🏷

Classifications

Harrison's Part

⚙

Pathophysiology

10

Ixodes-Borne Rickettsia australis Inoculation

Infected I. holocyclus or I. tasmani ticks inoculate R. australis into the dermis during a blood meal, initiating a localized cutaneous rickettsial infection at the bite site.

Downstream

Dermal Macrophage Rickettsia australis Infection Tick inoculation exposes dermal phagocytes to R. australis.

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Only two tick vectors of R. australis have been identified: Ixodes holocyclus and Ixodes tasmani."

The confirmed tick vectors define the arthropod route that deposits R. australis into skin.

Dermal Macrophage Rickettsia australis Infection

After tick inoculation, rickettsiae infect dermal mononuclear phagocytes. Mouse R. australis infection shows that macrophages are an early permissive niche at the inoculation site.

macrophage CL:0000235

symbiont entry into host cell GO:0046718

Downstream

Rickettsial Lymphatic Dissemination Rickettsiae disseminate from skin macrophages into lymphatics.

Eschar Local inoculation-site infection produces a necrotic eschar.

TLR4-ASC-MyD88 Rickettsia australis Innate Control Dermal macrophage infection activates innate cytokine control.

Show evidence (1 reference)

PMID:30297526 SUPPORT Model Organism

"Macrophages are one of the initial targets for rickettsiae after inoculation by ticks."

The R. australis mouse and macrophage study identifies macrophages as early host cells after tick inoculation.

Rickettsial Lymphatic Dissemination

Rickettsiae spread from the dermal inoculation site through lymphatic vessels to regional lymph nodes before hematogenous seeding of the systemic endothelium.

biological process involved in interaction with host GO:0051701

Downstream

Endothelial Cell Rickettsia australis Infection Lymphatic spread precedes hematogenous endothelial seeding.

Regional Lymphadenopathy Drainage from the inoculation site enlarges regional lymph nodes.

Show evidence (1 reference)

PMID:30148688 SUPPORT REVIEW SYNTHESIS Other

"Rickettsiae then spread via lymphatic vessels to the regional lymph nodes as has been observed vividly in the lymphangitis associated with R. sibirica mongolitimoniae infection"

The rickettsial pathogenesis review supports lymphatic spread from the inoculation site toward draining nodes as a conserved transition between dermal infection and systemic spread.

Endothelial Cell Rickettsia australis Infection

Disseminated R. australis is inferred, like pathogenic Rickettsia species generally, to infect microvascular endothelial cells.

endothelial cell of vascular tree CL:0002139

biological process involved in interaction with host GO:0051701

Downstream

Rickettsial Vasculitis and Vascular Leak Rickettsial endothelial tropism produces vascular inflammation and leak.

TLR4-ASC-MyD88 Rickettsia australis Innate Control Systemic endothelial infection contributes to innate cytokine activation.

Show evidence (1 reference)

PMID:19327117 SUPPORT Other

"It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability,..."

This conserved rickettsial mechanism supports endothelial tropism after R. australis leaves the inoculation site.

Rickettsial Vasculitis and Vascular Leak

Rickettsial endothelial infection provokes vascular inflammation, loss of endothelial integrity, and increased vascular permeability: the linked defects collectively termed rickettsial vasculitis.

endothelial cell of vascular tree CL:0002139

inflammatory response GO:0006954 positive regulation of vascular permeability GO:0043117 ↑ INCREASED

Downstream

Fever Systemic endothelial infection and inflammation produce fever.

Headache Systemic infection produces headache as part of the acute febrile syndrome.

Myalgia Systemic infection produces myalgia as part of the acute febrile syndrome.

Vesicular Rash Cutaneous rickettsial vasculitis produces the variable vesicular rash.

Maculopapular Rash Cutaneous rickettsial vasculitis produces the generalized rash.

Severe Microvascular Injury and Capillary Leak Severe systemic vascular leak can require ICU-level organ support.

Show evidence (1 reference)

PMID:19327117 SUPPORT Other

"It is now well established that a majority of sequelae associated with human rickettsioses are the outcome of the pathogen's affinity for endothelium lining the blood vessels, the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability,..."

The review defines vascular inflammation, integrity loss, and permeability compromise as the rickettsial vasculitis process that follows endothelial infection.

Severe Microvascular Injury and Capillary Leak

In a minority of adult QTT cases, rickettsial microvascular injury becomes severe enough to cause capillary leak, circulatory support needs, purpura fulminans, and multi-organ failure requiring ICU care.

Downstream

Multiple Organ Failure Severe QTT can require ICU-level multi-organ support.

Purpura Fulminans Fulminant microvascular injury can produce purpura fulminans.

Show evidence (1 reference)

PMID:32959771 SUPPORT Human Clinical

"One patient with QTT died, and two (8%) additional patients with QTT developed purpura fulminans requiring digital amputation."

The Queensland ICU series documents fatal QTT and severe microvascular skin injury in ICU-treated patients.

TLR4-ASC-MyD88 Rickettsia australis Innate Control

TLR4-dependent ASC inflammasome activation and MyD88-dependent dendritic-cell instruction promote IL-1 beta, IL-18, IL-6, IL-12, and IFN-gamma responses that restrict R. australis growth in macrophages and infected tissues.

toll-like receptor signaling pathway GO:0002224 innate immune response GO:0045087

Downstream

CD8 T Cell Rickettsia australis Clearance Innate cytokines help prime the adaptive response to infected cells.

Show evidence (2 references)

PMID:32014896 SUPPORT Model Organism

"Taken together, these observations indicate that activation of ASC inflammasome, most likely driven by interaction of TLR4 with rickettsial LPS, contributes to host protective immunity against R. australis"

R. australis mouse experiments place TLR4-driven ASC inflammasome activation in the protective innate response.

PMID:26755162 SUPPORT Model Organism

"Taken together, our results suggest that MyD88 signaling mediates instructive signals in DCs and secretion of IL-1β and type 1 immune cytokines, which may account for the protective inflammatory response during rickettsial infection."

R. australis-infected MyD88 knockout mice and dendritic cells support MyD88 as an instructive upstream signal for type 1 protective immunity.

CD8 T Cell Rickettsia australis Clearance

MHC class I-restricted CD8 cytotoxic T lymphocytes use perforin-dependent effector activity to clear R. australis from infected macrophages and endothelial cells in mice, providing a model for the adaptive immune arm that restrains human disease severity.

CD8-positive, alpha-beta T cell CL:0000625

T cell mediated cytotoxicity GO:0001913

Show evidence (1 reference)

PMID:11179362 SUPPORT Model Organism

"These results indicate that CTL activity was more critical to recovery from rickettsial infection than were the effects of IFN-gamma."

The study used R. australis infection of MHC class I, IFN-gamma, and perforin knockout mice to rank CD8 cytotoxicity as the key clearance arm.

Rickettsial Ribosomal Translation

R. australis, like other bacteria, depends on 70S ribosomal translation of its mRNA; doxycycline binds the 30S ribosomal subunit and blocks bacterial protein synthesis.

Translation GO:0006412

Show evidence (1 reference)

PMID:24336183 SUPPORT Other

"The ribosome is one of the main antibiotic targets in the bacterial cell."

Review evidence for the bacterial ribosome as the conserved antibiotic target class for tetracyclines such as doxycycline.

Intracytosolic Rickettsia australis Niche

Rickettsia species reside free in the host-cell cytosol and exploit host metabolites, so effective Queensland tick typhus therapy must reach the intracellular bacterial compartment.

biological process involved in interaction with host GO:0051701

Show evidence (1 reference)

PMID:30148688 SUPPORT Other

"Residing free in the cytosol of the host cell, they acquire many necessary components via transport mechanisms instead of maintaining genes for synthesizing sugars, lipids, nucleotides, and amino acids."

The review supports the free cytosolic niche for pathogenic Rickettsia species, including R. australis.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

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Phenotypes

9

Blood 1

Purpura Fulminans HP:0000979

Coarse binding: no hpo term

Ontology gap: HPO has no dedicated purpura-fulminans term; `uv run runoak -i ols:hp search "Purpura"` on 2026-09-28 returned HP:0000979 Purpura and specific distribution or thrombocytopenia terms, but not purpura fulminans.

Show evidence (1 reference)

PMID:32959771 SUPPORT Human Clinical

"One patient with QTT died, and two (8%) additional patients with QTT developed purpura fulminans requiring digital amputation."

The ICU case series documents purpura fulminans among severe QTT patients.

Cardiovascular 1

Regional Lymphadenopathy FREQUENT HP:0002716

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Patients often have regional lymphadenopathy and eschars."

The Australian case review identifies regional lymphadenopathy as a common QTT sign.

Immune 1

Maculopapular Rash Maculopapular exanthema HP:0040186

Show evidence (1 reference)

PMID:27172113 SUPPORT Human Clinical

"Rickettsia australis Fever, headache, myalgia, eschar, regional lymphadenopathy, and rash (maculopapular or vesicular); typically mild illness, can be severe"

The CDC table lists maculopapular rash among Queensland tick typhus manifestations.

Integument 2

Eschar FREQUENT HP:6000793

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Patients often have regional lymphadenopathy and eschars."

The Australian case review identifies eschars as a common QTT sign.

Vesicular Rash Skin vesicle HP:0200037

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Patients often have regional lymphadenopathy and eschars. Some have vesicular rashes."

The Australian case review identifies vesicular rash as a subset QTT manifestation.

Metabolism 1

Fever HP:0001945

Show evidence (1 reference)

PMID:28719297 SUPPORT Other

"Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia."

The review characterizes QTT as an acute febrile illness of eastern Australia.

Nervous System 1

Headache HP:0002315

Show evidence (1 reference)

PMID:27172113 SUPPORT Human Clinical

"Rickettsia australis Fever, headache, myalgia, eschar, regional lymphadenopathy, and rash"

The CDC table lists headache among the clinical manifestations of R. australis Queensland tick typhus.

Constitutional 1

Myalgia HP:0003326

Show evidence (1 reference)

PMID:27172113 SUPPORT Human Clinical

"Rickettsia australis Fever, headache, myalgia, eschar, regional lymphadenopathy, and rash (maculopapular or vesicular); typically mild illness, can be severe"

The CDC table lists myalgia among Queensland tick typhus manifestations.

Other 1

Multiple Organ Failure

Coarse binding: no hpo term

Ontology gap: HPO has no multiple-organ-failure term; `uv run runoak -i ols:hp search "multiple organ failure"` and `uv run runoak -i ols:hp search "organ failure"` on 2026-09-28 returned nothing. NCIT has C75568 Multiple Organ Failure, but `phenotype_term` only accepts HPO bindings.

