Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

• Disease Name: Human African trypanosomiasis
• MONDO ID: (if available)
• Category: Infectious Disease

Research Objectives

Please provide a comprehensive research report on Human African trypanosomiasis covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

• What is the disease? Provide a concise overview.
• What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
• What are the common synonyms and alternative names?
• Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

• Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
• Risk Factors:

  Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

• Genetic risk factors (causal variants, susceptibility loci, modifier genes)
• Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
• Protective Factors:

  Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

• Genetic protective factors (protective variants, modifier alleles)
• Environmental protective factors (diet, lifestyle, exposures that reduce risk)
• Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

  Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

• Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

  Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

• Pathogenic Variants:
• Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
• Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
• Variant type/class (missense, frameshift, nonsense, splice-site, structural)
• Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
• Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
• Functional consequences (loss of function, gain of function, dominant negative)
• Modifier Genes: Genes that modify disease severity or expression
• Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

  Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

• Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

  Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

• Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

  Search first: CDC databases, WHO, PubMed, NHANES

• Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

  Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

• Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

  Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

• Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

  Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

• Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

  Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

• Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

  Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

• Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

  Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

• Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

  Search first: PubMed, Gene Ontology, Reactome

• Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

  Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

• Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Molecular Profiling (if available):
• Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
• Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
• Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
• Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
• Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
• Advanced Technologies (if applicable):
• Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
• Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
• Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
• Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

• Organ Level:
• Primary organs directly affected
• Secondary organ involvement (complications, secondary effects)
• Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

  Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

• Tissue and Cell Level:
• Specific tissue types affected (epithelial, connective, muscle, nervous)
• Specific cell populations targeted (with Cell Ontology terms)

  Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

• Subcellular Level:
• Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

  Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

• Localization:
• Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
• Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

• Onset:
• Typical age of onset (congenital, pediatric, adult, geriatric)
• Onset pattern (acute, subacute, chronic, insidious)

  Search first: OMIM, Orphanet, HPO, PubMed

• Progression:
• Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
• Progression rate (rapid, slow, variable)
• Disease course pattern (episodic, relapsing-remitting, progressive, stable)
• Disease duration (self-limited, chronic lifelong)

  Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

• Patterns:
• Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
• Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

• Epidemiology:
• Prevalence (cases per 100,000 at given time)
• Incidence (new cases per 100,000 per year)

  Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

• For Genetic Etiology:
• Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
• Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
• Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
• Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
• Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
• Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
• Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
• Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
• Population Demographics:
• Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
• Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
• Geographic distribution of specific variants
• Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
• Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

• Clinical Tests:
• Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
• Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
• Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
• Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
• Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
• Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
• Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
• Genetic Testing:

  Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

• Overview of recommended genetic testing approach
• Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
• Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
• Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
• Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
• Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
• Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
• FISH > Search first: ClinVar, cytogenetics databases, PubMed
• Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
• Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
• Omics-Based Diagnostics (if applicable):
• RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
• Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
• Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
• Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
• Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
• Clinical Criteria:
• Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
• Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
• Screening:
• Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

• Survival and Mortality:
• Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
• Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
• Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
• Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
• Morbidity and Function:
• Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
• Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
• Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
• Disease Course:
• Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
• Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
• Prediction:
• Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
• Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

• Pharmacotherapy:
• Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
• Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
• Advanced Therapeutics:
• Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
• Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
• RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
• Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
• Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
• Surgical and Interventional:
• Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
• Supportive and Rehabilitative:
• Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
• Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
• Experimental:
• Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
• Treatment Outcomes:
• Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
• Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
• Treatment Strategy:
• Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
• Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
• Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest MAXO (Medical Action Ontology) terms where applicable.

13. Prevention

• Prevention Levels:
• Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
• Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
• Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
• Immunization: Vaccine strategies (if applicable)

  Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

• Screening and Early Detection:
• Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
• Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
• Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
• Behavioral Interventions: Lifestyle modifications to reduce risk

  Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

• Counseling: Genetic counseling (risk assessment, family planning guidance)

  Search first: NSGC resources, ACMG guidelines, GeneReviews

• Public Health:
• Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
• Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
• Prophylaxis: Preventive medications or procedures

  Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

• Taxonomy: Species affected (with NCBI Taxon identifiers)

  Search first: NCBI Taxonomy

• Breed: Specific breeds affected (with VBO identifiers if applicable)

