from docx import Document
from docx.shared import Pt, Inches, RGBColor, Cm
from docx.enum.text import WD_ALIGN_PARAGRAPH
from docx.enum.table import WD_TABLE_ALIGNMENT, WD_ALIGN_VERTICAL
from docx.oxml.ns import qn
from docx.oxml import OxmlElement
import copy

doc = Document()

# ─── PAGE SETUP ───────────────────────────────────────────────────────────────
section = doc.sections[0]
section.page_width  = Inches(8.27)   # A4
section.page_height = Inches(11.69)
section.left_margin   = Inches(1.0)
section.right_margin  = Inches(1.0)
section.top_margin    = Inches(0.9)
section.bottom_margin = Inches(0.9)

# ─── STYLES ───────────────────────────────────────────────────────────────────
normal_style = doc.styles["Normal"]
normal_style.font.name = "Arial"
normal_style.font.size = Pt(11)

def set_heading_style(para, size, bold=True, color=None, center=False, underline=False):
    para.clear()
    run = para.add_run()
    run.font.name = "Arial"
    run.font.size = Pt(size)
    run.bold = bold
    run.underline = underline
    if color:
        run.font.color.rgb = RGBColor(*color)
    if center:
        para.alignment = WD_ALIGN_PARAGRAPH.CENTER
    return run

def add_heading(doc, text, level=1, color=(0,70,127), center=False):
    p = doc.add_paragraph()
    p.paragraph_format.space_before = Pt(8)
    p.paragraph_format.space_after  = Pt(4)
    sizes = {1: 16, 2: 14, 3: 12, 4: 11}
    run = set_heading_style(p, sizes.get(level,12), bold=True, color=color,
                            center=center, underline=(level<=2))
    run.text = text
    return p

def add_body(doc, text, bold=False, italic=False, indent=0):
    p = doc.add_paragraph()
    p.paragraph_format.space_before = Pt(1)
    p.paragraph_format.space_after  = Pt(2)
    if indent:
        p.paragraph_format.left_indent = Inches(indent)
    run = p.add_run(text)
    run.font.name = "Arial"
    run.font.size = Pt(11)
    run.bold = bold
    run.italic = italic
    return p

def add_bullet(doc, text, level=0, bold_prefix=None):
    p = doc.add_paragraph(style="List Bullet")
    p.paragraph_format.space_before = Pt(1)
    p.paragraph_format.space_after  = Pt(1)
    p.paragraph_format.left_indent  = Inches(0.25 + level*0.2)
    if bold_prefix:
        r1 = p.add_run(bold_prefix)
        r1.bold = True
        r1.font.name = "Arial"
        r1.font.size = Pt(11)
        r2 = p.add_run(text)
        r2.font.name = "Arial"
        r2.font.size = Pt(11)
    else:
        run = p.add_run(text)
        run.font.name = "Arial"
        run.font.size = Pt(11)
    return p

def add_shaded_box(doc, title, content_lines, title_rgb=(0,70,127), shade_rgb="D6E4F0"):
    """Add a shaded table box with title and content lines"""
    table = doc.add_table(rows=1, cols=1)
    table.style = "Table Grid"
    cell = table.rows[0].cells[0]
    # shade
    tc = cell._tc
    tcPr = tc.get_or_add_tcPr()
    shd = OxmlElement("w:shd")
    shd.set(qn("w:val"), "clear")
    shd.set(qn("w:color"), "auto")
    shd.set(qn("w:fill"), shade_rgb)
    tcPr.append(shd)
    # title
    p_title = cell.paragraphs[0]
    p_title.clear()
    rt = p_title.add_run(title)
    rt.bold = True
    rt.font.name = "Arial"
    rt.font.size = Pt(11)
    rt.font.color.rgb = RGBColor(*title_rgb)
    # content
    for line in content_lines:
        p = cell.add_paragraph()
        r = p.add_run(line)
        r.font.name = "Arial"
        r.font.size = Pt(11)
    doc.add_paragraph()  # spacing

def add_flowchart_table(doc, steps, title, color_hex="1F6FAE"):
    """Build a simple vertical flowchart using table cells with arrows"""
    add_heading(doc, title, level=3, color=(31,111,174))
    for i, step in enumerate(steps):
        tbl = doc.add_table(rows=1, cols=1)
        tbl.alignment = WD_TABLE_ALIGNMENT.CENTER
        cell = tbl.rows[0].cells[0]
        # background color
        fill_color = "D6E4F0" if i % 2 == 0 else "E8F4FD"
        tc = cell._tc
        tcPr = tc.get_or_add_tcPr()
        shd = OxmlElement("w:shd")
        shd.set(qn("w:val"), "clear")
        shd.set(qn("w:color"), "auto")
        shd.set(qn("w:fill"), fill_color)
        tcPr.append(shd)
        p = cell.paragraphs[0]
        p.alignment = WD_ALIGN_PARAGRAPH.CENTER
        run = p.add_run(step)
        run.font.name = "Arial"
        run.font.size = Pt(10.5)
        run.bold = True
        # set cell width
        cell.width = Inches(5.0)
        if i < len(steps) - 1:
            arrow_p = doc.add_paragraph("▼")
            arrow_p.alignment = WD_ALIGN_PARAGRAPH.CENTER
            arrow_p.paragraph_format.space_before = Pt(1)
            arrow_p.paragraph_format.space_after  = Pt(1)
            run2 = arrow_p.runs[0]
            run2.font.size = Pt(14)
            run2.font.color.rgb = RGBColor(31,111,174)
    doc.add_paragraph()

