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pres.title = "Opportunistic Infections in HIV/AIDS";
pres.author = "Medical Education";

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// ─── HELPERS ─────────────────────────────────────────────────────
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// ═══════════════════════════════════════════════════════════════
// SLIDE 1 — Title
// ═══════════════════════════════════════════════════════════════
titleSlide(pres);

// ═══════════════════════════════════════════════════════════════
// SLIDE 2 — Overview / Learning Objectives
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "Learning Objectives", [
  "Define opportunistic infection (OI) and explain why HIV/AIDS patients are susceptible",
  "Describe the CD4 count thresholds at which specific OIs occur",
  "Classify major OIs by pathogen type: fungal, protozoal, bacterial, viral",
  "Identify clinical features, diagnosis and treatment of key OIs",
  "Understand primary and secondary prophylaxis strategies",
  "Recognize AIDS-defining conditions per CDC staging criteria"
], { accentColor: GOLD });

// ═══════════════════════════════════════════════════════════════
// SLIDE 3 — What is an Opportunistic Infection?
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "What Are Opportunistic Infections?", [
  "Infections caused by low-virulence organisms that do NOT cause significant disease in immunocompetent individuals",
  "They arise from reactivation of latent infections OR environmental microbes that healthy immunity keeps in check",
  "HIV destroys CD4+ T lymphocytes → progressive immunosuppression → OI susceptibility",
  "AIDS is defined (CDC Stage C/Stage 3) when CD4 <200 cells/µL OR an AIDS-defining OI/malignancy is diagnosed",
  "OIs account for most deaths in untreated HIV-infected patients",
  "Antiretroviral therapy (ART) has dramatically reduced OI incidence — but OIs still occur with late or failed ART",
  "Frequency and pattern of OIs varies by region (TB dominant in Sub-Saharan Africa; PCP historically common in the US)"
], { accentColor: ACCENT });

// ═══════════════════════════════════════════════════════════════
// SLIDE 4 — CD4 Count & OI Threshold (Section Divider)
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "01", "CD4 Count & OI Risk", "When the immune system fails, pathogens strike");

// ═══════════════════════════════════════════════════════════════
// SLIDE 5 — CD4 Count Thresholds Table
// ═══════════════════════════════════════════════════════════════
tableSlide(pres,
  "CD4 Count Thresholds for Key Opportunistic Infections",
  ["CD4 Count (cells/µL)", "Opportunistic Infection / Condition"],
  [
    ["> 500", "Acute retroviral syndrome, early constitutional symptoms"],
    ["200 – 500", "Oral candidiasis (thrush), Herpes zoster, Bacterial pneumonia, TB reactivation"],
    ["100 – 200", "Pneumocystis jirovecii pneumonia (PCP), Toxoplasma encephalitis (if seroneg.)"],
    ["50 – 100", "Cerebral toxoplasmosis, Cryptococcal meningitis, Progressive multifocal leukoencephalopathy (PML)"],
    ["< 50", "CMV retinitis/colitis, Disseminated MAC (M. avium complex), Disseminated histoplasmosis/coccidioidomycosis"],
  ],
  GOLD
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 6 — SECTION: Fungal Infections
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "02", "Fungal Opportunistic Infections", "Candida • Pneumocystis • Cryptococcus • Histoplasma • Coccidioides");

