The treponematoses (syphilis and the endemic treponematoses)

name: Treponematoses
display_name: The treponematoses (syphilis and the endemic treponematoses)
creation_date: "2026-08-08T05:40:00Z"
description: >-
  The treponematoses are the human diseases caused by the pathogenic
  treponemes: venereal syphilis (Treponema pallidum subsp. pallidum) and the
  three non-venereal endemic treponematoses - yaws (T. pallidum subsp.
  pertenue), bejel or endemic syphilis (T. pallidum subsp. endemicum), and
  pinta (T. carateum). The four are caused by organisms so closely related
  that they are morphologically identical, serologically indistinguishable by
  routine treponemal and nontreponemal tests, and until recently could not be
  told apart except by clinical and epidemiological context. They nonetheless
  differ sharply in transmission route, natural history, and the organ systems
  they ultimately damage, which is why they are curated as four separate
  Disease entries rather than merged.
grouping_basis:
- SHARED_MECHANISM
- SHARED_GENE_FAMILY
- CLINICAL_CONVENTION
grouping_rationale: >-
  Grouped on the near-identity of the causative organisms and the conserved
  mechanism that follows from it: every member is a chronic, stage-structured
  spirochetal infection that establishes itself at a mucocutaneous inoculation
  site, disseminates, evades sterilizing immunity, and remains curable with
  penicillin - no member has ever developed clinically significant penicillin
  resistance. "Treponematoses" is also a long-standing clinical and WHO
  programmatic category, so the grouping reflects how the field actually
  reasons about these diseases.

  The members are deliberately kept as four separate Disease entries rather
  than merged into one. They differ in transmission (sexual and vertical for
  syphilis; direct non-sexual skin contact in childhood for yaws and pinta;
  oral and household contact for bejel), in whether vertical transmission
  occurs at all (congenital disease is a feature of syphilis alone), in the
  organ systems ultimately involved (only syphilis produces cardiovascular and
  parenchymal neurological disease; pinta is confined to the skin), and in
  second-line drug susceptibility (23S rRNA macrolide resistance is prevalent
  in syphilis, while single-dose azithromycin still underpins WHO yaws
  eradication). Lumping them would erase precisely the distinctions that
  determine how each is transmitted, prevented, and treated.