def add_lab_table(doc, rows_data, headers):
    """Add a formatted lab diagnosis table"""
    table = doc.add_table(rows=1, cols=len(headers))
    table.style = "Table Grid"
    table.alignment = WD_TABLE_ALIGNMENT.CENTER
    # header row
    hdr_cells = table.rows[0].cells
    for i, h in enumerate(headers):
        hdr_cells[i].text = h
        p = hdr_cells[i].paragraphs[0]
        p.alignment = WD_ALIGN_PARAGRAPH.CENTER
        run = p.runs[0]
        run.bold = True
        run.font.name = "Arial"
        run.font.size = Pt(10.5)
        run.font.color.rgb = RGBColor(255,255,255)
        tc = hdr_cells[i]._tc
        tcPr = tc.get_or_add_tcPr()
        shd = OxmlElement("w:shd")
        shd.set(qn("w:val"), "clear")
        shd.set(qn("w:color"), "auto")
        shd.set(qn("w:fill"), "1F6FAE")
        tcPr.append(shd)
    for row_data in rows_data:
        row = table.add_row()
        for i, cell_text in enumerate(row_data):
            row.cells[i].text = cell_text
            p = row.cells[i].paragraphs[0]
            run = p.runs[0] if p.runs else p.add_run(cell_text)
            run.font.name = "Arial"
            run.font.size = Pt(10)
    doc.add_paragraph()

def add_memory_box(doc, story_text):
    """Add a yellow memory/story box"""
    tbl = doc.add_table(rows=1, cols=1)
    tbl.style = "Table Grid"
    cell = tbl.rows[0].cells[0]
    tc = cell._tc
    tcPr = tc.get_or_add_tcPr()
    shd = OxmlElement("w:shd")
    shd.set(qn("w:val"), "clear")
    shd.set(qn("w:color"), "auto")
    shd.set(qn("w:fill"), "FFF9C4")
    tcPr.append(shd)
    p = cell.paragraphs[0]
    p.clear()
    r = p.add_run("🧠 MEMORY STORY / MNEMONICS")
    r.bold = True
    r.font.name = "Arial"
    r.font.size = Pt(11)
    r.font.color.rgb = RGBColor(180,80,0)
    for line in story_text:
        pb = cell.add_paragraph()
        rb = pb.add_run(line)
        rb.font.name = "Arial"
        rb.font.size = Pt(11)
    doc.add_paragraph()

def add_page_break(doc):
    doc.add_page_break()

def add_separator(doc, text=""):
    p = doc.add_paragraph()
    p.paragraph_format.space_before = Pt(6)
    p.paragraph_format.space_after  = Pt(6)
    run = p.add_run("─" * 70)
    run.font.size = Pt(8)
    run.font.color.rgb = RGBColor(150,150,150)

# ══════════════════════════════════════════════════════════════════════════════
#  COVER PAGE
# ══════════════════════════════════════════════════════════════════════════════
p = doc.add_paragraph()
p.alignment = WD_ALIGN_PARAGRAPH.CENTER
r = p.add_run()
r.add_break()

p2 = doc.add_paragraph()
p2.alignment = WD_ALIGN_PARAGRAPH.CENTER
r2 = p2.add_run("DR. M.G.R. MEDICAL UNIVERSITY")
r2.bold = True; r2.font.name = "Arial"; r2.font.size = Pt(15)
r2.font.color.rgb = RGBColor(0,70,127)

p3 = doc.add_paragraph()
p3.alignment = WD_ALIGN_PARAGRAPH.CENTER
r3 = p3.add_run("2nd Year MBBS — Microbiology")
r3.bold = True; r3.font.name = "Arial"; r3.font.size = Pt(13)

p4 = doc.add_paragraph()
p4.alignment = WD_ALIGN_PARAGRAPH.CENTER
r4 = p4.add_run("ANSWER SHEET")
r4.bold = True; r4.font.name = "Arial"; r4.font.size = Pt(20)
r4.font.color.rgb = RGBColor(0,70,127)

p5 = doc.add_paragraph()
p5.alignment = WD_ALIGN_PARAGRAPH.CENTER
r5 = p5.add_run("Viral Hemorrhagic Fevers & Arboviral Diseases")
r5.bold = True; r5.font.name = "Arial"; r5.font.size = Pt(14)
r5.font.color.rgb = RGBColor(180,40,40)

doc.add_paragraph()
p6 = doc.add_paragraph()
p6.alignment = WD_ALIGN_PARAGRAPH.CENTER
r6 = p6.add_run("Topics Covered:")
r6.bold = True; r6.font.name = "Arial"; r6.font.size = Pt(12)