Show evidence (1 reference)

PMID:32959771 SUPPORT Human Clinical

"Queensland tick typhus and scrub typhus can cause multi-organ failure requiring ICU care in otherwise well individuals."

The ICU series reports multi-organ failure as a possible severe QTT manifestation.

💊

Medical Actions

1

Empiric doxycycline

Action: Pharmacotherapy NCIT:C15986

Agent: doxycycline CHEBI:50845

Platform: Small molecule

Doxycycline is first-line empiric therapy for suspected tick-borne rickettsial disease, including Queensland tick typhus, because it inhibits the rickettsial 30S ribosomal subunit and reaches the host-cell cytosol where R. australis resides.

Mechanism Target:

INHIBITS Rickettsial Ribosomal Translation — Doxycycline blocks rickettsial protein synthesis at the 30S ribosomal subunit.

BYPASSES Intracytosolic Rickettsia australis Niche — Doxycycline can reach the cytosolic rickettsial compartment.

Show evidence (2 references)

PMID:27172113 SUPPORT Human Clinical

"Doxycycline is the drug of choice for treatment of all tickborne rickettsial diseases in patients of all ages, including children aged <8 years, and should be initiated immediately in persons with signs and symptoms suggestive of rickettsial disease"

QTT is a tick-borne rickettsial disease, so this CDC first-line treatment recommendation covers empiric therapy for suspected QTT.

PMID:33075531 SUPPORT Human Clinical

"A significant proportion of patients with confirmed scrub typhus and QTT will remain febrile for >48 hours after appropriate anti-rickettsial therapy."

The tropical Australia cohort cautions that delayed defervescence after appropriate therapy can occur in confirmed QTT and does not by itself exclude the diagnosis.

🔬

Diagnosis

2

Rickettsial qPCR on blood or cutaneous lesions

Real-time PCR on early blood or cutaneous-lesion specimens can detect rickettsial DNA, with R. australis-specific assays available in reference laboratory panels.

polymerase chain reaction NCIT:C17003

Results: A positive PCR from blood, eschar swab, or biopsy supports early molecular confirmation.

Show evidence (2 references)

PMID:22092999 SUPPORT Other

"We retained sets of primers and probes to detect spotted fever group Rickettsia, typhus group Rickettsia,Rickettsia conorii,Rickettsia slovaca,Rickettsia africae and Rickettsia australis"

The molecular-diagnostics evaluation included a validated R. australis real-time PCR primer/probe set in its routine rickettsial panel.

PMID:31587667 SUPPORT Other

"It is likely that the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem."

The diagnostic review supports pairing early qPCR with serology to span the time windows of nucleic-acid and antibody detection.

Indirect immunofluorescence assay serology

Serology is needed to separate QTT from clinically overlapping Australian rickettsioses, although antibody results are often retrospective because acute samples can be negative before seroconversion.

indirect immunofluorescence assay serology NCIT:C217458

Results: A compatible illness plus rickettsial antibody rise supports retrospective confirmation.

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Because clinical features overlap, serologic tests are necessary to distinguish QTT from other endemic Australian rickettsial diseases (scrub and murine typhus)."

The Australian review identifies serology as necessary for distinguishing QTT from scrub typhus and murine typhus in the same region.

📈

Progression

1

Usually mild acute illness with rare severe adult progression

QTT is usually mild, but North Queensland adult SFG/QTT hospital cohorts document a severe minority that can require ICU care, progress to multi-organ failure, cause purpura fulminans with digital amputation, or end in death or permanent disability. Pediatric rickettsial infections in the same tropical-Australia setting appeared more benign in a small retrospective series.

Show evidence (3 references)

PMID:31318873 SUPPORT Human Clinical

"Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02)."

The North Queensland hospital audit documents death and permanent disability in a minority of spotted-fever-group patients.

PMID:32959771 SUPPORT Human Clinical

"Queensland tick typhus and scrub typhus can cause multi-organ failure requiring ICU care in otherwise well individuals."

The ICU case series establishes multi-organ failure as a possible severe course of QTT.

PMID:32252063 SUPPORT Human Clinical

"However, no child died or was admitted to ICU, compared with 18/120 (15%) adults who required ICU support during the study period, one of whom died."

The pediatric audit contrasts the benign pediatric course with the adult ICU burden in tropical Australia.

🌍

Epidemiology

1

Eastern coastal Australian tick exposure

Queensland tick typhus follows exposure to tick habitat along the eastern Australian coast, spanning tropical Queensland and temperate southeastern coastal regions.

eastern Australia tick exposure Ixodes tick exposure

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"However, available serologic, epidemiologic, and clinical data suggest that QTT is not confined to the area in which R. australis was first isolated (Queensland); rather, it occurs along a 3,200-km span of eastern coastal Australia, from tropical to temperate climates."

The review places QTT along the eastern Australian coastline rather than limiting it to Queensland.

🦠

Infectious Agent

1

Rickettsia australis

Obligate intracellular rickettsial bacterium that causes Queensland tick typhus.

Rickettsia australis NCBITaxon:787

Show evidence (1 reference)

PMID:28719297 SUPPORT Other

"Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is increasingly being recognized as a cause of community-acquired acute febrile illness in eastern Australia."

The review names R. australis as the etiologic agent of QTT.

↔️

Transmission

1

Ixodes tick bite inoculation

R. australis is transmitted to humans by the hard ticks Ixodes holocyclus and Ixodes tasmani in eastern Australia.

Show evidence (1 reference)

PMID:1962102 SUPPORT REVIEW SYNTHESIS Human Clinical

"Only two tick vectors of R. australis have been identified: Ixodes holocyclus and Ixodes tasmani."

The Australian spotted-fever review names the two confirmed vectors of the etiologic agent of Queensland tick typhus.

🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Queensland Tick Typhus:

Flinders Island spotted fever

Overlapping Features Flinders Island spotted fever is an overlapping Australian spotted-fever-group rickettsiosis caused by Rickettsia honei rather than R. australis; it should be considered in patients from southeastern Australia who present with fever, headache, rash, and tick exposure.

Distinguishing Features

R. honei causes Flinders Island spotted fever, whereas R. australis causes QTT.
Southeastern Australia exposure favors Flinders Island spotted fever over QTT.
Organism-specific PCR or culture distinguishes the two agents.

Show evidence (1 reference)

PMID:16175900 SUPPORT Human Clinical

"FISF should be considered as a differential diagnosis in patients from south-eastern Australia presenting with fever, headache and rash following a tick bite."

The case report series establishes Flinders Island spotted fever as a tick-associated spotted-fever differential diagnosis in southeastern Australia.

{ }

Source YAML

click to show

name: Queensland Tick Typhus
creation_date: "2026-09-25T12:20:56Z"
updated_date: "2026-09-25T12:20:56Z"
category: Infectious Disease
description: >-
  Queensland tick typhus is an acute tick-borne rickettsiosis caused by the
  obligately intracellular bacterium Rickettsia australis in eastern coastal
  Australia. Ixodes ticks inoculate the organism into skin, where early
  infection of dermal macrophages creates an eschar and draining-node
  lymphadenopathy before lymphatic and hematogenous spread reaches the
  microvascular endothelium. The resulting rickettsial vasculitis accounts for
  the fever and maculopapular or vesicular rash that distinguish Queensland tick
  typhus within the spotted-fever rickettsioses; a minority of adult infections
  progress to severe microvascular injury with purpura fulminans or multi-organ
  failure requiring intensive care.
disease_term:
  preferred_term: Queensland tick typhus
  term:
    id: MONDO:0001118
    label: Queensland tick typhus
parents:
- Spotted fever rickettsiosis
synonyms:
- Rickettsia australis infection
- Australian tick typhus
- North Queensland tick typhus
references:
- reference: PMID:1962102
  title: Spotted fever group rickettsial infections in Australia.
  found_in:
  - Queensland_Tick_Typhus-deep-research-openscientist.md
  findings:
  - statement: >-
      Queensland tick typhus is a usually mild Rickettsia australis infection
      with eschars, regional lymphadenopathy, occasional vesicular rash,
      Ixodes holocyclus and Ixodes tasmani tick vectors, and serologic overlap
      with other Australian rickettsioses.
    supporting_text: >-
      More than four decades ago, Rickettsia australis was discovered to be the
      etiologic agent of Queensland tick typhus (QTT)
- reference: PMID:19327117
  title: Host-cell interactions with pathogenic Rickettsia species.
  found_in:
  - Queensland_Tick_Typhus-deep-research-openscientist.md
  findings:
  - statement: >-
      Endothelial tropism, vascular inflammation, loss of vascular integrity,
      and increased permeability are conserved pathogenic features of spotted
      fever and typhus group rickettsioses.
    supporting_text: >-
      the consequences of which are vascular inflammation, insult to vascular
      integrity and compromised vascular permeability, collectively termed
      'Rickettsial vasculitis'
- reference: PMID:11179362
  title: Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection.
  found_in:
  - Queensland_Tick_Typhus-deep-research-openscientist.md
  findings:
  - statement: >-
      R. australis mouse experiments identify MHC class I-restricted,
      perforin-dependent CD8 T cells as decisive for rickettsial clearance.
    supporting_text: >-
      These results indicate that CTL activity was more critical to recovery
      from rickettsial infection than were the effects of IFN-gamma.
classifications:
  harrisons_chapter:
  - classification_value: INFECTIOUS_DISEASES
    evidence:
    - reference: PMID:28719297
      reference_title: >-
        Rickettsia australis and Queensland Tick Typhus: A Rickettsial Spotted Fever
        Group Infection in Australia.
      supports: SUPPORT
      evidence_source: OTHER
      snippet: >-
        Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is
        increasingly being recognized as a cause of community-acquired acute febrile
        illness in eastern Australia.
      explanation: >-
        The review identifies Queensland tick typhus as a bacterial spotted-fever
        rickettsiosis of eastern Australia, placing it in Harrison's Infectious
        Diseases Part.

infectious_agent:
- name: Rickettsia australis
  infectious_agent_term:
    preferred_term: Rickettsia australis
    term:
      id: NCBITaxon:787
      label: Rickettsia australis
  description: >-
    Obligate intracellular rickettsial bacterium that causes Queensland tick typhus.
  evidence:
  - reference: PMID:28719297
    reference_title: >-
      Rickettsia australis and Queensland Tick Typhus: A Rickettsial Spotted Fever
      Group Infection in Australia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is
      increasingly being recognized as a cause of community-acquired acute febrile
      illness in eastern Australia.
    explanation: The review names R. australis as the etiologic agent of QTT.

