Pleural Effusion - Pura Mechanism aur Treatment

mkdir -p /home/daytona/workspace/tb-assignment && ls /home/daytona/workspace/

~/tb-assignment/generate_tb_pdf.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import ListFlowable, ListItem

OUTPUT = "/home/daytona/workspace/tb-assignment/Tuberculosis_Assignment.pdf"

# ── Page layout ──────────────────────────────────────────────────────────────
doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=2.5*cm, rightMargin=2.5*cm,
    topMargin=2.5*cm, bottomMargin=2.5*cm,
    title="Tuberculosis – A Comprehensive Medical Assignment",
    author="MBBS Student"
)

W = A4[0] - 5*cm   # usable width

# ── Colour palette ────────────────────────────────────────────────────────────
MAROON   = colors.HexColor("#7B0000")
DARK_RED = colors.HexColor("#A30000")
LIGHT_BG = colors.HexColor("#FFF8F8")
HEADER_BG= colors.HexColor("#7B0000")
ROW_ALT  = colors.HexColor("#FDE8E8")
WHITE    = colors.white
GREY     = colors.HexColor("#555555")
BORDER   = colors.HexColor("#C0392B")

# ── Styles ────────────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

title_style = ParagraphStyle(
    "Title", parent=base["Title"],
    fontSize=22, textColor=MAROON, leading=28,
    alignment=TA_CENTER, spaceAfter=4
)
subtitle_style = ParagraphStyle(
    "Subtitle", parent=base["Normal"],
    fontSize=12, textColor=GREY, alignment=TA_CENTER, spaceAfter=2
)
meta_style = ParagraphStyle(
    "Meta", parent=base["Normal"],
    fontSize=10, textColor=GREY, alignment=TA_CENTER, spaceAfter=6
)
h1 = ParagraphStyle(
    "H1", parent=base["Heading1"],
    fontSize=15, textColor=WHITE, leading=20,
    backColor=HEADER_BG, borderPadding=(5, 8, 5, 8),
    spaceAfter=8, spaceBefore=14
)
h2 = ParagraphStyle(
    "H2", parent=base["Heading2"],
    fontSize=12, textColor=DARK_RED, leading=16,
    spaceAfter=4, spaceBefore=10, borderPadding=(0,0,2,0),
    underlineProportion=0
)
h3 = ParagraphStyle(
    "H3", parent=base["Heading3"],
    fontSize=11, textColor=MAROON, leading=14,
    spaceAfter=3, spaceBefore=7, fontName="Helvetica-BoldOblique"
)
body = ParagraphStyle(
    "Body", parent=base["Normal"],
    fontSize=10, leading=15, textColor=colors.black,
    alignment=TA_JUSTIFY, spaceAfter=5
)
bullet = ParagraphStyle(
    "Bullet", parent=base["Normal"],
    fontSize=10, leading=14, leftIndent=16,
    bulletIndent=4, spaceAfter=3, textColor=colors.black
)
table_header_style = ParagraphStyle(
    "TH", parent=base["Normal"],
    fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", leading=12
)
table_cell_style = ParagraphStyle(
    "TC", parent=base["Normal"],
    fontSize=9, textColor=colors.black, leading=12
)
ref_style = ParagraphStyle(
    "Ref", parent=base["Normal"],
    fontSize=9, textColor=GREY, leading=13, leftIndent=12,
    spaceAfter=2
)

def B(text): return f"<b>{text}</b>"
def I(text): return f"<i>{text}</i>"
def BI(text): return f"<b><i>{text}</i></b>"

def h1p(text):
    return Paragraph(f"  {text}", h1)

def h2p(text):
    return Paragraph(text, h2)

def h3p(text):
    return Paragraph(text, h3)

def bp(text):
    return Paragraph(text, body)

def bull(items):
    return [Paragraph(f"• &nbsp; {i}", bullet) for i in items]

def make_table(headers, rows, col_widths=None):
    data = [[Paragraph(h, table_header_style) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), table_cell_style) for c in row])
    if col_widths is None:
        col_widths = [W / len(headers)] * len(headers)
    style = TableStyle([
        ("BACKGROUND",  (0,0), (-1,0),  HEADER_BG),
        ("TEXTCOLOR",   (0,0), (-1,0),  WHITE),
        ("FONTNAME",    (0,0), (-1,0),  "Helvetica-Bold"),
        ("FONTSIZE",    (0,0), (-1,-1), 9),
        ("ROWBACKGROUNDS", (0,1), (-1,-1), [WHITE, ROW_ALT]),
        ("GRID",        (0,0), (-1,-1), 0.4, BORDER),
        ("VALIGN",      (0,0), (-1,-1), "TOP"),
        ("TOPPADDING",  (0,0), (-1,-1), 4),
        ("BOTTOMPADDING",(0,0),(-1,-1), 4),
        ("LEFTPADDING", (0,0), (-1,-1), 5),
        ("RIGHTPADDING",(0,0), (-1,-1), 5),
    ])
    return Table(data, colWidths=col_widths, style=style, hAlign="LEFT",
                 repeatRows=1)

def hr():
    return HRFlowable(width="100%", thickness=0.8, color=BORDER, spaceAfter=6, spaceBefore=6)

# ═══════════════════════════════════════════════════════════════════════════════
# BUILD CONTENT
# ═══════════════════════════════════════════════════════════════════════════════
story = []

# ── COVER PAGE ─────────────────────────────────────────────────────────────────
story.append(Spacer(1, 1.5*cm))
story.append(Paragraph("TUBERCULOSIS", title_style))
story.append(Paragraph("A Comprehensive Medical Assignment", subtitle_style))
story.append(hr())
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph("Course: MBBS | Subject: Respiratory Medicine / Community Medicine", meta_style))
story.append(Paragraph("Date of Submission: July 2026", meta_style))
story.append(Spacer(1, 0.5*cm))

# Cover box
cover_data = [
    [Paragraph(B("Topic"), table_header_style), Paragraph("Tuberculosis (TB)", table_cell_style)],
    [Paragraph(B("Subject Area"), table_header_style), Paragraph("Pulmonary Medicine, Microbiology, Pharmacology, Community Medicine", table_cell_style)],
    [Paragraph(B("Pathogen"), table_header_style), Paragraph(BI("Mycobacterium tuberculosis") + " (Robert Koch, 1882)", table_cell_style)],
    [Paragraph(B("Global Burden"), table_header_style), Paragraph("~10.6 million new cases/year; 2nd leading infectious disease killer (after HIV)", table_cell_style)],
    [Paragraph(B("India's Burden"), table_header_style), Paragraph("~26% of global TB burden; highest case load worldwide", table_cell_style)],
]
cover_table = Table(cover_data, colWidths=[5*cm, W-5*cm],
                    style=TableStyle([
                        ("BACKGROUND",  (0,0), (0,-1), MAROON),
                        ("TEXTCOLOR",   (0,0), (0,-1), WHITE),
                        ("BACKGROUND",  (1,0), (1,-1), LIGHT_BG),
                        ("GRID",        (0,0), (-1,-1), 0.5, BORDER),
                        ("VALIGN",      (0,0), (-1,-1), "MIDDLE"),
                        ("TOPPADDING",  (0,0), (-1,-1), 6),
                        ("BOTTOMPADDING",(0,0),(-1,-1), 6),
                        ("LEFTPADDING", (0,0), (-1,-1), 8),
                    ]))
story.append(cover_table)
story.append(Spacer(1, 0.5*cm))
story.append(PageBreak())