for topic in [
    "1. Kyasanur Forest Disease (KFD)",
    "2. Chikungunya",
    "3. Ebola Virus Disease (EVD)"
]:
    pt = doc.add_paragraph(topic)
    pt.alignment = WD_ALIGN_PARAGRAPH.CENTER
    pt.runs[0].font.name = "Arial"
    pt.runs[0].font.size = Pt(12)
    pt.runs[0].bold = True

doc.add_paragraph()
p7 = doc.add_paragraph()
p7.alignment = WD_ALIGN_PARAGRAPH.CENTER
r7 = p7.add_run("Sources: Park's Textbook of PSM | Jawetz Medical Microbiology\nHarrison's Principles | Goldman-Cecil Medicine | Red Book 2021")
r7.italic = True; r7.font.name = "Arial"; r7.font.size = Pt(10)
r7.font.color.rgb = RGBColor(80,80,80)

add_page_break(doc)

# ══════════════════════════════════════════════════════════════════════════════
#  SECTION 1 — KYASANUR FOREST DISEASE (KFD)
# ══════════════════════════════════════════════════════════════════════════════
add_heading(doc, "SECTION 1: KYASANUR FOREST DISEASE (KFD)", level=1, color=(0,70,127), center=True)
add_separator(doc)

add_heading(doc, "Q. Write short notes on Kyasanur Forest Disease.", level=2, color=(180,40,40))
add_body(doc, "(OR) Describe the epidemiology, clinical features, laboratory diagnosis, and control of KFD.", italic=True)
doc.add_paragraph()

# Definition
add_heading(doc, "DEFINITION", level=3)
add_body(doc, "Kyasanur Forest Disease (KFD) is an acute febrile hemorrhagic illness caused by KFD virus (KFDV), a member of the Flaviviridae family (Group B arbovirus / togavirus). It is transmitted to humans by the bite of infective hard ticks (Haemaphysalis species). Man is an incidental / dead-end host.")

# Flowchart 1 - Transmission Cycle
add_flowchart_table(doc, [
    "KFDV in Nature: Small mammals (rats, squirrels) = PRIMARY RESERVOIR",
    "Haemaphysalis ticks (H. spinigera, H. turtura) feed on infected rodents → Acquire virus",
    "Tick undergoes transstadial transmission (larva → nymph → adult) — virus persists",
    "Cattle enter forest → attract ticks → population explosion (AMPLIFICATION, not virus reservoir)",
    "Monkeys bitten by infected nymphal ticks → AMPLIFYING hosts → Die from KFD (sentinel event!)",
    "Humans bitten by nymphal ticks while working in forest → KFD disease",
    "NO human-to-human transmission"
], "FLOWCHART 1: KFD Transmission Cycle")

# Epidemiology Box
add_heading(doc, "EPIDEMIOLOGY / DETERMINANTS", level=3)

add_heading(doc, "(a) Agent", level=4, color=(0,100,0))
add_bullet(doc, "KFD virus (KFDV) — Flavivirus (Group B togavirus)")
add_bullet(doc, "Antigenically related to Far Eastern tick-borne encephalitis & Omsk Hemorrhagic Fever")
add_bullet(doc, "Prolonged viremia in man (~10 days) — unlike other arboviruses")
add_bullet(doc, "BSL-3 pathogen")

add_heading(doc, "(b) Host / Reservoir", level=4, color=(0,100,0))
add_bullet(doc, "Reservoir: Small mammals — rats, porcupines, squirrels")
add_bullet(doc, "Amplifying hosts: Monkeys (Bonnet macaque, Black-faced langur) — die from infection")
add_bullet(doc, "Incidental/dead-end host: Man, Cattle (provide blood meals for ticks only)")

add_heading(doc, "(c) Vector", level=4, color=(0,100,0))
add_bullet(doc, "Primary: Haemaphysalis spinigera and H. turtura (hard ticks, ≥15 species implicated)")
add_bullet(doc, "Soft ticks also implicated")
add_bullet(doc, "NYMPHAL stage is most dangerous to humans")

add_heading(doc, "(d) Host Factors", level=4, color=(0,100,0))
add_bullet(doc, "Age: 20–40 years most affected")
add_bullet(doc, "Sex: Males > females (occupational exposure)")
add_bullet(doc, "Occupation: Forest workers, cattle-herders, woodcutters")

add_heading(doc, "(e) Temporal / Geographic Distribution", level=4, color=(0,100,0))
add_bullet(doc, "Endemic foci: Shimoga, North Kannada, South Kannada, Chikmagalur (Karnataka)")
add_bullet(doc, "First recognized: 1957, Shimoga district (called 'Monkey Disease' by locals)")
add_bullet(doc, "Seasonal: January–June (dry months = peak nymphal tick activity)")
add_bullet(doc, "~400–500 cases per year; CFR = 5–10%")

