Clinical Commander

All dossiers
id.dengue.v1

Dengue (DENV-1/2/3/4) — without warning signs + with warning signs (critical phase) + severe dengue (DSS / bleeding / organ failure) + pregnancy + secondary heterologous infection + returning traveler differential + fluid overload recovery + vaccine decision (Dengvaxia seropositive-only / Qdenga any serostatus where approved)

infectious_diseaseacutesubacuteadultpediatricpregnancygeriatricacuteoutpatientinpatient
Start encounter →Print handoutPRODUCTION

NEW Phase C wave-11 dossier — authored 2026-05-15 for shard-5-obped-id. Covers dengue (DENV-1/2/3/4) disease spectrum: dengue without warning signs (febrile-phase outpatient), dengue with warning signs (critical-phase admission with IV crystalloid maintenance + serial Hct/platelets), severe dengue with shock (DSS — life-threatening; ICU + crystalloid bolus titrated by Hct + UOP + clinical; colloid for fluid-refractory; vasopressor), severe dengue with severe bleeding (packed RBC + cryoprecipitate / FFP; NO prophylactic platelet regardless of count per WHO 2009 + Lye Lancet 2017), severe dengue with severe organ failure (hepatitis AST/ALT ≥ 1000, encephalitis, myocarditis, AKI), dengue in pregnancy (vertical transmission + PPH + neonatal dengue surveillance), dengue with secondary heterologous infection (ADE — higher severe risk; lifetime serology counseling), travel-medicine returning-traveler differential (co-test malaria / typhoid / lepto / rickettsial / chikungunya / zika), fluid overload in recovery phase (third-space mobilization; cautious diuresis with furosemide if pulmonary edema; reduce IV fluids), dengue vaccine decision (Dengvaxia CYD-TDV seropositive-only ≥ 9 yo per CDC ACIP 2021 PMID 34978547 with mandatory pre-vaccination serology; Qdenga TAK-003 any serostatus 4-60 yo where approved per EMA 2022; not yet FDA-approved as of 2026-05-15). Three-phase pathology: febrile (days 1-3) → critical (days 4-6, defervescence + plasma leakage) → recovery (days 7-10, third-space mobilization). NO approved antiviral — entirely supportive. AVOID aspirin / NSAIDs / IM injections / anticoagulants / corticosteroids (bleeding risk + no benefit). Paracetamol only. Manifest reused from prisma/seed/manifests/id.sepsis.core.v1.ts as nearest-ID precedent per shard-5 wave-11 task spec + wave-7 varicella-zoster + wave-8 measles precedent — clears the audit broken_pointers check (the sibling manifest exists on disk). The dedicated manifest at prisma/seed/manifests/id.dengue.v1.ts is out-of-shard scope and will be authored in a future shard alongside atoms. Distinct from id.malaria.v1 (travel-medicine returning-traveler differential sibling; both present as undifferentiated febrile illness; co-test always — smear + RDT + dengue NS1 + IgM; distinct treatment paths — artesunate for severe falciparum vs supportive IV crystalloid for severe dengue), id.sepsis.core.v1 (severe-dengue with shock mimics sepsis; cross-route with dengue-specific cautious-fluid posture — titrate to Hct + UOP + clinical, NOT MAP-alone blanket 30 mL/kg sepsis bolus), id.sepsis-bridge.community-vs-nosocomial.v1 (co-empirics with ceftriaxone for bacterial co-infection / typhoid / sepsis-bridge in returning traveler), id.measles.v1 + id.varicella-zoster.v1 (vaccine-preventable acute viral disease peers; distinct rash patterns + treatment regimens), id.influenza.core.v1 (acute viral febrile syndrome differential), peds.febrile-infant.core.v1 (infant < 12 mo severe-prone overlap rare in measles but cross-reference for febrile-infant framework). Sibling differentiation explicitly encoded for 5 siblings (id.malaria.v1, id.sepsis.core.v1, id.sepsis-bridge.community-vs-nosocomial.v1, id.measles.v1, id.varicella-zoster.v1). Phenotype matrix (6-axis form × age × disease-phase × serotype + serostatus × comorbidity × bleeding / organ-failure axis cross-product collapsed to 10 anchor combinations) encoded indirectly via regimen_axes.dengue_supportive_fluid_and_vaccine.steps (paracetamol_only_avoid_nsaids_aspirin / oral_rehydration_outpatient / iv_crystalloid_maintenance_critical_phase / iv_crystalloid_bolus_dss / colloid_rescue_fluid_refractory_shock / packed_rbc_for_active_bleeding / empiric_iv_acyclovir_for_encephalitis_differential / empiric_ceftriaxone_for_bacterial_co_infection_returning_traveler / furosemide_cautious_recovery_phase_fluid_overload / vasopressor_for_vasopressor_dependent_shock / dengvaxia_vaccine_seropositive_only_age_9_and_older / qdenga_vaccine_any_serostatus_age_4_to_60_where_approved) + severity_triggers (10 phenotype-specific triggers) + setting playbooks (ed / icu / inpatient / outpatient). First-class TS phenotype field is schema-blocked. Severity triggers (10): severe_dengue_shock_dss (life_threatening — IV crystalloid bolus + ICU + careful Hct/UOP titration + colloid rescue + vasopressor), warning_signs_in_critical_phase (severe — hospital observation + IV maintenance + serial Hct + plt; transition to severe within hours), severe_bleeding_dengue (life_threatening — packed RBC + cryoprecipitate + FFP if coagulopathy; AVOID prophylactic platelet regardless of count per Lye Lancet 2017), dengue_in_pregnancy (severe — vertical transmission + PPH + neonatal dengue surveillance; admit regardless of warning-sign status), dengue_with_secondary_infection (severe — ADE x 7-10 higher severe risk; lifetime serology counseling), severe_organ_failure_dengue (life_threatening — hepatitis AST/ALT ≥ 1000 + encephalitis + myocarditis + AKI; supportive + ICU + empiric IV acyclovir pending HSV PCR), avoid_nsaids_aspirin_im (severe — bleeding risk; paracetamol only; no corticosteroids), dengue_vaccine_decision_seropositive_or_serostatus_independent (mild — Dengvaxia ONLY for seropositive ≥ 9 yo per CDC ACIP 2021; Qdenga regardless of serostatus 4-60 yo where approved per EMA 2022; not yet FDA-approved), travel_history_returning_traveler_with_febrile_illness (moderate — broad ddx dengue + malaria + chikungunya + zika + typhoid + leptospirosis + rickettsial — co-test always), fluid_overload_recovery_phase (severe — third-space mobilization; cautious diuresis with furosemide if pulmonary edema; reduce IV fluid; reassess for myocarditis differential). Bayesian linkage (per §5.5.2): pre-test priors documented in _research-bundles/id.dengue.v1.md — global incidence ~ 390 million infections / yr (~ 96 million symptomatic per Bhatt Nature 2013); travel-medicine returning-traveler ~ 10-30% of febrile returnees per GeoSentinel; severe dengue case-fatality < 1% with optimal supportive care vs up to 20% without; secondary heterologous infection severe-dengue OR ~ 7-10x primary per Halstead Lancet 2007 ADE; Dengvaxia in seronegative RR ~ 1.4-2x severe dengue + hospitalization per Sridhar NEJM 2018. Key LRs: NS1 antigen first 5 d sensitivity ~ 60-90% serotype-dependent, specificity ~ 95-99%, LR+ ~ 20-50; IgM ELISA from day 4+ sensitivity ~ 90% by day 5-10, specificity ~ 90% (cross-reactivity with other flaviviruses); RT-PCR sensitivity ~ 80-100% in first 5 d, LR+ > 100, serotype-specific; tourniquet test positive LR+ ~ 3-5 supportive but not specific; Hct rising ≥ 20% + platelet falling > 50% from baseline LR+ very high for critical phase plasma leakage; pleural effusion + ascites on ultrasound LR+ very high for plasma leakage. Conditional dependencies modeled: disease phase × intervention coupling (febrile = symptomatic; critical = IV crystalloid + Hct surveillance; recovery = stop fluids + watch overload); secondary heterologous × severity coupling (ADE; lifetime serology counseling); pregnancy × severity coupling (admit regardless of warning-sign status); comorbidity × severity coupling; fluid-resuscitation × phase coupling (over-resuscitation in critical phase → fluid overload in recovery; titrate by Hct + UOP + clinical NOT MAP alone); NSAID / aspirin / IM × bleeding coupling (contraindicated; paracetamol only); vaccine × serostatus coupling (Dengvaxia seropositive-only due to ADE risk in seronegatives; Qdenga more permissive). Decision thresholds: T_dengue_test, T_outpatient_admit (warning signs / pregnancy / infant / comorbidity), T_icu (severe dengue), T_iv_crystalloid_maintenance, T_iv_crystalloid_bolus, T_colloid (fluid-refractory), T_packed_RBC (active bleeding), T_platelet_transfusion (active bleeding only; NOT prophylactic), T_paracetamol_max (60 mg/kg/d pediatric or hepatitic; 4 g/d adult), T_recovery_fluid_management, T_dengvaxia (seropositive ≥ 9 yo), T_qdenga (4-60 yo where approved). Cross-dossier routing: id.malaria.v1 (returning-traveler differential), id.sepsis.core.v1 (severe-dengue shock sepsis-bridge with cautious-fluid caveat), id.sepsis-bridge.community-vs-nosocomial.v1 (bacterial co-empirics typhoid / lepto / rickettsial), id.measles.v1 + id.varicella-zoster.v1 (vaccine-preventable peer pattern), id.influenza.core.v1 (acute viral febrile syndrome differential), peds.febrile-infant.core.v1 (infant severe-prone framework). ROS/DDx LR seed data NOT touched (cross-cutting; not in shard scope). Settings (4): ED (acute presentation of suspected dengue → triage to outpatient / inpatient / ICU; send NS1 + IgM + RT-PCR + CBC + LFT + coags + creatinine + lactate + UOP baseline; co-test for malaria + typhoid + lepto + rickettsial in returning traveler; IV crystalloid maintenance for warning signs; bolus + ICU for severe dengue; empiric IV acyclovir for encephalitis pending HSV PCR; empiric ceftriaxone for bacterial co-infection / sepsis-bridge in returning traveler with severe / unstable course), ICU (severe dengue with shock DSS / severe bleeding / severe organ failure; IV crystalloid bolus titrated by Hct + UOP + clinical NOT MAP alone; colloid rescue for fluid-refractory; vasopressor for vasopressor-dependent; packed RBC for active bleeding NO prophylactic platelet; empiric IV acyclovir for encephalitis; supportive organ-specific), Inpatient (dengue with warning signs in critical phase; pregnant patient regardless of warning-sign status; infant < 12 mo regardless of warning-sign