transmission:
- name: Ixodes tick bite inoculation
  description: >-
    R. australis is transmitted to humans by the hard ticks Ixodes holocyclus
    and Ixodes tasmani in eastern Australia.
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Only two tick vectors of R. australis have been identified: Ixodes holocyclus and Ixodes tasmani."
    explanation: >-
      The Australian spotted-fever review names the two confirmed vectors of the
      etiologic agent of Queensland tick typhus.

epidemiology:
- name: Eastern coastal Australian tick exposure
  description: >-
    Queensland tick typhus follows exposure to tick habitat along the eastern
    Australian coast, spanning tropical Queensland and temperate southeastern
    coastal regions.
  factors:
  - eastern Australia tick exposure
  - Ixodes tick exposure
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      However, available serologic, epidemiologic, and clinical data suggest
      that QTT is not confined to the area in which R. australis was first
      isolated (Queensland); rather, it occurs along a 3,200-km span of eastern
      coastal Australia, from tropical to temperate climates.
    explanation: >-
      The review places QTT along the eastern Australian coastline rather than
      limiting it to Queensland.

progression:
- phase: Usually mild acute illness with rare severe adult progression
  notes: >-
    QTT is usually mild, but North Queensland adult SFG/QTT hospital cohorts
    document a severe minority that can require ICU care, progress to
    multi-organ failure, cause purpura fulminans with digital amputation, or
    end in death or permanent disability. Pediatric rickettsial infections in
    the same tropical-Australia setting appeared more benign in a small
    retrospective series.
  evidence:
  - reference: PMID:31318873
    reference_title: >-
      The epidemiology and clinical features of rickettsial diseases in North
      Queensland, Australia: Implications for patient identification and
      management.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Three (8%) of the 37 patients with SFG infection had severe disease (1
      died, 2 developed permanent disability) versus 0/95 scrub typhus patients
      (p = 0.02).
    explanation: >-
      The North Queensland hospital audit documents death and permanent
      disability in a minority of spotted-fever-group patients.
  - reference: PMID:32959771
    reference_title: >-
      The Characteristics and Clinical Course of Patients with Scrub Typhus and
      Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A
      23-year Case Series from Queensland, Tropical Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Queensland tick typhus and scrub typhus can cause multi-organ failure
      requiring ICU care in otherwise well individuals.
    explanation: >-
      The ICU case series establishes multi-organ failure as a possible severe
      course of QTT.
  - reference: PMID:32252063
    reference_title: >-
      Clinical Features of Rickettsial Infection in Children in Tropical
      Australia-A Report of 15 Cases.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      However, no child died or was admitted to ICU, compared with 18/120 (15%)
      adults who required ICU support during the study period, one of whom died.
    explanation: >-
      The pediatric audit contrasts the benign pediatric course with the adult
      ICU burden in tropical Australia.

pathophysiology:
- name: Ixodes-Borne Rickettsia australis Inoculation
  role: trigger
  description: >-
    Infected I. holocyclus or I. tasmani ticks inoculate R. australis into the
    dermis during a blood meal, initiating a localized cutaneous rickettsial
    infection at the bite site.
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: "Only two tick vectors of R. australis have been identified: Ixodes holocyclus and Ixodes tasmani."
    explanation: >-
      The confirmed tick vectors define the arthropod route that deposits R.
      australis into skin.
  downstream:
  - target: Dermal Macrophage Rickettsia australis Infection
    causal_link_type: DIRECT
    description: Tick inoculation exposes dermal phagocytes to R. australis.

- name: Dermal Macrophage Rickettsia australis Infection
  role: primary_infection
  description: >-
    After tick inoculation, rickettsiae infect dermal mononuclear phagocytes.
    Mouse R. australis infection shows that macrophages are an early permissive
    niche at the inoculation site.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: symbiont entry into host cell
    term:
      id: GO:0046718
      label: symbiont entry into host cell
  evidence:
  - reference: PMID:30297526
    reference_title: Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Macrophages are one of the initial targets for rickettsiae after
      inoculation by ticks.
    explanation: >-
      The R. australis mouse and macrophage study identifies macrophages as
      early host cells after tick inoculation.
  downstream:
  - target: Rickettsial Lymphatic Dissemination
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Rickettsiae disseminate from skin macrophages into lymphatics.
  - target: Eschar
    causal_link_type: DIRECT
    description: Local inoculation-site infection produces a necrotic eschar.
  - target: TLR4-ASC-MyD88 Rickettsia australis Innate Control
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Dermal macrophage infection activates innate cytokine control.

- name: Rickettsial Lymphatic Dissemination
  role: effector
  description: >-
    Rickettsiae spread from the dermal inoculation site through lymphatic vessels
    to regional lymph nodes before hematogenous seeding of the systemic
    endothelium.
  biological_processes:
  - preferred_term: biological process involved in interaction with host
    term:
      id: GO:0051701
      label: biological process involved in interaction with host
  evidence:
  - reference: PMID:30148688
    reference_title: "Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection."
    supports: SUPPORT
    evidence_source: OTHER
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Rickettsiae then spread via lymphatic vessels to the regional lymph nodes
      as has been observed vividly in the lymphangitis associated with R.
      sibirica mongolitimoniae infection
    explanation: >-
      The rickettsial pathogenesis review supports lymphatic spread from the
      inoculation site toward draining nodes as a conserved transition between
      dermal infection and systemic spread.
  downstream:
  - target: Endothelial Cell Rickettsia australis Infection
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Lymphatic spread precedes hematogenous endothelial seeding.
  - target: Regional Lymphadenopathy
    causal_link_type: DIRECT
    description: Drainage from the inoculation site enlarges regional lymph nodes.

- name: Endothelial Cell Rickettsia australis Infection
  role: effector
  description: >-
    Disseminated R. australis is inferred, like pathogenic Rickettsia species
    generally, to infect microvascular endothelial cells.
  cell_types:
  - preferred_term: endothelial cell of vascular tree
    term:
      id: CL:0002139
      label: endothelial cell of vascular tree
  biological_processes:
  - preferred_term: biological process involved in interaction with host
    term:
      id: GO:0051701
      label: biological process involved in interaction with host
  evidence:
  - reference: PMID:19327117
    reference_title: Host-cell interactions with pathogenic Rickettsia species.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now well established that a majority of sequelae associated with
      human rickettsioses are the outcome of the pathogen's affinity for
      endothelium lining the blood vessels, the consequences of which are
      vascular inflammation, insult to vascular integrity and compromised
      vascular permeability, collectively termed 'Rickettsial vasculitis'.
    explanation: >-
      This conserved rickettsial mechanism supports endothelial tropism after
      R. australis leaves the inoculation site.
  downstream:
  - target: Rickettsial Vasculitis and Vascular Leak
    causal_link_type: DIRECT
    description: Rickettsial endothelial tropism produces vascular inflammation and leak.
  - target: TLR4-ASC-MyD88 Rickettsia australis Innate Control
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic endothelial infection contributes to innate cytokine activation.

- name: Rickettsial Vasculitis and Vascular Leak
  role: vascular_response
  description: >-
    Rickettsial endothelial infection provokes vascular inflammation, loss of
    endothelial integrity, and increased vascular permeability: the linked
    defects collectively termed rickettsial vasculitis.
  cell_types:
  - preferred_term: endothelial cell of vascular tree
    term:
      id: CL:0002139
      label: endothelial cell of vascular tree
  biological_processes:
  - preferred_term: inflammatory response
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: positive regulation of vascular permeability
    modifier: INCREASED
    term:
      id: GO:0043117
      label: positive regulation of vascular permeability
  evidence:
  - reference: PMID:19327117
    reference_title: Host-cell interactions with pathogenic Rickettsia species.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is now well established that a majority of sequelae associated with
      human rickettsioses are the outcome of the pathogen's affinity for
      endothelium lining the blood vessels, the consequences of which are
      vascular inflammation, insult to vascular integrity and compromised
      vascular permeability, collectively termed 'Rickettsial vasculitis'.
    explanation: >-
      The review defines vascular inflammation, integrity loss, and permeability
      compromise as the rickettsial vasculitis process that follows endothelial
      infection.
  downstream:
  - target: Fever
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic endothelial infection and inflammation produce fever.
  - target: Headache
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic infection produces headache as part of the acute febrile syndrome.
  - target: Myalgia
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Systemic infection produces myalgia as part of the acute febrile syndrome.
  - target: Vesicular Rash
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Cutaneous rickettsial vasculitis produces the variable vesicular rash.
  - target: Maculopapular Rash
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Cutaneous rickettsial vasculitis produces the generalized rash.
  - target: Severe Microvascular Injury and Capillary Leak
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Severe systemic vascular leak can require ICU-level organ support.

- name: Severe Microvascular Injury and Capillary Leak
  role: consequence
  description: >-
    In a minority of adult QTT cases, rickettsial microvascular injury becomes
    severe enough to cause capillary leak, circulatory support needs, purpura
    fulminans, and multi-organ failure requiring ICU care.
  biological_scale: ORGANISM
  evidence:
  - reference: PMID:32959771
    reference_title: >-
      The Characteristics and Clinical Course of Patients with Scrub Typhus and
      Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A
      23-year Case Series from Queensland, Tropical Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      One patient with QTT died, and two (8%) additional patients with QTT
      developed purpura fulminans requiring digital amputation.
    explanation: >-
      The Queensland ICU series documents fatal QTT and severe microvascular
      skin injury in ICU-treated patients.
  downstream:
  - target: Multiple Organ Failure
    causal_link_type: DIRECT
    description: Severe QTT can require ICU-level multi-organ support.
  - target: Purpura Fulminans
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    description: Fulminant microvascular injury can produce purpura fulminans.

