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

# ── Colours ──────────────────────────────────────────────────────────────────
DARK_BLUE   = colors.HexColor("#1A3557")
MID_BLUE    = colors.HexColor("#2E6DA4")
LIGHT_BLUE  = colors.HexColor("#D6E8F7")
ACCENT      = colors.HexColor("#E8740C")
LIGHT_GREY  = colors.HexColor("#F4F6F8")
GREEN       = colors.HexColor("#1B6E3A")
LIGHT_GREEN = colors.HexColor("#D4EDDA")
RED_LIGHT   = colors.HexColor("#FDECEA")
RED         = colors.HexColor("#C0392B")
YELLOW_LIGHT= colors.HexColor("#FFF8E1")
WHITE       = colors.white
BLACK       = colors.black

# ── Styles ────────────────────────────────────────────────────────────────────
styles = getSampleStyleSheet()

def S(name, **kw):
    return ParagraphStyle(name, **kw)

COVER_TITLE   = S("CoverTitle",   fontSize=28, fontName="Helvetica-Bold",  textColor=WHITE,     alignment=TA_CENTER, leading=36)
COVER_SUB     = S("CoverSub",     fontSize=14, fontName="Helvetica",       textColor=LIGHT_BLUE, alignment=TA_CENTER, leading=22)
COVER_INFO    = S("CoverInfo",    fontSize=11, fontName="Helvetica",       textColor=LIGHT_BLUE, alignment=TA_CENTER, leading=18)

CHAPTER_TITLE = S("ChapterTitle", fontSize=18, fontName="Helvetica-Bold",  textColor=WHITE,     alignment=TA_LEFT,   spaceAfter=2)
SECTION_HEAD  = S("SectionHead",  fontSize=13, fontName="Helvetica-Bold",  textColor=DARK_BLUE, spaceBefore=10, spaceAfter=4)
SUBSEC_HEAD   = S("SubsecHead",   fontSize=11, fontName="Helvetica-Bold",  textColor=MID_BLUE,  spaceBefore=6,  spaceAfter=3)
BODY          = S("Body",         fontSize=9.5, fontName="Helvetica",      textColor=BLACK,     leading=14, spaceAfter=3)
BODY_BOLD     = S("BodyBold",     fontSize=9.5, fontName="Helvetica-Bold", textColor=BLACK,     leading=14)
SMALL         = S("Small",        fontSize=8.5, fontName="Helvetica",      textColor=colors.HexColor("#444444"), leading=13)
SMALL_BOLD    = S("SmallBold",    fontSize=8.5, fontName="Helvetica-Bold", textColor=BLACK, leading=13)
EXAM_TIP      = S("ExamTip",      fontSize=9,   fontName="Helvetica-Bold", textColor=ACCENT,    leading=13)
NOTE_STYLE    = S("Note",         fontSize=9,   fontName="Helvetica-Oblique", textColor=colors.HexColor("#555555"), leading=13)
TOC_ENTRY     = S("TOCEntry",     fontSize=10,  fontName="Helvetica",      textColor=DARK_BLUE, leading=18)
TOC_CH        = S("TOCCh",        fontSize=11,  fontName="Helvetica-Bold", textColor=DARK_BLUE, leading=20)

# ── Helpers ───────────────────────────────────────────────────────────────────
def chapter_header(title, subtitle=""):
    tbl_data = [[Paragraph(title, CHAPTER_TITLE)]]
    if subtitle:
        tbl_data.append([Paragraph(subtitle, S("CS", fontSize=10, fontName="Helvetica-Oblique", textColor=LIGHT_BLUE))])
    t = Table(tbl_data, colWidths=[17*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 10),
        ("BOTTOMPADDING", (0,0), (-1,-1), 10),
        ("LEFTPADDING",   (0,0), (-1,-1), 14),
        ("RIGHTPADDING",  (0,0), (-1,-1), 8),
        ("ROUNDEDCORNERS", (0,0), (-1,-1), 6),
    ]))
    return t

def tip_box(text):
    inner = Table([[Paragraph(f"<b>EXAM TIP:</b> {text}", EXAM_TIP)]], colWidths=[16.5*cm])
    inner.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), YELLOW_LIGHT),
        ("TOPPADDING",    (0,0), (-1,-1), 6),
        ("BOTTOMPADDING", (0,0), (-1,-1), 6),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("RIGHTPADDING",  (0,0), (-1,-1), 10),
        ("BOX", (0,0), (-1,-1), 1, ACCENT),
        ("ROUNDEDCORNERS", (0,0), (-1,-1), 4),
    ]))
    return inner

def clinical_vignette(text):
    inner = Table([[Paragraph(f"<b>CLINICAL VIGNETTE:</b> {text}", S("CV", fontSize=9, fontName="Helvetica-Oblique", textColor=colors.HexColor("#1A5276"), leading=13))]], colWidths=[16.5*cm])
    inner.setStyle(TableStyle([
        ("BACKGROUND",    (0,0), (-1,-1), LIGHT_BLUE),
        ("TOPPADDING",    (0,0), (-1,-1), 7),
        ("BOTTOMPADDING", (0,0), (-1,-1), 7),
        ("LEFTPADDING",   (0,0), (-1,-1), 10),
        ("RIGHTPADDING",  (0,0), (-1,-1), 10),
        ("BOX", (0,0), (-1,-1), 1, MID_BLUE),
    ]))
    return inner

def std_table(header_row, data_rows, col_widths=None):
    all_rows = [header_row] + data_rows
    if not col_widths:
        col_widths = [17*cm / len(header_row)] * len(header_row)
    t = Table(all_rows, colWidths=col_widths, repeatRows=1)
    style = [
        ("BACKGROUND",    (0,0), (-1,0),  DARK_BLUE),
        ("TEXTCOLOR",     (0,0), (-1,0),  WHITE),
        ("FONTNAME",      (0,0), (-1,0),  "Helvetica-Bold"),
        ("FONTSIZE",      (0,0), (-1,-1), 8.5),
        ("ROWBACKGROUNDS",(0,1), (-1,-1), [WHITE, LIGHT_GREY]),
        ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#CCCCCC")),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 6),
        ("RIGHTPADDING",  (0,0), (-1,-1), 6),
        ("VALIGN",        (0,0), (-1,-1), "TOP"),
    ]
    t.setStyle(TableStyle(style))
    return t

def P(text, style=None):
    return Paragraph(text, style or BODY)

def B(text):
    return Paragraph(text, BODY_BOLD)

def spacer(h=0.3):
    return Spacer(1, h*cm)

def hr():
    return HRFlowable(width="100%", thickness=0.5, color=colors.HexColor("#CCCCCC"), spaceAfter=4)

# ═══════════════════════════════════════════════════════════════════════════════
# CONTENT BUILDER
# ═══════════════════════════════════════════════════════════════════════════════
story = []