// ═══════════════════════════════════════════════════════════════
// SLIDE 7 — Candidiasis
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Candidiasis in HIV/AIDS",
  "Clinical Features",
  [
    "Most common fungal OI in AIDS",
    "Oral thrush: white plaques on buccal mucosa — often first sign of decompensation",
    "Esophageal candidiasis: dysphagia, odynophagia — AIDS-defining",
    "Vaginal candidiasis: recurrent in HIV+ women",
    "Invasive/disseminated candidiasis: rare, linked to neutropenia or catheters"
  ],
  "Diagnosis & Treatment",
  [
    "Dx: clinical ± KOH scraping (pseudohyphae)",
    "Esophageal: endoscopy + biopsy",
    "Oropharyngeal: fluconazole 100–200 mg/day × 7–14 days",
    "Esophageal: fluconazole 200–400 mg/day × 14–21 days",
    "Resistant: itraconazole, voriconazole, or echinocandin",
    "ART is key to long-term control"
  ],
  GOLD
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 8 — Pneumocystis jirovecii Pneumonia (PCP)
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Pneumocystis jirovecii Pneumonia (PCP)",
  "Pathology & Features",
  [
    "Formerly Pneumocystis carinii — reclassified to jirovecii in humans",
    "Occurs in 15–30% of untreated HIV+ patients (reactivation of latent fungus)",
    "Risk: CD4 <200 cells/µL",
    "Symptoms: fever, dry cough, progressive dyspnoea, hypoxia",
    "CXR: bilateral interstitial/perihilar infiltrates ('ground-glass')",
    "LDH elevated; O2 desaturation on exertion (classic)"
  ],
  "Diagnosis & Treatment",
  [
    "BAL/induced sputum: Gomori methenamine silver stain — cysts",
    "PCR: highly sensitive",
    "First-line: TMP-SMX (co-trimoxazole) × 21 days",
    "If PaO2 <70 mmHg: add corticosteroids (prednisone) to reduce inflammation",
    "Alternatives: pentamidine, dapsone + trimethoprim, atovaquone",
    "Prophylaxis: TMP-SMX 1 SS tablet daily when CD4 <200"
  ],
  ACCENT
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 9 — Cryptococcal Meningitis
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Cryptococcal Meningitis (Cryptococcus neoformans)",
  "Pathology & Features",
  [
    "Most common life-threatening meningitis in AIDS",
    "CD4 typically <100 cells/µL",
    "Subacute/chronic meningitis: headache, fever, malaise",
    "Classic: 'soap bubble' lesions in basal ganglia on MRI",
    "India ink stain of CSF: encapsulated yeast cells",
    "Raised intracranial pressure common — papilledema, altered mentation"
  ],
  "Diagnosis & Treatment",
  [
    "CSF: India ink stain; cryptococcal antigen (CrAg) — highly sensitive",
    "Serum CrAg useful for screening in endemic areas",
    "Induction: IV amphotericin B + oral flucytosine × 2 weeks",
    "Consolidation: fluconazole 400 mg/day × 8 weeks",
    "Maintenance: fluconazole 200 mg/day (until CD4 >200 on ART)",
    "Serial LPs to manage elevated ICP"
  ],
  ORANGE
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 10 — Histoplasma & Coccidioides
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "Disseminated Histoplasmosis & Coccidioidomycosis", [
  "## Histoplasma capsulatum",
  "Endemic: Mississippi/Ohio river valleys (US), Latin America, Sub-Saharan Africa",
  "CD4 <50: disseminated disease — fever, weight loss, hepatosplenomegaly, pancytopenia",
  "Dx: urine/serum antigen; cultures; Giemsa-stained bone marrow",
  "Rx: IV amphotericin B (induction) → itraconazole (maintenance)",
  "## Coccidioides immitis",
  "Endemic: US Southwest, Central/South America",
  "Disseminated: meningitis, skin lesions, arthritis",
  "Dx: serology (complement fixation); culture",
  "Rx: fluconazole (mild-moderate); amphotericin B (severe); lifelong suppression if meningeal"
], { accentColor: ORANGE });

// ═══════════════════════════════════════════════════════════════
// SLIDE 11 — SECTION: Protozoal Infections
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "03", "Protozoal Opportunistic Infections", "Toxoplasma • Cryptosporidium • Cystoisospora • Microspora");

// ═══════════════════════════════════════════════════════════════
// SLIDE 12 — Cerebral Toxoplasmosis
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Cerebral Toxoplasmosis (Toxoplasma gondii)",
  "Pathology & Features",
  [
    "Most common cause of focal CNS lesion in AIDS patients",
    "CD4 <100 cells/µL; results from reactivation of latent cysts",
    "Headache, focal neurological deficits, seizures, confusion",
    "CT/MRI: multiple ring-enhancing lesions with surrounding edema",
    "Usually bilateral, basal ganglia predominance",
    "Can mimic CNS lymphoma (single lesion more common in lymphoma)"
  ],
  "Diagnosis & Treatment",
  [
    "Dx: positive IgG serology + characteristic MRI + empiric response to treatment",
    "If no improvement in 10–14 days → biopsy to exclude lymphoma",
    "CSF PCR (if LP safe): moderate sensitivity",
    "First-line: pyrimethamine + sulfadiazine + leucovorin × 6 weeks",
    "Alternative: TMP-SMX (similar efficacy)",
    "Prophylaxis: TMP-SMX when CD4 <100 + positive Toxo IgG"
  ],
  ACCENT
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 13 — Cryptosporidium & Cystoisospora
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Intestinal Protozoal Infections in HIV",
  "Cryptosporidiosis",
  [
    "Cryptosporidium parvum — waterborne coccidian parasite",
    "CD4 <100: profuse, watery diarrhoea ('cholera-like')",
    "Can cause biliary disease: sclerosing cholangitis",
    "Dx: modified acid-fast stain of stool; stool antigen",
    "Rx: no curative agent — ART is cornerstone; nitazoxanide (partial)",
    "Supportive: fluid/electrolyte replacement"
  ],
  "Cystoisospora (formerly Isospora)",
  [
    "Cystoisospora belli — fecal-oral transmission",
    "Profuse, non-bloody watery diarrhoea; malabsorption",
    "Dx: modified acid-fast stain — large oocysts in stool",
    "Rx: TMP-SMX (highly effective)",
    "Secondary prophylaxis: TMP-SMX 3x/week until CD4 >200",
    "Eosinophilia sometimes present (distinguishes from Crypto)"
  ],
  GREEN
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 14 — SECTION: Bacterial Infections
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "04", "Bacterial Opportunistic Infections", "Mycobacteria • Nocardia • Salmonella");