# Clinical Features flowchart
add_flowchart_table(doc, [
    "INCUBATION PERIOD: 3–8 days after tick bite",
    "PHASE 1 (Acute): Sudden high fever + severe headache + myalgia + prostration\n+ GI disturbances (nausea, vomiting, diarrhea)\n+ Hemorrhages: gums, nose, GI tract (in severe cases)\nDuration: ~2 weeks",
    "AFEBRILE INTERVAL: 7–21 days (apparent recovery)",
    "PHASE 2 (Neurological, in ~20%): Return of fever + severe headache\n+ Neck stiffness + coarse tremors + abnormal reflexes + mental disturbances\n= Meningoencephalitis picture",
    "OUTCOME: CFR 5–10% | Survivors recover without sequelae"
], "FLOWCHART 2: KFD Biphasic Clinical Course")

# Lab Diagnosis
add_heading(doc, "LABORATORY DIAGNOSIS OF KFD", level=2, color=(0,70,127))
add_heading(doc, "(As per Apurba Sastry / Standard Microbiology)", level=4, color=(100,100,100))

add_lab_table(doc, [
    ["Specimen", "Blood (acute phase, days 1–10 — during viremia)"],
    ["1. Virus Isolation\n(Gold Standard)", "• Inoculate blood into suckling mice (intracerebral) or Vero cell culture\n• KFDV is a BSL-3 pathogen → requires BSL-3 facility\n• Identification: haemagglutination inhibition (HI), complement fixation (CF), neutralization test"],
    ["2. Molecular Diagnosis\n(Best rapid test)", "• RT-PCR on blood — most sensitive in first 5–7 days of illness\n• Detects KFDV RNA; highly specific\n• Preferred in acute phase when serology not yet positive"],
    ["3. Serology\n(Paired sera required)", "• Haemagglutination Inhibition (HI) test — standard method\n• Complement Fixation (CF) test\n• Serum Neutralization Test\n• ELISA — IgM (acute), IgG (convalescent)\n• ≥4-fold rise in titer between acute & convalescent (14–21 days apart) = diagnostic\n• IgM ELISA = early serodiagnosis"],
    ["4. Antigen Detection", "• Antigen capture ELISA on blood specimens"],
    ["CBC Findings", "• Leukopenia + thrombocytopenia (characteristic)\n• Elevated liver enzymes (ALT, AST)\n• Proteinuria possible"],
    ["Post-mortem", "• Immunohistochemistry (IHC) on liver, spleen, brain tissue"]
], ["Parameter", "Details"])

add_shaded_box(doc, "KEY POINTS: KFD Lab Diagnosis", [
    "• Virus isolation: suckling mice / Vero cells (BSL-3 required)",
    "• RT-PCR: best in acute viremic phase (days 1-10)",
    "• Serology: paired sera — HI, CF, ELISA IgM/IgG",
    "• 4-fold rise in antibody titre = diagnostic",
    "• CBC: leukopenia + thrombocytopenia = classic picture",
    "• Monkey deaths in a forest area = epidemiological alarm bell!"
], shade_rgb="D6E4F0")

# Control
add_heading(doc, "PREVENTION & CONTROL", level=3)
add_bullet(doc, "VACCINATION", bold_prefix="1. ")
add_body(doc, "   Killed KFD vaccine — given to population at risk in endemic areas. Primary schedule: 2 doses.", indent=0.3)
add_bullet(doc, "TICK CONTROL", bold_prefix="2. ")
add_body(doc, "   Acaricides (carbaryl, fenthion, naled, propoxur) — sprayed around monkey-death 'hot spots'", indent=0.3)
add_bullet(doc, "PERSONAL PROTECTION", bold_prefix="3. ")
add_body(doc, "   Full clothing + DEET/DMP insect repellents + daily tick checks + avoid lying on forest floor", indent=0.3)
add_bullet(doc, "CATTLE MOVEMENT RESTRICTION", bold_prefix="4. ")
add_body(doc, "   Restricts tick population explosion", indent=0.3)
add_bullet(doc, "SURVEILLANCE", bold_prefix="5. ")
add_body(doc, "   Karnataka Govt surveillance system: monitor monkey deaths as sentinels + human case tracking", indent=0.3)

# Memory Story for KFD
add_memory_box(doc, [
    "",
    "THE STORY OF 'KYASANUR KA JUNGLE'",
    "",
    "Imagine a forest in Karnataka (Kyasanur) in January 1957.",
    "A woodcutter walks in → steps on MONKEY BODIES all around (dead monkeys = alarm bell! 🐒)",
    "He doesn't know that tiny HAEMAPHYSALIS TICKS (the villains 🦠) are crawling on him.",
    "These ticks had a LONG JOURNEY: Rat → Tick larva → Tick nymph (the biter) → Tick adult",
    "",
    "The woodcutter comes home with FEVER + HEADACHE + MUSCLE PAIN for 2 weeks.",
    "He seems to recover for 2 weeks... then BAM! Brain problems return (Phase 2 = meningitis!)",
    "",
    "MNEMONIC FOR KFD:",
    "  F-L-A-V-I — Flavivirus, Karnataka, Animals(monkeys), Vector(ticks), Incidental host(man)",
    "  '5-10% die' — CFR is 5–10%",
    "  'January to June' — peak season",
    "  'H. spinigera STINGS' — primary vector",
    "",
    "LAB MNEMONIC: 'Very Real Samples Make Easy Confirmation'",
    "  V = Vero cells (isolation), R = RT-PCR, S = Serology (HI/CF/ELISA), M = Mice (suckling),",
    "  E = ELISA IgM, C = CBC (leukopenia + thrombocytopenia)"
])

add_page_break(doc)