- name: TLR4-ASC-MyD88 Rickettsia australis Innate Control
  description: >-
    TLR4-dependent ASC inflammasome activation and MyD88-dependent dendritic-cell
    instruction promote IL-1 beta, IL-18, IL-6, IL-12, and IFN-gamma responses
    that restrict R. australis growth in macrophages and infected tissues.
  biological_processes:
  - preferred_term: toll-like receptor signaling pathway
    term:
      id: GO:0002224
      label: toll-like receptor signaling pathway
  - preferred_term: innate immune response
    term:
      id: GO:0045087
      label: innate immune response
  evidence:
  - reference: PMID:32014896
    reference_title: Activation of ASC Inflammasome Driven by Toll-Like Receptor 4 Contributes to Host Immunity against Rickettsial Infection.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Taken together, these observations indicate that activation of ASC
      inflammasome, most likely driven by interaction of TLR4 with rickettsial
      LPS, contributes to host protective immunity against R. australis
    explanation: >-
      R. australis mouse experiments place TLR4-driven ASC inflammasome
      activation in the protective innate response.
  - reference: PMID:26755162
    reference_title: MyD88 Mediates Instructive Signaling in Dendritic Cells and Protective Inflammatory Response during Rickettsial Infection.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Taken together, our results suggest that MyD88 signaling mediates
      instructive signals in DCs and secretion of IL-1β and type 1 immune
      cytokines, which may account for the protective inflammatory response
      during rickettsial infection.
    explanation: >-
      R. australis-infected MyD88 knockout mice and dendritic cells support
      MyD88 as an instructive upstream signal for type 1 protective immunity.
  downstream:
  - target: CD8 T Cell Rickettsia australis Clearance
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    description: Innate cytokines help prime the adaptive response to infected cells.

- name: CD8 T Cell Rickettsia australis Clearance
  description: >-
    MHC class I-restricted CD8 cytotoxic T lymphocytes use perforin-dependent
    effector activity to clear R. australis from infected macrophages and
    endothelial cells in mice, providing a model for the adaptive immune arm that
    restrains human disease severity.
  cell_types:
  - preferred_term: CD8-positive, alpha-beta T cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: T cell mediated cytotoxicity
    term:
      id: GO:0001913
      label: T cell mediated cytotoxicity
  evidence:
  - reference: PMID:11179362
    reference_title: Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      These results indicate that CTL activity was more critical to recovery
      from rickettsial infection than were the effects of IFN-gamma.
    explanation: >-
      The study used R. australis infection of MHC class I, IFN-gamma, and
      perforin knockout mice to rank CD8 cytotoxicity as the key clearance arm.
- name: Rickettsial Ribosomal Translation
  role: therapeutic_vulnerability
  conforms_to: "bacterial_protein_synthesis_inhibition#Bacterial mRNA Translation by the Ribosome"
  description: >-
    R. australis, like other bacteria, depends on 70S ribosomal translation of
    its mRNA; doxycycline binds the 30S ribosomal subunit and blocks bacterial
    protein synthesis.
  biological_processes:
  - preferred_term: Translation
    term:
      id: GO:0006412
      label: translation
  evidence:
  - reference: PMID:24336183
    reference_title: "Ribosome-targeting antibiotics and mechanisms of bacterial resistance."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: The ribosome is one of the main antibiotic targets in the bacterial cell.
    explanation: >-
      Review evidence for the bacterial ribosome as the conserved antibiotic
      target class for tetracyclines such as doxycycline.

- name: Intracytosolic Rickettsia australis Niche
  role: intrinsic_resistance
  conforms_to: "intracellular_pathogen_persistence#Intracellular Niche and Beta-Lactam Exclusion"
  description: >-
    Rickettsia species reside free in the host-cell cytosol and exploit host
    metabolites, so effective Queensland tick typhus therapy must reach the
    intracellular bacterial compartment.
  biological_processes:
  - preferred_term: biological process involved in interaction with host
    term:
      id: GO:0051701
      label: biological process involved in interaction with host
  evidence:
  - reference: PMID:30148688
    reference_title: "Pathogenesis of Rickettsial Diseases: Pathogenic and Immune Mechanisms of an Endotheliotropic Infection."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Residing free in the cytosol of the host cell, they acquire many necessary
      components via transport mechanisms instead of maintaining genes for
      synthesizing sugars, lipids, nucleotides, and amino acids.
    explanation: >-
      The review supports the free cytosolic niche for pathogenic Rickettsia
      species, including R. australis.

phenotypes:
- name: Eschar
  category: Dermatologic
  frequency: FREQUENT
  description: QTT often produces an inoculation eschar at the tick-bite site.
  phenotype_term:
    preferred_term: Eschar
    term:
      id: HP:6000793
      label: Eschar
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: Patients often have regional lymphadenopathy and eschars.
    explanation: The Australian case review identifies eschars as a common QTT sign.

- name: Regional Lymphadenopathy
  category: Immune
  frequency: FREQUENT
  description: Draining lymph-node enlargement commonly accompanies the QTT eschar.
  phenotype_term:
    preferred_term: Regional lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: Patients often have regional lymphadenopathy and eschars.
    explanation: The Australian case review identifies regional lymphadenopathy as a common QTT sign.

- name: Fever
  category: Constitutional
  description: Fever is part of the acute community-acquired QTT syndrome.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:28719297
    reference_title: >-
      Rickettsia australis and Queensland Tick Typhus: A Rickettsial Spotted Fever
      Group Infection in Australia.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      Rickettsia australis, the etiologic agent of Queensland tick typhus (QTT), is
      increasingly being recognized as a cause of community-acquired acute febrile
      illness in eastern Australia.
    explanation: >-
      The review characterizes QTT as an acute febrile illness of eastern
      Australia.

- name: Headache
  category: Neurological
  description: Headache is part of the acute systemic spotted-fever syndrome.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:27172113
    reference_title: >-
      Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain
      Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses,
      and Anaplasmosis - United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Rickettsia australis Fever, headache, myalgia, eschar, regional
      lymphadenopathy, and rash
    explanation: >-
      The CDC table lists headache among the clinical manifestations of
      R. australis Queensland tick typhus.

- name: Vesicular Rash
  category: Dermatologic
  description: Some patients with QTT develop a vesicular rash.
  phenotype_term:
    preferred_term: Skin vesicle
    term:
      id: HP:0200037
      label: Skin vesicle
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Patients often have regional lymphadenopathy and eschars. Some have
      vesicular rashes.
    explanation: The Australian case review identifies vesicular rash as a subset QTT manifestation.

- name: Maculopapular Rash
  category: Dermatologic
  description: A generalized maculopapular rash is one morphology of the QTT rash.
  phenotype_term:
    preferred_term: Maculopapular rash
    term:
      id: HP:0040186
      label: Maculopapular exanthema
  evidence:
  - reference: PMID:27172113
    reference_title: >-
      Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain
      Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses,
      and Anaplasmosis - United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Rickettsia australis Fever, headache, myalgia, eschar, regional
      lymphadenopathy, and rash (maculopapular or vesicular); typically mild
      illness, can be severe
    explanation: >-
      The CDC table lists maculopapular rash among Queensland tick typhus
      manifestations.

- name: Myalgia
  category: Musculoskeletal
  description: Myalgia is part of the acute systemic QTT symptom complex.
  phenotype_term:
    preferred_term: Myalgia
    term:
      id: HP:0003326
      label: Myalgia
  evidence:
  - reference: PMID:27172113
    reference_title: >-
      Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain
      Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses,
      and Anaplasmosis - United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Rickettsia australis Fever, headache, myalgia, eschar, regional
      lymphadenopathy, and rash (maculopapular or vesicular); typically mild
      illness, can be severe
    explanation: >-
      The CDC table lists myalgia among Queensland tick typhus manifestations.

- name: Multiple Organ Failure
  category: Multisystem
  description: Severe QTT can progress to multi-organ failure requiring ICU care.
  phenotype_term:
    preferred_term: Multiple organ failure
    coarse_binding_basis: NO_HPO_TERM
    term_gap: >-
      HPO has no multiple-organ-failure term; `uv run runoak -i ols:hp search
      "multiple organ failure"` and `uv run runoak -i ols:hp search "organ
      failure"` on 2026-09-28 returned nothing. NCIT has C75568 Multiple Organ
      Failure, but `phenotype_term` only accepts HPO bindings.
  evidence:
  - reference: PMID:32959771
    reference_title: >-
      The Characteristics and Clinical Course of Patients with Scrub Typhus and
      Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A
      23-year Case Series from Queensland, Tropical Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Queensland tick typhus and scrub typhus can cause multi-organ failure
      requiring ICU care in otherwise well individuals.
    explanation: >-
      The ICU series reports multi-organ failure as a possible severe QTT
      manifestation.

- name: Purpura Fulminans
  category: Dermatologic
  description: Severe QTT can cause purpura fulminans requiring digital amputation.
  phenotype_term:
    preferred_term: Purpura fulminans
    term:
      id: HP:0000979
      label: Purpura
    coarse_binding_basis: NO_HPO_TERM
    term_gap: >-
      HPO has no dedicated purpura-fulminans term; `uv run runoak -i ols:hp
      search "Purpura"` on 2026-09-28 returned HP:0000979 Purpura and specific
      distribution or thrombocytopenia terms, but not purpura fulminans.
  evidence:
  - reference: PMID:32959771
    reference_title: >-
      The Characteristics and Clinical Course of Patients with Scrub Typhus and
      Queensland Tick Typhus Infection Requiring Intensive Care Unit Admission: A
      23-year Case Series from Queensland, Tropical Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      One patient with QTT died, and two (8%) additional patients with QTT
      developed purpura fulminans requiring digital amputation.
    explanation: >-
      The ICU case series documents purpura fulminans among severe QTT patients.

diagnosis:
- name: Rickettsial qPCR on blood or cutaneous lesions
  description: >-
    Real-time PCR on early blood or cutaneous-lesion specimens can detect
    rickettsial DNA, with R. australis-specific assays available in reference
    laboratory panels.
  diagnosis_term:
    preferred_term: polymerase chain reaction
    term:
      id: NCIT:C17003
      label: Polymerase Chain Reaction
  results: A positive PCR from blood, eschar swab, or biopsy supports early molecular confirmation.
  evidence:
  - reference: PMID:22092999
    reference_title: Widespread use of real-time PCR for rickettsial diagnosis.
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      We retained sets of primers and probes to detect spotted fever group
      Rickettsia, typhus group Rickettsia,Rickettsia conorii,Rickettsia
      slovaca,Rickettsia africae and Rickettsia australis
    explanation: >-
      The molecular-diagnostics evaluation included a validated R. australis
      real-time PCR primer/probe set in its routine rickettsial panel.
  - reference: PMID:31587667
    reference_title: "Diagnosis of spotted fever group Rickettsia infections: the Asian perspective."
    supports: SUPPORT
    evidence_source: OTHER
    snippet: >-
      It is likely that the best strategy is to use a real-time quantitative
      polymerase chain reaction (qPCR) and immunofluorescence assay in tandem.
    explanation: >-
      The diagnostic review supports pairing early qPCR with serology to span
      the time windows of nucleic-acid and antibody detection.