  Search first: VBO (Vertebrate Breed Ontology)

• Gene: Orthologous genes in other species (with NCBI Gene IDs)

  Search first: NCBI Gene

• Natural Disease:
• Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
• Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
• Comparative Biology:
• Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
• Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
• Transmission (if applicable):
• Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
• Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

• Model Types:
• Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
• Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
• Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
• Genetic Models:
• Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
• Model Characteristics:
• Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
• Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
• Applications:
• Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
• Resources:
• Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic and clinical claims
• Prioritize recent reviews and landmark papers
• Include direct quotes from abstracts where possible to support key statements
• Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, MAXO, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (MAXO terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Human African trypanosomiasis (HAT) — disease characteristics research report

Scope, evidence base, and evidence types

This report synthesizes evidence from (i) peer‑reviewed WHO monitoring analyses and expert reviews (2024–2025), (ii) primary clinical trials (NECT and fexinidazole pivotal trials; acoziborole phase 2/3), (iii) primary host‑genetics association studies (APOL1), and (iv) recent field/implementation and diagnostic-technology studies (including 2024 CRISPR-SHERLOCK resistance surveillance). Citations are provided for each major claim.

1. Disease information

1.1 Overview (what is the disease?)

Human African trypanosomiasis (HAT), commonly called sleeping sickness, is a neglected tropical disease caused by infection with the protozoan parasite Trypanosoma brucei, transmitted by the tsetse fly (Glossina). The disease occurs in sub‑Saharan Africa and is classically described as a two‑stage illness: an initial haemolymphatic stage followed by a central nervous system (CNS) meningoencephalitic stage that can progress to coma and death if untreated. (franco2024theeliminationof pages 2-4, barrett2025transformingthechemotherapy pages 2-4)

Two epidemiologically distinct forms dominate: - gambiense HAT (gHAT) due to T. b. gambiense: slower, often chronic, historically predominantly anthroponotic, in West/Central Africa. (franco2024theeliminationof pages 2-4, barrett2025transformingthechemotherapy pages 2-4) - rhodesiense HAT (rHAT) due to T. b. rhodesiense: faster, more acute, zoonotic with livestock/wildlife reservoirs, in East/Southern Africa. (franco2024theeliminationof pages 2-4, barrett2025transformingthechemotherapy pages 2-4)

1.2 Key identifiers (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)

Identifiers explicitly present in retrieved evidence: - MeSH: Trypanosomiasis, African — D014353 (listed in ClinicalTrials.gov trial metadata). (NCT03087955 chunk 3, NCT05256017 chunk 3)

Not found in retrieved corpus for this run (flagged as missing): ICD‑10, ICD‑11, MONDO ID, Orphanet/ORPHA identifiers were not explicitly present in the retrieved texts. (lindner2020newwhoguidelines pages 1-2, NCT03087955 chunk 3)

1.3 Synonyms and alternative names

Synonyms/variants appearing in the evidence include: - sleeping sickness (explicitly used as common name) (barrett2025transformingthechemotherapy pages 1-2) - African trypanosomiasis (imran2022discoverydevelopmentinventions pages 9-11) - HAT, gHAT, and rHAT (NCT05256017 chunk 3, barrett2024eliminationofhuman pages 1-2) - French acronym THA (trypanosomiase humaine africaine) appearing in facility name in trial context (NCT03087955 chunk 3)

1.4 Patient-level vs aggregated resources

The WHO monitoring analysis compiles country programme data (National Sleeping Sickness Control Programmes; atlas/georeferenced surveillance) and reports aggregated disease-level metrics (cases, risk area, screening volumes, facility counts). (franco2024theeliminationof pages 1-2, franco2024theeliminationof pages 9-11)

2. Etiology

2.1 Causal factors

• Infectious cause: infection with Trypanosoma brucei subspecies (T. b. gambiense or T. b. rhodesiense). (franco2024theeliminationof pages 2-4)
• Vector: tsetse fly (Glossina) bite. (franco2024theeliminationof pages 2-4)
• Reservoir ecology: gHAT is mainly anthroponotic; rHAT is zoonotic with livestock and wildlife reservoirs, making interruption of rHAT transmission far more dependent on veterinary interventions. (franco2024theeliminationof pages 2-4)

2.2 Risk factors

Environmental/exposure risk - Living/working in rural endemic foci with exposure to tsetse bites. (franco2024theeliminationof pages 1-2, franco2024theeliminationof pages 2-4)

Host genetic factors (protective and susceptibility) Evidence strongly implicates APOL1 (apolipoprotein L1) variants in differential susceptibility/outcomes.