# ══════════════════════════════════════════════════════════════════════════════
#  SECTION 2 — CHIKUNGUNYA
# ══════════════════════════════════════════════════════════════════════════════
add_heading(doc, "SECTION 2: CHIKUNGUNYA", level=1, color=(0,70,127), center=True)
add_separator(doc)

add_heading(doc, "Q. Write short notes on Chikungunya. / Describe the clinical features, lab diagnosis and prevention of Chikungunya.", level=2, color=(180,40,40))
doc.add_paragraph()

# Definition
add_heading(doc, "DEFINITION", level=3)
add_body(doc, "Chikungunya is an acute febrile arboviral illness caused by Chikungunya virus (CHIKV), a single-stranded RNA virus belonging to the genus Alphavirus, family Togaviridae. The name means 'that which bends up' (Kimakonde language, Tanzania) — reflecting the stooped posture due to severe joint pain.")

# Etiology box
add_shaded_box(doc, "ETIOLOGY AT A GLANCE", [
    "Virus: Chikungunya virus (CHIKV)",
    "Family: Togaviridae | Genus: Alphavirus",
    "Genome: Single-stranded (+) sense RNA",
    "First isolated: Tanzania, 1952–53 (epidemic in humans and Aedes mosquitoes)",
    "Vector: Aedes aegypti (primary) + Aedes albopictus (secondary)",
    "Three genotypes: Asian, East/Central/South African (ECSA), West African",
    "No animal reservoir — humans are primary amplifying host during epidemics"
], shade_rgb="E8F4FD")

# Transmission flowchart
add_flowchart_table(doc, [
    "Infected Aedes aegypti or Aedes albopictus mosquito\n(Feeds during DAYTIME — unlike Anopheles!)",
    "CHIKV enters human bloodstream → Viremia within 2 days of infection",
    "Another Aedes bites viremic human → Mosquito acquires virus",
    "Extrinsic incubation in mosquito → Infective to next human\n[Other routes: blood transfusion, needle-stick, vertical transmission (rare)]",
    "INCUBATION PERIOD: 4–7 days (range: 1–12 days)"
], "FLOWCHART 3: Chikungunya Transmission")

# Epidemiology
add_heading(doc, "EPIDEMIOLOGY", level=3)
add_bullet(doc, "Distribution: Sub-Saharan Africa, India, SE Asia, Indian Ocean islands, Americas (since 2013)")
add_bullet(doc, "India: Endemic in 24 states + 6 UTs; Karnataka most affected state")
add_bullet(doc, "Re-emergence in India: 2006 (major outbreak)")
add_bullet(doc, "Seasonal: Rainy season (peak Aedes mosquito breeding)")
add_bullet(doc, "Transmission: Aedes bites DURING DAYTIME (key point! — also why bednet is less effective)")
add_bullet(doc, "No human-to-human transmission in routine settings")

# Clinical Features - flowchart
add_flowchart_table(doc, [
    "INCUBATION: 4–7 days",
    "SUDDEN ONSET: High fever (>39°C), chills, headache, photophobia,\nanorexia, lumbago (low back pain), conjunctivitis, lymphadenopathy",
    "DAYS 2–3: Maculopapular rash on trunk & limbs (60–80% cases)\n+ Coffee-coloured vomiting + epistaxis + petechiae\nRash may recur every 3–7 days",
    "DAYS 3–5: ARTHRALGIA (hallmark!) — bilateral symmetric joint pain\nMCP, wrist, elbow, shoulder, knee, ankle, metatarsal joints\nArthritis: pain + swelling + stiffness (can persist months–years!)",
    "RESOLUTION: Fever resolves in 7–10 days (may be biphasic)\nArthralgia may persist as 'chronic chikungunya arthritis'",
    "COMPLICATIONS (rare): Meningoencephalitis, Guillain-Barré syndrome,\nmyocarditis, uveitis, hepatitis, bullous skin lesions\nAt-risk: Neonates (peripartum), >65 yrs, immunocompromised"
], "FLOWCHART 4: Chikungunya — Clinical Course")

# Lab Diagnosis Table
add_heading(doc, "LABORATORY DIAGNOSIS OF CHIKUNGUNYA", level=2, color=(0,70,127))
add_heading(doc, "(Standard / Apurba Sastry principles)", level=4, color=(100,100,100))