# ── COVER PAGE ─────────────────────────────────────────────────────────────────
cover_bg = Table(
    [[Paragraph("MBBS 2nd Year", COVER_INFO)],
     [Paragraph("Microbiology", COVER_TITLE)],
     [Paragraph("Paper 1 Study Guide", COVER_SUB)],
     [Spacer(1, 0.4*cm)],
     [Paragraph("General Microbiology  •  Immunology  •  CVS & Blood", COVER_INFO)],
     [Paragraph("GI & Hepatobiliary  •  CNS Infections", COVER_INFO)],
     [Spacer(1, 1.5*cm)],
     [Paragraph("NMC CBME Pattern  |  Clinical Scenario-Based  |  Chennai / India", COVER_INFO)],
    ],
    colWidths=[17*cm]
)
cover_bg.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",    (0,0), (-1,-1), 14),
    ("BOTTOMPADDING", (0,0), (-1,-1), 14),
    ("LEFTPADDING",   (0,0), (-1,-1), 16),
    ("RIGHTPADDING",  (0,0), (-1,-1), 16),
    ("ROUNDEDCORNERS",(0,0), (-1,-1), 8),
]))
story += [Spacer(1, 3*cm), cover_bg, Spacer(1, 2*cm)]
story += [P("This guide follows the NMC Competency-Based Medical Education (CBME) curriculum for MBBS Phase 2. "
            "Every section includes high-yield tables, organism comparison charts, and clinical vignettes that "
            "mirror the new Clinical Scenario-Based MCQ format. Use alongside Ananthnarayan & Paniker and "
            "Essentials of Medical Microbiology (Sastry).", NOTE_STYLE)]
story.append(PageBreak())

# ── TABLE OF CONTENTS ──────────────────────────────────────────────────────────
story += [chapter_header("Table of Contents"), spacer(0.4)]
toc_items = [
    ("1", "General Microbiology", "Gram stain, culture media, sterilization, microscopy, normal flora"),
    ("2", "Immunology",           "Innate/adaptive immunity, hypersensitivity (I-IV), vaccines, complement"),
    ("3", "CVS & Blood Infections","Infective endocarditis, septicaemia, rheumatic fever, blood-borne viruses"),
    ("4", "GI & Hepatobiliary",   "Cholera, typhoid, H. pylori, food poisoning, hepatitis A-E, amoebiasis"),
    ("5", "CNS Infections",       "Meningitis (bacterial/viral/TB/fungal), encephalitis, brain abscess, CSF analysis"),
    ("6", "Quick Revision Tables","Combined high-yield organism tables and last-minute MCQ facts"),
]
for num, title, desc in toc_items:
    story.append(P(f"<b>Section {num}</b>  —  <b>{title}</b>", TOC_CH))
    story.append(P(f"&nbsp;&nbsp;&nbsp;&nbsp;{desc}", SMALL))
    story.append(spacer(0.1))
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 1: GENERAL MICROBIOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 1 — General Microbiology", "Morphology · Stains · Culture · Sterilization · Normal Flora"), spacer(0.5)]

story += [P("""General microbiology forms the <b>foundation</b> for all system-wise topics. 
The CBME exam tests these through scenario MCQs like: <i>"A lab technician performs a stain on a 
sputum sample and sees pink/red rods — which stain was used and what organism is suspected?"</i>"""), spacer(0.2)]

# 1.1 Gram Stain
story += [P("<b>1.1 Gram Stain — Steps and Interpretation</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Step</b>", SMALL_BOLD), P("<b>Reagent</b>", SMALL_BOLD), P("<b>Purpose</b>", SMALL_BOLD), P("<b>Gram+ Result</b>", SMALL_BOLD), P("<b>Gram- Result</b>", SMALL_BOLD)],
    [
        [P("1",SMALL), P("Crystal Violet (primary)",SMALL), P("Stains all purple",SMALL), P("Purple",SMALL), P("Purple",SMALL)],
        [P("2",SMALL), P("Gram's Iodine (mordant)",SMALL), P("Fixes dye to cell wall",SMALL), P("Purple",SMALL), P("Purple",SMALL)],
        [P("3",SMALL), P("Acetone/Alcohol (decoloriser)",SMALL), P("Removes dye",SMALL), P("<b>Retains Purple</b>",SMALL_BOLD), P("Colorless",SMALL)],
        [P("4",SMALL), P("Safranin (counterstain)",SMALL), P("Colors decolorized cells",SMALL), P("Purple (unchanged)",SMALL), P("<b>Pink/Red</b>",SMALL_BOLD)],
    ],
    col_widths=[1.5*cm, 4.5*cm, 4*cm, 3.5*cm, 3.5*cm]
), spacer(0.3)]

story += [P("<b>Key Gram-Positive Organisms:</b>"), 
          P("Staphylococci, Streptococci, Pneumococci, Bacillus, Clostridium, Listeria, Corynebacterium"),
          P("<b>Key Gram-Negative Organisms:</b>"),
          P("E. coli, Klebsiella, Salmonella, Shigella, Vibrio, Neisseria, H. influenzae, Pseudomonas, Bordetella"),
          spacer(0.2)]

story += [tip_box("Gram stain FAILS for: Mycobacteria (use ZN), Mycoplasma (no cell wall), Treponema (too thin — use Dark field), Rickettsia (intracellular)."), spacer(0.3)]

# ZN Stain
story += [P("<b>1.2 Special Stains — High Yield Table</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Stain</b>", SMALL_BOLD), P("<b>Organism</b>", SMALL_BOLD), P("<b>Result</b>", SMALL_BOLD), P("<b>Used For</b>", SMALL_BOLD)],
    [
        [P("Ziehl-Neelsen (ZN)",SMALL), P("Mycobacteria, Nocardia",SMALL), P("Acid-fast bacilli = pink/red on blue",SMALL), P("TB, leprosy",SMALL)],
        [P("Modified ZN",SMALL), P("Cryptosporidium, Isospora",SMALL), P("Oocysts = pink/red",SMALL), P("Diarrhoea in immunocompromised",SMALL)],
        [P("India Ink / Nigrosin",SMALL), P("Cryptococcus neoformans",SMALL), P("Clear halo (capsule) on dark bg",SMALL), P("Fungal meningitis in HIV",SMALL)],
        [P("Giemsa",SMALL), P("Malaria, Leishmania, Rickettsia",SMALL), P("Parasites in RBCs",SMALL), P("Blood parasites",SMALL)],
        [P("PAS (Periodic Acid-Schiff)",SMALL), P("Fungi",SMALL), P("Fungal wall = magenta",SMALL), P("Tissue fungi",SMALL)],
        [P("Methenamine Silver",SMALL), P("Pneumocystis jirovecii, fungi",SMALL), P("Black organisms on green bg",SMALL), P("PCP pneumonia",SMALL)],
        [P("Albert's Stain",SMALL), P("Corynebacterium diphtheriae",SMALL), P("Metachromatic granules (volutin)",SMALL), P("Diphtheria diagnosis",SMALL)],
        [P("Dark Field Microscopy",SMALL), P("Treponema pallidum",SMALL), P("Motile spirochetes",SMALL), P("Primary syphilis",SMALL)],
    ],
    col_widths=[4*cm, 4*cm, 5*cm, 4*cm]
), spacer(0.3)]