// ═══════════════════════════════════════════════════════════════
// SLIDE 15 — Tuberculosis in HIV
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Tuberculosis (MTB) in HIV/AIDS",
  "Epidemiology & Features",
  [
    "Leading cause of death among AIDS patients worldwide (>1/3 of all AIDS deaths)",
    "Can occur at ANY CD4 count — most common OI in resource-poor settings",
    "Higher CD4: typical pulmonary TB (upper lobe cavitation)",
    "Lower CD4: atypical/extrapulmonary TB — miliary, lymphadenitis, CNS",
    "HIV+ patients may be TST-negative despite active TB (anergy)",
    "Immune Reconstitution Inflammatory Syndrome (IRIS) common with ART initiation"
  ],
  "Diagnosis & Treatment",
  [
    "Dx: AFB smear/culture; Xpert MTB/RIF (rapid PCR)",
    "CXR: lower lobe, hilar lymphadenopathy, miliary pattern in advanced HIV",
    "Standard 4-drug regimen: HRZE × 2 months → HR × 4 months",
    "ART: start after 2–8 weeks of TB treatment (CD4 <50 start earlier)",
    "Beware rifampin-ART drug interactions (use rifabutin if on PIs)",
    "IGRA preferred over TST in HIV+ for latent TB screening"
  ],
  GOLD
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 16 — MAC (Mycobacterium avium complex)
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Disseminated MAC (Mycobacterium avium Complex)",
  "Pathology & Features",
  [
    "Occurs at very low CD4: <50 cells/µL",
    "Ubiquitous environmental organism (water, soil, food)",
    "Disseminated: fever, night sweats, weight loss, diarrhoea",
    "Hepatosplenomegaly, lymphadenopathy, cytopenias",
    "Lab: elevated alkaline phosphatase; pancytopenia (bone marrow involvement)",
    "Chest X-ray often normal"
  ],
  "Diagnosis & Treatment",
  [
    "Dx: blood cultures (mycobacterial) — highest yield; bone marrow biopsy",
    "AFB stain/culture of stool, liver, lymph nodes",
    "Treatment: clarithromycin + ethambutol (±rifabutin) — lifelong unless CD4 recovers",
    "Never give monotherapy (rapid resistance emerges)",
    "Prophylaxis: azithromycin 1200 mg/week when CD4 <50",
    "Stop prophylaxis when CD4 >100 for >3 months on ART"
  ],
  ORANGE
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 17 — SECTION: Viral Infections
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "05", "Viral Opportunistic Infections", "CMV • HSV • VZV • JC Virus (PML)");