- name: Indirect immunofluorescence assay serology
  description: >-
    Serology is needed to separate QTT from clinically overlapping Australian
    rickettsioses, although antibody results are often retrospective because
    acute samples can be negative before seroconversion.
  diagnosis_term:
    preferred_term: indirect immunofluorescence assay serology
    term:
      id: NCIT:C217458
      label: Diagnostic Serology Testing
  results: A compatible illness plus rickettsial antibody rise supports retrospective confirmation.
  evidence:
  - reference: PMID:1962102
    reference_title: Spotted fever group rickettsial infections in Australia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    quote_role: REVIEW_SYNTHESIS
    snippet: >-
      Because clinical features overlap, serologic tests are necessary to
      distinguish QTT from other endemic Australian rickettsial diseases (scrub
      and murine typhus).
    explanation: >-
      The Australian review identifies serology as necessary for distinguishing
      QTT from scrub typhus and murine typhus in the same region.

differential_diagnoses:
- name: Flinders Island spotted fever
  description: >-
    Flinders Island spotted fever is an overlapping Australian
    spotted-fever-group rickettsiosis caused by Rickettsia honei rather than
    R. australis; it should be considered in patients from southeastern
    Australia who present with fever, headache, rash, and tick exposure.
  distinguishing_features:
  - R. honei causes Flinders Island spotted fever, whereas R. australis causes QTT.
  - Southeastern Australia exposure favors Flinders Island spotted fever over QTT.
  - Organism-specific PCR or culture distinguishes the two agents.
  evidence:
  - reference: PMID:16175900
    reference_title: "Not only 'Flinders Island' spotted fever."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      FISF should be considered as a differential diagnosis in patients from
      south-eastern Australia presenting with fever, headache and rash following
      a tick bite.
    explanation: >-
      The case report series establishes Flinders Island spotted fever as a
      tick-associated spotted-fever differential diagnosis in southeastern
      Australia.

treatments:
- name: Empiric doxycycline
  description: >-
    Doxycycline is first-line empiric therapy for suspected tick-borne
    rickettsial disease, including Queensland tick typhus, because it inhibits
    the rickettsial 30S ribosomal subunit and reaches the host-cell cytosol
    where R. australis resides.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
  target_mechanisms:
  - target: Rickettsial Ribosomal Translation
    treatment_effect: INHIBITS
    description: Doxycycline blocks rickettsial protein synthesis at the 30S ribosomal subunit.
  - target: Intracytosolic Rickettsia australis Niche
    treatment_effect: BYPASSES
    description: Doxycycline can reach the cytosolic rickettsial compartment.
  evidence:
  - reference: PMID:27172113
    reference_title: >-
      Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain
      Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses,
      and Anaplasmosis - United States.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Doxycycline is the drug of choice for treatment of all tickborne
      rickettsial diseases in patients of all ages, including children aged <8
      years, and should be initiated immediately in persons with signs and
      symptoms suggestive of rickettsial disease
    explanation: >-
      QTT is a tick-borne rickettsial disease, so this CDC first-line treatment
      recommendation covers empiric therapy for suspected QTT.
  - reference: PMID:33075531
    reference_title: "Prompt defervescence after initiation of treatment for rickettsial infections - time to dispense with the dogma?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      A significant proportion of patients with confirmed scrub typhus and QTT
      will remain febrile for >48 hours after appropriate anti-rickettsial
      therapy.
    explanation: >-
      The tropical Australia cohort cautions that delayed defervescence after
      appropriate therapy can occur in confirmed QTT and does not by itself
      exclude the diagnosis.

📚

References & Deep Research

References

3

PMID:1962102

Spotted fever group rickettsial infections in Australia.

1 finding

Queensland tick typhus is a usually mild Rickettsia australis infection with eschars, regional lymphadenopathy, occasional vesicular rash, Ixodes holocyclus and Ixodes tasmani tick vectors, and serologic overlap with other Australian rickettsioses.

"More than four decades ago, Rickettsia australis was discovered to be the etiologic agent of Queensland tick typhus (QTT)"

PMID:19327117

Host-cell interactions with pathogenic Rickettsia species.

1 finding

Endothelial tropism, vascular inflammation, loss of vascular integrity, and increased permeability are conserved pathogenic features of spotted fever and typhus group rickettsioses.

"the consequences of which are vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed 'Rickettsial vasculitis'"

PMID:11179362

Critical role of cytotoxic T lymphocytes in immune clearance of rickettsial infection.

1 finding

R. australis mouse experiments identify MHC class I-restricted, perforin-dependent CD8 T cells as decisive for rickettsial clearance.

"These results indicate that CTL activity was more critical to recovery from rickettsial infection than were the effects of IFN-gamma."

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (1)

Create: Queensland Tick Typhus · 2026-09-25T12:48:56Z · View source

Created a standalone Queensland Tick Typhus entry for MONDO:0001118 after ignored-file-inclusive local search found the MONDO ID, label, and Rickettsia australis strings only in the Spotted_Fever_Rickettsiosis subtype row, generated Spotted_Fever_Rickettsiosis Boomer/pages output, rare-disease mapping worklists, existing Rickettsia references, and one Murine_Typhus research/page echo. The only all-state PR match was the merged spotted-fever root PR (#8899), and all-state GitHub issue searches for both `Queensland tick typhus` and `MONDO:0001118` returned no matches. PROMOTION. Promoted the Queensland tick typhus subtype out of the deliberately thin Spotted_Fever_Rickettsiosis root while leaving that parent intact, and changed the subtype description there from "No standalone dismech entry yet" to `Curated in full in Queensland_Tick_Typhus.yaml`. DEEP RESEARCH. Seeded the QTT entry with its MONDO term, Rickettsia australis infectious-agent binding, and a cached QTT review (PMID:28719297), then ran `just research-disorder openscientist Queensland_Tick_Typhus`. The first OpenScientist call stayed silent for roughly 20 minutes without a report file, so it was interrupted; an immediate fallback-enabled rerun picked up the completed OpenScientist result in the provider cache and wrote `research/Queensland_Tick_Typhus-deep-research-openscientist.md`, its citation sidecar, and HTML/PDF artifacts. The report resolved all 24 references and marked 14 as on-topic. NEC. `just preflight-dr research/Queensland_Tick_Typhus-deep-research-openscientist.md MONDO:0001118` returned SKIP because MONDO records no RO:0004003 causal gene for this acquired infection. Manual identity review matched the report to QTT throughout: the report centered MONDO:0001118, Rickettsia australis, Ixodes tick transmission, and eastern Australian disease. The "Australian spotted fever" alias was treated as ambiguous with Flinders Island spotted fever and was not added as a synonym. TERM REVIEW. The report's term validation resolved every CURIE but correctly flagged two bad or misleading leads: `UBERON:0000465` was offered for "Lymphatic system" even though it resolves to "material anatomical entity", and `GO:0050830` was offered for Gram-negative bacterial defense even though it resolves to "defense response to Gram-positive bacterium". Neither was used. CONTENT. Curated Ixodes holocyclus/Ixodes tasmani transmission, eastern-coastal Australian exposure, R. australis infection of dermal macrophages, the conserved rickettsial endothelial vasculitis mechanism, TLR4/ASC/MyD88 innate control, CD8 T-cell cytotoxic clearance in the R. australis mouse model, the shared 70S-ribosome doxycycline target, and the shared intracytosolic Rickettsia niche. Added five phenotypes and wired all five to causal parents: eschar, regional lymphadenopathy, fever, headache, and vesicular rash. Added qPCR and indirect immunofluorescence diagnosis, plus empiric doxycycline treatment targeting both the ribosomal translation node and the intracellular niche. VALIDATION. `just validate kb/disorders/Queensland_Tick_Typhus.yaml` passed with 23 snippets checked, no skipped or unavailable snippets, and 26 titles checked. `just count-verified-snippets kb/disorders/Queensland_Tick_Typhus.yaml` reported 23/23 snippets verified against cached references. `just list-disconnected-phenotypes kb/disorders/Queensland_Tick_Typhus.yaml` reported 5/5 phenotype nodes causally connected. `just validate kb/disorders/Spotted_Fever_Rickettsiosis.yaml` passed after the parent row pointer edit.

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Queensland Tick Typhus (MONDO:0001118): A Comprehensive Disease-Characteristics Report

openscientist-autonomous 24 citations 2026-09-25T05:42:50.271391

Queensland Tick Typhus (MONDO:0001118): A Comprehensive Disease-Characteristics Report

Summary

Queensland Tick Typhus (QTT) is an acute, tick-borne spotted fever group (SFG) rickettsiosis caused by the obligate intracellular Gram-negative bacterium Rickettsia australis. It is transmitted to humans by the bite of hard (ixodid) ticks — principally Ixodes holocyclus (the eastern paralysis tick) and Ixodes tasmani — along a ~3,200-km strip of eastern coastal Australia, from tropical North Queensland to temperate Tasmania/Victoria. It is a non-genetic infectious disease: there are no causal human genes, no inherited susceptibility loci of established clinical importance, and the dominant risk factor is simply environmental/occupational/recreational exposure to tick habitat.

Clinically, QTT is usually a mild, self-limited eschar-associated febrile illness characterized by fever, headache, a maculopapular or vesicular rash, an inoculation eschar at the tick-bite site, and regional (draining) lymphadenopathy. However, a clinically significant minority of patients develop severe disease requiring intensive-care admission, and death and permanent disability are documented. After tick inoculation the organism first replicates in dermal/tissue macrophages, then disseminates to and infects vascular endothelial cells, producing the hallmark "rickettsial vasculitis" that underlies the rash, eschar, and (in severe cases) increased vascular permeability and multi-organ dysfunction. Host control depends on innate signaling (TLR4 → MyD88 → ASC inflammasome, dendritic-cell instruction, Th1/IFN-γ) and, decisively, on perforin-dependent, MHC class I-restricted CD8⁺ cytotoxic T lymphocytes (CTLs), which mouse-model gene-knockout studies show are even more critical to recovery than IFN-γ.

