12-phase flow (12)

1. 1FRAME
   Measles spectrum: primary measles (rubeola — 10-12 d incubation + 2-4 d prodrome + cephalocaudal rash + Koplik spots) + complications (pneumonia, otitis, croup, diarrhea, keratitis, ADEM) + SSPE (latent 7-10 yr, uniformly fatal) + atypical measles (immunocompromised) + immune amnesia (1-3 yr post-measles increased infection vulnerability) + post-exposure prophylaxis (MMR within 72 h immunocompetent ≥ 12 mo; IVIG within 6 d high-risk) + MMR vaccination eligibility (2-dose 12-15 mo + 4-6 yr routine; adult catch-up; 6-11 mo early-dose for travel + outbreak) (Moss Lancet 2017 PMID 28673424; Moss Lancet 2017 PMID 28673424)
   inputs: age, rash_onset_time_and_contagious_window
   actions: flag:public_health_emergency_every_measles_case_is_a_notifiable_disease (CDC; state law), flag:airborne_isolation_negative_pressure_room_N95_PPE (CDC)
   advance: Measles phenotype framed (primary / pneumonia / ADEM / SSPE / atypical / post-exposure / vaccination eligibility) and public-health-emergency posture activated
2. 2ENTRY
   Recognise via clinical features: 3 C's prodrome (cough + coryza + conjunctivitis) + fever ≥ 39 °C; Koplik spots (pathognomonic; transient 12-72 h; check buccal mucosa opposite molars); cephalocaudal maculopapular rash; respiratory features (pneumonia); neuro features (ADEM, SSPE); high-risk exposure (PEP); maternal exposure; immunocompromised host; vaccination-eligible age threshold
   inputs: rash_distribution_and_three_cs_prodrome, neurologic_features_adem_or_sspe
   advance: Phenotype hypothesis (primary measles / pneumonia / ADEM / SSPE / atypical / post-exposure / vaccination-eligible) framed
3. 3CONTEXT
   Age + vaccination history (MMR doses + serology if needed) + exposure history + outbreak context + immunocompromise status (HIV CD4, transplant, chemo nadir, chronic steroid, autoimmune biologic) + pregnancy gestational age; community / household / school / healthcare-setting exposure context; serology if vaccination decision needs immunity stratification
   inputs: vaccination_history_mmr_and_immunity, exposure_history_and_outbreak_context, pregnancy_status_and_gestational_age, immunocompromise_status
   advance: Host + exposure context captured
4. 4RED_FLAGS
   Life-threatening features: severe pneumonia (SpO2 < 94% + new bilateral infiltrates; bacterial superinfection — MRSA, S. aureus, S. pneumoniae), ADEM / acute postinfectious encephalitis (altered mental status, seizures, focal deficits within 2 wk of rash; HSV encephalitis is the major treatable mimic — empiric IV acyclovir pending HSV PCR), SSPE features (subacute neurologic decline 7-10 yr post measles), dehydration with inability to maintain oral intake, infant < 12 mo with active disease, pregnant with active disease (especially pneumonia), immunocompromised with active disease (atypical measles + giant-cell pneumonia + persistent shedding). PUBLIC HEALTH EMERGENCY — STAT notification + airborne isolation + outbreak investigation are FIRST-LINE actions before treatment workup completes (CDC ACIP; AAP Red Book 2024; Tunkel IDSA encephalitis 2008)
   inputs: oxygen_saturation, neurologic_features_adem_or_sspe, temperature_and_systemic_symptoms
   actions: flag:STAT_public_health_notification_do_not_wait_for_lab_confirmation (CDC; state notifiable-disease law), flag:airborne_isolation_negative_pressure_room_N95_PPE (CDC), flag:contact_tracing_4d_before_rash_to_4d_after_rash (CDC), flag:empiric_iv_acyclovir_for_adem_pending_hsv_pcr (Tunkel IDSA encephalitis 2008), flag:empiric_ceftriaxone_plus_vancomycin_for_bacterial_superinfection (IDSA/ATS CAP 2019), flag:vitamin_a_universal_pediatric_regardless_of_nutritional_status (WHO; Imdad Cochrane 2010 PMID 21154399)
   advance: Red flags actioned; public health notified; airborne isolation in place; empiric therapy initiated as indicated
5. 5INITIAL_WORKUP
   Clinical diagnosis is primary (3 C's + fever + Koplik + cephalocaudal rash + outbreak / exposure context). Laboratory confirmation = IgM serology + RT-PCR (throat / NP / urine swab) — both should be sent; PCR preferred for early-rash + vaccine-modified + immunocompromised scenarios where IgM may be falsely negative. CBC (leukopenia + lymphopenia typical; leukocytosis suggests bacterial superinfection), creatinine baseline. Procalcitonin if respiratory features. STAT public health notification + airborne isolation + outbreak investigation initiated in parallel with workup — do NOT wait for laboratory confirmation. Initiate Vitamin A on clinical recognition for all pediatric cases regardless of nutritional status (WHO universal; Imdad Cochrane 2010 PMID 21154399; D'Souza Cochrane 2002 PMID 21154399)
   inputs: measles_igm_serology, measles_rt_pcr_throat_np_or_urine, creatinine_and_renal_function
   actions: panel.cbc, panel.renal, panel.inflammation
   advance: Diagnosis confirmed clinically; serology + PCR sent; public health notified; airborne isolation in place; Vitamin A initiated for pediatric cases
