typhoid fever
Enable an AI agent to recognise suspected or confirmed typhoid fever, assess its course and transmission implications, and support evidence-based clinical and public-health decisions.
Research draft, second pass
A second pass drafted this model: the structure a model of this thing needs, and what is known about it in the world. The line under this one says how the second half was obtained - researched against sources, or recalled without web access, in which case nothing here was read anywhere and every claim is a lead to verify. Unreviewed either way.
Researched by: Codex + Grok
Purpose and description
Enable an AI agent to recognise suspected or confirmed typhoid fever, assess its course and transmission implications, and support evidence-based clinical and public-health decisions.
Typhoid fever is a human-restricted systemic infection caused by Salmonella enterica subsp. enterica serovar Typhi, acquired by faecal-oral ingestion, that produces a prolonged febrile bacteraemic illness and, in a minority of survivors, chronic biliary carriage.
It can be Assemble a typhoid-specific evidence summary and identify missing confirmation evidence.; Flag observations requiring urgent clinical assessment under an applicable care protocol.; Surface isolate susceptibility and treatment-response evidence for clinician review.; Track recovery and flag recurrent illness for assessment of relapse, reinfection or another diagnosis.; Prepare an episode-specific notification and transmission-precaution checklist for authorised review.; Identify outstanding shedding assessments and jurisdiction-specific clearance requirements..
Distinguishing features
Require Typhi-specific organism identification to distinguish confirmed typhoid from paratyphoid; their clinical presentations do not reliably separate them. [CDC Yellow Book](https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/typhoid-and-paratyphoid-fever.html)
Check the identified serovar before classifying Salmonella-associated diarrhoea or bloodstream infection as typhoid; a generic Salmonella result is insufficient. [CDC Yellow Book](https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/typhoid-and-paratyphoid-fever.html)
Distinguish compatible febrile illness from confirmed infection using microbiological evidence; neither a single negative blood culture nor a positive Widal test settles the diagnosis. [CDC clinical guidance](https://www.cdc.gov/typhoid-fever/hcp/clinical-guidance/index.html)
Separate acute illness from asymptomatic carriage by recording symptoms, specimen type and shedding duration; stool detection alone must not automatically create an acute episode. [CDC Yellow Book](https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/typhoid-and-paratyphoid-fever.html)
Scope
+ Attribution of an illness episode to Salmonella Typhi and explicit diagnostic uncertainty
+ Exposure history and the timing of fever and systemic illness
+ Diagnostic specimen interpretation and antimicrobial susceptibility evidence
+ Disease progression, complications and response to treatment
+ Recovery, recurrent illness, shedding and carriage follow-up
+ Episode-specific transmission precautions and public-health obligations
- Paratyphoid fever and other causes of undifferentiated fever
- Nontyphoidal Salmonella gastroenteritis and invasive infections
- Salmonella taxonomy, genome annotation and laboratory assay design
- Antibiotic product specifications and general prescribing protocols
- Vaccine products, immunisation programme design and sanitation infrastructure
- Population-level outbreak management and the complete longitudinal patient record
Characteristics
- Diagnostic classification
- Suspected, probable where defined, confirmed, excluded or unresolved; governing definition and date Separates clinical suspicion from microbiological confirmation and surveillance classification.
- Organism attribution
- Typhi identified, Paratyphi identified, other Salmonella identified, unresolved Salmonella or no organism identified Determines whether the episode belongs to this registered thing.
- Fever trajectory
- Temperature in degrees Celsius with timestamps, measurement method and days since onset Supports assessment of illness progression and response after treatment starts.
- Diagnostic evidence
- Linked specimen, collection time, test method, laboratory report and preceding antibiotic exposure Makes organism attribution and negative-result interpretation auditable.
- Complication status
- For each assessed complication: absent, suspected, confirmed, resolved or not assessed Supports escalation while preventing missing observations from being recorded as reassuring negatives.
- Antimicrobial susceptibility
- Per-agent laboratory interpretation with method, breakpoint standard, version and optional MIC in mg/L Connects treatment review to the episode's isolate rather than an assumed regional resistance pattern.
- Treatment exposure
- Linked prescribed and administered regimens, start and stop times, interruptions and clinical rationale Allows an agent to interpret response in relation to treatment actually received.
- Acquisition context
- Dated travel, residence, food or water exposures, carrier contacts and outbreak links, each with confidence Supports exposure assessment without converting a plausible association into a proven source.
- Shedding and carriage
- Unknown, shedding detected, follow-up negative, persistent carriage under evaluation or chronic carriage under a cited definition Keeps infectiousness assessment separate from symptom resolution.
- Public-health clearance
- Not assessed, requirements identified, restricted, awaiting clearance or cleared; authority and date Makes return-to-activity decisions traceable to applicable requirements.