// ═══════════════════════════════════════════════════════════════
// SLIDE 18 — CMV Disease
// ═══════════════════════════════════════════════════════════════
twoColSlide(pres,
  "Cytomegalovirus (CMV) Disease",
  "Clinical Manifestations",
  [
    "CMV retinitis: most common presentation; CD4 <50",
    "Floaters, visual field defects, photophobia → blindness if untreated",
    "Fundoscopy: 'pizza pie' appearance (hemorrhages + exudates)",
    "GI disease (5–10%): esophagitis, colitis — mucosal ulcerations, bleeding",
    "CMV encephalitis: rare; altered consciousness, cranial nerve palsies",
    "Pneumonitis: less common in AIDS (vs. transplant patients)"
  ],
  "Diagnosis & Treatment",
  [
    "Dx: PCR (blood/CSF); tissue biopsy — 'owl-eye' intranuclear inclusions",
    "Retinitis: ophthalmologic exam",
    "IV ganciclovir (induction) → oral valganciclovir (maintenance)",
    "Alternatives: foscarnet (nephrotoxic), cidofovir",
    "Intravitreal ganciclovir implant for retinitis",
    "ART: most important intervention to raise CD4 and prevent relapse"
  ],
  ACCENT
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 19 — HSV, VZV, PML
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "HSV, VZV & Progressive Multifocal Leukoencephalopathy (PML)", [
  "## Herpes Simplex Virus (HSV-1/2)",
  "Severe, chronic, ulcerating genital/perianal lesions; esophagitis; encephalitis in advanced AIDS",
  "Dx: PCR (CSF or swab); viral culture; Tzanck smear (non-specific)",
  "Rx: acyclovir / valacyclovir / famciclovir; IV acyclovir for severe/neurological disease",
  "## Varicella-Zoster Virus (VZV)",
  "Dermatomal zoster; multidermatomal or disseminated zoster in HIV",
  "Rx: high-dose acyclovir or valacyclovir; IV acyclovir if disseminated",
  "## PML — JC Virus (Polyomavirus)",
  "Demyelinating disease of CNS; CD4 <100; no direct antiviral treatment exists",
  "Asymmetric neurological deficits: weakness, ataxia, cognitive decline, visual loss",
  "MRI: white matter lesions (non-enhancing) — periventricular/subcortical",
  "Dx: CSF JC virus PCR; brain biopsy (if needed)",
  "Rx: ART alone — immune reconstitution is the only treatment; IRIS can occur"
], { accentColor: GOLD });

// ═══════════════════════════════════════════════════════════════
// SLIDE 20 — AIDS-Associated Malignancies
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "06", "AIDS-Defining Malignancies", "Kaposi Sarcoma • CNS Lymphoma • Invasive Cervical Cancer");

// ═══════════════════════════════════════════════════════════════
// SLIDE 21 — Malignancies detail
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "AIDS-Defining Malignancies", [
  "## Kaposi Sarcoma (KS) — HHV-8",
  "Violaceous skin/mucosal nodules; visceral KS in GI tract and lungs possible",
  "Dx: clinical + biopsy; CD4 any level (but more common <200)",
  "Rx: ART (first-line for mild cutaneous); chemotherapy (liposomal doxorubicin) for advanced disease",
  "## Primary CNS Lymphoma (PCNSL)",
  "B-cell lymphoma associated with EBV; CD4 <50",
  "Solitary ring-enhancing lesion (vs. multiple in toxoplasmosis) — key differentiator",
  "MRI + CSF EBV PCR + SPECT/PET; brain biopsy if needed",
  "Rx: high-dose methotrexate + whole-brain radiation; ART; poor prognosis",
  "## Invasive Cervical Cancer — HPV",
  "HPV more aggressive in immunocompromised; CD4 any level",
  "Regular Pap smears every 6–12 months for HIV+ women",
  "Rx: standard oncologic treatment + ART"
], { accentColor: ACCENT });

// ═══════════════════════════════════════════════════════════════
// SLIDE 22 — Prophylaxis Summary Table
// ═══════════════════════════════════════════════════════════════
sectionDivider(pres, "07", "OI Prophylaxis", "Primary & Secondary Prevention Strategies");

tableSlide(pres,
  "Opportunistic Infection Prophylaxis Summary",
  ["OI", "Indication", "Primary Prophylaxis", "Secondary Prophylaxis"],
  [
    ["PCP", "CD4 <200 or oral candidiasis", "TMP-SMX 1 SS tab daily", "TMP-SMX; stop when CD4 >200 × 3 mo"],
    ["Toxoplasmosis", "CD4 <100 + IgG+", "TMP-SMX 1 DS tab daily", "Pyrimethamine + sulfadiazine + leucovorin"],
    ["MAC", "CD4 <50", "Azithromycin 1200 mg/wk", "Clarithromycin + ethambutol (lifelong unless CD4 >100)"],
    ["Cryptococcus", "CD4 <100 (endemic areas)", "Fluconazole 100–200 mg/day", "Fluconazole 200 mg/day; stop CD4 >200 × 6 mo"],
    ["CMV", "CD4 <50 + prior CMV", "Not routinely recommended", "Valganciclovir; stop when CD4 >100–150 × 6 mo"],
    ["TB (latent)", "TST/IGRA positive", "INH 300 mg/day × 9 months + B6", "Full 4-drug treatment if active disease"],
  ],
  GREEN
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 23 — IRIS
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "Immune Reconstitution Inflammatory Syndrome (IRIS)", [
  "Paradoxical worsening of an existing or 'unmasking' of a subclinical OI after starting ART",
  "Occurs when CD4 count rapidly rises → restored immune response attacks pathogen antigens",
  "Typically within 4–8 weeks of ART initiation",
  "## Common IRIS-associated OIs",
  "TB-IRIS (most common globally): fever, lymphadenopathy, worsening pulmonary infiltrates",
  "Cryptococcal IRIS: raised ICP, worsening meningitis symptoms",
  "CMV IRIS: vitritis, retinal detachment despite virologic control",
  "MAC IRIS: lymphadenopathy, fever",
  "## Management",
  "Continue ART — do NOT stop (unless life-threatening)",
  "Treat the underlying OI appropriately",
  "Corticosteroids (prednisone) for moderate-severe TB or cryptococcal IRIS",
  "Therapeutic LPs for elevated ICP in cryptococcal IRIS"
], { accentColor: ORANGE });

