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Whipple Disease

Infectious MONDO:0005116 Systemic bacterial infection Malabsorption syndrome

Whipple disease is a chronic, multisystem infection caused by the actinomycete Tropheryma whipplei. It most commonly presents with weight loss, diarrhea, malabsorption, and migratory arthralgias, and can involve cardiac, neurologic, and ocular systems.

0
Mappings
0
Definitions
0
Inheritance
3
Pathophysiology
0
Histopathology
10
Phenotypes
0
Genes
2
Treatments
0
Subtypes
4
Differentials
0
Datasets
0
Trials
⚙

Pathophysiology

3
Macrophage dysfunction and malabsorption
Chronic small bowel infection by Tropheryma whipplei leads to lymphostasis and impaired nutrient absorption driven by macrophage dysfunction.
macrophage link
macrophage activation link
Show evidence (2 references)
PMID:26288590 SUPPORT
"The disease is a chronic infection of the intestinal mucosa with the bacterium Tropheryma whipplei, which leads to a lymphostasis with an impaired absorption of the nutrition."
Review describes lymphatic obstruction and malabsorption from chronic infection.
PMID:26288590 SUPPORT
"Recent studies suggest that a host-specific dysfunction of the intestinal macrophages is responsible for the chronic infection with T. whipplei."
Highlights macrophage functional defect underlying persistent infection.
Host susceptibility and immune dysregulation
Only a small fraction of exposed individuals develop Whipple disease, implicating rare inborn or acquired immune defects and risk from anti-TNF therapy.
immune system process link
Show evidence (4 references)
PMID:40062480 SUPPORT
"Half the world's population is exposed to T. whipplei, but only one in a million develop WD. This suggests that acquired or inborn errors of immunity (IEI) may underlie WD."
Genetic review links rare immune defects to disease susceptibility.
PMID:40062480 SUPPORT
"Anti-TNF treatment is a well established risk factor for flare-ups of WD."
Notes iatrogenic immune suppression as a trigger for disease activation.
PMID:32896657 PARTIAL
"About 60% were immunosuppressed. The most frequent clinical presentations were joint pain (16/22), weight loss (15/22) and/or digestive tract disorder (15/22)."
Cohort shows high immunosuppression rate among confirmed Whipple disease cases.
+ 1 more reference
TNF-inhibitor–driven macrophage apoptosis
Anti-TNF biologics can reprogram macrophages infected with Tropheryma whipplei, increasing bacterial replication and macrophage apoptosis, exacerbating latent disease.
macrophage link
apoptotic process link
Show evidence (2 references)
PMID:34093562 SUPPORT
"Etanercept, adalimumab or certolizumab treatment of monocyte-derived macrophages from healthy subjects significantly increased bacterial replication in vitro without affecting uptake."
Demonstrates TNF inhibitors increase T. whipplei replication within macrophages.
PMID:34093562 SUPPORT
"TNFI aggravate/exacerbate latent or subclinical undiagnosed Whipple's disease by promoting a strong inflammatory response and apoptosis."
Study links TNF blockade to apoptosis-driven exacerbation of Whipple disease.
●