Diagnosis rests on serology (indirect immunofluorescence assay [IFA]: a ≥4-fold rise in paired sera or a single IgG titre ≥1:64) combined with PCR (real-time qPCR of whole blood, eschar swab, or skin biopsy). First-line treatment is doxycycline, which is highly effective and protective against progression to severe disease; fluoroquinolones should be avoided because they are associated with worse outcomes in SFG rickettsioses. There is no licensed vaccine; prevention is entirely based on tick-bite avoidance, prompt tick removal, and environmental/personal protective measures. This report synthesizes 11 confirmed findings from 42 reviewed papers into the 15-section disease-characteristics template requested.

Section 1 — Disease Information

Overview. Queensland Tick Typhus is a zoonotic, vector-borne SFG rickettsiosis. It was first recognized clinically in Queensland, and its causative agent, Rickettsia australis, was isolated in Queensland in 1950 (type strain "Phillips") — over four decades before comprehensive case reviews consolidated it as a distinct endemic Australian rickettsiosis (PMID: 22933759; PMID: 1962102).

Key identifiers.

Resource	Identifier
MONDO	MONDO:0001118 (Queensland tick typhus)
Causative organism (NCBI Taxonomy)	Rickettsia australis (species)
MeSH concept	Spotted fever group rickettsiosis / Rickettsia infections (no unique QTT MeSH descriptor)
ICD-10	A77.3 (Spotted fever due to Rickettsia australis)
ICD-11	1C30.2 / spotted fever group rickettsiosis category
OMIM / Orphanet	Not applicable (infectious, non-Mendelian; no OMIM entry)

Synonyms / alternative names. Queensland tick typhus; Australian tick typhus; North Queensland tick typhus; Rickettsia australis infection; Australian spotted fever (in part — note that "Australian spotted fever" also encompasses Flinders Island spotted fever caused by R. honei, a distinct co-endemic agent).

Source of information. The knowledge base for QTT is derived from aggregated disease-level resources — published case series, hospital audits, serosurveys, microbiological/genomic characterizations, and animal-model immunology — rather than from individual-patient EHR data.

Section 2 — Etiology

Primary cause (infectious). QTT is caused by infection with Rickettsia australis, an obligately intracellular SFG rickettsia, delivered into the skin during the blood meal of an infected ixodid tick (PMID: 1962102). It is not a genetic, autoimmune, metabolic, or neoplastic disease.

Risk factors. - Genetic risk factors (human): None of established clinical relevance. No causal variants, susceptibility loci, or modifier genes have been identified for human QTT. Innate-immunity genes (MYD88, TLR4, inflammasome components, MHC-I, perforin/PRF1) are mechanistically important in animal models (see Sections 4 and 6) but are not validated human susceptibility markers. - Environmental / behavioral risk factors: Exposure to tick-infested vegetation in endemic eastern-coastal Australia is the principal risk factor — including bushwalking, gardening, camping, and outdoor occupations. Epidemiology shows a skew toward older males and a late spring/early summer (November–December) seasonal peak, reflecting exposure patterns and tick questing behavior (PMID: 31268225).

Protective factors. No genetic protective variants are described in humans. The single most effective environmental protective factor is tick-bite avoidance (protective clothing, repellents, tick checks, prompt removal). Prompt doxycycline after infection is protective against severe disease progression (PMID: 21642652).

Gene–environment interactions. Not characterized in humans. The relevant "gene–environment" axis is between the pathogen's virulence factors and the host's innate/adaptive immune genotype, demonstrated experimentally in mice (MyD88, TLR4/ASC, perforin, MHC-I).

Section 3 — Phenotypes

QTT produces a stereotyped SFG-rickettsiosis phenotype. Sexton et al. summarized the classic presentation: "QTT is usually a mild disease. Patients often have regional lymphadenopathy and eschars. Some have vesicular rashes." (PMID: 1962102).

Phenotype	Type	HPO suggestion	Typical frequency / notes
Fever	Symptom/sign	HP:0001945 (Fever)	Near-universal; commonly reported (PMID: 31268225)
Inoculation eschar (tache noire)	Clinical sign	HP:0200041 (Skin ulcer) / eschar	Frequent; hallmark at tick-bite site (PMID: 1962102)
Maculopapular / vesicular rash	Physical manifestation	HP:0000988 (Skin rash); HP:0200037 (Vesicle)	Common; vesicular rash a distinctive QTT feature
Regional lymphadenopathy	Clinical sign	HP:0002716 (Lymphadenopathy)	Common (draining nodes)
Headache	Symptom	HP:0002315 (Headache)	Common
Lethargy / malaise	Symptom	HP:0001254 (Lethargy)	Common (PMID: 31268225)
Myalgia	Symptom	HP:0003326 (Myalgia)	Common
Elevated transaminases	Lab abnormality	HP:0002910 (Elevated hepatic transaminase)	Frequent in SFG rickettsioses
Thrombocytopenia	Lab abnormality	HP:0001873 (Thrombocytopenia)	Variable; marks more severe disease
Severe disease (ICU / organ dysfunction)	Clinical course	critical illness	~13–22% ICU in SFG hospital cohorts (PMID: 31318873; PMID: 32959771)

Onset / severity / progression. Adult-onset predominant (any age exposed can be affected). Severity is variable — mild in most, but severe/fatal in a minority. Course is acute and self-limited with appropriate therapy. In a 20-year North Queensland audit of 135 cases (95 scrub typhus, 37 SFG/QTT), 18/135 (13%) required ICU; the SFG subgroup had a higher ICU rate (8/37, 22%) and 3/37 (8%) had severe disease — "1 died, 2 developed permanent disability" — versus 0/95 scrub typhus (p = 0.02) (PMID: 31318873). By contrast, paediatric rickettsial infection in tropical Australia has "a relatively benign clinical course" with no ICU admission or death among 15 children (PMID: 32252063).

Quality-of-life impact. Not formally measured with instruments (EQ-5D/SF-36) for QTT. For most patients the illness is acute and fully reversible; the QoL burden concentrates in the severe subset who suffer prolonged hospitalization, ICU stay, or (rarely) permanent disability.

Section 4 — Genetic/Molecular Information

Human genetics. QTT is an infectious disease with no causal human genes, no pathogenic germline/somatic variants, no modifier genes, no epigenetic disease signatures, and no chromosomal abnormalities. Sections requesting ClinVar/gnomAD/COSMIC variant data are not applicable.

Pathogen genome (the relevant molecular biology). The R. australis strain Phillips genome is a compact 1.29-Mb chromosome accompanied by two plasmids, and is "highly similar to that of Rickettsia akari" (PMID: 22933759). Phylogenetically, multiple independent gene analyses place R. australis firmly within the "Rickettsia akari group" of the SFG, alongside R. akari (rickettsialpox agent) and the ELB/R. felis agent (gene D: PMID: 11491333; citrate synthase gltA: PMID: 9103608). Notably, R. australis is described as "the most divergent rickettsia of the spotted fever group" on the basis of its outer-membrane protein A and B genes (PMID: 11034486). Key rickettsial virulence/antigen loci include ompA, ompB (surface cell antigens mediating adhesion/invasion), the 17-kDa antigen gene, and gltA.

Host immune-gene involvement (model organism). Genes shown experimentally to govern outcome are Myd88, Tlr4, inflammasome adaptor Pycard/ASC, MHC class I, and perforin (Prf1) — see Section 6.

Section 5 — Environmental Information

Environmental factors. The disease is defined by an environmental exposure: contact with tick habitat in the humid sclerophyll forests, coastal scrub, and peri-urban bushland of eastern Australia. No chemical toxin, radiation, or pollutant is involved.

Lifestyle factors. Outdoor recreation and occupation (bushwalking, camping, gardening, forestry, field work) increase exposure. Seasonality (late spring–summer) reflects tick activity (PMID: 31268225).

Infectious agent. Rickettsia australis — an obligately intracellular, cytosolically replicating, Gram-negative alphaproteobacterium (order Rickettsiales, SFG, R. akari group). It is a pathogen, not a chemical entity. Vectors Ixodes holocyclus and Ixodes tasmani maintain the organism; small native mammals (rodents, bandicoots, marsupials) serve as reservoir/amplifying hosts, with humans as accidental dead-end hosts (PMID: 1962102; PMID: 25434042).

Section 6 — Mechanism / Pathophysiology

Ordered causal chain

An infected ixodid tick (I. holocyclus / I. tasmani) attaches and takes a blood meal, inoculating R. australis into the dermis at the bite site. → (demonstrated)
Local infection and replication in dermal/tissue macrophages — "Macrophages are one of the initial targets for rickettsiae after inoculation by ticks" — leads to an early intracellular replication niche and a localized inflammatory/necrotic focus that becomes the eschar (PMID: 30297526). → (demonstrated in mouse model)
Rickettsiae disseminate (lymphatics → draining nodes, producing regional lymphadenopathy; and haematogenously) and infect vascular endothelial cells, the pathogen's principal target — "the pathogen's affinity for endothelium lining the blood vessels" — resulting in endothelial infection throughout small vessels (PMID: 19327117). → (demonstrated)
Endothelial infection causes "vascular inflammation, insult to vascular integrity and compromised vascular permeability, collectively termed 'Rickettsial vasculitis'" (PMID: 19327117). → (demonstrated)
Rickettsial vasculitis produces the clinical phenotype: perivascular mononuclear infiltrate → maculopapular/vesicular rash; microvascular injury → increased permeability. → (inferred from SFG pathology, consistent across the group)
Branch (host innate immunity): Pathogen-associated molecular patterns engage TLR4 → MyD88 signaling and activate the ASC inflammasome, driving dendritic-cell instruction, macrophage/neutrophil recruitment, and a Th1 cytokine milieu (IFN-γ, IL-6, IL-1β, IL-12p40) that restrains bacterial burden (PMID: 32014896; PMID: 26755162). → (demonstrated in mouse model)
Branch (host adaptive immunity, decisive): MHC class I-restricted, perforin-dependent CD8⁺ CTLs recognize and kill infected macrophages and endothelial cells, clearing the infection — this effector arm is "more critical to recovery… than were the effects of IFN-gamma" (PMID: 11179362). → (demonstrated in mouse model)
Outcome branch: When innate + CD8 CTL immunity (aided by timely doxycycline) controls the organism → mild, self-limited illness. When bacterial dissemination outpaces immunity (older age, delayed treatment) → widespread endothelial injury, capillary leak, organ dysfunction → severe disease / death (PMID: 31318873). → (inferred, supported by clinical severity data)

Detail by category

Molecular pathways: TLR4→MyD88→NF-κB innate signaling; ASC/NLR inflammasome → caspase-1 → IL-1β maturation; Th1/IFN-γ–STAT1 axis; MHC-I antigen-presentation and perforin/granzyme cytotoxicity pathway.
Cellular processes: Intracellular bacterial invasion and cytosolic replication; inflammation; macrophage and endothelial infection; CTL-mediated cytotoxicity of infected cells; endothelial activation and increased permeability.
Protein dysfunction: Not a protein-misfolding disease; pathology is driven by pathogen invasins (OmpA/OmpB) and host endothelial-barrier dysfunction.
Immune involvement: Central and protective (innate TLR4/MyD88/ASC; adaptive CD8 CTL). Loss of MyD88 causes "severely impaired bacterial clearance in vivo" (PMID: 26755162).
Tissue-damage mechanism: Rickettsial vasculitis — immune-mediated and infection-mediated microvascular injury with increased permeability (PMID: 19327117).

