12-phase flow (12)

1. 1FRAME
   Frame as subacute, REPORTABLE infectious disease. Differentiate active pulmonary TB vs latent TB infection vs prior-treated; scope is pulmonary DRUG-SUSCEPTIBLE TB + LTBI + diagnosis — DRUG-RESISTANT TB is owned by id.tb_drug_resistant.v1 (route on rifampin resistance / MDR contact). Place patient in airborne (negative-pressure) isolation the moment active pulmonary TB is suspected (WHO TB Module 4 2022; ATS/CDC/IDSA 2016 PMID 27516382)
   advance: Active vs latent vs prior-treated established AND airborne isolation initiated if active suspected
2. 2ENTRY
   Trigger from cough ≥2 wk + constitutional symptoms (WHO 4-symptom screen), abnormal upper-lobe/cavitary CXR, TB exposure / endemic origin, or a positive screening test (IGRA/TST). Symptom-screen sensitivity for active disease is lower in HIV — image and microbiologically test even if asymptomatic when HIV+ (WHO TB Module 4 2022)
   inputs: age
   advance: Entry trigger documented
3. 3CONTEXT
   Set the pretest prior (endemicity / exposure intensity / HIV / immunosuppression) and capture the regimen-selection axes: HIV status (mandatory), prior TB/treatment, MDR contact, hepatic disease/alcohol, renal function, pregnancy, diabetes, baseline vision/neuropathy, current meds (rifampin interaction map) (ATS/CDC/IDSA 2016 PMID 27516382)
   inputs: hiv_status, prior_tb_or_treatment, mdr_xdr_contact, liver_disease_or_alcohol, renal_disease, pregnancy_status, diabetes_status, visual_baseline, neuropathy_risk, current_meds
   advance: Pretest prior set + interaction/comorbidity map captured
4. 4RED_FLAGS
   Massive hemoptysis, miliary/disseminated TB, TB meningitis, acute respiratory failure/ARDS, rifampin-resistance signal on Xpert (→ route id.tb_drug_resistant.v1), pregnancy with active disease, severe immunocompromise (WHO TB Module 4 2022)
   inputs: cxr
   advance: Emergent management initiated OR no immediate threat
5. 5INITIAL_WORKUP
   DIAGNOSTIC Bayesian gate. Sputum ×3 (≥1 early-morning) for AFB smear + Xpert MTB/RIF Ultra + mycobacterial culture + phenotypic DST; CXR (PA + lateral); MANDATORY HIV test; baseline LFT/Cr/CBC, hepatitis B/C, glucose/A1c; baseline Snellen + Ishihara before ETB; ECG only if DR-TB regimen anticipated. Xpert Ultra rules IN fast (overall sens ~88%, smear-neg-culture-pos ~63%, HIV+ ~90%) but trace-positive specificity (~96%) is below Xpert (~98%) — confirm with culture in low-prior patients; Xpert-RIF-resistant → route id.tb_drug_resistant.v1 (Dorman Lancet ID 2018 PMID 29198911)
   inputs: sputum_xpert_mtb_rif_ultra, sputum_afb_smear_culture, cxr, baseline_lft, baseline_creatinine, cbc, hiv_test, hepatitis_bc_serology
   actions: workup.tb, panel.lft, panel.cbc, panel.renal
   advance: Microbiology sent + HIV tested + isolation in place
6. 6BRANCHING_WORKUP
   CT chest if CXR equivocal or to distinguish malignancy/NTM/sarcoid pattern; bronchoscopy + BAL / induced sputum if smear-negative but pretest high; tissue/fluid Xpert + culture + histopathology for extrapulmonary (pleural, nodal, CNS); IGRA/TST for LTBI in contacts; whole-genome sequencing for resistance prediction. NTM if non-cavitary bronchiectatic disease + repeatedly Xpert-negative AFB-positive (route differential — not TB regimen) (ATS/CDC/IDSA 2016 PMID 27516382)
   inputs: ct_chest
   actions: panel.glucose_a1c
   advance: Targeted confirmatory tests obtained
7. 7DIFFERENTIAL
   §5.5.2 — active pulmonary TB vs LTBI (IGRA/TST+ but asymptomatic, normal CXR, micro-negative) vs NTM (non-cavitary bronchiectasis, Xpert-negative repeated AFB+) vs bacterial CAP (acute, lobar, responds to β-lactam → pulm.cap.core.v1) vs lung cancer (mass, smoker, no micro → onc.lung-cancer.core.v1) vs endemic fungal histo/cocci/blasto (travel/endemic, urine antigen → id.invasive-aspergillosis.core.v1 for invasive-mould overlap) vs sarcoidosis (bilateral hilar adenopathy, non-caseating granulomas, micro-negative → pulm.sarcoidosis.v1) vs lymphoma. Pivots: Xpert Ultra sens/spec, AFB-smear sens, IGRA vs TST in BCG-vaccinated, CXR cavitation/upper-lobe distribution, urine fungal antigen (ATS/CDC/IDSA 2016 PMID 27516382; Dorman Lancet ID 2018 PMID 29198911)
