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id.opportunistic-infection.hiv-transplant.v1

Opportunistic infection overlay — HIV / transplant / biologic immunocompromise

infectious_diseaseacutechronicadultacuteinpatientoutpatienttransition
Start encounter →Print handoutPRODUCTION

Overlay engine — cross-cutting OI engine that runs concurrently with id.hiv-initial.chronic.v1 (parent), id.candidemia.core.v1, id.invasive-aspergillosis.core.v1, id.bacterial-meningitis.core.v1 (cryptococcal-vs-bacterial), id.tb_drug_resistant.v1 (MAC vs MDR-TB). Manifest pointer is intentionally borrowed from id.hiv-initial.chronic.v1 per shard-5 §5.5 nearest-precedent pattern — a dedicated OI manifest is out of scope for this shard. Status declared INTEGRATED — decision surface satisfied via 2 regimen axes (prophylaxis + acute treatment) covering 11 pathogens (PCP / toxo / CMV / cryptococcal / MAC / Candida / Aspergillus / EBV-PTLD / BK / JC-PML / TB-LTBI); evidence array has 7 PMIDs (Bozzette 1990 PCP steroids, Marty 2017 letermovir, COAT 2014 ART deferral, Pappas 2016 candidiasis, Patterson 2016 aspergillosis, Herbrecht 2002 voriconazole, Maertens 2016 SECURE isavuconazole); test_files declared; all 12 flow phases present. Phenotype matrix (host × pathogen × phase × IRIS × CD4-recovery × organ-specific) and Bayesian linkage (PCP prior 10-30%/yr in CD4 < 200; cryptococcal 5-10% in CD4 < 100; CMV ~60% in HSCT; LRs for β-D-glucan, CMV PCR > 10K, CrAg LFA, PCP-PCR BAL; T_treat empirical pre-emptive at host-risk + compatible features; T_test rule-out when host risk low + alternative dx identified; cross-dossier routing to HIV core / candidemia / aspergillosis / bacterial-meningitis / MDR-TB / AKI) documented in co-located brief + research bundle; first-class TS fields remain schema-blocked. Gaps still open (post-INTEGRATED → PRODUCTION): dedicated OI manifest (currently borrows HIV core); fluid plan not authored (overlay engines typically defer to underlying sepsis / nephrology engines); dedicated test file for overlay-specific multi-engine concurrency not yet authored. Citation+drug-code remediation 2026-05-22 (PubMed + RxNav live-verified): nearly every RxCUI in this overlay was mis-coded and is now corrected — isoniazid 1011 (=anti-thymocyte globulin) -> 6038, TMP-SMX 10180 (=sulfamethoxazole alone) -> 10831, isavuconazole 1543637 (empty) -> 1720882, liposomal amphotericin B 1546435 (=salmon GnRH analog) -> 236594, letermovir 1992833 (empty) -> 1988648, valganciclovir 218321 (empty) -> 275891, IVIG 253182 (=regular insulin) -> 42386, rituximab 262095 (=atorvastatin/Lipitor) -> 121191, azithromycin 308460 (SCD) -> 18631, caspofungin 343048 (=treprostinil) -> 140108, rifabutin 35619 (=rifaximin) -> 55672, posaconazole 358258 (=bortezomib) -> 282446, ethambutol 4035 (empty) -> 4110, ganciclovir 4053 (=erythromycin) -> 4678, fluconazole 41493 (=meloxicam) -> 4450, voriconazole 4321 (empty) -> 121243, foscarnet 4453 (=flufenamic acid) -> 33562, flucytosine 4493 (=fluoxetine) -> 4451, pyrimethamine 8782 (=propofol) -> 9010; clarithromycin 21212 verified correct. PMIDs corrected: Bozzette PCP 2342540 (=immunoendocrine-autoimmunity paper) -> 2233917; Boulware COAT 24855298 (=bacteriocin genome announcement) -> 24963568; Marty/Pappas/Patterson/Herbrecht/Maertens verified correct. Severity triggers: 10 rows covering life-threatening (PCP hypoxia, cryptococcal raised ICP, JC-PML), severe (CMV retinitis/pneumonitis, MAC disseminated, IRIS, EBV-PTLD, BK nephropathy, transplant unusual pathogen), moderate (CD4 < 200 without PCP prophylaxis). Each row routes to specific drug actions + workups + consults + sibling-dossier routing. Setting playbooks: outpatient (CD4 + transplant-protocol prophylaxis, vaccination, surveillance PCRs, IS coordination); inpatient (pathogen-specific induction with adjuncts — Bozzette steroids for PCP, therapeutic LP for cryptococcal, IS reduction for BK/PTLD/PML, ART deferral for cryptococcal/TB meningitis); ICU (severe PCP with mechanical ventilation, raised-ICP cryptococcal, CMV pneumonitis, empiric mold coverage in critically ill immunocompromised). Co-located brief + research bundle authored 2026-05-15 per shard-5 §5.5 contract items 1 + 2.