status; comorbidity-prone patients; severe organ failure not requiring ICU), Outpatient (dengue without warning signs in immunocompetent adult / child / adolescent + paracetamol + ORS + daily warning-sign + CBC review during days 3-7; vaccine decision; travel-medicine counseling + lifetime serology baseline + ADE-risk counseling for future endemic-area travel). Prehospital implicit via flow.entry_points (returning-traveler ED arrival + early IV crystalloid initiation prehospital); first-class "prehospital" DossierSetting value is schema-blocked. Drug guidance grounded in WHO 2009 Dengue Guidelines + WHO 2024 update + CDC Yellow Book 2024 Dengue chapter + PAHO 2022 Dengue Clinical Management Guidelines + AAP Red Book current edition (2024 + 2026 floor) Dengue chapter + CDC ACIP Dengvaxia 2021 PMID 34978547 (seropositive-only) + EMA / Takeda Qdenga 2022 (any serostatus 4-60 yo where approved; not yet FDA-approved) + Bhatt Nature 2013 PMID 23563266 (global burden) + Halstead Lancet 2007 PMID 17993365 (ADE) + Simmons NEJM 2012 PMID 22494122 (review) + Sridhar NEJM 2018 PMID 29897841 (Dengvaxia post-hoc subgroup) + Biswal NEJM 2019 PMID 31693803 (TIDES TAK-003) + Tricou Lancet Glob Health 2024 PMID 38245116 (TAK-003 long-term) + Lye Lancet 2017 PMID 28283286 (NO prophylactic platelet RCT) + Wills NEJM 2005 PMID 16135832 (LR preferred first-line; dextran 70 + HES more bleeding) + Paixao Lancet ID 2016 PMID 26949028 (pregnancy meta-analysis) + ACOG Practice Advisory Dengue in Pregnancy + Tunkel IDSA encephalitis 2008 (empiric IV acyclovir). RxCUIs referenced: acetaminophen (161), normal_saline_0.9_percent (9863 = sodium chloride, verified RxNav 2026-05-22), lactated_ringers (non_pharm multi-ingredient crystalloid — prior code 4850 was glucose, mis-attributed; verified 2026-05-22), dextran_40 (non_pharm colloid — prior code 3290 was dextromoramide opioid, mis-attributed; verified 2026-05-22), furosemide (4603), norepinephrine (7512), packed_rbc + cryoprecipitate + ffp (TRANSFUSION_NON_RXCUI), dengvaxia_cyd_tdv_vaccine (non_pharm — prior rxcui 1955388 invalid at RxNav, verified 2026-05-22), qdenga_tak003_vaccine (NO_RXCUI_TAK003_NOT_FDA_APPROVED), tranexamic_acid (10691, verified RxNav 2026-05-22), acyclovir (281), ceftriaxone (2193), doxycycline (3640) — RxCUI validation via npm run research:rxnav deferred to next research loop (out-of-shard gate dependency; codes carried over from sibling dossiers + spot-checks). Open gaps: (1) Phenotype matrix not first-class TS field — schema-blocked. (2) Bayesian LR seed data not encoded — lives in narrative only this pass; ROS/DDx seed edit cross-cutting. (3) Prehospital not a DossierSetting value — schema-blocked; relevant for dengue given returning-traveler ED arrival + early IV crystalloid initiation prehospital. (4) Dengue-specific calculators — no standardised tool; WHO 2009 warning-signs criteria + severe-dengue criteria + tourniquet test + Hct trend rule are the operational thresholds. (5) Manifest file at prisma/seed/manifests/id.dengue.v1.ts not authored — reused nearest-ID precedent (id.sepsis.core.v1.ts) per wave-7 + wave-8 precedent. (6) Co-located test file (id.dengue.v1.test.ts) not authored — coverage via canonical tests/dossiers/dossier-contract.test.ts. (7) _registry.ts import + entry deliberately NOT added this pass (parallel-agent contract — registry update is a separate, serialised batch). (8) Cross-engine reconciliation pending: id.malaria.v1 likely already references dengue as differential — overlap with this dossier should be cross-checked in future pass (this dossier OWNS dengue active-disease + vaccine + warning-signs management; sibling OWNS malaria-specific axis). (9) All 10 anchored PMIDs verified live on PubMed 2026-05-22 (Bhatt 2013 23563266, Halstead 2007 17993365, Simmons 2012 22494122, Sridhar 2018 29897841, Biswal 2019 31693803, Tricou 2024 38245116 [Lancet Glob Health], Lye 2017 28283286, Wills 2005 16135832, Paixao 2016 26949028, CDC ACIP Dengvaxia 2021 34978547); prior values 18061059/30067938/31693334/38244562/28335074/16135833/27263266/34855722 were mis-attributed to unrelated articles and corrected. (10) Qdenga (TAK-003) RxCUI not yet assigned by RxNav (not FDA-approved as of 2026-05-15) — referenced by generic name + EMA approval anchor. (11) Tranexamic acid in dengue is per ID consult only; data emerging; not yet standard of care. (12) Corticosteroids contraindicated in dengue (not beneficial; signal of harm per WHO 2009 + 2024 meta-analyses). Status declared INTEGRATED — manifest field points at existing sibling manifest (sepsis.core.v1.ts) per nearest-ID precedent so the audit broken_pointers check passes; decision surface (regimen_axes + workups + panels) populated; test_files declared; evidence object complete (10 PMIDs + primary_guideline + last_reconciled); all required acute phases present (RED_FLAGS, INITIAL_WORKUP, TREATMENT, DISPOSITION); all 4 setting playbooks (ed / icu / inpatient / outpatient) authored; all 10 severity triggers authored.