• APOL1 G2 (rs71785313; in-frame deletion) showed strong protection against T. b. rhodesiense HAT in a case-control setting: OR 0.20 (95% CI 0.07–0.48; p=0.0001), consistent with ~5‑fold reduced susceptibility. (cooper2017apol1renalrisk pages 4-5)
• Independent evidence in northern Malawi also found strong protection of APOL1 G2 against rHAT: OR 0.14 (95% CI 0.05–0.41; Bonferroni-corrected p=0.00068). (kamoto2019associationofapol1 pages 6-7)

For T. b. gambiense, APOL1 effects are more complex: - APOL1 G1 associated with reduced odds of progressing to clinical gHAT (OR 0.33, 95% CI 0.17–0.62; p=0.0005), interpreted as increased likelihood of latent/asymptomatic carriage. (cooper2017apol1renalrisk pages 4-5) - APOL1 G2 associated with increased risk of clinical progression in gHAT (OR 3.08, 95% CI 1.45–7.06; p=0.0025), strengthening to OR 5.87 (95% CI 2.16–20.01; p=0.0001) after excluding compound heterozygotes. (cooper2017apol1renalrisk pages 4-5)

A rare susceptibility-associated APOL1 variant: - APOL1 N264K: functional evidence suggests this substitution can reduce ApoL1 trypanolytic activity in contexts of atypical infection, potentially increasing risk in populations with high homozygous frequency. (cuypers2016apolipoproteinl1variant pages 1-2)

2.3 Protective factors

• Innate immunity via APOL1 in human serum lyses many non-human African trypanosomes; resistance mechanisms are required for human-infective subspecies. (currier2018decodingthenetwork pages 1-2)
• Specific APOL1 variant G2 is protective against rHAT in multiple populations (above). (cooper2017apol1renalrisk pages 4-5, kamoto2019associationofapol1 pages 6-7)

2.4 Gene–environment interactions

The evidence base in this run supports a conceptual interaction: vector-borne exposure determines infection risk, while APOL1 genotype modifies susceptibility and/or progression once exposed. However, explicit quantitative G×E interaction models were not retrieved in the available texts. (cooper2017apol1renalrisk pages 4-5, franco2024theeliminationof pages 2-4)

3. Phenotypes (clinical manifestations)

3.1 Stage 1 vs stage 2 (definitions and symptoms)

A consistent modern description separates:

Stage 1 (haemolymphatic) - Parasites multiply in blood and lymphatic system, producing non‑specific systemic symptoms. - Reported symptoms/signs include intermittent fever, headache, pruritus, lymphadenopathy, weakness, joint and muscle pain, swollen lymph nodes. (mesu2021oralfexinidazolefor pages 1-2, barrett2025transformingthechemotherapy pages 2-4)

Stage 2 (meningoencephalitic/CNS) - Parasites cross the blood–brain barrier and induce CNS changes. - Manifestations include disturbance of sleep–wake cycle (hallmark), sensory changes, abnormal muscle tone, ataxia, psychiatric symptoms, seizures, coma, and death if untreated. (barrett2025transformingthechemotherapy pages 2-4, mesu2021oralfexinidazolefor pages 1-2)

3.2 Temporal development (onset and progression)

• gHAT is typically chronic, often lasting months to years; a clinical description notes CNS involvement after “about 1 year or more” in gambiense infection. (mesu2021oralfexinidazolefor pages 1-2, imran2022discoverydevelopmentinventions pages 1-5)
• rHAT is typically acute, often developing over weeks, and is associated with higher parasitaemia, facilitating blood-based detection. (imran2022discoverydevelopmentinventions pages 1-5)