// ═══════════════════════════════════════════════════════════════
// SLIDE 24 — ART & OI Prevention
// ═══════════════════════════════════════════════════════════════
contentSlide(pres, "Role of Antiretroviral Therapy (ART) in OI Prevention", [
  "ART is the single most important intervention to prevent and treat OIs in HIV",
  "Suppresses viral replication → CD4 count recovery → immune reconstitution",
  "Guidelines recommend ART for ALL HIV-infected individuals regardless of CD4 count",
  "When OI is diagnosed simultaneously with new HIV dx: start OI treatment first, then ART within 2 weeks",
  "Exception: TB meningitis and PML — delay ART 4–8 weeks to avoid severe IRIS",
  "Prophylaxis can be discontinued once CD4 count is sustained above threshold on ART",
  "## Key ART classes used",
  "NRTIs (tenofovir, emtricitabine) + INSTI (dolutegravir/bictegravir) — preferred backbone",
  "Drug interactions: rifampin ↓ PI/NNRTI levels (use rifabutin); TMP-SMX + dapsone — avoid co-trimoxazole if on dapsone"
], { accentColor: GREEN });

// ═══════════════════════════════════════════════════════════════
// SLIDE 25 — Quick Reference Summary Table
// ═══════════════════════════════════════════════════════════════
tableSlide(pres,
  "Quick Reference: Major OIs in HIV/AIDS",
  ["Infection", "Pathogen", "CD4 Threshold", "Key Feature", "Treatment"],
  [
    ["PCP", "Pneumocystis jirovecii", "<200", "Bilateral ground-glass infiltrates, LDH↑", "TMP-SMX × 21 days"],
    ["Toxoplasmosis", "Toxoplasma gondii", "<100", "Ring-enhancing CNS lesions", "Pyrimethamine + sulfadiazine"],
    ["Cryptococcosis", "Cryptococcus neoformans", "<100", "Meningitis, India ink (+)", "Ampho B + flucytosine → fluconazole"],
    ["CMV Retinitis", "Cytomegalovirus", "<50", "'Pizza pie' fundus", "Valganciclovir"],
    ["MAC", "M. avium complex", "<50", "Fever, wasting, ↑ALP", "Clarithromycin + ethambutol"],
    ["TB", "M. tuberculosis", "Any", "AFB smear, Xpert+, IGRA+", "HRZE × 2m + HR × 4m"],
    ["Oral Candidiasis", "Candida albicans", "<200", "White plaques, thrush", "Fluconazole"],
    ["PML", "JC virus", "<100", "White matter lesions (MRI)", "ART only"],
    ["Histoplasmosis", "Histoplasma capsulatum", "<50", "Urine antigen (+)", "Ampho B → itraconazole"],
    ["Kaposi Sarcoma", "HHV-8", "Any", "Violaceous skin lesions", "ART ± chemotherapy"],
  ],
  ACCENT
);

// ═══════════════════════════════════════════════════════════════
// SLIDE 26 — Conclusion
// ═══════════════════════════════════════════════════════════════
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    "OIs are the hallmark of advanced HIV/AIDS and occur when CD4 counts fall below critical thresholds",
    "PCP (CD4 <200), Toxoplasmosis (CD4 <100), CMV & MAC (CD4 <50) are the sentinel thresholds",
    "TB is the leading cause of AIDS-related mortality globally and can occur at ANY CD4 count",
    "ART is the cornerstone of prevention — it restores immunity and prevents new OIs",
    "TMP-SMX provides dual prophylaxis against PCP and Toxoplasmosis",
    "IRIS must be anticipated when starting ART in the setting of active OI — especially TB",
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