# ── TABLE OF CONTENTS ─────────────────────────────────────────────────────────
story.append(h1p("TABLE OF CONTENTS"))
toc_items = [
    ("1.", "Introduction & Definition"),
    ("2.", "Epidemiology"),
    ("3.", "Etiology & Microbiology"),
    ("4.", "Classification of Tuberculosis"),
    ("5.", "Pathogenesis"),
    ("6.", "Clinical Features"),
    ("7.", "Investigations & Diagnosis"),
    ("8.", "Treatment"),
    ("9.", "Drug-Resistant Tuberculosis (MDR-TB / XDR-TB)"),
    ("10.", "Complications"),
    ("11.", "Prevention & Control (BCG, DOTS, RNTCP/NSP)"),
    ("12.", "Tuberculosis in Special Situations"),
    ("13.", "References"),
]
for num, topic in toc_items:
    story.append(Paragraph(f"{num}&nbsp;&nbsp;&nbsp;{topic}", body))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 1. INTRODUCTION
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("1. INTRODUCTION & DEFINITION"))
story.append(bp(
    "Tuberculosis (TB) is a chronic infectious disease caused by the acid-fast bacillus "
    + BI("Mycobacterium tuberculosis") +
    ". It primarily affects the lungs (pulmonary TB) but can involve virtually any organ system "
    "(extrapulmonary TB). The disease has plagued humanity for millennia — "
    "skeletal evidence of spinal TB has been found in Egyptian mummies. "
    "Robert Koch identified the causative organism in 1882, earning him the Nobel Prize."
))
story.append(bp(
    "Despite the availability of effective chemotherapy for over 70 years, TB remains one of the "
    "world's most devastating infectious diseases. The WHO Global TB Report estimates approximately "
    B("10.6 million new cases") + " and " + B("1.6 million deaths") +
    " annually. India bears the single largest national burden — approximately "
    B("26% of global incidence") + "."
))
story.append(Spacer(1, 0.3*cm))

# ─────────────────────────────────────────────────────────────────────────────
# 2. EPIDEMIOLOGY
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("2. EPIDEMIOLOGY"))
story.append(h2p("2.1 Global Burden"))
story += bull([
    "Approximately 10.6 million people developed TB in 2022.",
    "TB is the 2nd leading cause of death from a single infectious agent (after HIV/AIDS).",
    "Eight countries account for two-thirds of cases: India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.",
    "HIV co-infection dramatically increases TB risk: HIV+ individuals are 18× more likely to develop active TB.",
    "Drug-resistant TB (MDR-TB, XDR-TB) constitutes a growing global emergency.",
])
story.append(h2p("2.2 Epidemiology in India"))
story += bull([
    "India has the highest TB burden globally (~26% of world cases).",
    "Estimated 2.69 million incident cases per year (2022 data).",
    "Mortality: ~4.94 lakh deaths per year.",
    "High-risk groups: malnourished, HIV-positive, diabetics, prisoners, migrants, healthcare workers.",
    "Nikshay Poshan Yojana provides financial support to TB patients in India.",
])
story.append(h2p("2.3 Mode of Transmission"))
story.append(bp(
    "TB is transmitted via " + B("airborne droplet nuclei") + " (1–5 μm diameter) generated when "
    "infectious persons cough, sneeze, talk, or sing. These tiny particles can remain suspended "
    "in the air for hours. A single cough may generate ~3,000 droplet nuclei. "
    + B("Close indoor contact") + " with a smear-positive case is the major risk factor. "
    "Transmission via fomites, skin contact, or the GI tract (e.g., " + BI("M. bovis") + " via "
    "unpasteurized milk) is possible but uncommon."
))
story.append(Spacer(1, 0.3*cm))

# ─────────────────────────────────────────────────────────────────────────────
# 3. ETIOLOGY & MICROBIOLOGY
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("3. ETIOLOGY & MICROBIOLOGY"))
story.append(h2p("3.1 The Organism"))
story.append(bp(
    BI("Mycobacterium tuberculosis") + " belongs to the " + B("Mycobacterium tuberculosis complex (MTBC)") +
    ", which also includes " + BI("M. africanum, M. bovis, M. microti") + ", and " + BI("M. canettii") + ". "
    "Humans are the " + B("only significant reservoir") + " of " + BI("M. tuberculosis") + "."
))
story += bull([
    B("Morphology:") + " Slender, slightly curved, non-motile, non-spore-forming rod, 1–4 μm long.",
    B("Staining:") + " Acid-fast bacillus (AFB) — retains carbol fuchsin after acid-alcohol decolorization (Ziehl-Neelsen stain). Gram-positive but poorly Gram-stained.",
    B("Culture:") + " Grows on Lowenstein-Jensen (LJ) medium; forms rough, buff-coloured colonies in 3–8 weeks. Very slow growth (doubling time ~15–20 hours).",
    B("Cell wall:") + " Rich in mycolic acids (unique long-chain fatty acids, C70–C90), arabinogalactan, and peptidoglycan — responsible for acid-fastness, resistance to many antibiotics, and immune evasion.",
    B("Genome:") + " ~4.4 million bp, GC-rich (65.6%). Encodes type VII secretion systems (ESX-1 to ESX-5) crucial for virulence.",
    B("Virulence factors:") + " ESAT-6 (pore-forming, facilitates phagosomal escape), cord factor (trehalose-6,6'-dimycolate), sulfatides (inhibit phagolysosome fusion), LAM (lipoarabinomannan — immunomodulatory).",
])
story.append(Spacer(1, 0.3*cm))

# ─────────────────────────────────────────────────────────────────────────────
# 4. CLASSIFICATION
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("4. CLASSIFICATION OF TUBERCULOSIS"))
story.append(h2p("4.1 By Anatomical Site"))
class_data = [
    ["Type", "Description", "Frequency"],
    ["Pulmonary TB", "Lungs ± tracheobronchial tree", "~80–85% of cases"],
    ["Extrapulmonary TB", "Any organ outside the lungs", "~10–20% of cases"],
    ["Disseminated (Miliary) TB", "Haematogenous spread; multiple organs", "Immunocompromised/children"],
]
story.append(make_table(class_data[0], class_data[1:], [5*cm, 8*cm, 4.5*cm]))
story.append(Spacer(1, 0.2*cm))
story.append(bp("Common extrapulmonary sites include:"))
story += bull([
    "Pleura (Tuberculous pleurisy)",
    "Lymph nodes (Scrofula — commonest extrapulmonary in developing countries)",
    "Meninges (TB meningitis — most dangerous)",
    "Bone and joint (Pott's disease — vertebral TB)",
    "Genitourinary tract (Renal TB)",
    "Pericardium, peritoneum, adrenal glands",
])
story.append(h2p("4.2 By Disease Status"))
status_data = [
    ["Category", "Definition", "Infectivity"],
    ["Latent TB Infection (LTBI)", "Positive TST/IGRA; no symptoms; normal CXR; bacteria alive but inactive", "NOT infectious"],
    ["Active (Primary) TB", "First infection with TB; symptomatic disease", "Infectious if pulmonary"],
    ["Reactivation (Post-primary) TB", "Reactivation of old infection (typically upper lobes, cavitary)", "Highly infectious"],
]
story.append(make_table(status_data[0], status_data[1:], [4*cm, 8*cm, 4.5*cm]))
story.append(h2p("4.3 WHO/Rntcp Classification (by treatment history)"))
who_data = [
    ["Category", "Definition"],
    ["New", "Never treated for TB or treated for <1 month"],
    ["Relapse", "Previously treated, declared cured/treatment completed; now bacteriologically confirmed"],
    ["Treatment after failure", "Previously treated with outcome of failure"],
    ["Treatment after loss to follow-up", "Previously treated; was lost to follow-up"],
    ["Transferred in", "Transferred from another TB register"],
    ["Other previously treated", "Other previously treated with unknown history"],
]
story.append(make_table(who_data[0], who_data[1:], [5*cm, W-5*cm]))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 5. PATHOGENESIS
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("5. PATHOGENESIS"))
story.append(h2p("5.1 Stages of Infection"))
story.append(bp(
    "The pathogenesis of TB follows a well-defined sequence after inhalation of droplet nuclei "
    "containing " + BI("M. tuberculosis") + ":"
))

