodents (rats), dogs,
farm animals and wild animals
 Transmitted through breaks in the skin or intact
mucus membranes
 Indirect contact (soil, water, feed) with infected
urine from an animal with leptospiruria
 Occupational disease of animal handling

58. Comparison of Diagnostic Tests
for Leptospirosis