   advance: Active TB vs LTBI vs alternative-diagnosis category assigned
8. 8RISK_STRATIFICATION
   Regimen-selection gate. Active DS-TB: standard 6-month 2HRZE/4HR vs the 4-month INH+rifapentine+moxifloxacin+PZA regimen (eligible: age ≥12 yr, weight ≥40 kg, DS pulmonary TB, NOT severe/extensive disease, NOT pregnant, HIV acceptable if CD4 ≥100 on efavirenz-based ART). LTBI: 3HP vs 4R vs 3HR vs legacy 9H by HIV/ART compatibility, hepatic risk, age. Relapse risk: cavitation + positive month-2 culture → extend continuation to 7 mo (total 9). HIV / DM / extensive disease shift toward longer regimens (Dorman NEJM 2021 PMID 33951360; CDC LTBI 2020)
   inputs: hiv_status, weight, age
   actions: calc.ckd_epi_2021
   advance: Active-vs-LTBI fork resolved + regimen phenotype chosen
9. 9TREATMENT
   DS-TB: 2-month intensive RIPE (INH+RIF+PZA+ETB) → 4-month INH+RIF continuation (2HRZE/4HR, total 6 mo) — drop ETB once pan-susceptibility confirmed; OR the 4-month rifapentine-moxifloxacin regimen for eligible patients. LTBI: 3HP (12-dose weekly INH+rifapentine, DOT/SAT) preferred OR 4R OR 3HR OR 9H if rifamycin contraindicated. Pyridoxine 25-50 mg/day MANDATORY with INH. DOT (or video DOT) for all active disease. HIV co-treatment: start ART within 2 wk if CD4 <50, within 8 wk otherwise; use DTG- or efavirenz-based ART with rifampin (or substitute rifabutin for PI-based ART). DR-TB suspected/confirmed → route id.tb_drug_resistant.v1 (BPaL/BPaLM 6-mo all-oral) (ATS/CDC/IDSA 2016 PMID 27516382; Dorman NEJM 2021 PMID 33951360; CDC LTBI 2020)
   inputs: weight, baseline_lft, baseline_creatinine
   advance: Regimen + DOT + pyridoxine + ART-timing + adverse-effect monitoring plan documented
10. 10DISPOSITION
    Outpatient DOT if respiratory hygiene maintainable at home, no severe disease, public-health follow-up arranged, and household has no susceptible high-risk contacts (infants, HIV+, immunosuppressed). Admit (negative-pressure isolation) for hemoptysis, miliary/meningeal/disseminated disease, severe immunocompromise, respiratory failure, rifampin-resistance with infection-control risk (→ id.tb_drug_resistant.v1), or an unworkable home DOT plan (ATS/CDC/IDSA 2016 PMID 27516382)
    advance: Disposition + isolation + DOT plan set + public-health notified
11. 11MONITORING
    Sputum smear + culture monthly until two consecutive negative cultures (the month-2 culture is the key conversion endpoint; positive at 2 mo with cavitation → extend continuation). LFT at baseline then symptom-driven (monthly if hepatic risk/HBV/HCV/HIV/alcohol/pregnancy) — hold INH/RIF/PZA if ALT >3× ULN with symptoms or >5× ULN asymptomatic. Snellen + Ishihara monthly on ETB. Pyridoxine adherence. ART + IRIS surveillance during the first 3 months of ART. Monthly weight for re-dosing. DOT adherence each visit (ATS/CDC/IDSA 2016 PMID 27516382)
    advance: Culture conversion documented + regimen tolerated
12. 12FOLLOWUP
    End-of-treatment CURE assessment per WHO/ATS (clinical + microbiological — culture-negative at end of therapy; treatment completed if doses verified). Close-contact investigation → IGRA/TST + symptom screen + LTBI evaluation/treatment. Mandatory public-health reporting and case closure. Adherence/relapse education; relapse usually within 6-12 mo (highest if cavitary + positive month-2 culture). Long-term follow-up for late toxicity and post-TB lung function (ATS/CDC/IDSA 2016 PMID 27516382; CDC LTBI 2020)
    advance: Cure/completion documented + contact tracing + reporting complete