Suggested ontology terms. GO: GO:0002224 (toll-like receptor signaling pathway), GO:0045087 (innate immune response), GO:0001913 (T cell-mediated cytotoxicity), GO:0006954 (inflammatory response), GO:0050830 (defense response to Gram-negative bacterium). CL: CL:0000235 (macrophage), CL:0000071 (blood vessel endothelial cell), CL:0000625 (CD8-positive, alpha-beta T cell), CL:0000451 (dendritic cell).

Section 7 — Anatomical Structures Affected

Primary target: systemic small-vessel vascular endothelium (UBERON:0001986 endothelium; UBERON:0000115 endothelial layer of blood vessel) — the unifying lesion of SFG rickettsiosis (PMID: 19327117).
Skin (UBERON:0002097): eschar at inoculation site; maculopapular/vesicular rash.
Lymphatic system (UBERON:0000465): regional draining lymph nodes (UBERON:0000029) — lymphadenopathy.
Body systems involved: cardiovascular (microvasculature), integumentary, lymphoid/immune; in severe disease, potential secondary involvement of lung, liver, kidney, and CNS via generalized vasculitis/capillary leak.
Cell populations targeted: vascular endothelial cells (CL:0000071) and macrophages (CL:0000235); CD8⁺ CTLs (CL:0000625) are the key effector population.
Subcellular level: R. australis is a cytosolic pathogen — it replicates free in the host-cell cytoplasm (GO:0005829 cytosol), escaping the phagosome.
Lateralization: the eschar/lymphadenopathy are localized/unilateral to the bite site; the rash and vasculitis are generalized/bilateral.

Section 8 — Temporal Development

Onset: acute, following an incubation period of roughly 7–10 days after the tick bite; patients in the ICU series presented a median of 7 (IQR 5–10) days after symptom onset (PMID: 32959771).
Progression / course: self-limited in most, resolving over days to ~1–2 weeks with therapy; not chronic, relapsing, or lifelong. A minority progress to severe multi-organ disease.
Treatment-response kinetics: In hospitalized scrub typhus/QTT patients on anti-rickettsial therapy, 32/58 (56%) had delayed defervescence (>48 h); delayed defervescence was associated with older age (median 52 vs 40 y, p = 0.05), higher ICU admission (38% vs 12%, p = 0.02), and longer stay — challenging the dogma that persistent fever >48 h implies a wrong diagnosis (PMID: 33075531).
Critical period for intervention: early — doxycycline given "prior to deterioration of disease… protected patients from development of severe" disease in the analogous Mediterranean spotted fever cohort (PMID: 21642652).
Remission: treatment-induced (doxycycline) and, in mild cases, potentially spontaneous.

Section 9 — Inheritance and Population

Inheritance. Not applicable — infectious, non-heritable. No inheritance pattern, penetrance, expressivity, anticipation, mosaicism, founder effect, consanguinity, or carrier-frequency considerations.

Epidemiology. - QTT/Australian SFG rickettsiosis is a rare, notifiable, seasonally patterned infection. In Tasmania (2012–2017), "The mean number of cases per year was 3.0 (population rate 0.6 per 100,000 population/year); 60% of cases occurred in November and December. Cases were more commonly older males" (PMID: 31268225). (Note: Tasmanian SFG cases are predominantly Flinders Island spotted fever caused by R. honei, a co-endemic agent; true QTT/R. australis predominates on the mainland eastern seaboard.) - Ascertainment/incidence is rising: in a North Queensland tertiary hospital, "There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003)" (PMID: 31318873).

Population demographics. - Geographic distribution: eastern coastal Australia across a ~3,200-km span "from tropical to temperate climates" — Queensland, New South Wales, Victoria, and Tasmania (PMID: 1962102). - Sex / age: skewed to older males (PMID: 31268225); paediatric cases occur but run a milder course (PMID: 32252063).

Section 10 — Diagnostics

Clinical/laboratory tests. - Serology (mainstay): indirect immunofluorescence assay (IFA); diagnosis by a ≥4-fold rise in IgG between acute and convalescent sera, or a single IgG titre ≥1:64 with a compatible illness (PMID: 1962102; titre convention as applied in SFG serosurveys, PMID: 31288833). Limitation: antibodies are absent early in illness. - Molecular (PCR): real-time qPCR targeting SFG/R. australis-specific genes (e.g., gltA, ompA, ompB, 17-kDa) on whole blood, eschar swab, or skin biopsy; validated R. australis real-time PCR assays are in routine reference use (PMID: 22092999). - Recommended strategy: "the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem" (PMID: 31587667). - Supportive labs: mild thrombocytopenia, leukopenia/leukocytosis, elevated transaminases, elevated CRP (non-specific). - Culture: possible but hazardous/slow; restricted to reference labs.

Genetic testing / omics diagnostics. Human genetic testing is not applicable. Pathogen genomics (WGS/PCR) is used for organism identification and epidemiology, not for host diagnosis.

Clinical criteria & differential diagnosis. Because "clinical features overlap, serologic tests are necessary to distinguish QTT from other endemic Australian rickettsial diseases (scrub and murine typhus)" (PMID: 1962102). Key differentials: scrub typhus (Orientia tsutsugamushi), murine typhus (R. typhi), and Flinders Island spotted fever (R. honei), which "extends beyond Flinders Island" across south-east Australia (PMID: 16175900); also dengue, leptospirosis, and Q fever in the same region.

Screening. No population screening (acute, sporadic, environmentally acquired infection).

Section 11 — Outcome / Prognosis

Overall prognosis: Good with prompt doxycycline; usually mild and self-limited (PMID: 1962102).
Severe disease / mortality: A real minority. In the North Queensland audit, 3/37 (8%) SFG patients had severe disease (1 death, 2 permanent disability) versus 0/95 scrub typhus (p = 0.02) (PMID: 31318873); a 23-year ICU series included 9 QTT patients (median APACHE II 13) (PMID: 32959771).
Recovery: Complete recovery is the norm with treatment; residual disability is rare.
Prognostic factors: older age, ICU-level illness, and delayed defervescence (>48 h), which is "more common in patients with severe disease" (PMID: 33075531); paediatric age predicts a benign course (PMID: 32252063).

Section 12 — Treatment

First-line pharmacotherapy — doxycycline (NCIT: C312; tetracycline-class antibiotic). Doxycycline is the standard of care. In the analogous Mediterranean spotted fever cohort, "Doxycycline administration prior to deterioration of disease (in 31 patients) protected patients from development of severe MSF" (RR 0.248, 95% CI 0.08–0.76) with earlier defervescence (3.0 vs 7.1 days) (PMID: 21642652).

Avoid fluoroquinolones. In the same analysis, "fluoroquinolone treatment was associated with increased MSF disease severity" (RR 2.53, 95% CI 1.40–4.55) — so fluoroquinolones should be avoided in SFG rickettsioses (PMID: 21642652).

Alternatives. Macrolides (e.g., azithromycin) are considered for children/pregnancy in SFG rickettsioses, though experimental data (canine RMSF) suggest azithromycin is less efficacious than doxycycline (PMID: 10103185); chloramphenicol is a historical alternative.

Supportive care. Antipyretics, fluids, and — for the severe/ICU subset — organ support (vasopressors, ventilation) as needed (PMID: 32959771).

Advanced/experimental therapeutics, pharmacogenomics, surgery, targeted/immuno/cell/gene therapy: Not applicable — QTT is cured by a short antibiotic course.

Treatment-response caveat. Persistent fever >48 h after starting doxycycline does not necessarily indicate misdiagnosis; delayed defervescence occurs in ~56% and correlates with severity (PMID: 33075531).

Suggested NCIT term: Doxycycline (NCIT:C312); Tetracycline antibiotic therapy.

Section 13 — Prevention

Primary prevention: No vaccine exists. Prevention relies on tick-bite avoidance — protective clothing, DEET/permethrin repellents, avoiding tick habitat during peak season, systematic tick checks, and prompt, correct tick removal after exposure in endemic eastern Australia.
Chemoprophylaxis: Routine post-tick-bite antibiotic prophylaxis is not recommended; management is watchful waiting with early empiric doxycycline if symptoms develop.
Secondary prevention: Early recognition and prompt doxycycline to prevent progression to severe disease (PMID: 21642652).
Tertiary prevention: Supportive/ICU care to prevent complications in severe cases.
Public health: Clinician and public education (given rising ascertainment, PMID: 31318873), notifiable-disease surveillance, and environmental/personal tick-control measures. Genetic counseling is not applicable.

Section 14 — Other Species / Natural Disease

Vectors (NCBI Taxonomy): Ixodes holocyclus (paralysis tick) and Ixodes tasmani are the only two confirmed vectors of R. australis (PMID: 1962102). I. holocyclus is "the cause of the neurotoxic disease tick paralysis in humans and mammals" in densely populated eastern Australia (PMID: 25434042).
Reservoir hosts: native small mammals — rodents, bandicoots, and marsupials — maintain R. australis in nature; humans are accidental dead-end hosts.
Zoonotic transmission: QTT is a zoonosis transmitted only via tick bite; there is no human-to-human transmission.
Comparative biology / cross-species susceptibility: R. australis has been detected molecularly in Ixodes ricinus ticks in Europe, indicating a broader potential vector/host range than the Australian endemic cycle (PMID: 18355299); DNA identical/very close to R. australis has been found in mite endosymbiont surveys (PMID: 31549736). No significant naturally occurring clinical disease from R. australis is documented in companion animals (contrast R. rickettsii, which causes canine Rocky Mountain spotted fever, PMID: 10103185).