Phenotypes

10
Cardiovascular(1) Digestive(2) Metabolism(1) Nervous System(2) Respiratory(1) Constitutional(2) Growth(1)
Cardiovascular 1
Lymphadenopathy Lymphadenopathy (HP:0002716)
Show evidence (2 references)
PMID:26288590 SUPPORT
"The clinical symptoms of WD include chronic diarrhea, malnutrition (weight loss), migratory polyarthralgia, abdominal pain, and/or enlarged lymph nodes."
Review notes lymphadenopathy as part of the systemic presentation.
PMID:40398847 SUPPORT
"A supraclavicular lymph node excisional biopsy revealed complete architectural effacement by a diffuse foamy histiocytic infiltrate without granuloma formation or necrosis."
Case report shows lymph node involvement with foamy macrophages due to Whipple disease.
Digestive 2
Chronic diarrhea Diarrhea (HP:0002014)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms."
Review lists chronic diarrhea as hallmark of Whipple disease malabsorption.
Steatorrhea Steatorrhea (HP:0002570)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms."
Same review notes steatorrhea as part of the malabsorption syndrome.
Metabolism 1
Fever Fever (HP:0001945)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms (polyarthralgia, fever, fatigue)."
Notes fever among early systemic symptoms.
Nervous System 2
Cognitive dysfunction Cognitive impairment (HP:0100543)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"Patients complain of headaches, cognitive dysfunctions, and eye motility disorders."
Review notes cognitive dysfunction among neurological features of Whipple disease.
Spinal cord involvement Abnormality of the nervous system (HP:0000707)
Show evidence (1 reference)
PMID:38525769 SUPPORT
"We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus."
Case report highlights spinal cord involvement as a presentation of Whipple disease.
Respiratory 1
Respiratory involvement Dyspnea (HP:0002094)
Show evidence (2 references)
PMID:38414785 SUPPORT
"Whipple's disease (WD) is a multiple-system chronic disease caused by Tropheryma whipplei (T. whipplei) infection. The present study describes 3 cases of WD with clinical manifestations of cough, chest pain, headache, dyspnea, sputum, joint pain, abdominal pain, diarrhea and weight loss."
Case series documents pulmonary symptoms including dyspnea and chest pain.
PMID:38414785 SUPPORT
"Chest computed tomography (CT) showed signs of plaques, nodules and pleural thickening; and bronchoscopic alveolar lavage fluid metagenomic-sequencing indicated that it was T. whipplei."
Imaging and BAL sequencing confirm pulmonary involvement due to T. whipplei.
Constitutional 2
Migratory polyarthralgia Arthralgia (HP:0002829)
Show evidence (2 references)
PMID:26288590 SUPPORT
"Patients report a migrating polyarthritis of the peripheral joints (ankles, shoulders, knees, wrists, hands) and of the axial system."
Describes typical migratory joint involvement.
PMID:40204565 SUPPORT
"Joint involvement was similar, with initial episodic migratory arthritis (91 %) predominantly affecting large joints and lasting 2-7 days."
Cohort of isolated articular Whipple disease shows stereotyped migratory arthritis pattern.
Abdominal pain Abdominal pain (HP:0002027)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"The clinical symptoms of WD include chronic diarrhea, malnutrition (weight loss), migratory polyarthralgia, abdominal pain, and/or enlarged lymph nodes."
Review lists abdominal pain among common clinical symptoms.
Growth 1
Weight loss Weight loss (HP:0001824)
Show evidence (1 reference)
PMID:26288590 SUPPORT
"The weight loss is on average 11 kg (range: 3-36 kg)."
Quantifies typical weight loss in Whipple disease.
💊

Treatments

2
Ceftriaxone induction followed by trimethoprim/sulfamethoxazole MAXO:0000058
Drug: ceftriaxone ↗ trimethoprim ↗ sulfamethoxazole ↗
Two-week intravenous ceftriaxone induction followed by oral TMP-SMX maintenance to eradicate infection and prevent relapse.
Show evidence (1 reference)
PMID:26288590 SUPPORT
"The German treatment recommendations include a two-week intravenous induction therapy with ceftriaxone, which is followed by a three-month oral maintenance therapy with trimethoprim/sulfamethoxazole."
Details standard ceftriaxone induction and TMP-SMX maintenance regimen.
Doxycycline plus hydroxychloroquine regimen MAXO:0000058
Drug: doxycycline ↗ hydroxychloroquine ↗
Oral doxycycline and hydroxychloroquine for one year, followed by lifelong doxycycline for relapse prevention.
Show evidence (1 reference)
PMID:26288590 SUPPORT
"A French group favors a combination of doxycycline and hydroxychloroquine for 1 year, followed by a lifelong administration of doxycycline."
Review reports alternative long-course doxycycline plus hydroxychloroquine approach.
🌍