add_lab_table(doc, [
    ["Specimen", "Serum (acute phase: 1–7 days)"],
    ["1. Virus Isolation\n(Research / Reference Labs)", "• Intracerebral inoculation in suckling mice\n• Vero cell culture (CPE observed)\n• Requires BSL-2 facility\n• Gold standard but slow"],
    ["2. Molecular (RT-PCR)\n[BEST in first week]", "• Reverse Transcriptase PCR (RT-PCR) on acute serum\n• Detects CHIKV RNA during viremia (Days 1–7)\n• Nested RT-PCR also used\n• Sensitivity >90% in first 5 days\n• Positive result = Definitive diagnosis"],
    ["3. Serology\n[After 1st week]", "• IgM ELISA: Positive from end of 1st week; persists 3–90 days\n  (Remember: prolonged IgM = may indicate past infection!)\n• IgG ELISA: Convalescent phase (seroprotection confirmed)\n• Haemagglutination Inhibition (HI) test\n• Complement Fixation (CF) test\n• Serum Neutralization test\n• PRNT (Plaque Reduction Neutralization Test): Gold standard serology\n  — Discriminates from cross-reacting alphaviruses (Mayaro, O'nyong-nyong)\n• Paired sera: ≥4-fold rise in HI/CF titre = diagnostic"],
    ["4. Antigen Detection", "• Immunohistochemical (IHC) staining of fixed tissue — available at reference centers"],
    ["CBC Findings", "• Lymphopenia (characteristic!)\n• Thrombocytopenia\n• Elevated creatinine\n• Elevated AST, ALT"],
    ["Interpretation", "• Viremia + high fever → RT-PCR is best\n• After 1st week → IgM ELISA preferred\n• PRNT = used to confirm & differentiate from related alphaviruses"]
], ["Parameter", "Details"])

add_shaded_box(doc, "KEY POINTS: CHIKUNGUNYA Lab Diagnosis", [
    "• Phase 1 (acute, Days 1–7): RT-PCR on serum = test of choice",
    "• Phase 2 (after 7 days): IgM ELISA = test of choice",
    "• Virus isolation: suckling mice (intracerebral) / Vero cells",
    "• PRNT: gold standard for serology (discriminates alphaviruses)",
    "• CBC: LYMPHOPENIA + thrombocytopenia (unlike dengue which has more thrombocytopenia)",
    "• Paired sera (HI/CF/Neutralization): ≥4-fold rise = diagnostic"
], shade_rgb="D6E4F0")

# Differential Diagnosis
add_heading(doc, "DIFFERENTIAL DIAGNOSIS", level=3)
add_body(doc, "The 'Big 3' of tropical fever with rash:", bold=True)
add_lab_table(doc, [
    ["Feature", "Chikungunya", "Dengue", "Zika"],
    ["Arthralgia", "Severe, hallmark, persistent", "Mild (bone-breaking fever)", "Mild to moderate"],
    ["Rash", "Maculopapular, can recur", "Maculopapular ± petechiae", "Macular, mild"],
    ["Hemorrhage", "Rare", "Classic (DHF)", "Very rare"],
    ["Thrombocytopenia", "Mild", "Severe (hallmark)", "Mild"],
    ["Lymphopenia", "Present", "Present", "Present"],
    ["Chronic arthritis", "YES — months/years", "No", "No"],
    ["Vector", "Aedes aegypti/albopictus", "Aedes aegypti", "Aedes aegypti/albopictus"]
], ["Feature", "Chikungunya", "Dengue", "Zika"])

# Treatment and Control
add_heading(doc, "TREATMENT", level=3)
add_bullet(doc, "NO specific antiviral treatment available")
add_bullet(doc, "Supportive: rest, fluids, paracetamol/diclofenac sodium for fever & joint pain")
add_bullet(doc, "AVOID aspirin (Reye's syndrome risk in children) and steroids in acute phase")
add_bullet(doc, "AVOID NSAIDs initially in dengue co-endemic areas (risk of hemorrhage if co-infected with dengue)")
add_bullet(doc, "Chronic arthritis: NSAIDs, corticosteroids, physiotherapy; methotrexate, hydroxychloroquine for severe")

add_heading(doc, "PREVENTION & CONTROL", level=3)
add_bullet(doc, "No vaccine available")
add_bullet(doc, "Vector control: eliminate Aedes breeding sites (stagnant water in containers, tyres, coolers)")
add_bullet(doc, "Personal protection: DEET repellents, full-sleeve clothing, window screens")
add_bullet(doc, "Note: insecticide-treated bed nets less effective — Aedes bites during DAYTIME")
add_bullet(doc, "Blood/organ donation screening during outbreaks")
add_bullet(doc, "Targeted residual spraying + space spraying (fogging) during outbreak")

# Memory Story
add_memory_box(doc, [
    "",
    "THE STORY OF 'CHIKU THE BENT-OVER TRAVELER'",
    "",
    "Chiku is a traveler who visits Tanzania in the rainy season.",
    "An Aedes mosquito bites him in the DAYTIME (remember: Aedes = Daytime biter!).",
    "After 4–7 days: Chiku gets FEVER + bends over in joint pain (chi-KUN-gunya = bending up!)",
    "He gets a rash that keeps coming back every 3–7 days (like a 'recurring nightmare').",
    "After 10 days of fever... the joint pain REFUSES to leave for months! (chronic arthritis)",
    "",
    "MNEMONIC: 'Alpha Togavirus Arthralgia Aedes'",
    "  A = Alphavirus, T = Togaviridae, A = Arthralgia (hallmark), A = Aedes (vector)",
    "",
    "TRIAD TO REMEMBER: FEVER + RASH + ARTHRALGIA = CHIKUNGUNYA",
    "",
    "LAB MNEMONIC: 'PCR in Phase 1, IgM in Phase 2'",
    "  Days 1–7: RT-PCR (virus in blood = catch it!)",
    "  After Day 7: IgM ELISA (body making antibodies now)",
    "  PRNT = the final judge (differentiates from similar alphaviruses)",
    "",
    "VECTOR TIP: 'Aedes albopictus is the URBAN spreader' (breeding in flower pots/ACs)"
])

add_page_break(doc)