Where this came from
wikidata · CC0 1.0
Drafted structure
Bundle to layer to finding to question, as the second pass will find it: 6 bundles · 11 layers · 19 findings · 30 questions.
Typhi attribution Establish whether the episode is attributable to Salmonella Typhi and how certain that attribution is.
An enteric-fever presentation or generic Salmonella result does not establish typhoid.
Disease boundary
Separate typhoid from neighbouring infections and distinguish clinical from surveillance labels.
Episode classification
Record the evidence and named definition supporting the current typhoid classification.
- What definition establishes suspected, probable or confirmed typhoid in this clinical or surveillance context? definition
- What evidence separates this episode from paratyphoid, other Salmonella infections and competing febrile illnesses? boundary
Microbiological evidence
Interpret Typhi testing in relation to specimens, timing and treatment exposure.
Test interpretability
Blood culture is central to diagnosis; negative results and serology require explicit limitations. [CDC clinical guidance](https://www.cdc.gov/typhoid-fever/hcp/clinical-guidance/index.html)
- Which laboratory report identifies Typhi, using what specimen and method, collected when relative to onset and antibiotics? provenance
- What unresolved sampling or test limitations require further diagnostic review before confirming or excluding typhoid? action
Exposure and transmission Relate the episode to plausible acquisition routes and opportunities for onward transmission.
Typhoid assessment requires both an acquisition history and an account of potential exposure of others.
Acquisition history
Record dated exposures without assuming that travel or shared food proves acquisition.
Plausible acquisition
Typhoid commonly spreads through food or water contaminated by human faeces. [WHO typhoid fact sheet](https://www.who.int/news-room/fact-sheets/detail/typhoid)
- Which residence, travel, food, water or infected-contact exposures preceded onset, and on what dates? measurement
- Which exposures are reported, independently corroborated or linked by an investigation? provenance
Onward exposure
Identify activities and contacts relevant to transmission precautions.
Transmission opportunities
Record food preparation, sanitation conditions and relevant contacts alongside evidence of shedding.
- During which periods did the person prepare food for others or have contact circumstances relevant to faecal-oral transmission? measurement
- Which precautions or contact assessments are indicated by the responsible public-health authority? action
Illness course and severity Represent the typhoid episode over time and identify evidence of complications.
A diagnostic label alone cannot establish whether the person is stable, deteriorating or recovering.
Febrile course
Align symptoms and observations with onset, sampling and treatment.
Clinical trajectory
Track fever, gastrointestinal symptoms and functional change without requiring every typical symptom.
- When did fever and other symptoms begin, and how have measured temperature and clinical observations changed? measurement
- Which observations support improvement, deterioration or reconsideration of the typhoid attribution? boundary
Complication assessment
Distinguish suspected complications from confirmed findings and unperformed assessments.
Severe disease evidence
Relevant serious complications include gastrointestinal bleeding, intestinal perforation and encephalopathy. [CDC clinical guidance](https://www.cdc.gov/typhoid-fever/hcp/clinical-guidance/index.html)
- What examination, laboratory or imaging evidence supports or argues against each suspected complication? measurement
- Which findings meet the applicable protocol's criteria for urgent referral, hospital assessment or specialist intervention? action
Resistance and treatment response Connect treatment decisions and observed response to microbiology and actual medication exposure.
Antimicrobial resistance makes an undifferentiated record of 'treated typhoid' inadequate.
Treatment basis
Separate empirical treatment rationale from isolate-directed decisions.
Susceptibility-informed review
Record susceptibility results and acquisition history used to inform treatment. [CDC clinical guidance](https://www.cdc.gov/typhoid-fever/hcp/clinical-guidance/index.html)
- Which isolate results, dated guidance and acquisition evidence support the clinician's treatment choice? provenance
- Do new susceptibility results or patient-specific constraints require review of the current regimen? action
Response assessment
Evaluate clinical changes against treatment timing and delivery.
Response and nonresponse
Record response criteria and reasons for reassessment without equating continuing fever alone with resistance.
- How have fever and overall condition changed relative to doses actually received and treatment interruptions? measurement
- When does the applicable protocol call for reassessment of resistance, inadequate exposure, a persistent focus or an alternative diagnosis? action
Recovery, carriage and clearance Separate clinical recovery, recurrent illness, bacterial shedding and permission to resume activities.
Symptom resolution does not establish that transmission risk or follow-up obligations have ended.
Episode outcome
Record recovery and preserve uncertainty about subsequent illness.
Recovery and recurrence
Link recurrent fever to the earlier episode without automatically assigning relapse or reinfection.