# Culture Media
story += [P("<b>1.3 Culture Media — Must-Know for Spots and MCQs</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Medium</b>", SMALL_BOLD), P("<b>Type</b>", SMALL_BOLD), P("<b>Organism</b>", SMALL_BOLD), P("<b>Key Feature/Result</b>", SMALL_BOLD)],
    [
        [P("Blood Agar",SMALL),P("Enriched",SMALL),P("Most bacteria",SMALL),P("Alpha (green), Beta (clear), Gamma (no) haemolysis",SMALL)],
        [P("Chocolate Agar",SMALL),P("Enriched (heated blood)",SMALL),P("Neisseria, H. influenzae",SMALL),P("Brown colour; X+V factor growth",SMALL)],
        [P("MacConkey Agar",SMALL),P("Selective + Differential",SMALL),P("Gram-negative enteric",SMALL),P("Pink = lactose fermenter (E. coli); Colorless = non-fermenter (Salmonella/Shigella)",SMALL)],
        [P("TCBS",SMALL),P("Selective",SMALL),P("Vibrio cholerae",SMALL),P("Yellow colonies (sucrose fermenter)",SMALL)],
        [P("BCYE (Buffered charcoal yeast extract)",SMALL),P("Special",SMALL),P("Legionella",SMALL),P("Requires L-cysteine; grey-blue colonies",SMALL)],
        [P("LJ (Lowenstein-Jensen)",SMALL),P("Special",SMALL),P("Mycobacterium tuberculosis",SMALL),P("Buff/cream, rough colonies; takes 6-8 weeks",SMALL)],
        [P("Thayer-Martin",SMALL),P("Selective",SMALL),P("Neisseria gonorrhoeae",SMALL),P("Inhibits commensals; oxidase positive",SMALL)],
        [P("Tellurite / Hoyle's",SMALL),P("Selective",SMALL),P("C. diphtheriae",SMALL),P("Black colonies (tellurite reduction)",SMALL)],
        [P("CLED",SMALL),P("Selective",SMALL),P("UTI organisms",SMALL),P("No swarming; lactose fermenters = yellow",SMALL)],
        [P("Bordet-Gengou",SMALL),P("Special",SMALL),P("Bordetella pertussis",SMALL),P("Mercury drop colonies; nicotinamide required",SMALL)],
    ],
    col_widths=[4*cm, 3*cm, 4*cm, 6*cm]
), spacer(0.3)]

story += [clinical_vignette("A microbiologist cultures a urine sample on CLED agar and sees yellow colonies. The organism is oxidase-negative and ferments lactose. Most likely organism: E. coli. Next step: Sensitivity testing."), spacer(0.3)]

# Sterilization
story += [P("<b>1.4 Sterilization and Disinfection</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Method</b>", SMALL_BOLD), P("<b>Temp / Details</b>", SMALL_BOLD), P("<b>Kills</b>", SMALL_BOLD), P("<b>Does NOT Kill</b>", SMALL_BOLD), P("<b>Used For</b>", SMALL_BOLD)],
    [
        [P("Autoclave (moist heat)",SMALL),P("121°C / 15 min at 15 psi\n134°C / 3 min",SMALL),P("All including spores",SMALL),P("Prions (needs 134°C longer)",SMALL),P("Surgical instruments, media",SMALL)],
        [P("Hot Air Oven (dry heat)",SMALL),P("160°C / 60 min OR 180°C / 30 min",SMALL),P("All including spores",SMALL),P("—",SMALL),P("Glassware, sharp instruments, oils",SMALL)],
        [P("Pasteurization",SMALL),P("HTST: 72°C / 15 sec\nLTLT: 63°C / 30 min",SMALL),P("Vegetative bacteria",SMALL),P("Spores, hepatitis A virus (sometimes)",SMALL),P("Milk, dairy",SMALL)],
        [P("Boiling (100°C)",SMALL),P("100°C / 15-20 min",SMALL),P("Vegetative forms",SMALL),P("Spores, hepatitis B, prions",SMALL),P("Emergency instrument decontam",SMALL)],
        [P("Incineration",SMALL),P("340°C+ (red heat / flaming)",SMALL),P("Everything",SMALL),P("—",SMALL),P("Inoculation loops, infected material",SMALL)],
        [P("Filtration",SMALL),P("0.22 μm membrane filter",SMALL),P("Bacteria, fungi",SMALL),P("Viruses (pass through)",SMALL),P("Heat-sensitive liquids, sera",SMALL)],
        [P("UV Radiation",SMALL),P("253.7 nm wavelength",SMALL),P("Vegetative organisms",SMALL),P("Spores, cannot penetrate",SMALL),P("OT air, laminar flow",SMALL)],
        [P("Glutaraldehyde (2%)",SMALL),P("Contact 10h = sterilize; 20min = disinfect",SMALL),P("All including spores (prolonged)",SMALL),P("—",SMALL),P("Endoscopes, delicate instruments",SMALL)],
    ],
    col_widths=[3.5*cm, 3.5*cm, 3.5*cm, 3.5*cm, 3*cm]
), spacer(0.3)]

story += [tip_box("Memory: Autoclave = 121-15-15 (°C - min - psi). Hot air oven = 160-60 (or 180-30). Dry heat needs HIGHER temp than moist heat because water is a better conductor."), spacer(0.3)]

# Normal Flora
story += [P("<b>1.5 Normal Flora — High Yield Sites</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Site</b>", SMALL_BOLD), P("<b>Predominant Organisms</b>", SMALL_BOLD), P("<b>Clinical Significance</b>", SMALL_BOLD)],
    [
        [P("Skin",SMALL), P("Staph. epidermidis, Propionibacterium acnes, Corynebacterium",SMALL), P("Coagulase-negative Staph = infection in prosthetic devices",SMALL)],
        [P("Mouth/Throat",SMALL), P("Viridans streptococci, Neisseria commensals, Candida",SMALL), P("Viridans Strep = subacute infective endocarditis after dental procedure",SMALL)],
        [P("Colon",SMALL), P("E. coli, Bacteroides fragilis (anaerobe — most common!), Bifidobacterium",SMALL), P("Bacteroides = post-surgical abdominal infections",SMALL)],
        [P("Vagina",SMALL), P("Lactobacillus (acidophilus) — pH 4.5",SMALL), P("Disruption → BV (Gardnerella), candidiasis",SMALL)],
        [P("Nasal",SMALL), P("Staph. aureus (carried asymptomatically)",SMALL), P("~30% population carry; source of MRSA spread",SMALL)],
    ],
    col_widths=[3*cm, 7*cm, 7*cm]
), spacer(0.3)]
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 2: IMMUNOLOGY
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 2 — Immunology", "Innate & Adaptive · Hypersensitivity · Complement · Vaccines · Immunodeficiency"), spacer(0.5)]

# 2.1 Overview
story += [P("<b>2.1 Innate vs Adaptive Immunity — Key Differences</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Feature</b>", SMALL_BOLD), P("<b>Innate Immunity</b>", SMALL_BOLD), P("<b>Adaptive Immunity</b>", SMALL_BOLD)],
    [
        [P("Speed",SMALL), P("Immediate (minutes-hours)",SMALL), P("Days to weeks (first exposure)",SMALL)],
        [P("Specificity",SMALL), P("Non-specific (PAMPs via PRRs, TLRs)",SMALL), P("Highly specific (antigen-specific)",SMALL)],
        [P("Memory",SMALL), P("No immunological memory",SMALL), P("Yes — basis of vaccination",SMALL)],
        [P("Components",SMALL), P("Skin, mucus, phagocytes, NK cells, complement, fever",SMALL), P("B cells (antibodies), T cells (cell-mediated)",SMALL)],
        [P("Cells",SMALL), P("Neutrophils, macrophages, dendritic cells, NK cells, mast cells",SMALL), P("T lymphocytes (CD4, CD8), B lymphocytes, plasma cells",SMALL)],
    ],
    col_widths=[4*cm, 6.5*cm, 6.5*cm]
), spacer(0.3)]