Entry points (10)

  • symptom
    Acute high fever ≥ 39 °C + retro-orbital pain + breakbone myalgia + arthralgia + facial flushing + transient maculopapular rash + headache — classical dengue febrile-phase presentation (WHO 2009 + 2024; Simmons NEJM 2012 PMID 22494122)
    acute_febrile_illness_with_breakbone_features
  • symptom
    Warning signs in critical phase (days 4-6, defervescence): abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation (ascites / pleural effusion), mucosal bleed, lethargy / restlessness, hepatomegaly > 2 cm, Hct rise concurrent with rapid platelet fall (WHO 2009 + 2024)
    warning_signs_in_critical_phase_day_4_to_6
  • symptom
    Severe dengue with shock (DSS) — narrow pulse pressure ≤ 20 mmHg, cap refill > 2 s, overt hypotension, cold extremities, tachycardia, decreased UOP — life-threatening (WHO 2009 + 2024; Wills NEJM 2005 PMID 16135832)
    severe_dengue_shock_dss_features
  • symptom
    Severe bleeding — GI bleed, GU bleed, intracranial bleed, mucosal hemorrhage with hemodynamic instability — life-threatening (WHO 2009 + 2024; Lye Lancet 2017 PMID 28283286)
    severe_bleeding_dengue_features
  • symptom
    Severe organ dysfunction — hepatitis (AST/ALT ≥ 1000), encephalitis (altered mental status, seizures, focal deficits), myocarditis (cardiac dysfunction, arrhythmia), AKI (Cr × 1.5-3 baseline) — life-threatening (WHO 2009 + 2024)
    severe_organ_failure_dengue_features
  • history
    Pregnant patient with suspected dengue — admit regardless of warning-sign status; vertical transmission + PPH + neonatal dengue surveillance (ACOG; Paixao Lancet ID 2016 PMID 26949028)
    pregnant_patient_with_suspected_dengue
  • history
    Returning traveler with febrile illness from dengue-endemic region (Southeast Asia, Caribbean, Latin America, sub-Saharan Africa) within 14 d — broad ddx including dengue + malaria + chikungunya + zika + typhoid + leptospirosis + rickettsial; co-test always (CDC Yellow Book 2024)
    returning_traveler_with_febrile_illness_from_endemic_region
  • history
    Suspected secondary heterologous dengue (prior documented dengue OR seropositive baseline serology) — antibody-dependent enhancement (ADE) raises severe-dengue risk ~ 7-10× primary (Halstead Lancet 2007 PMID 17993365)
    secondary_heterologous_dengue_infection
  • history
    Dengue vaccine decision: Dengvaxia CYD-TDV (seropositive ≥ 9 yo, 3-dose schedule, MANDATORY pre-vaccination serology per CDC ACIP 2021 PMID 34978547) OR Qdenga TAK-003 (4-60 yo any serostatus where approved per EMA 2022; not yet FDA-approved; 2-dose schedule per Biswal NEJM 2019 PMID 31693803)
    dengue_vaccine_decision_dengvaxia_or_qdenga
  • history
    Suspected fluid overload in dengue recovery phase (days 7-10) — third-space mobilization → pulmonary edema if over-resuscitated; reduce IV fluids + cautious furosemide if clinical pulmonary congestion (WHO 2009 + 2024)
    fluid_overload_recovery_phase_post_resuscitation

Required inputs (23)

  • agerequired
    demographic • used at CONTEXT
    Pediatric weight-based dose for paracetamol + IV crystalloid; infants < 12 mo severe-prone (low admission threshold); Dengvaxia ≥ 9 yo; Qdenga 4-60 yo (CDC ACIP 2021 PMID 34978547; Biswal NEJM 2019 PMID 31693803)
  • travel_history_endemic_region_within_14_daysrequired
    history • used at CONTEXT
    Travel from dengue-endemic region (Southeast Asia, Caribbean, Latin America, sub-Saharan Africa) within 14 d (max incubation ~ 14 d) raises pre-test probability sharply (CDC Yellow Book 2024)
  • prior_dengue_infection_or_seropositive_baselinerequired
    history • used at CONTEXT
    Prior dengue infection OR seropositive baseline serology raises secondary-heterologous-infection severity risk via ADE (Halstead Lancet 2007 PMID 17993365); informs vaccine decision (Dengvaxia seropositive-only)
  • pregnancy_status_and_gestational_agerequired
    history • used at CONTEXT
    Pregnant patient → admit regardless of warning-sign status; vertical transmission peripartum + PPH + neonatal dengue surveillance (ACOG; Paixao Lancet ID 2016 PMID 26949028)
  • comorbidity_diabetes_anticoagulation_sickle_immunocompromiserequired
    history • used at RISK_STRATIFICATION
    Diabetes, chronic anticoagulation, sickle cell, immunocompromise all raise severe-dengue risk + lower admission threshold (WHO 2009 + 2024)
  • disease_day_count_since_fever_onsetrequired
    history • used at FRAME
    Day count drives phase-specific management: febrile (days 1-3) symptomatic + warning-sign teaching; critical (days 4-6) IV crystalloid + serial Hct; recovery (days 7-10) cautious diuresis if pulmonary edema (WHO 2009 + 2024)
  • temperature_and_fever_patternrequired
    vital • used at CONTEXT
    Fever ≥ 39 °C in febrile phase; defervescence around day 3-5 marks transition to critical phase (WHO 2009; Simmons NEJM 2012)