Environmental Factors

2
Sewage exposure
Higher carriage rates reported in sewage workers, suggesting wastewater as a reservoir.
Show evidence (4 references)
PMID:26288590 SUPPORT
"High prevalences (approximately 12%) were found in workers who were responsible for the cleaning of sewers."
Review notes elevated Tropheryma whipplei DNA prevalence in sewer workers.
PMID:37727483 PARTIAL
"whipplei) is a Gram-positive actinomycete widely found in soil, sewage, and"
Case report reiterates sewage as an environmental reservoir.
PMID:40660514 PARTIAL
"Legionella pneumophila (LP) and Tropheryma whipplei (TW) have been identified as pathogens that can coexist in sewage environments."
Notes coexistence of T. whipplei with other pathogens in sewage.
+ 1 more reference
Soil exposure
Soil reported as an environmental reservoir for Tropheryma whipplei.
Show evidence (1 reference)
PMID:37727483 SUPPORT
"whipplei) is a Gram-positive actinomycete widely found in soil, sewage, and"
Notes soil as a reservoir where T. whipplei can be encountered.
🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Whipple Disease:

Crohn disease MONDO:0005011
Distinguishing Features
  • Transmural granulomatous inflammation with skip lesions; lacks PAS-positive macrophages filled with bacteria.
Show evidence (1 reference)
PMID:26288590 PARTIAL
"The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis)."
Review notes Crohn disease as a common granulomatous differential for Whipple disease presentations.
Intestinal tuberculosis Not Yet Curated MONDO:0001678
Distinguishing Features
  • Caseating granulomas and acid-fast bacilli on Ziehl-Neelsen staining; typically ileocecal involvement.
Show evidence (1 reference)
PMID:26288590 PARTIAL
"The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis)."
Article lists tuberculosis among frequent differential diagnoses for Whipple disease.
Sarcoidosis MONDO:0019338
Distinguishing Features
  • Noncaseating granulomas without pathogen; may mimic multisystem involvement but lacks PAS-positive macrophages.
Show evidence (1 reference)
PMID:26288590 PARTIAL
"The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis)."
Review highlights sarcoidosis as a granulomatous differential for Whipple disease.
HIV enteropathy Not Yet Curated MONDO:0005109
Distinguishing Features
  • Occurs with advanced HIV and opportunistic infections; confirmed by HIV testing and low CD4 counts.
Show evidence (1 reference)
PMID:26288590 PARTIAL
"The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis)."
Paper lists AIDS enteropathy as a key differential diagnosis for Whipple disease.
{ }