# ══════════════════════════════════════════════════════════════════════════════
#  SECTION 3 — EBOLA VIRUS DISEASE (EVD)
# ══════════════════════════════════════════════════════════════════════════════
add_heading(doc, "SECTION 3: EBOLA VIRUS DISEASE (EVD)", level=1, color=(0,70,127), center=True)
add_separator(doc)

add_heading(doc, "Q. Write short notes on Ebola virus. / Describe the clinical features, pathogenesis, lab diagnosis and management of EVD.", level=2, color=(180,40,40))
doc.add_paragraph()

# Definition & Virus
add_heading(doc, "DEFINITION", level=3)
add_body(doc, "Ebola Virus Disease (EVD) is a severe, often fatal viral hemorrhagic fever caused by Ebola virus (EBOV), a member of the family Filoviridae, genus Ebolavirus. It causes massive systemic viral replication, hemorrhage, and multiorgan failure with a case fatality rate of 25–90%.")

add_shaded_box(doc, "VIROLOGY AT A GLANCE", [
    "Family: Filoviridae | Genus: Ebolavirus",
    "Genome: Single-stranded negative-sense RNA",
    "Shape: Filamentous (characteristic 'shepherd's crook' or '6' shape)",
    "5 species: Zaire (most fatal), Sudan, Bundibugyo, Tai Forest (Ivory Coast), Reston (non-pathogenic in humans)",
    "BSL-4 pathogen — highest biosafety level required for handling!",
    "Zaire ebolavirus = responsible for largest outbreaks (including 2014–2016 West Africa epidemic)"
])

# Epidemiology
add_heading(doc, "EPIDEMIOLOGY", level=3)
add_bullet(doc, "Geographic distribution: Sub-Saharan Africa (Congo basin, West Africa)")
add_bullet(doc, "Largest outbreak: 2014–2016 West Africa (Guinea, Liberia, Sierra Leone): 28,652 cases, 11,325 deaths")
add_bullet(doc, "2nd largest: 2018–2020 DRC: ~3,470 cases, ~2,287 deaths (66% CFR)")
add_bullet(doc, "Reservoir: Fruit bats (Pteropodidae) — suspected but not yet definitively proven")
add_bullet(doc, "Zoonotic spillover: Primary transmission from infected animals (bats, apes, duikers) to humans")
add_bullet(doc, "Index cases: Often hunters/bush meat handlers")
add_bullet(doc, "Amplification: Person-to-person via direct contact with body fluids")

# Transmission Flowchart
add_flowchart_table(doc, [
    "PRIMARY RESERVOIR: Fruit bats (Pteropodidae)\n[also: non-human primates — apes, monkeys, duikers]",
    "SPILLOVER EVENT: Humans contact infected animal\n(Hunting, handling bushmeat, cave exploration)",
    "INDEX CASE in humans: Viremia + hemorrhagic disease",
    "SECONDARY TRANSMISSION (person-to-person):\nDirect contact with blood/body fluids of sick/deceased patient\nRoutes: broken skin, mucous membranes (eyes, nose, mouth)\nFluids: blood, urine, saliva, sweat, feces, vomit, semen, breastmilk",
    "AMPLIFICATION in hospital / funeral settings\n[Healthcare workers, family caregivers, funeral handlers = HIGH RISK]",
    "IMPORTANT: Ebola is NOT airborne | No food/water transmission\nVirus persists in semen 3–9 months post-recovery!"
], "FLOWCHART 5: Ebola Transmission Chain")

# Pathogenesis
add_heading(doc, "PATHOGENESIS (Simplified)", level=3)
add_body(doc, "Ebola infects monocytes/macrophages and dendritic cells first → massive cytokine storm → endothelial damage → vascular leakage → DIC + coagulopathy + multiorgan failure → hemorrhage.")

add_lab_table(doc, [
    ["Step", "What happens", "Result"],
    ["1", "EBOV infects monocytes, macrophages, dendritic cells", "Impaired innate immunity, antigen presentation failure"],
    ["2", "Massive cytokine release (TNF-α, IL-1, IL-6, IL-8)", "Systemic inflammatory response — 'cytokine storm'"],
    ["3", "Endothelial cell infection → increased vascular permeability", "Fluid leak → hypovolemic shock"],
    ["4", "Hepatocyte infection → liver damage", "Elevated AST, ALT; clotting factor deficiency"],
    ["5", "DIC (disseminated intravascular coagulation)", "Hemorrhage + thrombocytopenia"],
    ["6", "Adrenal gland infection", "Adrenal insufficiency"],
    ["7", "Multiorgan failure", "Death in untreated severe cases (CFR 25–90%)"]
], ["Step", "Event", "Consequence"])