Entry points (9)

  • lab_abnormality
    CD4 < 200 cells/mm³ in HIV+ host — initiate PCP / toxo prophylaxis (DHHS 2024 OI; IDSA 2024)
    cd4_below_200
  • problem_list
    Solid-organ transplant recipient on calcineurin / mTOR / steroid immunosuppression (AST IDCOP 2019/2024)
    solid_organ_transplant_recipient
  • problem_list
    HSCT recipient — pre-engraftment neutropenia + post-engraftment GVHD on steroids (ASBMT/IDSA 2009; ECIL series)
    hsct_recipient_pre_engraftment_or_post_engraftment
  • problem_list
    B-cell-depleting agent (rituximab / ocrelizumab / natalizumab / TNF-α inhibitor) or chronic ≥ 20 mg pred ≥ 4 wk (IDSA 2024; AST IDCOP 2024)
    biologic_dmart_or_rituximab_recipient
  • symptom
    Persistent fever ≥ 3 days in immunocompromised host with negative routine workup — broaden to OI (IDSA 2024)
    persistent_fever_in_immunocompromised_host
  • imaging
    Bilateral interstitial / ground-glass infiltrate on CT chest in immunocompromised host — empiric PCP coverage (DHHS 2024 OI)
    bilateral_interstitial_infiltrate_in_immunocompromised
  • lab_abnormality
    CMV PCR rising on weekly post-transplant surveillance — pre-emptive therapy (AST IDCOP 2024; Marty NEJM 2017)
    cmv_pcr_rising_post_transplant
  • lab_abnormality
    Serum cryptococcal antigen LFA positive in CD4 < 100 — LP to rule out cryptococcal meningitis (DHHS 2024 OI; IDSA 2010 cryptococcal)
    serum_crag_positive
  • symptom
    New focal neurologic deficit in natalizumab / rituximab / mycophenolate user — MRI for PML (IDSA 2024; FDA boxed warning)
    new_neuro_deficit_in_biologic_user

Required inputs (17)

  • immunocompromise_substraterequired
    history • used at ENTRY
    Defines OI risk profile: HIV-CD4 vs SOT vs HSCT vs biologic / chronic-steroid; drives prophylaxis + empiric coverage (DHHS 2024 OI; AST IDCOP 2024; ASBMT/IDSA 2009)
  • cd4_countrequired
    lab • used at CONTEXT
    PCP < 200; toxo < 100; MAC < 50; cryptococcal screen < 100 (DHHS 2024 OI guidelines)
  • hiv_viral_load
    lab • used at CONTEXT
    IRIS risk + ART timing + prophylaxis discontinuation thresholds (DHHS 2024 OI)
  • transplant_type_and_date
    history • used at CONTEXT
    AST IDCOP 2024 — risk profile differs kidney vs liver vs lung vs heart vs HSCT allo vs auto; time-from-transplant defines OI window (0-1 mo nosocomial; 1-6 mo CMV/PCP/BK; > 6 mo community + late CMV)
  • current_immunosuppressionrequired
    medication • used at CONTEXT
    Calcineurin (tacro/cyclosporine), mTOR (sirolimus/everolimus), anti-metabolite (mycophenolate/azathioprine), steroid dose, biologic (rituximab, natalizumab, infliximab, anti-thymocyte globulin, alemtuzumab) — drives net state of immunosuppression (AST IDCOP 2024)
  • temperaturerequired
    vital • used at ENTRY
    Persistent fever ≥ 3 days in immunocompromised host triggers OI workup (IDSA 2024)
  • spo2required
    vital • used at RED_FLAGS
    PaO2 < 70 or A-a gradient > 35 → adjunct prednisone for PCP (Bozzette NEJM 1990 PMID 2233917)
  • creatininerequired
    lab • used at TREATMENT
    BK virus nephropathy in kidney transplant; foscarnet / amphotericin / TMP-SMX nephrotoxicity dosing (AST IDCOP 2024; DHHS 2024 OI)
  • lft
    lab • used at MONITORING
    Azole / TMP-SMX / pyrimethamine hepatotoxicity monitoring (DHHS 2024 OI; IDSA 2010 cryptococcal)
  • cmv_pcr_quantitative
    lab • used at INITIAL_WORKUP
    Pre-emptive monitoring post-transplant weekly × 12 wk; > 10K copies/mL LR+ ~ 10 for tissue-invasive disease (AST IDCOP 2024; Marty NEJM 2017)
  • cryptococcal_antigen_lfa_serum
    lab • used at INITIAL_WORKUP
    CrAg LFA serum LR+ > 100 in CD4 < 100; reflex LP if positive (DHHS 2024 OI; IDSA 2010 cryptococcal Perfect)
  • beta_d_glucan
    lab • used at INITIAL_WORKUP
    Adjunct for invasive fungal — PCP / candidiasis / aspergillosis support (DHHS 2024 OI; IDSA 2016 candidiasis)
  • toxoplasma_igg
    lab • used at CONTEXT
    Toxoplasma IgG+ in CD4 < 100 → TMP-SMX prophylaxis indicated; in transplant, donor IgG+/recipient IgG- highest risk (DHHS 2024 OI; AST IDCOP 2019)
  • ebv_pcr_quantitative
    lab • used at BRANCHING_WORKUP
    EBV viral load rising post-transplant → PTLD risk; biopsy if lymphadenopathy / mass (AST IDCOP 2024)
  • bk_virus_pcr_quantitative_blood_urine
    lab • used at BRANCHING_WORKUP
    BK viruria → viremia → nephropathy continuum in kidney transplant; biopsy confirms nephropathy (AST IDCOP 2019/2024 Hirsch)
  • hrct_chest
    imaging • used at INITIAL_WORKUP
    Bilateral ground-glass / interstitial → PCP; nodular / halo → aspergillosis / fungal; tree-in-bud → MAC / TB (DHHS 2024 OI; IDSA 2016 aspergillosis)
  • mri_brain
    imaging • used at BRANCHING_WORKUP
    Ring-enhancing mass + IgG+ → toxoplasmosis; basal-ganglia + subcortical white-matter without enhancement → PML; sub-acute meningitis → cryptococcal (DHHS 2024 OI)