# 2.2 Hypersensitivity
story += [P("<b>2.2 Hypersensitivity Reactions (Gell & Coombs Classification) — MOST TESTED</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Type</b>", SMALL_BOLD), P("<b>Name</b>", SMALL_BOLD), P("<b>Mediator</b>", SMALL_BOLD), P("<b>Time</b>", SMALL_BOLD), P("<b>Classic Examples</b>", SMALL_BOLD)],
    [
        [P("Type I",SMALL), P("Anaphylactic / Immediate",SMALL), P("IgE + mast cells → histamine",SMALL), P("Seconds-minutes",SMALL), P("Anaphylaxis, allergic asthma, urticaria, hay fever, penicillin allergy (IgE-mediated)",SMALL)],
        [P("Type II",SMALL), P("Cytotoxic / Antibody-mediated",SMALL), P("IgG/IgM → complement or ADCC",SMALL), P("Hours",SMALL), P("Haemolytic disease of newborn (Rh), autoimmune haemolytic anaemia, Goodpasture's (anti-GBM), ITP, myasthenia gravis",SMALL)],
        [P("Type III",SMALL), P("Immune Complex",SMALL), P("Antigen-antibody complexes → complement → neutrophil",SMALL), P("Hours-days",SMALL), P("SLE, serum sickness, post-streptococcal GN, Farmer's lung, Arthus reaction",SMALL)],
        [P("Type IV",SMALL), P("Delayed / Cell-Mediated (DTH)",SMALL), P("Sensitized T cells (Th1), macrophages",SMALL), P("48-72 hours",SMALL), P("Contact dermatitis (nickel, poison ivy), Mantoux/PPD test, TB granuloma, graft rejection",SMALL)],
    ],
    col_widths=[1.5*cm, 3.5*cm, 4*cm, 2.5*cm, 5.5*cm]
), spacer(0.3)]

story += [tip_box("Mnemonic: Types I-II-III = Antibody mediated (IgE, IgG/M, immune complexes). Only Type IV = T-cell mediated (no antibody). Mantoux test = Type IV."), spacer(0.3)]

story += [clinical_vignette("A nurse gives a patient a penicillin injection. Within 5 minutes he develops hypotension, urticaria, and wheezing. Type: I (IgE-mediated anaphylaxis). Mediator: Histamine from mast cells. Management: Adrenaline 0.5 mg IM."), spacer(0.3)]

# 2.3 Complement
story += [P("<b>2.3 Complement System</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Pathway</b>", SMALL_BOLD), P("<b>Trigger</b>", SMALL_BOLD), P("<b>Key Components</b>", SMALL_BOLD)],
    [
        [P("Classical",SMALL), P("IgG/IgM-antigen complex",SMALL), P("C1q → C1r → C1s → C4, C2 → C3 convertase",SMALL)],
        [P("Lectin (MBL)",SMALL), P("Mannose residues on microbes",SMALL), P("MBL → MASP1/2 → same as classical after C4",SMALL)],
        [P("Alternative",SMALL), P("Spontaneous C3 hydrolysis on foreign surfaces",SMALL), P("C3b + Factor B + Factor D → C3 convertase",SMALL)],
    ],
    col_widths=[4*cm, 6*cm, 7*cm]
), spacer(0.2)]
story += [P("<b>End result (all pathways):</b> MAC (Membrane Attack Complex) C5b-C9 → cell lysis")]
story += [P("<b>Key Complement Deficiency Clinical Correlates:</b>")]
story += [std_table(
    [P("<b>Deficiency</b>", SMALL_BOLD), P("<b>Consequence</b>", SMALL_BOLD)],
    [
        [P("C1q, C2, C4 (early classical)",SMALL), P("Recurrent SLE-like illness, immune complex disease",SMALL)],
        [P("C3",SMALL), P("Recurrent severe bacterial infections (most serious deficiency)",SMALL)],
        [P("C5-C9 (terminal / MAC)",SMALL), P("Recurrent Neisseria infections (gonorrhoea, meningococcal)",SMALL)],
        [P("DAF / CD55 (complement regulator)",SMALL), P("PNH — paroxysmal nocturnal haemoglobinuria",SMALL)],
    ],
    col_widths=[7*cm, 10*cm]
), spacer(0.3)]

# 2.4 Vaccines
story += [P("<b>2.4 Vaccines — Types and Indian NIP Schedule (Key Facts)</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Vaccine Type</b>", SMALL_BOLD), P("<b>Examples</b>", SMALL_BOLD), P("<b>Key Features</b>", SMALL_BOLD)],
    [
        [P("Live attenuated",SMALL), P("BCG, OPV, MMR, Varicella, Yellow Fever, Rotavirus",SMALL), P("Strong immunity (humoral + cellular); can cause disease in immunocompromised; needs cold chain",SMALL)],
        [P("Killed (inactivated)",SMALL), P("IPV, Hepatitis A, Influenza (injectable), Rabies, Typhoid Vi",SMALL), P("Safer; multiple doses needed; only humoral",SMALL)],
        [P("Toxoid",SMALL), P("Diphtheria (DT), Tetanus",SMALL), P("Inactivated exotoxin; stimulates antitoxin antibodies",SMALL)],
        [P("Subunit / Recombinant",SMALL), P("Hepatitis B (HBsAg), HPV, acellular Pertussis",SMALL), P("Very safe; no live organism",SMALL)],
        [P("Conjugate",SMALL), P("Hib, Meningococcal, Pneumococcal (PCV)",SMALL), P("Polysaccharide + carrier protein → T-dependent response; works in infants",SMALL)],
    ],
    col_widths=[4*cm, 6*cm, 7*cm]
), spacer(0.3)]

story += [tip_box("Cold chain: 2–8°C for most vaccines. OPV stored at -20°C. BCG and OPV are live — NEVER give in HIV-positive, immunocompromised, or during pregnancy."), spacer(0.3)]
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 3: CVS & BLOOD INFECTIONS
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 3 — CVS & Blood Infections", "Infective Endocarditis · Septicaemia · Rheumatic Fever · Blood-Borne Viruses"), spacer(0.5)]

story += [P("<b>3.1 Infective Endocarditis (IE) — Organism by Risk Factor</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Risk Factor / Patient</b>", SMALL_BOLD), P("<b>Most Likely Organism</b>", SMALL_BOLD), P("<b>Notes</b>", SMALL_BOLD)],
    [
        [P("Dental procedure / native valve",SMALL), P("Streptococcus viridans (alpha-haemolytic strep)",SMALL), P("Most common cause of subacute IE; Strep mitis, Strep sanguinis",SMALL)],
        [P("IV drug user",SMALL), P("Staphylococcus aureus",SMALL), P("Tricuspid valve involvement; acute course",SMALL)],
        [P("Prosthetic valve (early <60 days)",SMALL), P("Staph. epidermidis (CoNS)",SMALL), P("Coagulase-negative, biofilm on prosthesis",SMALL)],
        [P("Prosthetic valve (late >60 days)",SMALL), P("Strep. viridans, Staph. epidermidis",SMALL), P("Similar to native valve",SMALL)],
        [P("GI/GU procedure",SMALL), P("Enterococcus faecalis",SMALL), P("Group D streptococcus",SMALL)],
        [P("HACEK organisms",SMALL), P("Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella",SMALL), P("Gram-neg, slow-growing; culture >5 days; culture-negative IE",SMALL)],
        [P("Colon cancer / elderly",SMALL), P("Streptococcus bovis (S. gallolyticus)",SMALL), P("ALWAYS screen for colorectal cancer",SMALL)],
    ],
    col_widths=[4.5*cm, 5.5*cm, 7*cm]
), spacer(0.3)]