story.append(h3p("Stage 1 — Inhalation and Alveolar Deposition"))
story.append(bp(
    "Droplet nuclei (1–5 μm) containing 1–3 bacilli bypass upper airway defenses and reach the "
    "alveoli, typically in the " + B("lower lobes") + " (better ventilation). Here they are "
    "phagocytosed by " + B("alveolar macrophages") + "."
))

story.append(h3p("Stage 2 — Intracellular Survival and Early Spread"))
story.append(bp(
    BI("M. tuberculosis") + " is an " + B("intracellular pathogen") + " that has evolved "
    "sophisticated mechanisms to survive inside macrophages:"
))
story += bull([
    B("Phagosome arrest:") + " ESX-3 secretes EsxH which impedes phagosome maturation and MHC II antigen presentation.",
    B("Phagolysosome fusion inhibition:") + " Sulfatides and LAM prevent acidification and fusion with lysosomes.",
    B("Escape to cytosol:") + " ESAT-6 perforates the phagosomal membrane, facilitating cytosolic access.",
    B("Cord factor:") + " Trehalose-6,6'-dimycolate inhibits leukocyte migration and induces granuloma formation.",
])
story.append(bp(
    "Infected macrophages spread bacilli through lymphatics to the " + B("hilar lymph nodes") +
    ". The initial lung focus + enlarged hilar lymph node = " + B("Ghon's complex") +
    " (Ghon's focus + lymph node involvement = Ranke complex)."
))

story.append(h3p("Stage 3 — Innate Immune Response"))
story.append(bp(
    "Within days, " + B("neutrophils") + " and " + B("natural killer (NK) cells") +
    " are recruited. Macrophages release pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-12). "
    "TNF-α is critical for granuloma formation. "
    "IFN-γ activates macrophages to kill intracellular mycobacteria via reactive oxygen species (ROS) "
    "and reactive nitrogen intermediates (RNI, including nitric oxide)."
))

story.append(h3p("Stage 4 — Adaptive Immunity and Granuloma Formation"))
story.append(bp(
    "2–8 weeks after infection, " + B("T-cell–mediated immunity (CMI)") + " develops. "
    + B("CD4+ T cells") + " (Th1 type) are " + B("essential") +
    " — they produce IFN-γ and TNF which activate macrophages. Depletion of CD4+ T cells "
    "(as in HIV infection) leads to rapid progression to active disease."
))
story.append(bp(
    "The hallmark lesion of TB is the " + B("granuloma (tubercle)") + " — a compact aggregate of:"
))
story += bull([
    "Central area of " + B("caseous necrosis") + " (cheese-like; due to hypersensitivity reaction)",
    "Surrounded by " + B("epithelioid macrophages") + " (activated macrophages)",
    B("Langhans giant cells") + " (multinucleated, peripherally arranged nuclei)",
    "Rim of " + B("lymphocytes") + " and fibroblasts",
])
story.append(bp(
    "In immunocompetent hosts, granulomas " + B("contain") + " (not eliminate) the bacilli. "
    "The bacteria can survive in a " + B("dormant state") + " for decades within granulomas "
    "(latent TB). When immunity wanes, reactivation can occur."
))

story.append(h3p("Stage 5 — Progressive Primary TB or Latency"))
story.append(bp(
    "In ~90–95% of immunocompetent individuals, primary infection is " + B("contained") +
    " → " + B("Latent TB Infection (LTBI)") + ". The individual has a positive TST/IGRA "
    "but no symptoms or active disease."
))
story.append(bp(
    "In ~5–10% of infected persons (especially children, immunocompromised, malnourished), "
    "progressive primary TB occurs. Haematogenous dissemination can lead to "
    + B("miliary TB") + " (diffuse millet-seed lesions) or " + B("TB meningitis") + "."
))

story.append(h3p("Stage 6 — Reactivation TB (Post-primary TB)"))
story.append(bp(
    "5–10% of LTBI individuals will reactivate at some point in their lifetime. "
    "Reactivation preferentially occurs in " + B("upper lobes") +
    " (apex and posterior segments) due to higher oxygen tension. "
    "Tissue destruction leads to " + B("cavitation") + ", which is the hallmark of "
    "post-primary (reactivation) TB and is associated with high bacillary load and infectivity."
))
story.append(Spacer(1, 0.3*cm))