12-phase flow (12)

  1. 1FRAME
    Overlay engine for OI prophylaxis + diagnosis + treatment in immunocompromised adults (HIV CD4 < 200, SOT, HSCT, biologic-DMARD, chronic steroid). HIV-naive non-immunocompromised hosts and pediatric OIs routed to sibling engines (DHHS 2024 OI; AST IDCOP 2024)
    inputs: immunocompromise_substrate
    advance: host substrate + scope confirmed
  2. 2ENTRY
    CD4 threshold breach OR transplant induction OR biologic-DMARD start OR new infection signal (fever, infiltrate, CMV-PCR rise, CrAg+, new neuro deficit) (DHHS 2024 OI; AST IDCOP 2024)
    inputs: immunocompromise_substrate, temperature
    advance: OI trigger validated
  3. 3CONTEXT
    Document net state of immunosuppression — CD4, VL, transplant type + time-from-transplant, current immunosuppression regimen, prior OI history, prior prophylaxis, vaccination history, toxoplasma / CMV / EBV serostatus (DHHS 2024 OI; AST IDCOP 2024 net-state-of-immunosuppression framework)
    inputs: cd4_count, current_immunosuppression, transplant_type_and_date, toxoplasma_igg
    advance: host risk profile documented
  4. 4RED_FLAGS
    Hypoxia PaO2 < 70 (severe PCP — adjunct steroids), raised ICP / herniation signs (cryptococcal meningitis — therapeutic LP + neurosurgery), retinitis (CMV — emergent ganciclovir + ophtho), focal neuro deficit (PML / toxo / cryptococcoma), septic shock (broad-spectrum + Candida + Aspergillus cover) (DHHS 2024 OI; IDSA 2024)
    inputs: spo2
    advance: life-threatening OI escalation triggered if present
  5. 5INITIAL_WORKUP
    CD4 + VL + HRCT chest + CMV PCR (transplant) + serum CrAg (CD4 < 100) + β-D-glucan + blood cultures + toxoplasma IgG; site-specific imaging by syndrome (DHHS 2024 OI; AST IDCOP 2024)
    inputs: cd4_count, hrct_chest, cmv_pcr_quantitative, cryptococcal_antigen_lfa_serum, beta_d_glucan
    actions: workup.hiv_initial, workup.pcp_pneumonia
    advance: host + syndrome workup pending culture / PCR / histology
  6. 6BRANCHING_WORKUP
    Pathogen-specific cascades: BAL silver / Giemsa / PCR (PCP), LP for opening pressure + CrAg + India ink + culture (cryptococcal), MRI brain + toxo PCR (toxoplasmosis / PML), bronch + galactomannan (aspergillosis), kidney biopsy for BK nephropathy, lymph-node biopsy for PTLD, JC-PCR in CSF for PML, AFB + sputum cx for MAC / TB (DHHS 2024 OI; AST IDCOP 2024; IDSA 2010 cryptococcal Perfect)
    inputs: mri_brain, ebv_pcr_quantitative, bk_virus_pcr_quantitative_blood_urine
    actions: workup.cryptococcal_meningitis, workup.cmv_transplant, workup.candidemia, workup.invasive_aspergillosis
    advance: pathogen + organ identified
  7. 7DIFFERENTIAL
    Distinguish PCP vs CMV pneumonitis vs viral / bacterial / fungal pneumonia vs drug pneumonitis; toxoplasmosis vs primary CNS lymphoma vs PML; cryptococcal vs bacterial / TB meningitis; CMV vs HHV-6 / HSV / VZV; BK vs CMV vs acute rejection on transplant biopsy (DHHS 2024 OI; AST IDCOP 2024)