6. 6BRANCHING_WORKUP
   Site-directed: CXR if respiratory (primary viral = diffuse interstitial; bacterial superinfection = focal consolidation); LP + CSF studies (cell count, protein, glucose, measles PCR, HSV PCR, VZV PCR, bacterial culture, Gram stain, in SSPE add intrathecal antibody index) if ADEM / encephalitis / SSPE; MRI brain (ADEM = white-matter lesions especially periventricular + subcortical; SSPE = diffuse white-matter changes; HSV encephalitis = temporal-lobe / limbic predilection); EEG (SSPE = burst suppression; ADEM = focal slowing); slit-lamp if keratitis suspected (Vitamin A-responsive corneal ulceration); procalcitonin trend for bacterial superinfection differential
   inputs: chest_xray_if_respiratory, mri_brain_if_neuro_features, eeg_if_subacute_neurologic_decline, csf_studies_if_neuro, procalcitonin_for_bacterial_superinfection
   advance: Site-specific complications evaluated; sub-specialty consults engaged
7. 7DIFFERENTIAL
   Primary measles vs rubella (separate togavirus; milder + lymphadenopathy + TORCH-teratogenic in pregnancy — distinguished by serology), scarlet fever (sandpaper rash + strawberry tongue + recent strep — distinguished by rapid strep), roseola (fever then rash AFTER defervescence; HHV-6/7), drug eruption (no Koplik, no prodrome, recent drug exposure), Kawasaki disease (5+ d fever + extremity changes + coronary aneurysm risk), dengue (retro-orbital + thrombocytopenia + geographic exposure), erythema infectiosum (parvovirus B19 — slapped cheek + lace pattern), enteroviral exanthem, mononucleosis (EBV) with ampicillin-induced rash. Measles ADEM vs HSV encephalitis (HSV temporal-lobe predilection + HSV PCR positive; empiric IV acyclovir for both pending PCR). SSPE vs other progressive neurodegenerative disorders in young (history of early-life primary measles + EEG burst suppression + CSF measles IgG with elevated CSF:serum IgG index). Atypical measles (vaccine-modified or immunocompromised) vs other viral exanthem (PCR + IgM serology; outbreak context) (Moss Lancet 2017; AAP Red Book 2024)
   advance: Look-alikes evaluated; PCR + IgM differentiate in atypical or vaccine-modified scenarios
8. 8RISK_STRATIFICATION
   Stratify by phenotype + host: (1) primary measles immunocompetent child / adult = outpatient supportive + Vitamin A pediatric + airborne isolation home until 4 d after rash; (2) measles pneumonia = inpatient (or ICU if respiratory failure) + empiric ceftriaxone + vancomycin if bacterial superinfection features; (3) ADEM = ICU + empiric IV acyclovir pending HSV PCR + neurology + supportive; (4) SSPE = palliative + neurology + ID + family education (uniformly fatal; no curative therapy); (5) atypical measles immunocompromised = inpatient + ID + bacterial co-empirics + ribavirin off-label considered; (6) pregnant active disease = inpatient + maternal-fetal medicine + IV supportive + bacterial co-empirics if pneumonia; (7) infant < 12 mo active disease = inpatient + Vitamin A age-adjusted + supportive; (8) PEP MMR within 72 h susceptible immunocompetent ≥ 12 mo; (9) PEP IVIG within 6 d susceptible high-risk; (10) MMR vaccination 2-dose schedule (CDC ACIP; AAP Red Book 2024)
   inputs: immunocompromise_status, pregnancy_status_and_gestational_age
   advance: Severity tier + setting assigned
9. 9TREATMENT
   Supportive care + Vitamin A pediatric (universal regardless of nutritional status; 200,000 IU PO day 1 + day 2 for ≥ 12 mo; 100,000 IU at 6-11 mo; 50,000 IU < 6 mo) + airborne isolation + STAT public health notification + outbreak investigation are the FIRST-LINE actions. NO FDA-approved antiviral for measles. Empiric ceftriaxone + vancomycin if bacterial superinfection features (focal consolidation, procalcitonin > 0.25, leukocytosis, clinical deterioration; cross-route to pulm.cap.core.v1). Empiric IV acyclovir 10 mg/kg q8h (adult) or 60 mg/kg/d divided q8h (neonate) for measles ADEM differential pending HSV PCR (do NOT delay; HSV encephalitis is the major treatable mimic per Tunkel IDSA encephalitis 2008). PEP: MMR 0.5 mL SC within 72 h for susceptible immunocompetent ≥ 12 mo (NOT pregnant, NOT severely immunocompromised); IVIG 0.5 g/kg IV (max 15 g) within 6 d for susceptible high-risk (immunocompromised, pregnant, infant < 12 mo). Ribavirin off-label per ID consult for severe atypical measles in immunocompromised (giant-cell pneumonia; data weak; case-series only; NOT routine). Steroids for ADEM controversial — high-dose IV methylprednisolone (30 mg/kg/d × 3-5 d) considered per neurology but evidence weak. SSPE: NO curative therapy (intraventricular interferon-α + isoprinosine + ribavirin combinations explored — at best slow progression); palliative care. Antipyretics — acetaminophen (AVOID aspirin per Reye syndrome risk like varicella). Catch-up vaccination of all previously-incomplete routine vaccinations in measles survivors (immune amnesia 1-3 yr post-measles per Mina Science 2019 PMID 31672891). RZV/MMR routine schedule per ACIP (separate from acute disease treatment).