# ─────────────────────────────────────────────────────────────────────────────
# 6. CLINICAL FEATURES
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("6. CLINICAL FEATURES"))
story.append(h2p("6.1 Constitutional (Systemic) Symptoms"))
story += bull([
    B("Fever:") + " Low-grade, afternoon rise; may be associated with evening pyrexia.",
    B("Night sweats:") + " Drenching night sweats — classic symptom.",
    B("Weight loss:") + " Significant, unexplained (>10% body weight); anorexia, fatigue.",
    B("Malaise and fatigue:") + " General weakness and tiredness.",
])
story.append(h2p("6.2 Pulmonary Symptoms"))
story += bull([
    B("Cough:") + " Initially dry, progressively productive; >3 weeks duration is a key alarm symptom.",
    B("Hemoptysis:") + " Blood-streaked or frank hemoptysis — occurs in cavitary TB from erosion of blood vessels (Rasmussen's aneurysm).",
    B("Dyspnea:") + " Due to extensive parenchymal disease, large pleural effusion, pneumothorax.",
    B("Chest pain:") + " Pleuritic chest pain (sharp, worse on breathing) with pleural involvement.",
])
story.append(h2p("6.3 Extrapulmonary TB — Specific Features"))
ext_data = [
    ["Site", "Specific Features"],
    ["Pleural TB", "Unilateral exudative effusion, pleuritic pain, dyspnea; lymphocytic exudate"],
    ["TB Lymphadenitis", "Painless cervical lymphadenopathy; may caseate and form 'collar stud' abscess"],
    ["TB Meningitis", "Subacute headache, meningism, cranial nerve palsies, hydrocephalus; CSF: lymphocytic, high protein, low glucose"],
    ["Pott's Disease (Spinal TB)", "Back pain, kyphosis (gibbus deformity), paraplegia from cord compression; affects lower thoracic / upper lumbar vertebrae"],
    ["Renal TB", "Sterile pyuria, haematuria, dysuria; 'putty kidney' on imaging; 'moth-eaten' calyces on IVP"],
    ["Miliary TB", "Acute febrile illness; classic CXR: diffuse millet-seed nodules (1–2 mm) in all lung fields"],
    ["Pericardial TB", "Pericarditis, pericardial effusion, constrictive pericarditis"],
    ["Adrenal TB", "Addison's disease (adrenal insufficiency); bilateral adrenal calcification"],
]
story.append(make_table(ext_data[0], ext_data[1:], [5*cm, W-5*cm]))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 7. INVESTIGATIONS & DIAGNOSIS
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("7. INVESTIGATIONS & DIAGNOSIS"))
story.append(h2p("7.1 Bacteriological (Gold Standard)"))
story.append(h3p("Sputum Smear Microscopy (Ziehl-Neelsen Stain)"))
story += bull([
    "Simplest, cheapest, fastest method.",
    "Two sputum samples (spot-morning-spot): at least 1 AFB-positive confirms pulmonary TB.",
    "Sensitivity: ~45–80% (lower in HIV co-infection); Specificity: ~98%.",
    "Detects NTM as well; cannot differentiate from " + BI("M. tuberculosis") + ".",
    B("Fluorescence microscopy") + " (auramine-rhodamine stain) is more sensitive and faster.",
])
story.append(h3p("Sputum Culture"))
story += bull([
    B("Lowenstein-Jensen (LJ) medium:") + " Solid egg-based medium; takes 3–8 weeks.",
    B("MGIT (Mycobacteria Growth Indicator Tube):") + " Liquid broth; fluorescence-based; results in 1–3 weeks.",
    "Gold standard for diagnosis and drug susceptibility testing (DST).",
    "Minimum detectable: ~10 bacilli/mL.",
])
story.append(h3p("Molecular Tests"))
story += bull([
    B("GeneXpert MTB/RIF (Xpert):") + " WHO-endorsed point-of-care test. Detects " + BI("M. tuberculosis") + " DNA AND rifampicin resistance in ~2 hours. Sensitivity ~89%, Specificity ~99%. Recommended as initial diagnostic test.",
    B("CBNAAT (Cartridge-Based Nucleic Acid Amplification Test):") + " Used in RNTCP/NSP India.",
    B("Line Probe Assay (LPA):") + " Detects resistance to INH and RIF; used for MDR-TB diagnosis.",
    B("Whole genome sequencing (WGS):") + " Research/reference labs; detects all resistance patterns.",
])
story.append(h2p("7.2 Immunological Tests"))
story.append(h3p("Tuberculin Skin Test (TST / Mantoux Test)"))
story += bull([
    "Intradermal injection of " + B("5 TU PPD (Purified Protein Derivative)") + " on volar forearm.",
    "Reading at " + B("48–72 hours") + "; measure induration (not erythema).",
    B("Interpretation:") + " ≥10 mm = positive (general population); ≥5 mm = positive in HIV/immunosuppressed; ≥15 mm = low-risk individuals.",
    "False positives: BCG vaccination, NTM infection.",
    "False negatives: HIV, malnutrition, miliary TB, steroid use (anergy).",
])
story.append(h3p("Interferon-Gamma Release Assays (IGRAs)"))
story += bull([
    B("QuantiFERON-TB Gold Plus (QFT-Plus)") + " and " + B("T-SPOT.TB") + ".",
    "Measure IFN-γ released by T cells in response to TB-specific antigens (ESAT-6, CFP-10).",
    "More specific than TST (not affected by BCG vaccination).",
    "One-time blood draw; no 48-hour return visit needed.",
    "Preferred for LTBI diagnosis in low-incidence countries.",
])
story.append(h2p("7.3 Radiological Investigations"))
story += bull([
    B("Chest X-ray:") + " Mandatory for all suspected TB cases. Primary TB: lower/mid zone consolidation + hilar lymphadenopathy. Reactivation TB: upper lobe infiltrates, cavities, nodules, fibrosis.",
    B("CT Chest:") + " Superior for detecting subtle lesions, lymphadenopathy, mediastinal involvement, miliary disease.",
    B("Chest Ultrasound:") + " Pleural effusion detection and guidance for thoracentesis.",
]
)
story.append(h2p("7.4 Other Investigations"))
inv_data = [
    ["Investigation", "Findings in TB"],
    ["CBC", "Normocytic anemia, raised ESR, leukopenia (miliary TB), monocytosis"],
    ["ESR", "Elevated (non-specific but useful for monitoring)"],
    ["LFT", "Mild elevation (hepatic TB; also drug monitoring)"],
    ["Pleural fluid analysis", "Exudate; lymphocytic predominance; glucose low; protein >3g/dL; ADA elevated (>40 IU/L strongly suggests TB)"],
    ["CSF analysis (TB meningitis)", "Clear/xanthochromic; lymphocytes ↑; glucose ↓; protein ↑; AFB smear/culture/GeneXpert"],
    ["Adenosine Deaminase (ADA)", "Elevated in pleural fluid (>40), CSF, ascitic fluid — highly suggestive of TB"],
    ["Biopsy (pleura/lymph node/liver)", "Caseating granulomas with Langhans giant cells; AFB on histology"],
]
story.append(make_table(inv_data[0], inv_data[1:], [5*cm, W-5*cm]))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 8. TREATMENT
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("8. TREATMENT"))
story.append(h2p("8.1 Principles of Anti-Tuberculosis Therapy"))
story += bull([
    "Combination therapy to prevent emergence of drug resistance.",
    "Sufficient duration to eliminate all bacterial populations (replicating, dormant, intracellular).",
    "Directly Observed Treatment, Short-course (" + B("DOTS") + ") to ensure adherence.",
    "Daily treatment is preferred over intermittent (ATS/CDC/IDSA guidelines 2022).",
])
story.append(h2p("8.2 First-Line Anti-TB Drugs — RIPE"))
drug_data = [
    ["Drug", "Abbreviation", "Mechanism of Action", "Key Side Effects"],
    ["Isoniazid", "H / INH", "Inhibits mycolic acid synthesis (InhA enzyme); bactericidal", "Hepatotoxicity, peripheral neuropathy (prevent with pyridoxine), rash"],
    ["Rifampicin", "R / RIF", "Inhibits bacterial RNA polymerase (β-subunit); bactericidal; sterilizing", "Hepatotoxicity, orange discolouration of body fluids, drug interactions (CYP450 inducer)"],
    ["Pyrazinamide", "Z / PZA", "Active against intracellular/latent bacilli in acidic pH; sterilizing", "Hepatotoxicity, hyperuricaemia, arthralgia, photosensitivity"],
    ["Ethambutol", "E / EMB", "Inhibits arabinosyl transferase → blocks arabinogalactan synthesis; bacteriostatic", "Optic neuritis (dose-dependent, monitor visual acuity)"],
    ["Streptomycin", "S", "Aminoglycoside; inhibits 30S ribosomal subunit; bactericidal", "Ototoxicity (vestibular > auditory), nephrotoxicity, avoid in pregnancy"],
]
story.append(make_table(drug_data[0], drug_data[1:], [3.5*cm, 2.5*cm, 5.5*cm, 6*cm]))
story.append(Spacer(1, 0.3*cm))

story.append(h2p("8.3 Standard Treatment Regimen for Drug-Susceptible TB"))
story.append(bp(
    "The standard 6-month regimen consists of two phases:"
))
reg_data = [
    ["Phase", "Duration", "Drugs", "Purpose"],
    ["Intensive Phase", "2 months", "HRZE (INH + RIF + PZA + EMB) daily", "Rapid killing of actively replicating bacilli; reduce infectivity"],
    ["Continuation Phase", "4 months", "HR (INH + RIF) daily", "Elimination of dormant/residual bacilli; prevent relapse"],
]
story.append(make_table(reg_data[0], reg_data[1:], [3.5*cm, 2.5*cm, 5.5*cm, 6*cm]))
story.append(Spacer(1, 0.2*cm))
story += bull([
    B("Total duration:") + " 6 months (2HRZE + 4HR) for drug-susceptible pulmonary TB.",
    B("TB meningitis, bone/joint TB:") + " Extended to 9–12 months (some guidelines recommend 2HRZE + 10HR).",
    B("HIV co-infected:") + " Same 6-month regimen. ART should be started early (within 2 weeks for severe immunosuppression, CD4 <50).",
    B("Pyridoxine (Vitamin B6) 25–50 mg/day:") + " Given with INH to prevent peripheral neuropathy.",
    B("Adjunct corticosteroids:") + " Indicated in TB meningitis and pericarditis.",
])
story.append(h2p("8.4 Monitoring During Treatment"))
story += bull([
    "Monthly clinical review: weight, symptoms, adherence.",
    "Sputum AFB smear at end of month 2 (intensive phase); months 5 and 6.",
    "LFT baseline and as clinically indicated (especially PZA/INH/RIF).",
    "Visual acuity and colour vision: monthly if on EMB (especially if renal impairment).",
    "CXR at baseline and on completion.",
])
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 9. MDR-TB / XDR-TB
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("9. DRUG-RESISTANT TUBERCULOSIS"))
story.append(h2p("9.1 Definitions"))
dr_data = [
    ["Type", "Definition"],
    ["Mono-resistant TB", "Resistant to exactly one first-line anti-TB drug"],
    ["Poly-resistant TB", "Resistant to more than one first-line drug, but not both INH and RIF together"],
    ["MDR-TB", "Resistant to at least " + B("Isoniazid AND Rifampicin") + " (the two most potent first-line drugs)"],
    ["Pre-XDR-TB", "MDR-TB + resistance to any fluoroquinolone"],
    ["XDR-TB", "MDR-TB + resistance to fluoroquinolone + at least one of bedaquiline or linezolid"],
    ["TDR-TB", "Totally drug-resistant TB (resistance to all tested drugs)"],
]
story.append(make_table(dr_data[0], dr_data[1:], [4*cm, W-4*cm]))
story.append(Spacer(1, 0.3*cm))
story.append(h2p("9.2 Causes of Drug Resistance (MDR-TB is Man-Made)"))
story += bull([
    "Inadequate or irregular treatment (poor compliance).",
    "Subtherapeutic drug doses or poor-quality drugs.",
    "Premature discontinuation of treatment.",
    "Monotherapy (adding a single drug to a failing regimen).",
    "Transmission of already-resistant strains (primary resistance).",
    "HIV co-infection (promotes mutation and spread).",
])
story.append(h2p("9.3 Treatment of MDR-TB"))
story.append(bp(
    "MDR-TB treatment requires " + B("second-line drugs") + " administered for 18–24 months "
    "(or shorter 9–12 month regimens under specific criteria). "
    "WHO 2022 guidelines prioritise a " + B("BPaL or BPaLM regimen") + " (Bedaquiline + Pretomanid + Linezolid ± Moxifloxacin)."
))
mdr_data = [
    ["Drug Group", "Examples", "Notes"],
    ["Group A (Prioritize all 3)", "Levofloxacin/Moxifloxacin, Bedaquiline, Linezolid", "Cornerstone of MDR-TB regimen"],
    ["Group B (Add one or both)", "Clofazimine, Cycloserine/Terizidone", "Added when Group A drugs cannot be used"],
    ["Group C (Add to complete)", "Ethambutol, Delamanid, Pyrazinamide, Imipenem, Amikacin, Ethionamide", "Use only if Groups A and B insufficient"],
]
story.append(make_table(mdr_data[0], mdr_data[1:], [4*cm, 6*cm, W-10*cm]))
story.append(Spacer(1, 0.3*cm))