- What dated observations establish clinical recovery or another episode outcome? measurement
- If illness recurs, what timing, exposure and microbiological evidence supports relapse, reinfection or an unrelated cause? boundary
Carriage and public-health disposition
Track shedding evidence and the authority responsible for clearance.
Shedding status
People may continue shedding Typhi after symptoms resolve. [WHO typhoid fact sheet](https://www.who.int/news-room/fact-sheets/detail/typhoid)
- Which dated follow-up specimens establish detected shedding or negative results, and what remains untested? measurement
- Which duration and evidence criteria define chronic carriage in the adopted reference? definition
Notification and clearance
Record applicable reporting and return-to-activity requirements; follow-up clearance depends on local public-health guidance. [CDC Yellow Book](https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/typhoid-and-paratyphoid-fever.html)
- Which authority and dated rule govern notification, food-handling restrictions and return to work, school or childcare? provenance
- What outstanding tests, reviews or documented decisions must be completed before restrictions can be lifted? action
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Kinds and varieties
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Uncomplicated acute typhoid fever
- Complicated typhoid fever (intestinal haemorrhage or perforation, encephalopathy, myocarditis, hepatitis)
- Relapsing typhoid after apparent recovery
- Chronic biliary or gallbladder carrier state
- Multidrug-resistant typhoid (classic chloramphenicol-ampicillin-trimethoprim/sulfamethoxazole resistance)
- Extensively drug-resistant typhoid (MDR plus fluoroquinolone and third-generation cephalosporin resistance)
- Laboratory-confirmed typhoid (blood or bone-marrow culture, or validated molecular detection of S. Typhi)
- Travel-associated typhoid in non-endemic settings
- Which of these kinds and varieties hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Identifiers and schemes
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Wikidata - Q83319 - Item for typhoid fever as a disease.
- ICD-10 - A01.0 - Typhoid fever; parent A01 is typhoid and paratyphoid fevers.
- ICD-10-CM - A01.00 - Typhoid fever, unspecified; further fifth-character codes cover complications (e.g. meningitis, pneumonia, arthritis).
- ICD-11 - 1A07 - Typhoid fever.
- SNOMED CT - 4834000 - Typhoid fever (disorder).
- MeSH - D014435 - Typhoid Fever.
- Disease Ontology - DOID:13258 - typhoid fever.
- NCBI Taxonomy (causal agent) - 90370 - Salmonella enterica subsp. enterica serovar Typhi, not the disease itself.
- Which of these identifiers and schemes hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Standards and regulation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- World Health Organization - Typhoid vaccines: WHO position paper (Weekly Epidemiological Record, March 2018), recommending typhoid conjugate vaccine for endemic use.
- World Health Organization - prequalification of typhoid conjugate vaccines (notably Typbar-TCV) for UN supply.
- CDC Advisory Committee on Immunization Practices (United States) - typhoid vaccine recommendations for travellers, laboratory workers, and selected household contacts.
- Health Protection (Notification) Regulations 2010 (England) - typhoid fever is a notifiable disease to public health authorities.
- CLSI M100 (Clinical and Laboratory Standards Institute) - interpretive criteria for Salmonella antimicrobial susceptibility testing used to classify MDR/XDR isolates.
- WHO Model List of Essential Medicines / AWaRe - preferred antimicrobials for enteric fever, adjusted for local resistance.
- U.S. FDA and corresponding national regulators - licensure of oral live-attenuated (Ty21a) and parenteral Vi polysaccharide and conjugate typhoid vaccines.
- Which of these standards and regulation hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Real-world use
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Blood-culture work-up of prolonged undifferentiated fever in South Asia and parts of sub-Saharan Africa.
- Empirical treatment of suspected enteric fever where culture is unavailable, still often guided by Widal or rapid serology despite poor accuracy.
- Pre-travel vaccination and counselling for visitors to endemic regions.
- School-age and catch-up typhoid conjugate vaccine campaigns in high-incidence countries.
- Outbreak investigation of water- or food-borne clusters, including screening of food handlers for chronic carriage.
- WASH and food-safety programmes aimed at interrupting faecal-oral transmission.
- Reference-laboratory surveillance of S. Typhi antimicrobial resistance, including detection of XDR lineages in travellers.
- Which of these real-world use hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Typical measurements
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Incubation period - 7-14 (extremes about 3-30) - days
- Peak body temperature in acute illness - 39-40.5 - °C
- Duration of untreated fever - about 21-28 - days
- Case-fatality ratio, untreated - 10-20 - %
- Case-fatality ratio with prompt effective antimicrobials - <1 - %
- Chronic biliary carriage after acute infection - 2-5 - %
- Blood-culture diagnostic sensitivity (lower after prior antibiotics) - 40-80 - %
- Typhoid conjugate vaccine efficacy against typhoid fever in field trials (Typbar-TCV class) - about 80-85 - %
- Which of these typical measurements hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Failure modes and hazards
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Missed or late diagnosis because the early illness is a nonspecific febrile syndrome.