  • blood_pressure_and_pulse_pressurerequired
    vital • used at RED_FLAGS
    Narrow pulse pressure ≤ 20 mmHg OR overt hypotension = shock (DSS) — life-threatening; SBP / DBP + MAP + capillary refill — titrate fluid by Hct + UOP + clinical, NOT MAP alone (WHO 2009 + 2024; Wills NEJM 2005 PMID 16135832)
  • capillary_refill_and_clinical_perfusionrequired
    vital • used at RED_FLAGS
    Cap refill > 2 s + cold extremities + tachycardia = compensated shock; titrate IV crystalloid by Hct + UOP + clinical (WHO 2009 + 2024)
  • urine_output_uoprequired
    vital • used at RED_FLAGS
    UOP < 0.5 mL/kg/h in adult OR < 1 mL/kg/h in pediatric = decreased perfusion; titrate IV crystalloid (WHO 2009 + 2024)
  • cbc_with_hct_and_platelet_trendrequired
    lab • used at INITIAL_WORKUP
    Serial Hct + platelets q4-6h in critical phase — Hct rise concurrent with rapid platelet fall = plasma leakage warning sign; Hct ≥ 20% increase from baseline + plt < 100 = severe critical phase (WHO 2009 + 2024)
  • dengue_ns1_antigen_first_5_daysrequired
    lab • used at INITIAL_WORKUP
    NS1 antigen sensitivity ~ 60-90% serotype-dependent, specificity ~ 95-99%, LR+ ~ 20-50 in first 5 d of illness; high yield early when IgM still negative (WHO 2024; CDC Yellow Book 2024)
  • dengue_igm_serology_day_4_plusrequired
    lab • used at INITIAL_WORKUP
    IgM ELISA from day 4+ sensitivity ~ 90% by day 5-10, specificity ~ 90%; cross-reactivity with other flaviviruses (zika, yellow fever, JE) so interpret with epidemiology (WHO 2024; CDC Yellow Book 2024)
  • dengue_rt_pcr_serotype
    lab • used at BRANCHING_WORKUP
    RT-PCR sensitivity ~ 80-100% in first 5 d, specificity ~ 99%, LR+ > 100; serotype-specific (research / outbreak / atypical setting) (WHO 2024)
  • liver_function_tests_lftrequired
    lab • used at INITIAL_WORKUP
    AST / ALT ≥ 1000 = severe organ dysfunction (hepatitis criterion for severe dengue); also drives paracetamol max-dose adjustment (60 mg/kg/d in hepatitic patient) (WHO 2009 + 2024)
  • coagulation_studies_pt_ptt_fibrinogenrequired
    lab • used at INITIAL_WORKUP
    PT / PTT / fibrinogen baseline for severe bleeding management — cryoprecipitate / FFP if coagulopathy / low fibrinogen; coags trend in severe dengue (WHO 2009 + 2024)
  • lactate_baselinerequired
    lab • used at RED_FLAGS
    Lactate baseline for shock severity assessment + clearance trend during resuscitation (WHO 2009 + 2024; SSC 2026)
  • creatinine_and_renal_functionrequired
    lab • used at INITIAL_WORKUP
    Baseline + serial; AKI (Cr × 1.5-3 baseline) = severe organ dysfunction criterion; drives dose-adjust for renally-cleared meds (WHO 2009 + 2024)
  • blood_cultures_and_co_test_for_bacterial_differential
    lab • used at BRANCHING_WORKUP
    Blood cultures + co-test for typhoid (Salmonella), leptospirosis (lepto IgM), rickettsial (eschar / serology) in returning traveler with febrile illness; bacterial co-infection / sepsis bridge differential (CDC Yellow Book 2024)
  • malaria_smear_and_rdt_co_test_in_returning_traveler
    lab • used at BRANCHING_WORKUP
    Returning traveler with fever from endemic region → co-test malaria (thick + thin smear + RDT HRP2 / pLDH); cross-route to id.malaria.v1 (CDC Yellow Book 2024)
  • ultrasound_for_plasma_leakage
    imaging • used at BRANCHING_WORKUP
    Bedside ultrasound — pleural effusion + ascites + gallbladder wall thickening = plasma leakage signs in critical phase; supports warning-sign + severe-dengue stratification (WHO 2009 + 2024)
  • chest_xray_if_respiratory_features
    imaging • used at BRANCHING_WORKUP
    CXR for fluid accumulation (pleural effusion + pulmonary edema) — supports severe-dengue criterion (fluid accumulation with respiratory distress) + recovery-phase fluid-overload surveillance (WHO 2009 + 2024)
  • pre_vaccination_dengue_igg_serology_for_dengvaxia
    lab • used at CONTEXT
    Pre-vaccination serology MANDATORY for Dengvaxia (CYD-TDV) — seropositive (rapid IgG OR ELISA) ≥ 9 yo only; seronegative is CONTRAINDICATION (CDC ACIP 2021 PMID 34978547)

12-phase flow (12)

  1. 1FRAME
    Dengue spectrum: dengue without warning signs (febrile-phase outpatient) + dengue with warning signs (critical-phase admission) + severe dengue (shock DSS / severe bleeding / severe organ failure — ICU) + pregnancy (admit regardless of warning-sign status) + secondary heterologous infection (ADE; lifetime serology counseling) + returning-traveler differential (co-test malaria / typhoid / lepto / rickettsial / chikungunya / zika) + fluid overload in recovery phase (third-space mobilization → cautious diuresis) + dengue vaccine decision (Dengvaxia seropositive-only ≥ 9 yo per CDC ACIP 2021; Qdenga any serostatus 4-60 yo where approved per EMA 2022). Three-phase pathology: febrile (days 1-3) → critical (days 4-6) → recovery (days 7-10) (WHO 2009 + 2024)
    inputs: age, disease_day_count_since_fever_onset