# ─────────────────────────────────────────────────────────────────────────────
# 10. COMPLICATIONS
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("10. COMPLICATIONS"))
comp_data = [
    ["Complication", "Mechanism"],
    ["Hemoptysis", "Erosion of pulmonary vessel; rupture of Rasmussen's aneurysm (in cavitary TB)"],
    ["Pneumothorax / Empyema", "Rupture of cavity into pleural space; secondary infection"],
    ["Respiratory failure", "Extensive bilateral disease; miliary TB"],
    ["Aspergilloma (Mycetoma)", "Aspergillus colonisation of old TB cavity"],
    ["Cor pulmonale", "Chronic hypoxia, pulmonary hypertension from fibrotic destruction"],
    ["Bronchopleural fistula", "Communication between bronchus and pleural space"],
    ["SIADH", "TB meningitis or pulmonary TB stimulating ADH secretion"],
    ["Addison's disease", "Bilateral adrenal destruction by TB"],
    ["Constrictive pericarditis", "Fibrocalcific healing of pericardial TB"],
    ["Drug-induced hepatitis", "INH, RIF, PZA hepatotoxicity"],
]
story.append(make_table(comp_data[0], comp_data[1:], [6*cm, W-6*cm]))
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 11. PREVENTION & CONTROL
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("11. PREVENTION & CONTROL"))
story.append(h2p("11.1 BCG Vaccination"))
story += bull([
    B("Bacille Calmette-Guérin (BCG)") + " is the only licensed TB vaccine.",
    "Live attenuated " + BI("Mycobacterium bovis") + " strain, developed by Calmette and Guérin (1921).",
    B("Route and dose:") + " 0.1 mg / 0.1 mL " + B("intradermal") + " injection; site: just above left deltoid insertion. Newborns <4 weeks: 0.05 mL.",
    B("Age:") + " At birth (institutional deliveries) or at 6 weeks (along with DPT and Polio) in India.",
    B("Efficacy:") + " 80% protective against TB meningitis and miliary TB in children; variable protection against pulmonary TB.",
    B("Post-vaccination reaction:") + " Papule develops at 2–3 weeks → ulcerates → heals in 6–12 weeks → permanent 4–8 mm scar.",
    B("Contraindications:") + " Symptomatic HIV, severe immunodeficiency, active TB.",
    B("Complications:") + " Suppurative lymphadenitis (1–10%); disseminated BCG (<1/million doses).",
])
story.append(h2p("11.2 DOTS — Directly Observed Treatment, Short-Course"))
story += bull([
    "The " + B("cornerstone") + " of global TB control; recommended by WHO since 1993.",
    "A healthcare worker or trained person " + B("directly observes") + " the patient swallowing every dose.",
    "Ensures treatment completion and prevents drug resistance.",
    B("Five components of DOTS:") + " (1) Government commitment; (2) Case detection by sputum smear microscopy; (3) Standardised short-course chemotherapy; (4) Uninterrupted drug supply; (5) Monitoring and evaluation system.",
])
story.append(h2p("11.3 RNTCP / National TB Elimination Programme (NTEP) — India"))
story += bull([
    "India launched " + B("RNTCP (Revised National TB Control Programme)") + " in 1997.",
    "Renamed " + B("National TB Elimination Programme (NTEP)") + " in 2020 with goal to eliminate TB by 2025 (ahead of SDG target of 2030).",
    B("Nikshay Portal:") + " Digital platform for TB notification, patient tracking, and supply management.",
    B("Nikshay Poshan Yojana:") + " ₹500/month direct benefit transfer to TB patients for nutritional support.",
    B("Universal Drug Susceptibility Testing (UDST):") + " GeneXpert/CBNAAT for all new TB patients.",
    B("Private sector engagement:") + " Mandatory TB notification from private practitioners.",
    B("TB-Harega Desh-Jeetega") + " campaign: national movement to end TB.",
])
story.append(h2p("11.4 Other Prevention Measures"))
story += bull([
    B("Infection control:") + " Adequate ventilation, UV germicidal irradiation, N-95 respirator for healthcare workers.",
    B("Contact tracing:") + " Screen household and close contacts of index cases.",
    B("Treatment of LTBI:") + " INH for 6 months (6H) or Rifapentine + INH for 12 weeks (3HP) for high-risk contacts.",
    B("Nutritional support:") + " Malnutrition is a major risk factor; protein-calorie supplementation.",
    B("HIV management:") + " ART reduces TB incidence by ~65% in HIV+ persons; Cotrimoxazole prophylaxis.",
])
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 12. SPECIAL SITUATIONS
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("12. TUBERCULOSIS IN SPECIAL SITUATIONS"))
story.append(h2p("12.1 TB in HIV Co-infection"))
story += bull([
    "HIV is the " + B("single greatest risk factor") + " for progression from LTBI to active TB (18× increased risk).",
    "Atypical presentation: lower lobe/diffuse infiltrates, absence of cavitation, frequent extrapulmonary TB.",
    "CXR may be normal in advanced immunosuppression.",
    "Treatment: Same 6-month regimen; ART started within 2 weeks (CD4 <50) or within 8 weeks.",
    "Avoid rifampicin + protease inhibitors (drug interaction); use rifabutin instead.",
    "Immune Reconstitution Inflammatory Syndrome (IRIS): paradoxical worsening after ART initiation.",
]
)
story.append(h2p("12.2 TB in Pregnancy"))
story += bull([
    "Active TB in pregnancy is associated with adverse outcomes: premature delivery, low birth weight, fetal loss.",
    "Treatment: HRZE is safe in pregnancy. " + B("Streptomycin is contraindicated") + " (ototoxicity in fetus).",
    "INH + pyridoxine: safe throughout pregnancy.",
    "Breastfeeding: Safe while on anti-TB treatment; continue therapy.",
])
story.append(h2p("12.3 TB in Renal Failure"))
story += bull([
    "INH and RIF are hepatically metabolised — conventional dosing used.",
    "EMB and PZA: reduce frequency (daily → 3×/week) in CrCl <30 mL/min.",
    "Administer post-dialysis for patients on haemodialysis.",
    "Monitor EMB toxicity (optic neuritis) closely.",
])
story.append(h2p("12.4 TB in Children"))
story += bull([
    "Children are more prone to primary progressive TB and dissemination (miliary TB, TB meningitis).",
    "Diagnosis is more difficult: sputum rarely obtainable; use gastric lavage or induced sputum.",
    "TST and CXR are key diagnostic tools in children.",
    "BCG vaccination is highly effective against childhood TB meningitis.",
    "Treatment: Same HRZE regimen with weight-adjusted dosing.",
])
story.append(PageBreak())