Source YAML

click to show 
name: Whipple Disease
creation_date: '2026-01-14T23:44:48Z'
updated_date: '2026-02-27T21:53:05Z'
category: Infectious
description: >
  Whipple disease is a chronic, multisystem infection caused by the actinomycete
  Tropheryma whipplei. It most commonly presents with weight loss, diarrhea,
  malabsorption, and migratory arthralgias, and can involve cardiac, neurologic,
  and ocular systems.
disease_term:
  preferred_term: Whipple disease
  term:
    id: MONDO:0005116
    label: Whipple disease
parents:
- Systemic bacterial infection
- Malabsorption syndrome
infectious_agent:
- name: Tropheryma whipplei
  infectious_agent_term:
    preferred_term: Tropheryma whipplei
    term:
      id: NCBITaxon:2039
      label: Tropheryma whipplei
  description: Gram-positive actinomycete responsible for Whipple disease.
pathophysiology:
- name: Macrophage dysfunction and malabsorption
  description: Chronic small bowel infection by Tropheryma whipplei leads to lymphostasis and impaired nutrient absorption driven by macrophage dysfunction.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: macrophage activation
    term:
      id: GO:0042116
      label: macrophage activation
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: The disease is a chronic infection of the intestinal mucosa with the bacterium Tropheryma whipplei, which leads to a lymphostasis with an impaired absorption of the nutrition.
    explanation: Review describes lymphatic obstruction and malabsorption from chronic infection.
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Recent studies suggest that a host-specific dysfunction of the intestinal macrophages is responsible for the chronic infection with T. whipplei.
    explanation: Highlights macrophage functional defect underlying persistent infection.
- name: Host susceptibility and immune dysregulation
  description: Only a small fraction of exposed individuals develop Whipple disease, implicating rare inborn or acquired immune defects and risk from anti-TNF therapy.
  biological_processes:
  - preferred_term: immune system process
    term:
      id: GO:0002376
      label: immune system process
  evidence:
  - reference: PMID:40062480
    supports: SUPPORT
    snippet: Half the world's population is exposed to T. whipplei, but only one in a million develop WD. This suggests that acquired or inborn errors of immunity (IEI) may underlie WD.
    explanation: Genetic review links rare immune defects to disease susceptibility.
  - reference: PMID:40062480
    supports: SUPPORT
    snippet: Anti-TNF treatment is a well established risk factor for flare-ups of WD.
    explanation: Notes iatrogenic immune suppression as a trigger for disease activation.
  - reference: PMID:32896657
    supports: PARTIAL
    snippet: About 60% were immunosuppressed. The most frequent clinical presentations were joint pain (16/22), weight loss (15/22) and/or digestive tract disorder (15/22).
    explanation: Cohort shows high immunosuppression rate among confirmed Whipple disease cases.
  - reference: PMID:37727483
    supports: PARTIAL
    snippet: The patient was admitted to the hospital due to recurrent diarrhea for 1 mo, shortness of breath, and 1 wk of fever, after 3 years of renal transplantation.
    explanation: Post-transplant case illustrates Whipple disease emerging under chronic immunosuppression.
- name: TNF-inhibitor–driven macrophage apoptosis
  description: Anti-TNF biologics can reprogram macrophages infected with Tropheryma whipplei, increasing bacterial replication and macrophage apoptosis, exacerbating latent disease.
  cell_types:
  - preferred_term: macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: apoptotic process
    term:
      id: GO:0006915
      label: apoptotic process
  evidence:
  - reference: PMID:34093562
    supports: SUPPORT
    snippet: Etanercept, adalimumab or certolizumab treatment of monocyte-derived macrophages from healthy subjects significantly increased bacterial replication in vitro without affecting uptake.
    explanation: Demonstrates TNF inhibitors increase T. whipplei replication within macrophages.
  - reference: PMID:34093562
    supports: SUPPORT
    snippet: TNFI aggravate/exacerbate latent or subclinical undiagnosed Whipple's disease by promoting a strong inflammatory response and apoptosis.
    explanation: Study links TNF blockade to apoptosis-driven exacerbation of Whipple disease.
phenotypes:
- name: Chronic diarrhea
  category: Gastrointestinal
  description: Persistent watery or steatorrheal stools reflecting malabsorption.
  phenotype_term:
    preferred_term: Diarrhea
    term:
      id: HP:0002014
      label: Diarrhea
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms.
    explanation: Review lists chronic diarrhea as hallmark of Whipple disease malabsorption.
- name: Steatorrhea
  category: Gastrointestinal
  description: Fatty, malabsorptive stools accompanying chronic infection.
  phenotype_term:
    preferred_term: Steatorrhea
    term:
      id: HP:0002570
      label: Steatorrhea
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms.
    explanation: Same review notes steatorrhea as part of the malabsorption syndrome.
- name: Weight loss
  category: Constitutional