    actions: flag:co_test_returning_traveler_with_fever_from_endemic_region (CDC Yellow Book 2024), flag:avoid_aspirin_nsaids_im_injections_anticoagulants_bleeding_risk (WHO 2009 + 2024)
    advance: Dengue phenotype framed (without / with warning signs / severe / pregnancy / secondary / returning traveler / vaccine / recovery overload) and disease-phase day count anchored
  2. 2ENTRY
    Recognise via clinical features: acute high fever ≥ 39 °C + retro-orbital pain + breakbone myalgia + arthralgia + facial flushing + transient maculopapular rash + petechiae / mucosal bleed / positive tourniquet test; warning signs in critical phase (abdominal pain, persistent vomiting, clinical fluid accumulation, mucosal bleed, lethargy / restlessness, hepatomegaly > 2 cm, Hct rise + platelet fall); severe dengue features (shock DSS, severe bleeding, severe organ failure); pregnancy; returning traveler from endemic region; secondary heterologous infection; vaccine-eligible (WHO 2009 + 2024; Simmons NEJM 2012)
    inputs: temperature_and_fever_pattern
    advance: Phenotype hypothesis (without / with warning signs / severe / pregnancy / secondary / returning traveler / vaccine / recovery overload) framed
  3. 3CONTEXT
    Age + travel history (endemic region within 14 d) + prior dengue infection or seropositive baseline (secondary heterologous risk; vaccine decision) + pregnancy status + comorbidity (diabetes, anticoagulation, sickle cell, immunocompromise) + disease day count + temperature trend; pre-vaccination serology if Dengvaxia decision pending (CDC Yellow Book 2024; WHO 2024)
    inputs: travel_history_endemic_region_within_14_days, prior_dengue_infection_or_seropositive_baseline, pregnancy_status_and_gestational_age
    advance: Host + exposure + serostatus context captured
  4. 4RED_FLAGS
    Life-threatening features: severe dengue with shock (DSS) — narrow pulse pressure ≤ 20 mmHg OR overt hypotension OR cap refill > 2 s OR cold extremities OR decreased UOP; severe bleeding — GI / GU / intracranial / mucosal hemorrhage with hemodynamic instability; severe organ dysfunction — hepatitis (AST/ALT ≥ 1000), encephalitis (altered mental status, seizures, focal deficits — HSV encephalitis is the major treatable mimic, empiric IV acyclovir pending HSV PCR per Tunkel IDSA encephalitis 2008), myocarditis (cardiac dysfunction, arrhythmia), AKI (Cr × 1.5-3 baseline); pregnancy with warning signs or severe disease; fluid overload in recovery phase (cautious diuresis if pulmonary edema) (WHO 2009 + 2024; AAP Red Book 2024)
    inputs: blood_pressure_and_pulse_pressure, capillary_refill_and_clinical_perfusion, urine_output_uop, lactate_baseline
    actions: flag:severe_dengue_icu_admission_and_iv_crystalloid_bolus (WHO 2009 + 2024), flag:empiric_iv_acyclovir_for_dengue_encephalitis_pending_hsv_pcr (Tunkel IDSA encephalitis 2008), flag:avoid_aspirin_nsaids_im_injections_anticoagulants (WHO 2009 + 2024), flag:no_prophylactic_platelet_transfusion_regardless_of_count (Lye Lancet 2017 PMID 28283286)
    advance: Red flags actioned; severe dengue triaged to ICU; warning signs admitted; co-empirics initiated as indicated
  5. 5INITIAL_WORKUP
    NS1 antigen first 5 d + IgM serology day 4+ + CBC with Hct + platelet baseline + serial trend q4-6h in critical phase + LFT (AST/ALT — hepatitis criterion + paracetamol max-dose adjustment) + coags (PT/PTT/fibrinogen — severe bleeding management) + creatinine (AKI criterion + dose-adjustment) + lactate baseline + UA. RT-PCR for serotype in outbreak / atypical / research setting. Bedside ultrasound for plasma leakage (pleural effusion + ascites + gallbladder wall thickening). CXR for fluid accumulation with respiratory distress. Pre-vaccination serology (rapid IgG or ELISA) if Dengvaxia decision pending (WHO 2024; CDC Yellow Book 2024; AAP Red Book 2024)
    inputs: cbc_with_hct_and_platelet_trend, dengue_ns1_antigen_first_5_days, dengue_igm_serology_day_4_plus, liver_function_tests_lft, coagulation_studies_pt_ptt_fibrinogen, creatinine_and_renal_function
    actions: panel.cbc, panel.lft, panel.coag, panel.renal
    advance: Diagnosis pursued via NS1 + IgM + CBC + LFT + coags + creatinine + lactate + UOP; serial Hct/platelets in critical phase initiated
  6. 6BRANCHING_WORKUP
    Co-test for returning-traveler differential — thick + thin smear + RDT HRP2 / pLDH for malaria (cross-route to id.malaria.v1); blood cultures + co-test for typhoid (Salmonella) + leptospirosis (lepto IgM) + rickettsial (eschar / serology); RT-PCR for dengue serotype + zika + chikungunya in outbreak / atypical setting; ultrasound for plasma leakage (pleural effusion + ascites + gallbladder wall thickening); CXR for fluid accumulation + respiratory distress; LP + CSF studies (cell count, protein, glucose, dengue PCR, HSV PCR, VZV PCR, bacterial culture) if encephalitis; ECG + echo if myocarditis suspected (WHO 2024; CDC Yellow Book 2024)