# ─────────────────────────────────────────────────────────────────────────────
# 13. REFERENCES
# ─────────────────────────────────────────────────────────────────────────────
story.append(h1p("13. REFERENCES"))
refs = [
    "Murray & Nadel's Textbook of Respiratory Medicine, 7th Edition (Elsevier, 2022) — Chapters 52 & 54.",
    "Fishman's Pulmonary Diseases and Disorders, 6th Edition (McGraw-Hill, 2023).",
    "Park's Textbook of Preventive and Social Medicine, 25th Edition (M/s Banarasidas Bhanot, 2021).",
    "Textbook of Family Medicine, 9th Edition (Elsevier, 2016).",
    "Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition (McGraw-Hill, 2023).",
    "WHO Global Tuberculosis Report 2023. World Health Organization, Geneva.",
    "WHO Consolidated Guidelines on Tuberculosis — Module 4: Treatment (2022).",
    "ATS/CDC/IDSA: Official American Thoracic Society/CDC/IDSA Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. CID 2016;63(7):e147–e195.",
    "National TB Elimination Programme (NTEP) — India. Ministry of Health & Family Welfare, Govt. of India. www.ntep.in",
    "Rajagopalan S, Yoshikawa TT. Tuberculosis in the elderly. Z Gerontol Geriatr. 2000;33(5):374–380.",
]
for i, ref in enumerate(refs, 1):
    story.append(Paragraph(f"{i}.  {ref}", ref_style))

story.append(Spacer(1, 0.5*cm))
story.append(hr())
story.append(Paragraph(
    "This assignment was prepared for academic purposes. Content is based on standard medical textbooks and WHO guidelines (2022–2023).",
    ParagraphStyle("Footer", parent=base["Normal"], fontSize=8, textColor=GREY, alignment=TA_CENTER)
))

# ── Build ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"PDF saved to: {OUTPUT}")

cd /home/daytona/workspace/tb-assignment && python generate_tb_pdf.py 2>&1

cd /home/daytona/workspace/tb-assignment && python -c " content = open('generate…

cd /home/daytona/workspace/tb-assignment && python generate_tb_pdf.py 2>&1

cd /home/daytona/workspace/tb-assignment && python -c " import ast, sys with ope…

cd /home/daytona/workspace/tb-assignment && python -c " with open('generate_tb_p…

cd /home/daytona/workspace/tb-assignment && python -c " with open('generate_tb_p…

cd /home/daytona/workspace/tb-assignment && python -c " with open('generate_tb_p…

ls /home/daytona/workspace/tb-assignment/ && python /home/daytona/workspace/tb-a…

ls -lh /home/daytona/workspace/tb-assignment/Tuberculosis_Assignment.pdf

~/tb-assignment/generate_cheatsheet.py

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, FrameBreak, Frame, PageTemplate, BaseDocTemplate
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import KeepTogether

OUTPUT = "/home/daytona/workspace/tb-assignment/TB_Cheatsheet.pdf"

W, H = A4  # 595 x 842 pts
MARGIN = 0.7 * cm

# ── Colours ───────────────────────────────────────────────────────────────────
C_RED     = colors.HexColor("#B71C1C")
C_DRED    = colors.HexColor("#7B0000")
C_ORANGE  = colors.HexColor("#E65100")
C_GREEN   = colors.HexColor("#1B5E20")
C_BLUE    = colors.HexColor("#0D47A1")
C_PURPLE  = colors.HexColor("#4A148C")
C_TEAL    = colors.HexColor("#004D40")
C_BGRED   = colors.HexColor("#FFEBEE")
C_BGORANGE= colors.HexColor("#FFF3E0")
C_BGGREEN = colors.HexColor("#E8F5E9")
C_BGBLUE  = colors.HexColor("#E3F2FD")
C_BGPURPLE= colors.HexColor("#F3E5F5")
C_BGTEAL  = colors.HexColor("#E0F2F1")
C_YELLOW  = colors.HexColor("#F57F17")
C_BGYELLOW= colors.HexColor("#FFFDE7")
C_GREY    = colors.HexColor("#424242")
C_LGREY   = colors.HexColor("#F5F5F5")
C_ALTROW  = colors.HexColor("#FFCDD2")
WHITE     = colors.white
BLACK     = colors.black

# ── Two-column layout ─────────────────────────────────────────────────────────
col_w = (W - 2*MARGIN - 0.3*cm) / 2
col_h = H - 2*MARGIN - 1.2*cm   # leave room for header strip

frame_left  = Frame(MARGIN,         MARGIN, col_w, col_h, leftPadding=2, rightPadding=4, topPadding=2, bottomPadding=2, id='left')
frame_right = Frame(MARGIN+col_w+0.3*cm, MARGIN, col_w, col_h, leftPadding=4, rightPadding=2, topPadding=2, bottomPadding=2, id='right')

# ── Header drawn on every page ────────────────────────────────────────────────
def draw_header(canvas, doc):
    canvas.saveState()
    # Top banner
    canvas.setFillColor(C_DRED)
    canvas.rect(0, H - 1.1*cm, W, 1.1*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica-Bold", 14)
    canvas.drawCentredString(W/2, H - 0.75*cm, "TUBERCULOSIS  |  QUICK REFERENCE CHEAT SHEET")
    canvas.setFont("Helvetica", 8)
    canvas.drawRightString(W - MARGIN, H - 0.92*cm, "Murray & Nadel  |  Park's  |  WHO 2022")
    # Bottom strip
    canvas.setFillColor(C_DRED)
    canvas.rect(0, 0, W, 0.45*cm, fill=1, stroke=0)
    canvas.setFillColor(WHITE)
    canvas.setFont("Helvetica", 7)
    canvas.drawCentredString(W/2, 0.12*cm, "For educational/academic use only  |  MBBS Quick Reference")
    canvas.restoreState()

doc = BaseDocTemplate(OUTPUT, pagesize=A4,
                      leftMargin=MARGIN, rightMargin=MARGIN,
                      topMargin=MARGIN + 1.15*cm, bottomMargin=MARGIN + 0.45*cm)
pt = PageTemplate(id='TwoCol', frames=[frame_left, frame_right], onPage=draw_header)
doc.addPageTemplates([pt])

# ── Style helpers ─────────────────────────────────────────────────────────────
base = getSampleStyleSheet()

def sec_head(text, bg=C_RED, fg=WHITE):
    """Section title bar."""
    s = ParagraphStyle("SH", fontSize=8, fontName="Helvetica-Bold",
                       textColor=fg, backColor=bg,
                       borderPadding=(3,5,3,5), leading=11, spaceAfter=3, spaceBefore=5)
    return Paragraph(text.upper(), s)

def sub_head(text, color=C_DRED):
    s = ParagraphStyle("sub", fontSize=7.5, fontName="Helvetica-Bold",
                       textColor=color, leading=10, spaceBefore=4, spaceAfter=2)
    return Paragraph(text, s)

def body(text, size=7):
    s = ParagraphStyle("bd", fontSize=size, fontName="Helvetica",
                       textColor=BLACK, leading=9.5, spaceAfter=1)
    return Paragraph(text, s)

def bull(text, color=C_DRED):
    s = ParagraphStyle("bu", fontSize=7, fontName="Helvetica",
                       textColor=BLACK, leading=9, leftIndent=8, spaceAfter=1)
    return Paragraph(f'<font color="{color.hexval()}"><b>•</b></font> {text}', s)