Section 15 — Model Organisms

Principal model — mouse (Mus musculus, NCBI Taxon 10090): The C57BL/6 mouse is the workhorse for R. australis immunopathogenesis. Gene-knockout and adoptive-transfer studies established the protective hierarchy of host immunity:
Perforin⁻/⁻ and IFN-γ⁻/⁻ mice are "more than 100-fold more susceptible" and MHC class I⁻/⁻ mice ">50,000-fold" more susceptible to lethal R. australis; "CTL activity was more critical to recovery from rickettsial infection than were the effects of IFN-gamma" (PMID: 11179362).
MyD88⁻/⁻ mice show "severely impaired bacterial clearance in vivo" with blunted IFN-γ/IL-6/IL-1β and defective dendritic-cell maturation (PMID: 26755162).
TLR4/ASC-inflammasome contributes to host immunity against R. australis (PMID: 32014896).
Macrophage-tropism studies use R. australis in mice to show macrophages as an early target (PMID: 30297526).
Model type: mammalian in vivo (genetic knockouts: Prf1, Ifng, B2m/MHC-I, Myd88, Pycard/ASC); plus in vitro infection of macrophage-like and microvascular endothelial cells.
Phenotype recapitulation: The mouse model faithfully reproduces disseminated rickettsial infection, endothelial/macrophage targeting, and lethal severe disease, making it well suited to dissect protective immunity.
Limitations: Mouse studies emphasize immunology and lethality; they do not reproduce the human eschar/rash phenotype in detail, and inbred knockouts do not capture human genetic diversity.

Mechanistic Model (synthesis)

 Infected Ixodes tick bite
  │  inoculation of R. australis into dermis
  ▼
 [1] DERMAL MACROPHAGES  ── early replication niche ──►  ESCHAR (inoculation site)
  │  lymphatic + haematogenous spread
  ├────────────────────────────►  DRAINING LYMPH NODES ─► regional lymphadenopathy
  ▼
 [2] VASCULAR ENDOTHELIAL CELLS (systemic small vessels)
  │  cytosolic replication, endothelial injury
  ▼
 [3] RICKETTSIAL VASCULITIS
├─ perivascular infiltrate ─► maculopapular / vesicular RASH
└─ ↑ vascular permeability ─► (severe) capillary leak, organ dysfunction

   HOST DEFENSE (determines outcome)
     TLR4 → MyD88 → NF-κB / ASC inflammasome → IFN-γ, IL-6, IL-1β, IL-12  (innate restraint)
                   │
                   ▼
     MHC-I-restricted, PERFORIN-dependent CD8+ CTL  ──►  kill infected macrophages/endothelium
                   │                       (decisive clearance > IFN-γ)
┌──────────────────────────┴───────────────────────────┐
   controlled (mild, self-limited)                    outpaced (severe / fatal:
   + timely DOXYCYCLINE                                older age, delayed Rx)

Evidence Base

PMID	Title (abbrev.)	Role in this report
1962102	Spotted fever group rickettsial infections in Australia	Etiology, vectors, geography, mild phenotype, serologic diagnosis, differentials
22933759	Genome sequence of R. australis	1.29-Mb genome, 2 plasmids, R. akari similarity, 1950 isolation
11034486	ompA/ompB of R. australis	"Most divergent" SFG rickettsia; SFG classification
11491333	Phylogeny via gene D	Places R. australis in the R. akari group
9103608	gltA citrate synthase phylogeny	Confirms SFG/R. akari-group placement
19327117	Host-cell interactions with pathogenic Rickettsia	Endothelial tropism → "rickettsial vasculitis" core mechanism
30297526	Rickettsial macrophage tropism	Macrophages as early target preceding endothelium
32014896	ASC inflammasome / TLR4 vs R. australis	Innate immune control of R. australis
26755162	MyD88 in dendritic cells	MyD88-dependent protective Th1 immunity; impaired clearance in KO
11179362	Cytotoxic T lymphocytes in rickettsial clearance	CD8/perforin/MHC-I decisive, > IFN-γ
31318873	Rickettsial diseases in North Queensland	Severity (8% severe SFG; 1 death), rising incidence
32959771	ICU case series (QTT + scrub typhus)	9 ICU QTT cases; APACHE II 13; presentation timing
32252063	Rickettsial infection in children	Benign paediatric course
33075531	Prompt defervescence dogma	56% delayed defervescence; links to severity
21642652	Risk factors for malignant MSF	Doxycycline protective; fluoroquinolones deleterious
31587667	Diagnosis of SFG rickettsioses	qPCR + IFA in tandem
22092999	Real-time PCR for rickettsial diagnosis	Validated R. australis qPCR; eschar/blood samples
31268225	Tasmanian rickettsial hotspots	Incidence 0.6/100,000/yr, seasonality, older males
25434042	Ixodes holocyclus as vector	I. holocyclus human-biting tick / paralysis
16175900	Not only 'Flinders Island' spotted fever	R. honei differential across SE Australia
10103185	Doxycycline vs azithromycin vs trovafloxacin (canine RMSF)	Comparative antibiotic efficacy
18355299	Ixodes ricinus bacterial communities	R. australis DNA detected in European ticks

Limitations and Knowledge Gaps

Mechanistic data are largely from mouse models. The pivotal immunology (perforin/CD8 CTL dominance, MyD88, TLR4/ASC) derives from R. australis mouse experiments (PMID: 11179362; PMID: 26755162; PMID: 32014896); human immunopathology is inferred, not directly measured.
Endothelial-injury step is cross-group inference. The "rickettsial vasculitis" mechanism is established for SFG rickettsiae broadly (PMID: 19327117) and applied to R. australis; species-specific human histopathology of QTT is sparsely quantified.
Epidemiology conflates agents. The best incidence figure (0.6/100,000/yr, Tasmania) largely reflects R. honei (Flinders Island spotted fever), not pure R. australis (PMID: 31268225; PMID: 16175900). Mainland R. australis incidence is not precisely quantified.
Treatment evidence borrows from MSF. The strongest doxycycline-benefit / fluoroquinolone-harm data come from R. conorii MSF (PMID: 21642652); no QTT-specific randomized trial exists.
No human host-genetics data. Whether human innate-immunity polymorphisms modulate QTT severity is unknown.
No quality-of-life or long-term-outcome studies specific to QTT.

Proposed Follow-up Experiments / Actions

Species-resolved surveillance: Report R. australis versus R. honei separately in Australian notifiable-disease data to obtain a true QTT incidence and geographic map.
Prospective QTT cohort capturing eschar/blood qPCR positivity, IFA kinetics, defervescence time, severity predictors, and QoL (EQ-5D/SF-36) at 30/90 days.
Human immunogenetics/immunophenotyping: Test whether TLR4/MYD88/inflammasome/PRF1 variants or peripheral CD8 CTL responses correlate with QTT severity, to validate the mouse-derived model in humans.
Diagnostic optimization: Define the sensitivity/timing window of eschar-swab qPCR versus blood qPCR versus paired IFA in prospectively enrolled QTT patients (PMID: 31587667; PMID: 22092999).
Treatment-timing study: Quantify the effect of early empiric doxycycline on progression to severe QTT specifically (mirroring the MSF analysis), and formally test avoidance of fluoroquinolones.
Vector/reservoir ecology & One Health mapping of I. holocyclus/I. tasmani infection prevalence and reservoir hosts to guide targeted public-health messaging in expanding peri-urban endemic zones (PMID: 31318873).

Evidence-source key: Human clinical (case series/audits/serosurveys — PMIDs 1962102, 31318873, 32959771, 32252063, 33075531, 21642652, 31587667, 22092999, 16175900); Model organism (mouse — PMIDs 11179362, 26755162, 32014896, 30297526); Microbiology/genomics (PMIDs 22933759, 11034486, 11491333, 9103608); In vitro/vector (PMIDs 25434042, 18355299, 10103185).

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0rc1.

Outcome	Count
References checked	24
Resolved	24
Unresolved (possible confabulation)	0
Unverifiable	0
References weighed for topical relevance	24
On topic	14
Off topic	0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome	Count
Terms checked	27
Resolved	27
Unresolved (possible confabulation)	0
Obsolete	0
Unverifiable	0
Terms whose name was checked	21
Terms named correctly	15
Terms named as a different term	1
Terms whose name is worth a second look	5

Terms the report names something else

These identifiers resolve, so nothing about them looks wrong, and the ontology calls them something unrelated to what the report calls them. That usually means the identifier is not the one the sentence needs:

UBERON:0000465 (1 mention) - the report calls it "Lymphatic system"; UBERON calls it material anatomical entity

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

HP:0200041 (1 mention) - the report calls it "Skin ulcer"; HP calls it Skin erosion
HP:0002910 (1 mention) - the report calls it "Elevated hepatic transaminase"; HP calls it Elevated circulating hepatic transaminase concentration, and lists "Elevated transaminases" among its other names
GO:0050830 (1 mention) - the report calls it "defense response to Gram-negative bacterium"; GO calls it defense response to Gram-positive bacterium
CL:0000071 (2 mentions) - the report calls it "blood vessel endothelial cell", "Cell populations targeted: vascular endothelial cells"; CL calls it blood vessel endothelial cell**
UBERON:0002097 (1 mention) - the report calls it "Skin"; UBERON calls it skin of body, and lists "skin" among its other names

Terms named inconsistently

The report gives these identifiers more than one name of its own:

CL:0000071 - called "blood vessel endothelial cell", "Cell populations targeted:** vascular endothelial cells"

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Classifications

Pathophysiology

Pathograph

Phenotypes

Medical Actions

Diagnosis

Progression

Epidemiology

Infectious Agent

Transmission

Differential Diagnoses

Source YAML

References & Deep Research

References

Deep Research

Queensland Tick Typhus (MONDO:0001118): A Comprehensive Disease-Characteristics Report

Summary

Section 1 — Disease Information

Section 2 — Etiology

Section 3 — Phenotypes

Section 4 — Genetic/Molecular Information

Section 5 — Environmental Information

Section 6 — Mechanism / Pathophysiology

Ordered causal chain

Detail by category

Section 7 — Anatomical Structures Affected

Section 8 — Temporal Development

Section 9 — Inheritance and Population

Section 10 — Diagnostics

Section 11 — Outcome / Prognosis

Section 12 — Treatment

Section 13 — Prevention

Section 14 — Other Species / Natural Disease

Section 15 — Model Organisms

Mechanistic Model (synthesis)

Evidence Base

Limitations and Knowledge Gaps

Proposed Follow-up Experiments / Actions

Artifacts

Reference Validation

Term Validation

Terms the report names something else

Terms whose name is worth a second look

Terms named inconsistently