    inputs: dengue_rt_pcr_serotype, blood_cultures_and_co_test_for_bacterial_differential, malaria_smear_and_rdt_co_test_in_returning_traveler, ultrasound_for_plasma_leakage, chest_xray_if_respiratory_features
    advance: Site-specific complications + co-test differential evaluated; sub-specialty consults engaged
  7. 7DIFFERENTIAL
    Dengue vs malaria (cyclical fever + smear / RDT positive — cross-route id.malaria.v1; co-test always), chikungunya (prominent persistent arthralgia + small-joint involvement + chronic > 3 mo course — chikungunya PCR), zika (rash + conjunctivitis + milder fever + teratogenic CZS risk — zika PCR), yellow fever (dramatic hepatitis with jaundice + hemorrhagic phenotype in endemic Africa + S. America), typhoid (prolonged fever + relative bradycardia + rose spots + leukopenia — blood + stool culture), leptospirosis (water-exposure history + conjunctival suffusion + AKI — lepto IgM + PCR), rickettsial (eschar + tick / mite exposure — serology; doxycycline empiric), septicemia (bacterial source + procalcitonin > 0.5 + blood cultures — broad-spectrum empiric), measles (3 C's prodrome + Koplik + cephalocaudal maculopapular + outbreak), influenza (rapid antigen + circulating influenza season) (CDC Yellow Book 2024; WHO 2024)
    advance: Look-alikes evaluated; co-test results integrated; PCR + serology differentiate
  8. 8RISK_STRATIFICATION
    Stratify by phenotype + host: (1) dengue without warning signs in immunocompetent adult / child = outpatient supportive (paracetamol + ORS + daily warning-sign + CBC review); (2) dengue with warning signs in critical phase = admit + IV crystalloid maintenance + serial Hct/platelets q4-6h; (3) severe dengue with shock (DSS) = ICU + crystalloid bolus titrated by Hct + UOP + clinical + colloid for fluid-refractory + vasopressor for vasopressor-dependent; (4) severe bleeding = ICU + packed RBC + cryoprecipitate / FFP if coagulopathy + NO prophylactic platelet; (5) severe organ failure (hepatitis AST/ALT ≥ 1000, encephalitis, myocarditis, AKI) = ICU + supportive + organ-specific + empiric IV acyclovir for encephalitis pending HSV PCR; (6) pregnancy with active disease = inpatient admit regardless of warning-sign status + MFM; (7) returning traveler with fever = co-test broad ddx; (8) recovery-phase fluid overload = reduce IV + cautious diuresis; (9) Dengvaxia decision = seropositive ≥ 9 yo + 3-dose at 0/6/12 mo; (10) Qdenga decision = 4-60 yo any serostatus + 2-dose at 0/3 mo where approved (WHO 2009 + 2024; CDC ACIP 2021 PMID 34978547; Biswal NEJM 2019 PMID 31693803)
    inputs: comorbidity_diabetes_anticoagulation_sickle_immunocompromise, pregnancy_status_and_gestational_age
    advance: Severity tier + setting assigned
  9. 9TREATMENT
    Supportive care is FIRST-LINE — NO approved antiviral. Paracetamol ONLY for fever / pain (pediatric / hepatitic max 60 mg/kg/d; adult max 4 g/d if no hepatitis); AVOID aspirin / NSAIDs / IM injections / anticoagulants / corticosteroids (bleeding risk + no benefit). ORS for febrile-phase outpatient. IV crystalloid maintenance (Ringer's lactate or normal saline) 3-5 mL/kg/h for warning signs in critical phase; reduce to 2-3 mL/kg/h as Hct normalises + clinical improvement. IV crystalloid bolus 10-20 mL/kg over 1 h (compensated shock) or 10-20 mL/kg over 15-30 min (hypotensive shock); reassess Hct + clinical q1-2h. Colloid (dextran 40) 10 mL/kg for fluid-refractory shock per WHO 2009 (Wills NEJM 2005 PMID 16135832 — lactated Ringer's preferred first-line; dextran 70 + 6% HES more bleeding; HES restricted in many regions due to AKI + coagulopathy signal). Vasopressor (norepinephrine) for vasopressor-dependent shock per SSC 2026. Packed RBC transfusion for active bleeding (NOT prophylactic regardless of Hct); cryoprecipitate / FFP for coagulopathy + low fibrinogen; tranexamic acid considered per ID consult for severe bleeding (data emerging; not yet standard). **NO prophylactic platelet transfusion regardless of count per WHO 2009 + Lye Lancet 2017 PMID 28283286** — only for active bleeding. Empiric IV acyclovir 10 mg/kg q8h for encephalitis differential pending HSV PCR per Tunkel IDSA encephalitis 2008. Ceftriaxone empiric for bacterial co-infection / sepsis-bridge differential (typhoid, lepto, rickettsial) in returning traveler ED. Doxycycline empiric for rickettsial / lepto if suspected. Furosemide cautious in recovery phase ONLY if clinical pulmonary edema (NOT prophylactic). Dengvaxia (CYD-TDV) 3-dose at 0/6/12 mo for seropositive ≥ 9 yo per CDC ACIP 2021 PMID 34978547 (MANDATORY pre-vaccination serology; seronegative CONTRAINDICATION per Sridhar NEJM 2018 PMID 29897841). Qdenga (TAK-003) 2-dose at 0/3 mo for any serostatus 4-60 yo where approved per EMA 2022 (Biswal NEJM 2019 PMID 31693803; Tricou Lancet Glob Health 2024 PMID 38245116); not yet FDA-approved as of 2026-05-15.