def note(text, bg=C_BGYELLOW, border=C_YELLOW):
    s = ParagraphStyle("nt", fontSize=6.8, fontName="Helvetica-Oblique",
                       textColor=C_GREY, backColor=bg,
                       borderPadding=(2,4,2,4), leading=9, spaceAfter=3, spaceBefore=2)
    return Paragraph(text, s)

def mini_table(headers, rows, col_widths, hbg=C_RED, altbg=C_BGRED):
    th_s = ParagraphStyle("TH", fontSize=6.5, fontName="Helvetica-Bold",
                          textColor=WHITE, leading=9)
    td_s = ParagraphStyle("TD", fontSize=6.5, fontName="Helvetica",
                          textColor=BLACK, leading=9)
    data = [[Paragraph(h, th_s) for h in headers]]
    for row in rows:
        data.append([Paragraph(str(c), td_s) for c in row])
    st = TableStyle([
        ("BACKGROUND",    (0,0), (-1,0),  hbg),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [WHITE, altbg]),
        ("GRID",          (0,0), (-1,-1), 0.3, hbg),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
        ("TOPPADDING",    (0,0), (-1,-1), 2),
        ("BOTTOMPADDING", (0,0), (-1,-1), 2),
        ("LEFTPADDING",   (0,0), (-1,-1), 3),
        ("RIGHTPADDING",  (0,0), (-1,-1), 3),
    ])
    return Table(data, colWidths=col_widths, style=st, hAlign="LEFT", repeatRows=1)

def hr(color=C_RED):
    return HRFlowable(width="100%", thickness=0.5, color=color, spaceAfter=2, spaceBefore=2)

def sp(h=0.15):
    return Spacer(1, h*cm)

# ═══════════════════════════════════════════════════════════════════════════════
# STORY
# ═══════════════════════════════════════════════════════════════════════════════
story = []

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# LEFT COLUMN
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

# 1. KEY FACTS BOX
story.append(sec_head("Key Facts at a Glance", C_DRED))
kf_data = [
    ["Pathogen", "<i>Mycobacterium tuberculosis</i> (MTBC)"],
    ["Discovered", "Robert Koch, 1882"],
    ["Transmission", "Airborne droplet nuclei (1-5 um)"],
    ["Global burden", "~10.6 million new cases/year"],
    ["India burden", "~26% of global cases (#1 worldwide)"],
    ["Mortality", "~1.6 million deaths/year (WHO 2022)"],
    ["Latency rate", "90-95% infected persons remain latent"],
    ["Reactivation", "5-10% LTBI reactivate in lifetime"],
    ["HIV risk", "18x increased risk in HIV+ persons"],
]
kf_table = Table(
    [[Paragraph(f"<b>{r[0]}</b>",
        ParagraphStyle("kk",fontSize=6.5,fontName="Helvetica-Bold",textColor=C_DRED,leading=9)),
      Paragraph(r[1],
        ParagraphStyle("kv",fontSize=6.5,fontName="Helvetica",textColor=BLACK,leading=9))]
     for r in kf_data],
    colWidths=[2.2*cm, col_w-2.5*cm],
    style=TableStyle([
        ("ROWBACKGROUNDS",(0,0),(-1,-1),[C_BGRED, WHITE]),
        ("GRID",(0,0),(-1,-1),0.3,C_RED),
        ("TOPPADDING",(0,0),(-1,-1),2),("BOTTOMPADDING",(0,0),(-1,-1),2),
        ("LEFTPADDING",(0,0),(-1,-1),3),("RIGHTPADDING",(0,0),(-1,-1),3),
    ]))
story.append(kf_table)
story.append(sp(0.15))

# 2. CLASSIFICATION
story.append(sec_head("Classification", C_BLUE))
story.append(sub_head("By site:", C_BLUE))
story.append(bull("<b>Pulmonary TB</b> - 80-85% of cases"))
story.append(bull("<b>Extrapulmonary TB</b> - 15-20% (pleural, lymph node, meningeal, bone, renal, pericardial)"))
story.append(bull("<b>Miliary/Disseminated TB</b> - haematogenous spread"))
story.append(sub_head("By disease status:", C_BLUE))
cls_rows = [
    ["LTBI","TST/IGRA +ve; no symptoms; NOT infectious; 5-10% reactivate"],
    ["Primary TB","1st infection; lower/mid zones; Ghon complex"],
    ["Reactivation TB","Upper lobe cavitary; high infectivity; endogenous reactivation"],
]
story.append(mini_table(["Type","Features"], cls_rows, [1.5*cm, col_w-1.8*cm], C_BLUE, C_BGBLUE))
story.append(sp(0.1))
story.append(sub_head("WHO Treatment Categories:", C_BLUE))
who_rows = [
    ["New","Never treated / <1 month"],
    ["Relapse","Previously cured; now bacteriologically +ve again"],
    ["Tx after failure","Previously treated; outcome = failure"],
    ["LTFU","Previously treated; lost to follow-up"],
]
story.append(mini_table(["Category","Definition"], who_rows, [2*cm, col_w-2.3*cm], C_BLUE, C_BGBLUE))
story.append(sp(0.1))

# 3. PATHOGENESIS FLOWCHART (as table)
story.append(sec_head("Pathogenesis - Step by Step", C_TEAL))
path_steps = [
    ["1","Inhalation","Droplet nuclei (1-5 um) reach alveoli (lower lobes)"],
    ["2","Macrophage uptake","Alveolar macrophages phagocytose bacilli"],
    ["3","Intracellular survival","ESX-3 blocks phagosome maturation; sulfatides inhibit phagolysosome fusion; ESAT-6 perforates membrane"],
    ["4","Lymphatic spread","Bacilli drain to hilar nodes -> Ghon complex (focus + node)"],
    ["5","Innate response","Neutrophils, NK cells; TNF-alpha, IL-12, IFN-gamma released"],
    ["6","Adaptive CMI","CD4+ Th1 cells (essential!); granuloma formation (2-8 wks)"],
    ["7","Granuloma","Caseous necrosis + epithelioid macrophages + Langhans giant cells + lymphocytes"],
    ["8a","LTBI (90-95%)","Bacteria contained in dormant state; TST/IGRA +ve"],
    ["8b","Active TB (5-10%)","Progressive disease; immunocompromised/children/HIV"],
    ["9","Reactivation","Upper lobes (high O2); cavitation; high bacillary load"],
]
story.append(mini_table(["#","Stage","Key Events"], path_steps,
                         [0.4*cm, 1.8*cm, col_w-2.5*cm], C_TEAL, C_BGTEAL))

# FRAME BREAK - switch to right column
story.append(FrameBreak())

# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━
# RIGHT COLUMN
# ━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━

# 4. DIAGNOSIS ALGORITHM
story.append(sec_head("Diagnosis Algorithm", C_ORANGE))
story.append(sub_head("Step 1 - Clinical Suspicion:", C_ORANGE))
story.append(bull("Cough >2 weeks + any of: fever, night sweats, weight loss, hemoptysis"))
story.append(bull("High-risk: HIV+, DM, malnourished, close contact with TB case"))

story.append(sub_head("Step 2 - Sputum Tests (Pulmonary TB):", C_ORANGE))
dx_rows = [
    ["ZN Smear","Spot + Morning sample; AFB = pink rods on blue; Sens 45-80%; Spec 98%; CHEAP & FAST","1st line"],
    ["Fluorescence","Auramine-rhodamine; faster screening; higher sensitivity","1st line"],
    ["GeneXpert MTB/RIF","Detects MTB DNA + Rifampicin resistance; 2 hrs; Sens 89%, Spec 99%; WHO recommended","1st line"],
    ["Culture (LJ/MGIT)","Gold standard; 3-8 wks (LJ) / 1-3 wks (MGIT); DST possible","Confirmatory"],
    ["LPA (Line Probe)","Detects INH + RIF resistance; for MDR-TB diagnosis","MDR workup"],
]
story.append(mini_table(["Test","Details","Use"], dx_rows,
                         [1.8*cm, col_w-3.5*cm, 1.4*cm], C_ORANGE, C_BGORANGE))