story += [P("<b>3.2 Duke's Criteria for IE Diagnosis</b>", SUBSEC_HEAD)]
story += [P("<b>Major Criteria:</b>")]
story += [P("1. Positive blood cultures: ≥2 positive cultures with typical IE organism OR persistently positive cultures")]
story += [P("2. Evidence of endocardial involvement: positive echo (vegetation / abscess) or new valvular regurgitation")]
story += [spacer(0.1), P("<b>Minor Criteria:</b> Predisposing condition, fever >38°C, vascular phenomena (septic emboli, Janeway lesions), immunological phenomena (Osler nodes, Roth spots, RF positive), positive culture not meeting major criteria")]
story += [spacer(0.1), P("<b>Definite IE:</b> 2 major / 1 major + 3 minor / 5 minor criteria")]
story += [spacer(0.2)]

story += [tip_box("Janeway lesions = painless (embolic, on palms/soles). Osler nodes = painful (immune complex, on fingertips). Roth spots = retinal haemorrhages with pale centre."), spacer(0.3)]

story += [clinical_vignette("A 35-year-old with a history of dental extraction 2 weeks ago presents with 3 weeks of low-grade fever, night sweats, and a new murmur. Blood cultures x3 grow alpha-haemolytic Streptococcus. Echo shows a vegetation on the mitral valve. Diagnosis: Subacute IE (Strep viridans). Treatment: IV Benzylpenicillin + Gentamicin for 4-6 weeks."), spacer(0.3)]

# 3.3 Septicaemia
story += [P("<b>3.3 Septicaemia — Blood Culture and Key Organisms</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Setting</b>", SMALL_BOLD), P("<b>Organism</b>", SMALL_BOLD), P("<b>Key Feature</b>", SMALL_BOLD)],
    [
        [P("Community-acquired",SMALL), P("E. coli (most common), Staph. aureus, Strep. pneumoniae",SMALL), P("Source usually UTI, pneumonia, skin",SMALL)],
        [P("Hospital-acquired",SMALL), P("E. coli, Klebsiella, Pseudomonas, MRSA, CoNS",SMALL), P("IV line, catheter, ventilator",SMALL)],
        [P("Neonatal (early <7d)",SMALL), P("Group B Streptococcus (GBS), E. coli, Listeria",SMALL), P("Maternal colonization, vaginal delivery",SMALL)],
        [P("Neonatal (late >7d)",SMALL), P("Staph. epidermidis, Klebsiella, Pseudomonas",SMALL), P("IV catheter, prematurity",SMALL)],
        [P("Asplenic patient",SMALL), P("S. pneumoniae, H. influenzae, N. meningitidis — 'PHN'",SMALL), P("Overwhelming post-splenectomy sepsis; vaccinate before splenectomy",SMALL)],
        [P("Meningococcaemia",SMALL), P("Neisseria meningitidis",SMALL), P("Non-blanching petechial / purpuric rash — EMERGENCY",SMALL)],
    ],
    col_widths=[4*cm, 5.5*cm, 7.5*cm]
), spacer(0.3)]

# Blood borne viruses
story += [P("<b>3.4 Blood-Borne Viruses (BBV)</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Virus</b>", SMALL_BOLD), P("<b>Route</b>", SMALL_BOLD), P("<b>Incubation</b>", SMALL_BOLD), P("<b>Chronicity</b>", SMALL_BOLD), P("<b>Cancer Risk</b>", SMALL_BOLD), P("<b>Vaccine</b>", SMALL_BOLD)],
    [
        [P("Hepatitis B",SMALL), P("Blood, sex, vertical",SMALL), P("60-90 days",SMALL), P("10% adults, 90% neonates",SMALL), P("HCC",SMALL), P("Yes (recombinant)",SMALL)],
        [P("Hepatitis C",SMALL), P("Blood (mainly IVDU)",SMALL), P("2-26 weeks",SMALL), P("75-85% (high!)",SMALL), P("HCC, cirrhosis",SMALL), P("No",SMALL)],
        [P("HIV",SMALL), P("Blood, sex, vertical",SMALL), P("2-4 weeks (ARS)",SMALL), P("Chronic (lifelong)",SMALL), P("AIDS-defining cancers",SMALL), P("No (trials ongoing)",SMALL)],
        [P("HTLV-1",SMALL), P("Blood, sex, breastfeeding",SMALL), P("Years",SMALL), P("Yes",SMALL), P("Adult T-cell leukaemia",SMALL), P("No",SMALL)],
    ],
    col_widths=[2.5*cm, 3.5*cm, 3*cm, 3.5*cm, 3*cm, 1.5*cm]
), spacer(0.3)]
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 4: GI & HEPATOBILIARY INFECTIONS
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 4 — GI & Hepatobiliary Infections", "Cholera · Typhoid · H. pylori · Food Poisoning · Hepatitis · Amoebiasis"), spacer(0.5)]

story += [P("<b>4.1 Diarrhoea — Organism by Clinical Pattern (MOST TESTED)</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Organism</b>", SMALL_BOLD), P("<b>Mechanism</b>", SMALL_BOLD), P("<b>Stool Character</b>", SMALL_BOLD), P("<b>Key Feature</b>", SMALL_BOLD), P("<b>Test/Medium</b>", SMALL_BOLD)],
    [
        [P("V. cholerae O1",SMALL), P("CT toxin → ↑cAMP → secretory diarrhoea",SMALL), P("Rice water — massive, painless",SMALL), P("Darting motility; fish in stream appearance on dark field",SMALL), P("TCBS (yellow); string test positive",SMALL)],
        [P("ETEC (E. coli)",SMALL), P("Heat-labile (LT) + heat-stable (ST) toxins",SMALL), P("Watery, painless",SMALL), P("Traveller's diarrhoea; most common cause",SMALL), P("MacConkey pink colonies",SMALL)],
        [P("Salmonella typhi",SMALL), P("Intracellular invasion; endotoxin",SMALL), P("Watery → constipation in 2nd week",SMALL), P("Relative bradycardia, rose spots, splenomegaly",SMALL), P("Blood cx (1st week); bone marrow cx (gold std); Widal",SMALL)],
        [P("Shigella dysenteriae",SMALL), P("Cell invasion + Shiga toxin",SMALL), P("Blood + mucus (dysentery)",SMALL), P("HUS in children (Shiga toxin → TTP)",SMALL), P("MacConkey (colourless); XLD",SMALL)],
        [P("EHEC O157:H7",SMALL), P("Shiga-like toxin",SMALL), P("Bloody diarrhoea",SMALL), P("HUS (haemolytic uraemic syndrome)",SMALL), P("Sorbitol-MacConkey (colourless)",SMALL)],
        [P("Campylobacter jejuni",SMALL), P("Invasion + cytotoxin",SMALL), P("Blood + mucus",SMALL), P("#1 cause bacterial diarrhoea in UK/India; raw chicken; may trigger Guillain-Barré",SMALL), P("CCDA medium; 42°C microaerophilic",SMALL)],
        [P("C. difficile",SMALL), P("Toxin A (enterotoxin) + Toxin B (cytotoxin)",SMALL), P("Profuse, foul-smelling watery",SMALL), P("Post-antibiotic use; pseudomembranous colitis",SMALL), P("Toxin EIA; culture on CCFA",SMALL)],
        [P("Rotavirus",SMALL), P("Villous destruction",SMALL), P("Watery, vomiting predominant",SMALL), P("#1 viral cause of diarrhoea in infants < 2 yrs; winter",SMALL), P("ELISA for rotavirus Ag; EM shows wheel appearance",SMALL)],
    ],
    col_widths=[3*cm, 3.5*cm, 3*cm, 4*cm, 3.5*cm]
), spacer(0.3)]

story += [clinical_vignette("A 25-year-old man from a village develops sudden-onset profuse watery ('rice water') diarrhoea after a flood. No fever or pain. Stool shows 'darting motility' on dark field microscopy. Organism: V. cholerae. Treatment: ORS (primary) + Doxycycline (adults) or Azithromycin. Notifiable disease."), spacer(0.3)]