3.3 Staging thresholds (CSF WBC)

Cutoffs in use vary by guideline and operational decisions: - A gHAT cohort study described early stage 2 as 6–20 CSF WBC/µL and late stage 2 as >20 CSF WBC/µL. (mesu2021oralfexinidazolefor pages 1-2) - WHO/operational definitions discussed include second-stage defined by >5 CSF WBC/µL (contested) and trial inclusion criteria using >20 CSF WBC/µL or trypanosomes in CSF. (capewell2014normalhumanserum pages 210-212, lindner2020newwhoguidelines pages 2-4) - WHO guideline-linked treatment stratification defines “severe” second stage by CSF WBC ≥100/µL for choosing NECT over fexinidazole. (lindner2020newwhoguidelines pages 2-4)

3.4 Suggested HPO terms (non-exhaustive, inferred from evidence)

Mapping suggestions (not all explicitly validated by HPO in retrieved texts): - Fever (HP:0001945) - Headache (HP:0002315) - Pruritus (HP:0000989) - Lymphadenopathy (HP:0002716) - Sleep disturbance / abnormal sleep-wake cycle (e.g., HP:0002360) - Ataxia (HP:0001251) - Seizures (HP:0001250) - Coma (HP:0001259) - Psychiatric/behavioral abnormalities (broad category) Evidence base: symptom lists and stage definitions from clinical reviews and cohort descriptions. (barrett2025transformingthechemotherapy pages 2-4, mesu2021oralfexinidazolefor pages 1-2)

Phenotype frequencies: quantitative symptom frequencies were not broadly available in the retrieved clinical phenotype texts; an exception is the dermal-reservoir cohort reporting dermatological symptoms in specific groups, but this is not a generalizable clinical frequency for all HAT. (soumah2024prevalenceofdermal pages 7-8)

4. Genetic / molecular information

4.1 Causal genes

HAT is not a Mendelian genetic disorder; primary causation is infectious. Host genetics influence susceptibility/outcome.

4.2 Host susceptibility/protective genes (human)

APOL1 (HGNC:613) is the central host gene in retrieved evidence: - Variants G1 (rs73885319; rs60910145) and G2 (rs71785313) show subspecies‑specific associations with rHAT and gHAT clinical outcomes. (cooper2017apol1renalrisk pages 4-5) - N264K is a functional variant associated with reduced ApoL1 lytic activity in a documented atypical infection context. (cuypers2016apolipoproteinl1variant pages 1-2)

4.3 Parasite molecular determinants relevant to human infection and therapy

Human serum resistance (parasite side): - T. b. rhodesiense resists ApoL1 via SRA binding in the endosomal-lysosomal system, preventing pore formation. (currier2018decodingthenetwork pages 1-2)

Drug resistance determinants and surveillance targets: - Melarsoprol/pentamidine cross-resistance is linked to changes in transporters/channels, including an AQP2/3(814) chimera; acoziborole resistance can be driven by CPSF3 single-nucleotide variants (e.g., N232H in vitro). (anton2024anextgeneration pages 1-4)

5. Environmental information

5.1 Infectious agent and vector (primary environmental determinant)

Exposure is driven by tsetse fly presence and vector–human contact in endemic foci. (franco2024theeliminationof pages 2-4)

5.2 Non-genetic protective factors

Population-level protection is primarily programmatic (vector control, surveillance, early diagnosis and treatment) rather than individual lifestyle factors. (franco2024theeliminationof pages 2-4, franco2024theeliminationof pages 13-15)