   inputs: age, creatinine_and_renal_function
   advance: Supportive care + Vitamin A pediatric + bacterial co-empirics if indicated + empiric IV acyclovir if ADEM differential + PEP if exposed; STAT public health notified; airborne isolation in place; vaccination plan for catch-up + susceptibles ordered
10. 10DISPOSITION
    Outpatient: uncomplicated immunocompetent measles in child / adult on supportive care + Vitamin A + airborne isolation at home until 4 d after rash onset; PEP for susceptible contacts; vaccination reconciliation; immune-amnesia post-measles surveillance for 1-3 yr. Inpatient: measles pneumonia (admitted, not ICU), infant < 12 mo with measles, pregnant with measles, immunocompromised with measles, ADEM observation 24-48 h. ICU: respiratory failure (PaO2/FiO2 ≤ 200 OR mechanical ventilation), ADEM with encephalopathy / seizures / focal deficits, multi-organ dysfunction. Transfer to specialty centre if SSPE or refractory ADEM (neurology + ID).
    inputs: oxygen_saturation
    advance: Setting + duration of care assigned
11. 11MONITORING
    Outpatient: rash resolution 7-10 d (cephalocaudal pattern desquamates with hyperpigmentation); fever should resolve 48-72 h after rash onset; return precautions for new respiratory / neuro / dehydration features; isolation until 4 d after rash onset; immune-amnesia surveillance 1-3 yr (catch-up vaccination + close monitoring + lower threshold for empiric antibiotics in febrile illness). Inpatient / ICU: daily reassessment of respiratory + neuro status; serial creatinine + UOP for IV acyclovir + IVIG monitoring; procalcitonin trend if antibiotics started; CSF reassessment if ADEM not improving (consider HSV / VZV / bacterial differential). SSPE: palliative + family + neurology + ID; progression monitoring (EEG, MRI, functional assessment). Vaccination tracking: routine pediatric 2-dose schedule audit (12-15 mo + 4-6 yr); adult catch-up tracked to completion; early-dose MMR (6-11 mo) does not count toward standard 2-dose schedule which continues at 12-15 mo + 4-6 yr.
    inputs: creatinine_and_renal_function
    actions: panel.renal, panel.inflammation
    advance: Response confirmed; isolation expired (4 d after rash onset); vaccination catch-up + immune-amnesia surveillance plan in place
12. 12FOLLOWUP
    Post-measles: immune-amnesia surveillance for 1-3 yr — catch-up vaccination of all previously-incomplete routine vaccinations + close monitoring + lower threshold for empiric antibiotics in febrile illness in measles survivors (Mina Science 2019 PMID 31672891); routine pediatric vaccinations re-administered if pre-measles immunity is impaired. Post-pneumonia: respiratory recovery + lung function; ID follow-up if immunocompromised. Post-ADEM: neurology + neuropsychology + rehabilitation; ~ 15% mortality + ~ 25% permanent neuro sequelae; serial imaging + functional assessment. Post-SSPE: palliative care + family education + neurology + ID; progression to vegetative state + death within 1-3 yr. Vaccination reconciliation: MMR 2-dose pediatric schedule audit; adult catch-up; early-dose MMR for travel + outbreak; high-risk catch-up (HCW, students, international travelers, outbreak contacts). Family education + contact tracing if institutional outbreak; public health reporting through resolution.
    advance: Follow-up + immune-amnesia surveillance + vaccination plan + family education delivered