# 4.2 Typhoid
story += [P("<b>4.2 Typhoid (Enteric Fever) — Week-by-Week Features</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Week</b>", SMALL_BOLD), P("<b>Clinical Features</b>", SMALL_BOLD), P("<b>Best Diagnostic Test</b>", SMALL_BOLD)],
    [
        [P("Week 1",SMALL), P("Step-ladder fever, headache, relative bradycardia, coated tongue",SMALL), P("Blood culture (highest sensitivity — 90%)",SMALL)],
        [P("Week 2",SMALL), P("Rose spots (10%), splenomegaly, constipation (adults)",SMALL), P("Blood culture; Widal test rising titres",SMALL)],
        [P("Week 3",SMALL), P("Intestinal haemorrhage, perforation risk",SMALL), P("Stool + urine culture",SMALL)],
        [P("Any week",SMALL), P("Bone marrow culture = GOLD STANDARD (positive even after antibiotics)",SMALL), P("Bone marrow culture (95%)",SMALL)],
    ],
    col_widths=[2*cm, 7.5*cm, 7.5*cm]
), spacer(0.2)]
story += [P("Treatment: <b>Ceftriaxone</b> (first-line now, due to MDR strains) | Azithromycin for uncomplicated | Ciprofloxacin (resistance rising)")]
story += [spacer(0.2), tip_box("Widal test interpretation: Single titre O ≥1:160 / H ≥1:160 suggestive, but endemic area baseline is higher. Always send blood cultures — do NOT rely on Widal alone."), spacer(0.3)]

# 4.3 Hepatitis
story += [P("<b>4.3 Hepatitis Viruses — Comparison Table</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Feature</b>", SMALL_BOLD), P("<b>Hep A</b>", SMALL_BOLD), P("<b>Hep B</b>", SMALL_BOLD), P("<b>Hep C</b>", SMALL_BOLD), P("<b>Hep D (Delta)</b>", SMALL_BOLD), P("<b>Hep E</b>", SMALL_BOLD)],
    [
        [P("Virus",SMALL), P("Picornavirus (ssRNA)",SMALL), P("Hepadnavirus (dsDNA)",SMALL), P("Flavivirus (ssRNA)",SMALL), P("Defective RNA virus",SMALL), P("Hepevirus (ssRNA)",SMALL)],
        [P("Transmission",SMALL), P("Faeco-oral",SMALL), P("Blood/sex/vertical",SMALL), P("Blood (IVDU)",SMALL), P("Blood (needs HBV)",SMALL), P("Faeco-oral",SMALL)],
        [P("Chronicity",SMALL), P("Never",SMALL), P("10% adults",SMALL), P("75-85%",SMALL), P("Co-infect: rare; Super-infect: 80%",SMALL), P("Never (except immunocomp)",SMALL)],
        [P("Fulminant",SMALL), P("Rare",SMALL), P("Rare",SMALL), P("Rare",SMALL), P("Yes (super-infection)",SMALL), P("30% in pregnancy!",SMALL)],
        [P("Vaccine",SMALL), P("Yes",SMALL), P("Yes",SMALL), P("No",SMALL), P("HBV vaccine prevents HDV",SMALL), P("Yes (China); not NIP India",SMALL)],
    ],
    col_widths=[3*cm, 2.8*cm, 2.8*cm, 2.8*cm, 2.8*cm, 2.8*cm]
), spacer(0.2)]

story += [P("<b>HBV Serological Markers — Must Know:</b>", SUBSEC_HEAD)]
story += [std_table(
    [P("<b>Marker</b>", SMALL_BOLD), P("<b>Meaning</b>", SMALL_BOLD)],
    [
        [P("HBsAg (surface Ag)",SMALL), P("Indicates current HBV infection (acute or chronic) — FIRST marker to appear",SMALL)],
        [P("Anti-HBs",SMALL), P("Recovery / immunity (after infection or vaccination)",SMALL)],
        [P("HBeAg",SMALL), P("Marker of HIGH infectivity and active viral replication",SMALL)],
        [P("Anti-HBe",SMALL), P("Seroconversion — infectivity decreasing",SMALL)],
        [P("Anti-HBc IgM",SMALL), P("Acute infection; also present during 'window period' (only marker positive)",SMALL)],
        [P("Anti-HBc IgG",SMALL), P("Past infection; lifelong marker",SMALL)],
        [P("HBV DNA",SMALL), P("Active replication; monitored during antiviral therapy",SMALL)],
    ],
    col_widths=[5*cm, 12*cm]
), spacer(0.3)]

story += [tip_box("Window period = HBsAg gone, Anti-HBs not yet appeared. ONLY Anti-HBc IgM is positive. This is the key MCQ trap."), spacer(0.3)]
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 5: CNS INFECTIONS
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 5 — CNS Infections", "Meningitis · Encephalitis · Brain Abscess · CSF Analysis"), spacer(0.5)]

story += [P("<b>5.1 Meningitis — Organism by Age Group</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Age Group</b>", SMALL_BOLD), P("<b>Most Likely Organisms</b>", SMALL_BOLD), P("<b>Notes</b>", SMALL_BOLD)],
    [
        [P("Neonates (0-3 months)",SMALL), P("GBS (Group B Strep), E. coli (K1), Listeria monocytogenes",SMALL), P("Gram-positive rods = Listeria; treat empirically with Ampicillin + Gentamicin",SMALL)],
        [P("Children (3mo - 5yr)",SMALL), P("N. meningitidis, S. pneumoniae, H. influenzae type b (Hib)",SMALL), P("Hib now rare post-vaccination; petechial rash = meningococcal",SMALL)],
        [P("Adolescents & Young adults",SMALL), P("N. meningitidis (serogroup B, C, W, Y)",SMALL), P("University students, close quarters; most epidemic-prone",SMALL)],
        [P("Adults",SMALL), P("S. pneumoniae (most common overall), N. meningitidis",SMALL), P("Post-neurosurgery: Gram-negative bacilli, Staph. aureus",SMALL)],
        [P("Elderly / Immunocomp.",SMALL), P("S. pneumoniae, Listeria, Gram-negatives, Cryptococcus",SMALL), P("Cryptococcus in HIV — India ink capsule",SMALL)],
        [P("TB meningitis",SMALL), P("Mycobacterium tuberculosis",SMALL), P("Subacute onset, basal meningitis, CN palsies",SMALL)],
    ],
    col_widths=[4*cm, 6.5*cm, 6.5*cm]
), spacer(0.3)]