6. Mechanism / pathophysiology

6.1 Causal chain (from exposure to clinical disease)

1. Tsetse inoculation introduces parasites into host → bloodstream/lymph multiplication (stage 1 systemic symptoms). (franco2024theeliminationof pages 2-4, barrett2025transformingthechemotherapy pages 2-4)
2. Immune evasion and survival in human serum: Human trypanolytic factors contain ApoL1 which can kill susceptible trypanosomes via pore formation after endocytosis and trafficking through endosomal-lysosomal compartments with pH-dependent activation. (currier2018decodingthenetwork pages 1-2)
3. Human-infective subspecies have evolved resistance; for rHAT, SRA binding prevents ApoL1 pore formation. (currier2018decodingthenetwork pages 1-2)
4. Tissue reservoirs and low-parasitaemia states: For gHAT, evidence supports an extravascular skin (dermal) reservoir, with parasites in basal dermis transmissible to tsetse even when blood parasites are undetectable. (soumah2024prevalenceofdermal pages 2-4)
5. CNS invasion: Over time, parasites cross the blood–brain barrier, leading to stage 2 neuropsychiatric and sleep/wake disturbances and potentially seizures/coma/death. (barrett2025transformingthechemotherapy pages 2-4, mesu2021oralfexinidazolefor pages 1-2)

6.2 Dermal reservoir as a mechanism relevant to elimination

A 2024 prospective study in Guinea found dermal parasites by PCR and/or immunohistochemistry in up to 71% of confirmed cases and 41% of unconfirmed seropositive individuals, supporting a hidden reservoir that could sustain transmission in low-endemic settings. (soumah2024prevalenceofdermal pages 1-2) Persistence after treatment was reduced but not eliminated in all individuals: skin detection dropped to 17% in treated confirmed cases and persisted up to 25% in untreated seropositives at follow-up. (soumah2024prevalenceofdermal pages 1-2)

6.3 Suggested ontology mappings (mechanisms)

GO biological process (suggested): endocytosis; lysosomal trafficking; pore formation; immune evasion; response to protozoan; blood–brain barrier traversal. Mechanistic basis: ApoL1 uptake and trafficking; CNS stage transition. (currier2018decodingthenetwork pages 1-2, barrett2025transformingthechemotherapy pages 2-4)

Cell types (CL, suggested): endothelial cells (blood–brain barrier), mononuclear phagocytes, neurons/astrocytes (CNS manifestations). (barrett2025transformingthechemotherapy pages 2-4)

7. Anatomical structures affected

Primary anatomical compartments: - Blood and lymphatic system (stage 1) (barrett2025transformingthechemotherapy pages 2-4) - CNS / brain and cerebrospinal fluid (stage 2) (barrett2025transformingthechemotherapy pages 2-4, mesu2021oralfexinidazolefor pages 1-2) - Skin dermis as extravascular reservoir (soumah2024prevalenceofdermal pages 2-4, soumah2024prevalenceofdermal pages 1-2)

Suggested UBERON terms (illustrative): blood, lymph node, skin dermis, cerebrospinal fluid, brain, blood–brain barrier.

8. Temporal development (natural history)

• gHAT often progresses slowly; CNS stage is described as occurring after ~1 year or more in one clinical description; rHAT is more acute (weeks). (mesu2021oralfexinidazolefor pages 1-2, imran2022discoverydevelopmentinventions pages 1-5)
• Elimination-phase programs emphasize the need for prolonged surveillance after last case because resurgence is possible. (franco2024theeliminationof pages 13-15, barrett2024eliminationofhuman pages 1-2)

9. Inheritance and population

9.1 Epidemiology and burden (recent)

The WHO monitoring analysis reports: - 802 global HAT cases in 2021 and 837 in 2022; 94% were gambiense. (franco2024theeliminationof pages 1-2) - Estimated 41.5 million people live in areas at risk (2018–2022), with 1.5 million at moderate-or-higher risk. (franco2024theeliminationof pages 9-11) - Areas reporting ≥1 case/10,000 inhabitants/year (2018–2022) covered 73,134 km², with 3,013 km² at high/very high risk. (franco2024theeliminationof pages 1-2)

For auditability, Figure/Table crops were retrieved for screened numbers and case tables from the WHO monitoring paper. (franco2024theeliminationof media 72eedba2, franco2024theeliminationof media 237c981b, franco2024theeliminationof media 1786e4aa, franco2024theeliminationof media 65382298)

9.2 Host genetics (not inheritance of disease)

Host APOL1 variants (G1/G2) exhibit population-specific frequencies and associations; some studies show strong protection (rHAT), while others show no association in certain populations, underscoring heterogeneity. (kamoto2019associationofapol1 pages 6-7, cooper2017apol1renalrisk pages 1-2)