  Note on scope: this grouping covers the human treponematoses, and its
  membership criterion is therefore "a pathogenic treponeme" rather than "a
  T. pallidum subspecies". Pinta is caused by T. carateum, a distinct species
  rather than a T. pallidum subspecies, so a subspecies-based criterion would
  wrongly exclude it.
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0007000
      label: Treponema infectious disease
    mapping_predicate: skos:closeMatch
    mapping_source: MONDO
    mapping_justification: >-
      closeMatch rather than exactMatch: the MONDO class is defined by causative
      genus and so is broader than the clinical category "the treponematoses",
      which conventionally denotes the four systemic human treponemal diseases
      grouped here and excludes other Treponema-associated conditions such as
      the polymicrobial periodontal and digital dermatitis diseases involving
      commensal treponemes.
membership_criteria:
- description: >-
    A disease belongs to the treponematoses if it is a chronic systemic
    infection caused by a pathogenic treponeme (T. pallidum subsp. pallidum,
    subsp. pertenue, subsp. endemicum, or T. carateum) AND its treponemal
    target is pharmacologically susceptible - that is, it conforms to at least
    one of the two antimicrobial-target mechanism modules that between them
    cover the penicillin and the ribosome-targeting regimens used across the
    group.
  criteria_semantics: NECESSARY
  logic:
    operator: AND
    operands:
    - criterion_predicate: OTHER
      description: >-
        Caused by a pathogenic treponeme - Treponema pallidum subsp. pallidum,
        subsp. pertenue, or subsp. endemicum, or Treponema carateum.
    - operator: OR
      description: >-
        Conforms to at least one antimicrobial-target module covering the
        regimens used across the group.
      operands:
      - criterion_predicate: CONFORMS_TO_MODULE
        module: bacterial_cell_wall_synthesis_inhibition#Peptidoglycan Cross-Linking by Penicillin-Binding Proteins
        description: >-
          Has a pathophysiology node conforming to the penicillin-binding-protein
          cross-linking target, the basis of penicillin cure in every member.
      - criterion_predicate: CONFORMS_TO_MODULE
        module: bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome
        description: >-
          Has a pathophysiology node conforming to the treponemal ribosome, the
          target of the azithromycin and doxycycline regimens.
members:
- member: Syphilis
  member_type: DISEASE
  display_name: Syphilis (venereal)
  differentiating_mechanisms:
  - description: >-
      The only venereally and vertically transmitted member, and the only one
      that produces cardiovascular (aortitis) and parenchymal neurological
      (general paresis, tabes dorsalis) disease, or congenital infection. It is
      also the only member in which 23S rRNA macrolide resistance is prevalent
      enough to have removed azithromycin from routine use, which is why it
      alone conforms to the ribosomal-target-resistance module node.
    module: bacterial_protein_synthesis_inhibition#Ribosomal Target Resistance
- member: Yaws
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      Transmitted by direct non-sexual skin contact between children in warm,
      humid rural settings. Disease is confined to skin, bone, and cartilage
      with no cardiovascular, neurological, or congenital involvement. Yaws is
      the target of a WHO eradication programme built on single-dose oral
      azithromycin, the therapeutic inverse of syphilis, where macrolide
      resistance has foreclosed that option.
    module: bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome
- member: Bejel
  member_type: DISEASE
  display_name: Bejel (endemic syphilis)
  differentiating_mechanisms:
  - description: >-
      Transmitted by oral and household contact in arid regions, so the primary
      lesion is usually an unnoticed oral mucous patch rather than a
      cutaneous or genital one. Progresses to mucocutaneous and osteoperiosteal
      involvement and to destructive gummatous disease of the nasopharynx
      (gangosa), but spares the cardiovascular system and produces no
      congenital infection.
    module: bacterial_cell_wall_synthesis_inhibition#Peptidoglycan Cross-Linking by Penicillin-Binding Proteins
- member: Pinta
  member_type: DISEASE
  differentiating_mechanisms:
  - description: >-
      The only member caused by a distinct species, Treponema carateum, rather
      than a T. pallidum subspecies, and the only one whose disease is confined
      to the skin throughout its entire course - producing dyschromic,
      achromic, and finally depigmented lesions with no visceral, skeletal,
      cardiovascular, or neurological involvement at any stage. Now the rarest
      of the four and possibly extinct in much of its former range in Latin
      America.
references:
- reference: PMID:24396138
  title: The endemic treponematoses.
  findings:
  - statement: >-
      The three endemic treponematoses grouped here alongside venereal syphilis
      are caused by T. pallidum subsp. pertenue, T. pallidum subsp. endemicum,
      and T. carateum respectively, establishing both the membership of the
      group and the fact that pinta's agent is a separate species.
    supporting_text: >-
      T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum
      are the agents of the endemic treponematoses yaws, bejel (or endemic
      syphilis), and pinta, respectively.
notes: >-
  Curation gaps and boundary notes.

  How the advisory evaluator reads these criteria. `just check-groupings`
  reports `structure: OK` and all four members as `UNKNOWN`, not `SATISFIED`.
  That is the correct three-valued answer, not a defect in the members: the
  `OTHER` leaf ("caused by a pathogenic treponeme") is not machine-evaluable,
  so the conjunction it sits in can never resolve to SATISFIED however complete
  the members are. The module branch it is ANDed with *is* satisfied by every
  member - Syphilis satisfies both arms of the OR, Bejel and Pinta the
  cell-wall arm, Yaws the ribosome arm. Note that the evaluator prints a
  per-leaf `NOT_SATISFIED` line for the unsatisfied arm of that OR (e.g. Yaws
  against the cell-wall leaf); those lines are expected and are not violations,
  since only one arm of an OR need hold.

  No `SUFFICIENT` criteria block is provided, deliberately. "Caused by a
  pathogenic treponeme" is close to definitional of a treponematosis, but
  encoding it as SUFFICIENT would invite the classifier to propose any
  Treponema-associated entry as a candidate member, including the
  polymicrobial periodontal diseases in which commensal treponemes are one of
  several organisms. The boundary the clinical category actually draws is
  around the four systemic human treponematoses, and that boundary is recorded
  in the rationale rather than as machine-checkable sufficiency.

  The criteria use an `OTHER` leaf to express "caused by a pathogenic
  treponeme" because `CriterionPredicateEnum` has no infectious-agent
  predicate. A `HAS_INFECTIOUS_AGENT` predicate taking an NCBITaxon-bound
  `infectious_agent_term` would let this criterion be machine-checked against
  each member's `infectious_agent` block instead of sitting in free text, and
  would generalize to any infectious-disease grouping. Worth raising as a
  schema enhancement.