  description: Progressive weight loss due to malabsorption.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: "The weight loss is on average 11 kg (range: 3-36 kg)."
    explanation: Quantifies typical weight loss in Whipple disease.
- name: Migratory polyarthralgia
  category: Musculoskeletal
  description: Migratory peripheral joint pain often preceding gastrointestinal symptoms.
  phenotype_term:
    preferred_term: Arthralgia
    term:
      id: HP:0002829
      label: Arthralgia
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Patients report a migrating polyarthritis of the peripheral joints (ankles, shoulders, knees, wrists, hands) and of the axial system.
    explanation: Describes typical migratory joint involvement.
  - reference: PMID:40204565
    supports: SUPPORT
    snippet: Joint involvement was similar, with initial episodic migratory arthritis (91 %) predominantly affecting large joints and lasting 2-7 days.
    explanation: Cohort of isolated articular Whipple disease shows stereotyped migratory arthritis pattern.
- name: Cognitive dysfunction
  category: Neurologic
  description: Cognitive impairment and other CNS manifestations that can occur with systemic or isolated CNS disease.
  phenotype_term:
    preferred_term: Cognitive impairment
    term:
      id: HP:0100543
      label: Cognitive impairment
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Patients complain of headaches, cognitive dysfunctions, and eye motility disorders.
    explanation: Review notes cognitive dysfunction among neurological features of Whipple disease.
- name: Fever
  category: Constitutional
  description: Low-grade to episodic fever during prodromal phase.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: Prior to patients reporting symptoms of a malabsorption syndrome (chronic diarrhea/steatorhea, weight loss), they often suffer from non-specific symptoms (polyarthralgia, fever, fatigue).
    explanation: Notes fever among early systemic symptoms.
- name: Abdominal pain
  category: Gastrointestinal
  description: Colicky abdominal pain accompanying diarrhea and malabsorption.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: The clinical symptoms of WD include chronic diarrhea, malnutrition (weight loss), migratory polyarthralgia, abdominal pain, and/or enlarged lymph nodes.
    explanation: Review lists abdominal pain among common clinical symptoms.
- name: Lymphadenopathy
  category: Hematologic/Immune
  description: Enlarged lymph nodes reflecting systemic infection.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: The clinical symptoms of WD include chronic diarrhea, malnutrition (weight loss), migratory polyarthralgia, abdominal pain, and/or enlarged lymph nodes.
    explanation: Review notes lymphadenopathy as part of the systemic presentation.
  - reference: PMID:40398847
    supports: SUPPORT
    snippet: A supraclavicular lymph node excisional biopsy revealed complete architectural effacement by a diffuse foamy histiocytic infiltrate without granuloma formation or necrosis.
    explanation: Case report shows lymph node involvement with foamy macrophages due to Whipple disease.
- name: Respiratory involvement
  category: Respiratory
  description: Pulmonary symptoms such as cough, chest pain, and dyspnea with plaques or nodules on imaging.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:38414785
    supports: SUPPORT
    snippet: Whipple's disease (WD) is a multiple-system chronic disease caused by Tropheryma whipplei (T. whipplei) infection. The present study describes 3 cases of WD with clinical manifestations of cough, chest pain, headache, dyspnea, sputum, joint pain, abdominal pain, diarrhea and weight loss.
    explanation: Case series documents pulmonary symptoms including dyspnea and chest pain.
  - reference: PMID:38414785
    supports: SUPPORT
    snippet: Chest computed tomography (CT) showed signs of plaques, nodules and pleural thickening; and bronchoscopic alveolar lavage fluid metagenomic-sequencing indicated that it was T. whipplei.
    explanation: Imaging and BAL sequencing confirm pulmonary involvement due to T. whipplei.
- name: Spinal cord involvement
  category: Neurologic
  description: Isolated spinal cord inflammation leading to neurologic damage.
  phenotype_term:
    preferred_term: Abnormality of the nervous system
    term:
      id: HP:0000707
      label: Abnormality of the nervous system
  evidence:
  - reference: PMID:38525769
    supports: SUPPORT
    snippet: We describe an atypical case of Whipple disease exclusively involving the spinal cord in an adolescent receiving immunosuppressive therapy for systemic lupus erythematosus.
    explanation: Case report highlights spinal cord involvement as a presentation of Whipple disease.
differential_diagnoses:
- name: Crohn disease
  distinguishing_features:
  - Transmural granulomatous inflammation with skip lesions; lacks PAS-positive macrophages filled with bacteria.
  disease_term:
    preferred_term: Crohn disease
    term:
      id: MONDO:0005011
      label: Crohn disease
  evidence:
  - reference: PMID:26288590
    supports: PARTIAL
    snippet: The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis).
    explanation: Review notes Crohn disease as a common granulomatous differential for Whipple disease presentations.
- name: Intestinal tuberculosis