story += [P("<b>5.2 CSF Analysis — Key Differential Diagnosis Table</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Feature</b>", SMALL_BOLD), P("<b>Normal</b>", SMALL_BOLD), P("<b>Bacterial</b>", SMALL_BOLD), P("<b>Viral</b>", SMALL_BOLD), P("<b>TB / Fungal</b>", SMALL_BOLD)],
    [
        [P("Appearance",SMALL), P("Clear",SMALL), P("Turbid / Purulent",SMALL), P("Clear / Slightly turbid",SMALL), P("Clear / Xanthochromic; may clot",SMALL)],
        [P("Pressure",SMALL), P("70-180 mmH₂O",SMALL), P("Raised",SMALL), P("Normal/Slightly raised",SMALL), P("Raised",SMALL)],
        [P("WBC",SMALL), P("0-5 lymphocytes",SMALL), P("1000-10,000 (Neutrophils)",SMALL), P("50-500 (Lymphocytes)",SMALL), P("50-500 (Lymphocytes)",SMALL)],
        [P("Protein",SMALL), P("15-45 mg/dL",SMALL), P("Very high (>100 mg/dL)",SMALL), P("Mild rise (50-100)",SMALL), P("High (100-500); forms cobweb clot",SMALL)],
        [P("Glucose",SMALL), P(">60% of serum",SMALL), P("Very low (<40 mg/dL)",SMALL), P("Normal",SMALL), P("Low (<40)",SMALL)],
        [P("Gram Stain",SMALL), P("Negative",SMALL), P("Positive in 60-80%",SMALL), P("Negative",SMALL), P("ZN stain (AFB) for TB",SMALL)],
        [P("Special Tests",SMALL), P("—",SMALL), P("Culture on blood / chocolate agar; latex agglutination",SMALL), P("PCR (HSV, enteroviruses)",SMALL), P("India ink (Cryptococcus); CRAG Ag; AFB culture",SMALL)],
    ],
    col_widths=[3*cm, 3*cm, 3.5*cm, 3*cm, 4.5*cm]
), spacer(0.3)]

story += [clinical_vignette("A 20-year-old college student presents with sudden high fever, severe headache, neck stiffness, and a petechial rash not blanching on glass test. CSF: turbid, WBC 5000 (neutrophils), protein 200, glucose 20. Gram stain: gram-negative diplococci. Organism: Neisseria meningitidis. Immediate treatment: IV Ceftriaxone. Prophylaxis for contacts: Rifampicin or Ciprofloxacin."), spacer(0.3)]

story += [P("<b>5.3 Brain Abscess — Key Organisms by Source</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Source</b>", SMALL_BOLD), P("<b>Organism</b>", SMALL_BOLD), P("<b>Location</b>", SMALL_BOLD)],
    [
        [P("Dental / sinusitis",SMALL), P("Streptococcus (viridans, milleri group), anaerobes, mixed",SMALL), P("Frontal lobe",SMALL)],
        [P("Otitis media / mastoiditis",SMALL), P("Strep. milleri, anaerobes, Enterobacteriaceae",SMALL), P("Temporal lobe / cerebellum",SMALL)],
        [P("Haematogenous (lung abscess, IE, IVDU)",SMALL), P("Staph. aureus, Strep., Gram-negatives",SMALL), P("Multiple / grey-white junction",SMALL)],
        [P("Post-neurosurgery / trauma",SMALL), P("Staph. aureus, Gram-negatives",SMALL), P("Near wound site",SMALL)],
        [P("Immunocompromised (HIV)",SMALL), P("Toxoplasma gondii (most common ring-enhancing lesion in AIDS), Cryptococcus, Listeria",SMALL), P("Multiple",SMALL)],
    ],
    col_widths=[4.5*cm, 7*cm, 5.5*cm]
), spacer(0.3)]

story += [tip_box("Ring-enhancing lesion on MRI in HIV patient: #1 Toxoplasma. If no response to empirical pyrimethamine + sulfadiazine in 2 weeks, biopsy to rule out CNS lymphoma (EBV-related)."), spacer(0.3)]
story.append(PageBreak())

# ══════════════════════════════════════════════════════════════════════════════
# SECTION 6: QUICK REVISION TABLES
# ══════════════════════════════════════════════════════════════════════════════
story += [chapter_header("Section 6 — Quick Revision Tables", "Last-Minute MCQ Facts · Organism Mnemonics · Vignette Patterns"), spacer(0.5)]

story += [P("<b>6.1 Exotoxins vs Endotoxins</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Feature</b>", SMALL_BOLD), P("<b>Exotoxin</b>", SMALL_BOLD), P("<b>Endotoxin (LPS)</b>", SMALL_BOLD)],
    [
        [P("Produced by",SMALL), P("Gram-positive AND Gram-negative",SMALL), P("Only Gram-negative (outer membrane)",SMALL)],
        [P("Chemistry",SMALL), P("Protein",SMALL), P("Lipopolysaccharide (Lipid A = toxic part)",SMALL)],
        [P("Heat stability",SMALL), P("Labile (destroyed at 60-80°C)",SMALL), P("Stable (withstands autoclaving)",SMALL)],
        [P("Toxoid formation",SMALL), P("Yes (formalin treatment → toxoid vaccine)",SMALL), P("No",SMALL)],
        [P("Potency",SMALL), P("Extremely potent (botulinum = most toxic)",SMALL), P("Less potent",SMALL)],
        [P("Effect",SMALL), P("Specific: neurotoxin, enterotoxin, cytotoxin",SMALL), P("Non-specific: fever, shock, DIC, complement activation",SMALL)],
        [P("Key examples",SMALL), P("Cholera CT, Diphtheria, Tetanus, Botulinum, Staph TSST-1, ETEC LT/ST",SMALL), P("Salmonella, E. coli, Neisseria, all Gram-negatives",SMALL)],
    ],
    col_widths=[3.5*cm, 6.5*cm, 7*cm]
), spacer(0.3)]

story += [P("<b>6.2 Anti-Microbial Classes — Mechanism and Key Organism Coverage</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Drug Class</b>", SMALL_BOLD), P("<b>Mechanism</b>", SMALL_BOLD), P("<b>Coverage</b>", SMALL_BOLD), P("<b>Key Drug</b>", SMALL_BOLD)],
    [
        [P("Beta-lactams",SMALL), P("Inhibit cell wall synthesis (PBPs)",SMALL), P("Broad; Gram+ (penicillin) and Gram- (cephalosporins, carbapenems)",SMALL), P("Amoxicillin, Cefazolin, Meropenem",SMALL)],
        [P("Aminoglycosides",SMALL), P("Irreversible 30S ribosome binding → mistranslation",SMALL), P("Gram-negative aerobes; TB (Streptomycin)",SMALL), P("Gentamicin, Amikacin",SMALL)],
        [P("Macrolides",SMALL), P("Reversible 50S ribosome binding",SMALL), P("Atypicals (Mycoplasma, Legionella, Chlamydia), Gram+ strep",SMALL), P("Azithromycin, Erythromycin",SMALL)],
        [P("Fluoroquinolones",SMALL), P("Inhibit DNA gyrase (topoisomerase II)",SMALL), P("Broad Gram-neg + some Gram+, Mycobacteria",SMALL), P("Ciprofloxacin, Levofloxacin",SMALL)],
        [P("Tetracyclines",SMALL), P("30S ribosome, reversible",SMALL), P("Atypicals, Rickettsia, Brucella, Chlamydia, cholera",SMALL), P("Doxycycline",SMALL)],
        [P("Glycopeptides",SMALL), P("Inhibit cell wall (D-Ala-D-Ala terminus)",SMALL), P("Gram-positive only; MRSA, VRE (Linezolid/Daptomycin if VRE)",SMALL), P("Vancomycin, Teicoplanin",SMALL)],
        [P("Metronidazole",SMALL), P("DNA strand breakage (anaerobes)",SMALL), P("Anaerobes, C. difficile, H. pylori, Entamoeba, Giardia",SMALL), P("Metronidazole",SMALL)],
    ],
    col_widths=[3.5*cm, 4.5*cm, 5.5*cm, 3.5*cm]
), spacer(0.3)]