- Ileal perforation or intestinal haemorrhage, classically in the third week, with high surgical mortality where care is delayed.
- Antimicrobial treatment failure from MDR or XDR S. Typhi, leaving few oral options.
- Relapse after too-short therapy even when the isolate was susceptible.
- Chronic faecal shedding from gallbladder carriers, which seeds household and food-borne outbreaks.
- False-positive or false-negative Widal and other serologic tests driving wrong treatment or missed cases.
- Neurologic complications (encephalopathy) and myocarditis in severe disease.
- Vi polysaccharide and conjugate vaccines do not protect against paratyphoid fever, so vaccinated people may still present with an enteric-fever syndrome.
- Which of these failure modes and hazards hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Regional variation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Highest reported incidence remains in South Asia (India, Pakistan, Bangladesh); parts of sub-Saharan Africa have substantial but historically under-cultured burden.
- XDR S. Typhi has been concentrated in Sindh, Pakistan, since 2016, with exported travel-associated cases elsewhere.
- In high-income countries almost all cases are travel-associated rather than locally acquired.
- Historical endemic typhoid in Europe and North America receded with municipal water treatment and sanitation rather than vaccination alone.
- Widal agglutination remains first-line in many South Asian and African facilities, whereas reference centres rely on blood culture and PCR.
- In several languages and older clinical usage, "typhoid" is still confused with louse-borne typhus.
- Vi-negative S. Typhi has been reported in some Asian settings, which can blunt Vi serology and theoretically affect Vi-based vaccine or diagnostic performance.
- Which of these regional variation hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Neighbouring kinds and how to tell them apart
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Paratyphoid fever (Salmonella Paratyphi A, B, or C) - Serovar identification from a cultured isolate, or a validated S. Typhi-specific PCR/genotyping assay; clinical enteric fever is otherwise indistinguishable.
- Malaria - Blood-film microscopy or malaria antigen RDT; malaria does not yield S. Typhi bacteraemia.
- Epidemic or murine typhus (Rickettsia prowazekii or R. typhi) - Rickettsial serology or PCR and vector exposure (lice or fleas); blood cultures remain negative for Salmonella.
- Dengue and other arboviral fevers - NS1 antigen or virus-specific IgM/PCR, a shorter febrile course, and absence of sustained S. Typhi bacteraemia.
- Non-typhoidal Salmonella bacteraemia - Serotyping or genomic identification of serovars such as Enteritidis or Typhimurium rather than Typhi; different host-risk profile (often invasive disease in young children, malaria, or HIV).
- Leptospirosis - Leptospira PCR or microscopic agglutination test plus water/animal exposure; Salmonella culture negative.
- Acute viral hepatitis - Marked transaminase rise with hepatitis A/B/E serology or PCR; typhoid can cause a milder hepatitis-like picture but is confirmed by S. Typhi detection.
- Brucellosis - Brucella culture or serology and livestock/dairy exposure; distinct from S. Typhi on isolate identification.
- Which of these neighbouring kinds and how to tell them apart hold for the sense of typhoid fever this model covers, and on what evidence? provenance
Sources
- Typhoid (fact sheet) - Causal agent, faecal-oral transmission, clinical course, case-fatality with and without treatment, chronic carriage, and the role of vaccines and WASH.
- Typhoid vaccines: WHO position paper - March 2018. Weekly Epidemiological Record, 93(13):153-172. World Health Organization - Vaccine products and schedules (including typhoid conjugate vaccine), burden in endemic regions, and public-health use of TCV.
- Typhoid and Paratyphoid Fever. CDC Yellow Book. Centers for Disease Control and Prevention - Travel-associated disease, incubation range, diagnostic preference for culture, antimicrobial-resistance patterns including XDR S. Typhi from Pakistan, and traveller vaccination practice.
- ICD-10: A01.0 Typhoid fever. International Statistical Classification of Diseases and Related Health Problems, 10th Revision. World Health Organization - The standard diagnostic code that names this disease in mortality, morbidity, and notifiable-disease systems.
What the second pass must settle
- Which clinical and surveillance case definitions should this model adopt across jurisdictions, especially where culture is unavailable?
- Which validated diagnostic pathways and evidence thresholds should govern culture-negative illness after antibiotic exposure?
- Which current regional resistance sources and care protocols should govern treatment-review triggers, including paediatric and pregnancy contexts?
- What evidence is sufficient to distinguish relapse, reinfection and persistent infection when paired isolates are unavailable?
- Which carriage definitions and jurisdiction-specific follow-up schedules govern clearance for food handlers, school attendance and childcare?