story.append(sub_head("Step 3 - Immunological Tests:", C_ORANGE))
imm_rows = [
    ["Mantoux TST","5 TU PPD intradermal; read at 48-72h; measure induration (not redness)","BCG affects result"],
    ["IGRA (QFT/T-SPOT)","IFN-gamma response to ESAT-6 & CFP-10; blood test; unaffected by BCG","Preferred for LTBI"],
]
story.append(mini_table(["Test","Method","Advantage"], imm_rows,
                         [1.8*cm, col_w-3.6*cm, 1.5*cm], C_ORANGE, C_BGORANGE))

story.append(sub_head("TST Interpretation Cutoffs:", C_ORANGE))
tst_rows = [
    [">=5 mm","HIV+; recent TB contact; immunosuppressed; organ transplant"],
    [">=10 mm","General population; high-endemic country; healthcare worker; DM; CKD"],
    [">=15 mm","No known risk factors"],
]
story.append(mini_table(["Induration","Positive if..."], tst_rows,
                         [1.3*cm, col_w-1.6*cm], C_ORANGE, C_BGORANGE))

story.append(sub_head("Key Fluid Tests (Extrapulmonary TB):", C_ORANGE))
story.append(bull("<b>Pleural fluid</b>: Exudate; lymphocytes dominant; ADA >40 IU/L (highly suggestive); protein >3g/dL; low glucose"))
story.append(bull("<b>CSF (TB meningitis)</b>: Clear/xanthochromic; lymphocytes; glucose LOW; protein HIGH; AFB smear/GeneXpert"))
story.append(bull("<b>ADA (Adenosine Deaminase)</b>: Elevated in pleural, CSF, ascitic fluid -- key TB marker"))
story.append(sp(0.1))

# 5. TREATMENT SECTION
story.append(sec_head("Treatment - Drug-Susceptible TB (DOTS)", C_GREEN))
story.append(note("DOTS = Directly Observed Treatment Short-course | Daily > Intermittent (ATS/CDC/IDSA 2022)"))

story.append(sub_head("Standard 6-Month Regimen (2HRZE + 4HR):", C_GREEN))
reg_rows = [
    ["Intensive\n2 months","H+R+Z+E (HRZE)\nAll 4 drugs DAILY","Rapidly kill replicating bacilli\nReduce infectivity within 2 weeks"],
    ["Continuation\n4 months","H+R (HR)\nBoth drugs DAILY","Eliminate dormant bacilli\nPrevent relapse"],
]
story.append(mini_table(["Phase","Drugs","Purpose"], reg_rows,
                         [1.6*cm, 2.5*cm, col_w-4.4*cm], C_GREEN, C_BGGREEN))
story.append(note("TB Meningitis / Bone-Joint TB: extend continuation to 7-10 months (total 9-12 months) | Add Pyridoxine 25-50mg/day with INH"))

story.append(sub_head("First-Line Drug Summary (RIPE):", C_GREEN))
drug_rows = [
    ["H - Isoniazid","Inhibits mycolic acid synthesis (InhA)","Hepatotoxicity, Peripheral neuropathy*","5 mg/kg/day (max 300mg)"],
    ["R - Rifampicin","Inhibits RNA polymerase (beta-subunit)","Hepatotox; Orange body fluids; CYP450 inducer","10 mg/kg/day (max 600mg)"],
    ["Z - Pyrazinamide","Active at acidic pH; kills intracellular/dormant bacilli","Hepatotox; Hyperuricaemia; Arthralgia","25 mg/kg/day"],
    ["E - Ethambutol","Inhibits arabinosyl transferase (cell wall)","Optic neuritis** (check vision monthly)","15-25 mg/kg/day"],
    ["S - Streptomycin","30S ribosome inhibitor; bactericidal","Ototoxicity; Nephrotoxicity; AVOID in pregnancy","15 mg/kg IM/day"],
]
story.append(mini_table(["Drug","Mechanism","Key Side Effect","Dose"],
                         drug_rows,
                         [2.3*cm, 2.5*cm, 2.5*cm, col_w-7.6*cm], C_GREEN, C_BGGREEN))
story.append(note("*Give Pyridoxine (Vit B6) 25-50mg with INH to prevent neuropathy  |  **Monitor visual acuity & colour vision on EMB"))

story.append(sub_head("MDR-TB / XDR-TB:", C_PURPLE))
mdr_rows = [
    ["MDR-TB","Resistant to INH + RIF","18-24 months; BPaL/BPaLM regimen"],
    ["Pre-XDR TB","MDR + fluoroquinolone resistance","WHO Group A drugs priority"],
    ["XDR-TB","MDR + fluroquinolone + bedaquiline or linezolid resistance","Highly specialist centre"],
]
story.append(mini_table(["Type","Definition","Treatment"],
                         mdr_rows, [1.5*cm, 2.8*cm, col_w-4.6*cm], C_PURPLE, C_BGPURPLE))
story.append(note("MDR-TB is MAN-MADE: caused by irregular/incomplete treatment, poor drugs, monotherapy, poor adherence"))

story.append(sub_head("WHO Drug Groups for MDR-TB:", C_PURPLE))
story.append(bull("<b>Group A (use all 3):</b> Levofloxacin/Moxifloxacin, Bedaquiline, Linezolid"))
story.append(bull("<b>Group B (add 1-2):</b> Clofazimine, Cycloserine"))
story.append(bull("<b>Group C (add to complete):</b> EMB, Delamanid, PZA, Imipenem, Amikacin"))

# Special situations compact box
story.append(sp(0.1))
story.append(sec_head("Special Situations - Quick Notes", C_DRED))
sp_rows = [
    ["HIV+","Same 6-month regimen; start ART within 2 wks (CD4<50) or 8 wks; IRIS possible; use Rifabutin if on PIs"],
    ["Pregnancy","HRZE safe; STREPTOMYCIN CONTRAINDICATED (fetal ototoxicity); Pyridoxine essential"],
    ["Renal failure","INH+RIF: normal dose; EMB+PZA: reduce to 3x/week if CrCl<30; give post-dialysis"],
    ["Hepatic disease","Avoid PZA if ALT>3xULN; use 9-month INH+RIF+EMB regimen"],
    ["Children","Gastric lavage/induced sputum for diagnosis; weight-adjusted dosing; BCG very protective"],
    ["Steroid use","Add steroids in TB meningitis (Dexamethasone) & pericarditis"],
]
story.append(mini_table(["Situation","Key Points"], sp_rows,
                         [1.8*cm, col_w-2.1*cm], C_DRED, C_BGRED))

# Prevention strip
story.append(sp(0.1))
story.append(sec_head("Prevention & Control", C_TEAL))
story.append(bull("<b>BCG vaccine:</b> Live attenuated M. bovis; intradermal; at birth (India); 80% protective vs childhood TB meningitis & miliary TB"))
story.append(bull("<b>DOTS:</b> Directly observed every dose; cornerstone of TB control worldwide"))
story.append(bull("<b>NTEP/India:</b> Goal - eliminate TB by 2025; GeneXpert for ALL; Nikshay portal; Rs 500/month Nikshay Poshan Yojana"))
story.append(bull("<b>LTBI treatment:</b> INH x 6 months (6H) OR Rifapentine+INH x 12 weeks (3HP) for high-risk contacts"))
story.append(bull("<b>Infection control:</b> N-95 masks; UV germicidal irradiation; adequate ventilation"))

# ── Build ─────────────────────────────────────────────────────────────────────
doc.build(story)
print(f"Cheat sheet saved to: {OUTPUT}")

cd /home/daytona/workspace/tb-assignment && python generate_cheatsheet.py 2>&1

ls -lh /home/daytona/workspace/tb-assignment/TB_Cheatsheet.pdf