story += [P("<b>6.3 Organisms with Unique Identifying Features (Spot & MCQ)</b>", SECTION_HEAD)]
story += [std_table(
    [P("<b>Organism</b>", SMALL_BOLD), P("<b>Unique Feature</b>", SMALL_BOLD)],
    [
        [P("Staph. aureus",SMALL), P("Coagulase positive; golden colonies; TSST-1 (toxic shock); Protein A (anti-phagocytic); novobiocin sensitive",SMALL)],
        [P("Staph. epidermidis",SMALL), P("Coagulase negative; novobiocin sensitive; biofilm former",SMALL)],
        [P("Staph. saprophyticus",SMALL), P("Coagulase negative; novobiocin RESISTANT; young women UTI",SMALL)],
        [P("Strep. pyogenes (Group A)",SMALL), P("Beta-haemolytic; M protein (antiphagocytic); ASO titre; causes rheumatic fever + PSGN",SMALL)],
        [P("Strep. agalactiae (Group B)",SMALL), P("Beta-haemolytic; neonatal meningitis + sepsis; CAMP test positive",SMALL)],
        [P("S. pneumoniae",SMALL), P("Optochin sensitive; bile soluble; lancet-shaped diplococci; Quellung reaction; causes CAP, meningitis, otitis media",SMALL)],
        [P("E. coli",SMALL), P("Indole positive; ferments lactose; K1 antigen in neonatal meningitis; IMViC = + + - -",SMALL)],
        [P("Klebsiella",SMALL), P("Mucoid colonies; non-motile; capsule (Friedlander's bacillus); currant jelly sputum in alcoholics",SMALL)],
        [P("N. meningitidis",SMALL), P("Gram-neg diplococci; ferments glucose + maltose; capsule types A,B,C,W,Y; petechial rash",SMALL)],
        [P("N. gonorrhoeae",SMALL), P("Ferments glucose ONLY (not maltose); intracellular diplococci in neutrophils; oxidase positive",SMALL)],
        [P("M. tuberculosis",SMALL), P("Acid-fast (ZN); slow growing (6-8 wks); LJ medium; Cord factor (virulence); Mantoux type IV hypersensitivity",SMALL)],
        [P("C. diphtheriae",SMALL), P("Metachromatic granules (Albert's/Loeffler's); grey-white pseudomembrane; Nagler's reaction; Elek's test for toxin",SMALL)],
        [P("B. anthracis",SMALL), P("Medusa head colonies; non-motile; capsule (poly-D-glutamate); string of pearls in penicillin (McFadyean)",SMALL)],
    ],
    col_widths=[5*cm, 12*cm]
), spacer(0.3)]

story += [P("<b>6.4 Key Mnemonics</b>", SECTION_HEAD)]
mnemonics = [
    ("<b>AEIOU for asplenia vaccination:</b>", "Antibiotic prophylaxis (Penicillin V), Education, Immunization (PHN: Pneumo, Haemophilus, Neisseria), Observe, Urgent treatment"),
    ("<b>TORCH:</b>", "Toxoplasma, Others (syphilis, VZV, parvovirus B19), Rubella, CMV, Herpes — congenital infections"),
    ("<b>HACEK:</b>", "Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella — culture-negative endocarditis organisms"),
    ("<b>Types of diarrhoea:</b>", "Secretary = no blood (cholera, ETEC); Invasive = blood + mucus (Shigella, Campylobacter, EHEC, Entamoeba); Osmotic = stops with fasting"),
    ("<b>Live vaccines (don't give in pregnancy/immunocomp):</b>", "BCG, OPV, MMR, Varicella, Yellow fever, Rotavirus — 'Be Open, Make More Vaccine Yesterday, Routinely'"),
]
for bold_part, rest in mnemonics:
    story.append(P(f"{bold_part} {rest}"))
    story.append(spacer(0.1))

story += [spacer(0.3)]

# Final note
final_box = Table([[
    Paragraph("<b>How to Use This Guide:</b><br/>"
              "1. Read each section once for understanding.<br/>"
              "2. Cover the tables and recall — don't just re-read passively.<br/>"
              "3. For every organism, write your own clinical vignette (it trains exam thinking).<br/>"
              "4. Do 20 MCQs after each section using CBME-pattern question books.<br/>"
              "5. Review the CSF table, hepatitis markers, and IE organism table until automatic.",
              S("FinalNote", fontSize=9, fontName="Helvetica", textColor=colors.HexColor("#1A3557"), leading=14))
]], colWidths=[17*cm])
final_box.setStyle(TableStyle([
    ("BACKGROUND",    (0,0), (-1,-1), LIGHT_GREEN),
    ("TOPPADDING",    (0,0), (-1,-1), 10),
    ("BOTTOMPADDING", (0,0), (-1,-1), 10),
    ("LEFTPADDING",   (0,0), (-1,-1), 14),
    ("RIGHTPADDING",  (0,0), (-1,-1), 14),
    ("BOX",           (0,0), (-1,-1), 1.5, GREEN),
    ("ROUNDEDCORNERS",(0,0), (-1,-1), 6),
]))
story.append(final_box)

# ── BUILD ─────────────────────────────────────────────────────────────────────
OUT = "/tmp/workspace/micro-guide/Microbiology_Paper1_Study_Guide.pdf"

def header_footer(canvas, doc):
    canvas.saveState()
    # Header line
    canvas.setStrokeColor(DARK_BLUE)
    canvas.setLineWidth(1)
    canvas.line(2*cm, A4[1] - 1.5*cm, A4[0] - 2*cm, A4[1] - 1.5*cm)
    canvas.setFont("Helvetica-Bold", 8)
    canvas.setFillColor(DARK_BLUE)
    canvas.drawString(2*cm, A4[1] - 1.3*cm, "Microbiology Paper 1 — MBBS 2nd Year (NMC CBME)")
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(colors.HexColor("#666666"))
    canvas.drawRightString(A4[0] - 2*cm, A4[1] - 1.3*cm, "General Micro · Immunology · CVS · GI · CNS")
    # Footer
    canvas.setStrokeColor(colors.HexColor("#CCCCCC"))
    canvas.line(2*cm, 1.5*cm, A4[0] - 2*cm, 1.5*cm)
    canvas.setFont("Helvetica", 8)
    canvas.setFillColor(colors.HexColor("#666666"))
    canvas.drawCentredString(A4[0]/2, 1*cm, f"Page {doc.page}")
    canvas.restoreState()

doc = SimpleDocTemplate(
    OUT, pagesize=A4,
    leftMargin=2*cm, rightMargin=2*cm,
    topMargin=2.2*cm, bottomMargin=2.2*cm,
    title="Microbiology Paper 1 Study Guide — MBBS 2nd Year",
    author="Orris AI"
)
doc.build(story, onFirstPage=header_footer, onLaterPages=header_footer)
print(f"PDF created: {OUT}")