9.3 Demographics and geography

• gHAT is concentrated in West/Central Africa; rHAT in East/Southern Africa; risk and remaining high-risk pockets are geographically focal. (franco2024theeliminationof pages 2-4, franco2024theeliminationof pages 9-11)

10. Diagnostics

10.1 Screening and confirmation (gHAT)

A two-step algorithm is described: 1. Serological screening: CATT whole blood (CATTwb) or RDTs (examples listed: SD Bioline HAT, Abbott Bioline HAT 2.0, HAT Sero‑K‑SeT). (soumah2024prevalenceofdermal pages 2-4) 2. Parasitological confirmation: microscopy on blood using concentration methods such as mAECT buffy coat, plus lymph node aspirate when indicated; and CSF examination for staging. (soumah2024prevalenceofdermal pages 2-4)

10.2 Staging diagnostics and performance statistics

• Blood parasitaemia can fluctuate to <100 trypanosomes/mL, while mAECT on buffy coat has sensitivity about 10 trypanosomes/mL, explaining missed cases by standard parasitology. (soumah2024prevalenceofdermal pages 12-13)
• WHO criteria often use >5 CSF WBC/µL to define second stage, but cutoffs are contested; some settings use 20 WBC/µL. (capewell2014normalhumanserum pages 210-212)
• One molecular staging approach reported 18S PCR sensitivity 88% and specificity 83% for stage determination, but persistence of DNA after cure limits use as a test-of-cure. (capewell2014normalhumanserum pages 210-212)

10.3 rHAT diagnostics

Serology is not as developed for rHAT; parasitological detection in blood is often easier because parasitaemia tends to be higher in acute disease. (imran2022discoverydevelopmentinventions pages 1-5, barrett2025transformingthechemotherapy pages 2-4)

10.4 Differential diagnosis

A structured differential diagnosis list was not explicitly retrieved in this run; given the non‑specific febrile presentation in stage 1, differential diagnosis typically includes malaria and other febrile illnesses, and for stage 2 includes meningitis/encephalitis and other neuropsychiatric causes, but these statements would require additional sourced evidence beyond the retrieved corpus.

10.5 Recent diagnostic development (2024)

A 2024 preprint describes SHERLOCK (Cas13) assays to detect known and emergent drug-resistance genotypes (AQP2/3(814) chimera; CPSF3 SNV conferring in vitro acoziborole resistance), supporting surveillance in the elimination era. (anton2024anextgeneration pages 1-4)

11. Outcome / prognosis

Without treatment, HAT is described as almost invariably fatal. (franco2024theeliminationof pages 2-4)

During the elimination era, mortality is strongly influenced by access to diagnosis and effective therapy; some legacy therapies carry notable toxicity. For example, melarsoprol is noted as potentially killing up to 5% of treated patients in one expert elimination commentary. (barrett2024eliminationofhuman pages 1-2)

12. Treatment

12.1 Current standard and emerging regimens (key trials and outcomes)

Therapeutic practice has shifted toward simplified oral regimens where feasible.

• Fexinidazole (oral): In a pivotal randomized non-inferiority trial for late-stage gHAT, 18‑month success was 91% (239/264) with fexinidazole vs 98% (124/130) with NECT; difference −6.4% within a −13% non-inferiority margin. (mesu2018oralfexinidazolefor pages 1-2)
• WHO guideline synthesis indicates fexinidazole is recommended for first-stage and non-severe second-stage (CSF WBC <100/µL), while severe second-stage (CSF WBC ≥100/µL) should receive NECT because failure is higher with fexinidazole. (lindner2020newwhoguidelines pages 2-4)

• A cohort of stage 1/early stage 2 gHAT reported high success: 99% at 12 months and 98% at 18 months. (mesu2021oralfexinidazolefor pages 1-2)

• NECT (nifurtimox–eflornithine combination therapy): In an RCT in Congo, cure was 96.2% with NECT vs 94.1% with eflornithine monotherapy (18 months). (priotto2007nifurtimoxeflornithinecombinationtherapy pages 1-2)