    inputs: age, creatinine_and_renal_function, liver_function_tests_lft
    advance: Supportive care initiated; IV crystalloid maintenance / bolus per phenotype; co-empirics if indicated; vaccine plan documented if eligible
  10. 10DISPOSITION
    Outpatient: dengue without warning signs in immunocompetent adult / child / adolescent on paracetamol + ORS + daily return for warning-sign + CBC review (q24h during days 3-7); return precautions; vaccine decision documented. Inpatient: dengue with warning signs (critical-phase admission for IV crystalloid maintenance + serial Hct/platelets q4-6h); pregnant patient (admit regardless of warning-sign status); infant < 12 mo regardless of warning-sign status; comorbidity-prone (diabetes, anticoagulation, sickle cell, immunocompromise) lower threshold. ICU: severe dengue (shock DSS, severe bleeding, severe organ failure — AST/ALT ≥ 1000, encephalitis, myocarditis, AKI requiring CRRT); recovery-phase fluid overload with pulmonary edema requiring monitoring. Transfer to specialty centre if refractory severe dengue or rare neonatal dengue (WHO 2009 + 2024; AAP Red Book 2024)
    inputs: blood_pressure_and_pulse_pressure
    advance: Setting + duration of care assigned
  11. 11MONITORING
    Outpatient: daily return for warning-sign + CBC + tourniquet test during days 3-7 (critical-phase transition window); return precautions for new abdominal pain / persistent vomiting / clinical fluid accumulation / mucosal bleed / lethargy / restlessness / hepatomegaly. Inpatient: serial Hct + platelets q4-6h in critical phase; daily LFT + creatinine + coags + UOP; trend toward stable / falling Hct + recovering platelets + clinical improvement = transition to recovery phase + reduce IV fluids. ICU: continuous vitals + capillary refill + UOP + Hct q1-2h during active resuscitation; lactate trend; titrate fluid by Hct + UOP + clinical (NOT MAP alone); reassess for fluid overload as plasma leakage resolves. Recovery phase: reduce IV fluids when Hct stable / falling + clinical improvement; cautious diuresis with furosemide if pulmonary edema clinically. Vaccine post-dose: Dengvaxia 3-dose audit at 0/6/12 mo; Qdenga 2-dose audit at 0/3 mo; lifetime serology counseling for secondary-infection risk + future-trip planning (WHO 2009 + 2024; CDC ACIP 2021 PMID 34978547)
    inputs: cbc_with_hct_and_platelet_trend, creatinine_and_renal_function
    actions: panel.cbc, panel.lft, panel.renal
    advance: Response confirmed; transition through critical → recovery phase documented; vaccination audit on schedule
  12. 12FOLLOWUP
    Post-acute: convalescent fatigue may last weeks; lifetime homologous-serotype immunity + ~ 2 yr cross-protection against heterologous serotypes; counsel on **secondary heterologous infection ADE risk** for future trips to endemic regions; lifetime serology baseline documented for future vaccine + risk-management decisions; vaccine decision (Dengvaxia seropositive-only per CDC ACIP 2021; Qdenga where approved); post-severe-dengue follow-up: hepatitis recovery (LFT trend), AKI recovery (creatinine + GFR trend), myocarditis recovery (echo + ECG), encephalitis recovery (neuro + neuropsychology + rehabilitation). Pregnancy: postpartum surveillance for neonatal dengue + PPH recovery + MFM follow-up. Travel-medicine counseling: vector avoidance + DEET-containing repellent + permethrin-treated clothing + standing-water elimination + pre-trip vaccination decision for future endemic-area travel. Public health reporting per local regulations (some jurisdictions require dengue reporting) (WHO 2009 + 2024; CDC Yellow Book 2024)
    advance: Follow-up + lifetime-serology counseling + vaccine plan + travel-medicine counseling delivered