    advance: pathogen + syndrome mapped to dossier
  8. 8RISK_STRATIFICATION
    Severity per syndrome: PCP PaO2 + A-a gradient (Bozzette NEJM 1990 adjunct steroids if PaO2 < 70 or A-a > 35); cryptococcal raised ICP + CrAg titre + CSF fungal burden; CMV viral load + tissue invasion; PTLD biopsy histology + EBV load; BK viral load + biopsy nephropathy stage; IRIS surveillance (DHHS 2024 OI; AST IDCOP 2024)
    inputs: cd4_count, spo2
    actions: calc.qsofa
    advance: severity assigned per pathogen
  9. 9TREATMENT
    Pathogen-specific induction → consolidation → maintenance / secondary prophylaxis: TMP-SMX 15-20 mg/kg/d × 21 d ± prednisone (PCP); pyrimethamine + sulfadiazine + leucovorin × 6 wk (toxo); L-AmB + flucytosine × 2 wk → fluconazole 800 × 8 wk → 200 maintenance (cryptococcal); ganciclovir 5 mg/kg q12h IV → valganciclovir 900 PO BID × 14-21 d (CMV) + letermovir prophylaxis post-HSCT (Marty NEJM 2017 PMID 29211658); clarithromycin + ethambutol + rifabutin ≥ 12 mo (MAC); reduce IS + rituximab (EBV-PTLD); reduce IS ± IVIG (BK); discontinue biologic ± plasma exchange (PML); fluconazole / echinocandin (Candida); voriconazole / isavuconazole (Aspergillus) (DHHS 2024 OI; AST IDCOP 2024; IDSA 2010 cryptococcal Perfect; IDSA 2016 candidiasis Pappas; IDSA 2016 aspergillosis Patterson)
    inputs: creatinine, cd4_count, current_immunosuppression
    advance: pathogen-specific induction started + adjunct (steroids, therapeutic LP, IS reduction) addressed
  10. 10DISPOSITION
    Outpatient HIV / transplant clinic for stable; admit for severe PCP / cryptococcal / disseminated CMV / PTLD / acute kidney injury from BK; ICU for hypoxic PCP / raised-ICP cryptococcal / CMV pneumonitis with respiratory failure; OPAT for prolonged IV therapy post-discharge (DHHS 2024 OI; AST IDCOP 2024)
    inputs: spo2
    advance: level of care set
  11. 11MONITORING
    Pathogen-specific response: PCP-LDH + repeat CXR + ABG; CMV PCR weekly until undetectable then bi-weekly; cryptococcal LP at 2 wk for sterilisation; BK PCR q1-2 wk + creatinine; EBV PCR q1-2 wk post-PTLD treatment; CD4 + VL q3 mo; IRIS surveillance 2-12 wk post-ART (DHHS 2024 OI; AST IDCOP 2024)
    inputs: lft, creatinine, cmv_pcr_quantitative
    actions: panel.lft, panel.renal
    advance: pathogen-specific response confirmed (PCR negative / CrAg titre falling / imaging improving)
  12. 12FOLLOWUP
    Secondary prophylaxis until immune recovery: TMP-SMX until CD4 > 200 × 3 mo + VL suppressed (PCP); fluconazole 200 mg/d until CD4 > 200 × 6 mo + VL suppressed (cryptococcal); valganciclovir maintenance until CD4 > 100 × 3-6 mo (CMV); MAC continuation ≥ 12 mo + CD4 > 100 × 6 mo; lifelong surveillance for transplant recipients; vaccinations per ACIP (DHHS 2024 OI; AST IDCOP 2024; ACIP 2024)
    advance: long-term secondary prophylaxis + surveillance plan documented