• Field pharmacovigilance across 1,735 treated patients reported ≥1 adverse event in 60.1%, serious adverse events 1.1%, and case fatality 0.5% (2010–2011 routine use). (franco2012monitoringtheuse pages 1-2)

• Acoziborole (single-dose oral; pipeline/late-stage): Phase 2/3 single-arm trial in gHAT showed late-stage success 95.2% at 18 months (159/167), with evaluable population success 98.1% (159/162); early/intermediate stage success 100% (41/41). (kumeso2023efficacyandsafety pages 1-2, kumeso2023efficacyandsafety pages 6-7)

• Safety signals in that trial: treatment-emergent adverse events in 14%, all mild/moderate, and serious events not judged drug-related. (kumeso2023efficacyandsafety pages 6-7)

12.2 Real-world implementation of treatment

WHO monitoring data for 2021–2022 show among 1,473 treated gambiense cases, 43.52% received fexinidazole, 35.78% received NECT, and 20.71% received pentamidine. (franco2024theeliminationof pages 11-13)

12.3 Suggested MAXO terms (illustrative)

• Antiprotozoal drug therapy
• Combination drug therapy (NECT)
• Oral drug administration (fexinidazole; acoziborole)
• Intravenous infusion (eflornithine) Evidence base: regimen descriptions and implementation constraints. (mesu2018oralfexinidazolefor pages 1-2, priotto2007nifurtimoxeflornithinecombinationtherapy pages 1-2)

13. Prevention

13.1 Primary prevention (vector control)

Vector control is a core elimination pillar alongside case detection and treatment. WHO monitoring notes expansion of tsetse-control activities supporting gHAT control in multiple countries (e.g., Angola, Cameroon, Chad, Côte d’Ivoire, DRC, Guinea, Uganda), and multisectoral/One Health implementation in others. (franco2024theeliminationof pages 11-13)

13.2 Secondary prevention (surveillance and screening)

• 2021–2022 screening totals for gHAT were approximately 4.5 million screened (3.6 million active screening; ~0.9 million passive screening). (franco2024theeliminationof pages 1-2)
• Active screening volume was 3,599,039 in 2021–2022, with a noted decline relative to 2019–2020. (franco2024theeliminationof pages 9-11)

13.3 Tertiary prevention (preventing complications)

Timely diagnosis and effective therapy prevent progression to CNS stage and death; programs emphasize maintaining diagnostic capacity and integrating activities into primary care as incidence declines. (franco2024theeliminationof pages 13-15)

13.4 Elimination targets and verification

WHO 2021–2030 roadmap: elimination of gambiense transmission aims for zero reported cases and verification in 15 countries by 2030; verification requires ≥5 consecutive years of zero reported T. b. gambiense cases with evidence of adequate surveillance and dossier submission. (franco2024theeliminationof pages 2-4, franco2024theeliminationof pages 13-15)

14. Other species / natural disease (reservoirs, zoonotic aspects)

• rHAT is zoonotic with livestock and wildlife reservoirs and limited human-to-human transmission, contributing to why interruption is not considered readily achievable without major veterinary interventions. (franco2024theeliminationof pages 2-4, kamoto2019associationofapol1 pages 1-2)
• Potential reservoirs for gHAT include domestic pigs (noted as potential reservoir, although some sources suggest infections may clear) and other domestic animals in certain settings. (capewell2014normalhumanserum pages 146-149, chukwudi2025prevalenceofhuman pages 1-2)
• A 2024 Nigeria scoping review reported average prevalence 3.3% for HAT and 27.3% for animal African trypanosomiasis (AAT) in compiled studies, and identified cattle, pigs, and dogs as carriers of human-infective trypanosomes in Nigeria. (odebunmi2024prevalenceofhuman pages 1-4)