  distinguishing_features:
  - Caseating granulomas and acid-fast bacilli on Ziehl-Neelsen staining; typically ileocecal involvement.
  disease_term:
    preferred_term: intestinal tuberculosis
    term:
      id: MONDO:0001678
      label: intestinal tuberculosis
  evidence:
  - reference: PMID:26288590
    supports: PARTIAL
    snippet: The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis).
    explanation: Article lists tuberculosis among frequent differential diagnoses for Whipple disease.
- name: Sarcoidosis
  distinguishing_features:
  - Noncaseating granulomas without pathogen; may mimic multisystem involvement but lacks PAS-positive macrophages.
  disease_term:
    preferred_term: sarcoidosis
    term:
      id: MONDO:0019338
      label: sarcoidosis
  evidence:
  - reference: PMID:26288590
    supports: PARTIAL
    snippet: The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis).
    explanation: Review highlights sarcoidosis as a granulomatous differential for Whipple disease.
- name: HIV enteropathy
  distinguishing_features:
  - Occurs with advanced HIV and opportunistic infections; confirmed by HIV testing and low CD4 counts.
  disease_term:
    preferred_term: HIV infectious disease
    term:
      id: MONDO:0005109
      label: HIV infectious disease
  evidence:
  - reference: PMID:26288590
    supports: PARTIAL
    snippet: The clinical symptoms are heterogeneous and challenge differential diagnoses, such as rheumatic diseases, vasculitides, AIDS enteropathy, tuberculosis, or other chronic granulomatous diseases (Crohn's disease, sarcoidosis).
    explanation: Paper lists AIDS enteropathy as a key differential diagnosis for Whipple disease.
environmental:
- name: Sewage exposure
  description: Higher carriage rates reported in sewage workers, suggesting wastewater as a reservoir.
  environment_context:
    preferred_term: sewage
    term:
      id: ENVO:00002018
      label: sewage
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: High prevalences (approximately 12%) were found in workers who were responsible for the cleaning of sewers.
    explanation: Review notes elevated Tropheryma whipplei DNA prevalence in sewer workers.
  - reference: PMID:37727483
    supports: PARTIAL
    snippet: whipplei) is a Gram-positive actinomycete widely found in soil, sewage, and
    explanation: Case report reiterates sewage as an environmental reservoir.
  - reference: PMID:40660514
    supports: PARTIAL
    snippet: Legionella pneumophila (LP) and Tropheryma whipplei (TW) have been identified as pathogens that can coexist in sewage environments.
    explanation: Notes coexistence of T. whipplei with other pathogens in sewage.
  - reference: PMID:38525769
    supports: PARTIAL
    snippet: The diagnosis was particularly difficult since lupus and Whipple disease can present similar clinical features and the patient's prolonged contact with sewage was initially not mentioned.
    explanation: Highlights sewage exposure preceding Whipple disease presentation.
- name: Soil exposure
  description: Soil reported as an environmental reservoir for Tropheryma whipplei.
  environment_context:
    preferred_term: soil
    term:
      id: ENVO:00001998
      label: soil
  evidence:
  - reference: PMID:37727483
    supports: SUPPORT
    snippet: whipplei) is a Gram-positive actinomycete widely found in soil, sewage, and
    explanation: Notes soil as a reservoir where T. whipplei can be encountered.
treatments:
- name: Ceftriaxone induction followed by trimethoprim/sulfamethoxazole
  description: Two-week intravenous ceftriaxone induction followed by oral TMP-SMX maintenance to eradicate infection and prevent relapse.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: ceftriaxone
      term:
        id: CHEBI:29007
        label: ceftriaxone
    - preferred_term: trimethoprim
      term:
        id: CHEBI:45924
        label: trimethoprim
    - preferred_term: sulfamethoxazole
      term:
        id: CHEBI:9332
        label: sulfamethoxazole
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: The German treatment recommendations include a two-week intravenous induction therapy with ceftriaxone, which is followed by a three-month oral maintenance therapy with trimethoprim/sulfamethoxazole.
    explanation: Details standard ceftriaxone induction and TMP-SMX maintenance regimen.
- name: Doxycycline plus hydroxychloroquine regimen
  description: Oral doxycycline and hydroxychloroquine for one year, followed by lifelong doxycycline for relapse prevention.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: doxycycline
      term:
        id: CHEBI:50845
        label: doxycycline
    - preferred_term: hydroxychloroquine
      term:
        id: CHEBI:5801
        label: hydroxychloroquine
  evidence:
  - reference: PMID:26288590
    supports: SUPPORT
    snippet: A French group favors a combination of doxycycline and hydroxychloroquine for 1 year, followed by a lifelong administration of doxycycline.
    explanation: Review reports alternative long-course doxycycline plus hydroxychloroquine approach.
notes: >
  Evidence-backed phenotypes, pathophysiology, differentials, and environmental context were added using curated abstracts; further curation can expand treatments and additional organ manifestations.