15. Model organisms and experimental systems

Commonly referenced research and preclinical systems in the retrieved evidence include: - Laboratory rodents/mouse models to study infection outcomes and serum resistance (noting parallels to “trypanotolerance” and that rhodesiense can be manipulated in rodents). (kamoto2019associationofapol1 pages 1-2, capewell2014normalhumanserum pages 146-149) - In vitro assays of trypanolysis using recombinant APOL proteins and bloodstream-form parasites. (fontaine2017apolswithlow pages 1-2, cooper2016aprimateapol1 pages 1-2) - Functional genetic screens in T. brucei (genome-scale RNAi screen) identifying determinants of ApoL1 sensitivity and endocytic trafficking dependencies. (currier2018decodingthenetwork pages 1-2)

Recent developments (prioritizing 2023–2024)

1. Elimination monitoring (2024): WHO-aligned monitoring shows sustained low case counts (802 in 2021; 837 in 2022) with extensive screening and shrinking risk areas; seven countries validated for elimination as a public health problem, and surveillance integration challenges highlighted for the “last mile.” (franco2024theeliminationof pages 1-2, franco2024theeliminationof pages 13-15)
2. Acoziborole phase 2/3 results (Apr 2023): single-dose oral efficacy and tolerability for gHAT across stages suggests potential to simplify treatment pathways and reduce staging dependence. (kumeso2023efficacyandsafety pages 1-2, kumeso2023efficacyandsafety pages 6-7)
3. Dermal reservoir epidemiology (Aug 2024): quantification of extravascular dermal parasites in confirmed and seropositive unconfirmed individuals adds urgency to address cryptic reservoirs for elimination. (soumah2024prevalenceofdermal pages 1-2, soumah2024prevalenceofdermal pages 12-13)
4. CRISPR-SHERLOCK resistance surveillance (Sep 2024): development of field-relevant molecular surveillance assays for resistance genotypes linked to pentamidine/melarsoprol and acoziborole. (anton2024anextgeneration pages 1-4)

Embedded synthesis tables

The following tables consolidate identifiers, epidemiology, and therapeutics for knowledge-base use.

Table: This table summarizes the identifiers and naming variants for human African trypanosomiasis that were explicitly available in the retrieved evidence. It highlights the MeSH identifier that was found, maps common synonyms and causative agents, and notes identifier systems that were not recoverable from the available corpus.

Table: This table compiles the main recent epidemiology, surveillance, risk-area, and elimination-validation metrics for human African trypanosomiasis reported in Franco et al. 2024 and contextualized by Barrett et al. 2024. It is useful as a quick reference for populating disease knowledge base fields with quantitative, source-linked values.

Table: This table summarizes the main current, legacy, and emerging therapies for human African trypanosomiasis, separating evidence-backed indications, outcomes, and safety constraints. It is useful for comparing how oral regimens like fexinidazole and acoziborole contrast with NECT and older injectable therapies in current practice and elimination planning.

Key quantitative evidence highlights (selected)

• Cases: 802 (2021) and 837 (2022); 94% gambiense. (franco2024theeliminationof pages 1-2)
• Screening: 3,599,039 actively screened (2021–2022); 900,407 passively screened for gambiense serology (2021–2022). (franco2024theeliminationof pages 9-11)
• Risk population: 41.5 million at risk (2018–2022), with 1.5 million at moderate+ risk. (franco2024theeliminationof pages 9-11)
• Dermal reservoir: dermal parasites detected up to 71% of confirmed gHAT and 41% of seropositive unconfirmed in one Guinea cohort. (soumah2024prevalenceofdermal pages 1-2)
• Key trial outcomes: fexinidazole 91% vs NECT 98% success at 18 months in late-stage gHAT RCT; acoziborole late-stage success 95.2% (ITT) at 18 months. (mesu2018oralfexinidazolefor pages 1-2, kumeso2023efficacyandsafety pages 1-2)

Limitations of this run

• ICD‑10/ICD‑11, MONDO, and Orphanet identifiers were not captured in the retrieved evidence and therefore are not provided as verified, citable codes in this report. (NCT03087955 chunk 3, lindner2020newwhoguidelines pages 1-2)
• Several sections in the template (e.g., detailed differential diagnosis lists, formal QoL instruments and frequencies for many phenotypes, comprehensive biomarker performance statistics) would require additional targeted retrieval beyond the available corpus.

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