# Clinical Features
add_flowchart_table(doc, [
    "INCUBATION: 2–21 days (average 8–10 days)",
    "PHASE 1 — Dry Phase (Days 1–3): Flu-like\nSudden fever + severe headache + myalgia + arthralgia\n+ Sore throat + weakness",
    "PHASE 2 — Wet Phase (Days 3–7): GI involvement\nWatery diarrhea + vomiting (up to 10L fluid/day!)\n+ Abdominal pain + hiccups",
    "PHASE 3 — Hemorrhagic Phase (Days 7–10 in severe cases):\nGI bleeding + oozing from venepuncture sites\n+ Maculopapular rash (purplish-red) + conjunctival injection\n+ Internal bleeding → melena, hematemesis",
    "COMPLICATIONS: Encephalopathy, delirium, seizures\nShock + multiorgan failure → DEATH (in ~50–90% untreated)",
    "SURVIVORS (if immune response adequate):\nRecovery in 2–3 weeks; long-term: joint pain, eye problems\nVirus persists in immunologically protected sites\n(semen 3–9 months, eye, CNS)"
], "FLOWCHART 6: EVD Clinical Phases")

# Lab Diagnosis (KEY SECTION)
add_heading(doc, "LABORATORY DIAGNOSIS OF EBOLA VIRUS DISEASE", level=2, color=(0,70,127))
add_heading(doc, "(As per standard Microbiology — Apurba Sastry / Jawetz principles)", level=4, color=(100,100,100))

add_shaded_box(doc, "BIOSAFETY WARNING", [
    "All Ebola specimens MUST be handled under BSL-4 conditions.",
    "Virus isolation ONLY at specialized reference/BSL-4 laboratories.",
    "Notify local/state/national health authorities IMMEDIATELY when EVD is suspected.",
    "PPE (full-body suit + gloves + face shield + respirator) mandatory for sample collection."
], title_rgb=(180,0,0), shade_rgb="FFCCCC")

add_lab_table(doc, [
    ["Specimen Type", "Blood (EDTA / serum) for molecular/serology\nOral swabs in deceased patients\nUrine, semen (late stage/surveillance)\nBiopsy: skin, liver, spleen (post-mortem)"],
    ["Timing of Tests", "Viral RNA detectable by RT-PCR within 3 days of symptom onset\n[Note: If sample taken <3 days → need 2 negative PCR ≥48 hrs apart to rule out!]"],
    ["1. RT-PCR\n(TEST OF CHOICE — First-line)", "• Real-time RT-PCR (rRT-PCR) on blood/serum\n• MOST sensitive and specific method\n• Detects EBOV RNA from Day 3 of illness\n• Used by reference labs (CDC/NCDC) and LRN laboratories\n• Sensitivity & specificity >90%\n• Semi-automated cartridge PCR available for field use"],
    ["2. Antigen Detection\n(Rapid field diagnosis)", "• Antigen-Capture ELISA: detects viral proteins (VP40, NP, GP)\n• OraQuick Ebola Rapid Antigen Test (FDA-approved 2019)\n   — First approved RDT for Ebola in USA\n   — Used in symptomatic patients AND recently deceased\n   — All OraQuick results are PRESUMPTIVE — must be confirmed by rRT-PCR"],
    ["3. Virus Isolation\n(Gold Standard — Reference only)", "• Culture in BSL-4 cell lines (Vero E6 cells)\n• Identification by electron microscopy (filamentous morphology!)\n• AND confirmed by RT-PCR / immunofluorescence\n• ONLY at BSL-4 reference laboratories"],
    ["4. Serology\n(Later in disease / survivors)", "• IgM ELISA: appears ~2 weeks after onset; used with RT-PCR\n• IgG ELISA: convalescent phase; persists for 10+ years\n• Antibody detection limited in early/fatal cases (patients die before seroconversion)\n• Important for retrospective studies & surveillance"],
    ["5. Immunohistochemistry\n(Post-mortem)", "• IHC staining of formalin-fixed skin, liver, or spleen tissue\n• Used for postmortem confirmation\n• Detects EBOV antigens in tissue"],
    ["CBC / Chemistry", "• Leukopenia (early) → leukocytosis (later)\n• Thrombocytopenia (severe)\n• ↑ AST, ALT (liver damage)\n• ↑ Creatinine, ↓ Na+ (electrolyte imbalance)\n• Prolonged PT/aPTT → DIC picture"],
    ["Differential Diagnosis\n(Must rule out first!)", "Malaria (MOST IMPORTANT) + Typhoid + Dengue + Lassa fever\n+ Measles + Influenza + Gram-negative sepsis\n(These are MUCH more common than Ebola in endemic areas!)"]
], ["Parameter", "Details"])

add_shaded_box(doc, "KEY POINTS: EBOLA Lab Diagnosis", [
    "• First-line test: rRT-PCR (detects RNA, available Day 3 onwards)",
    "• Gold standard: Virus isolation in BSL-4 lab (Vero E6 cells)",
    "• Rapid field test: OraQuick Antigen RDT (all results presumptive — confirm by PCR!)",
    "• Serology: limited early (patients may die before antibodies form); IgM/IgG ELISA",
    "• Post-mortem: IHC on skin/liver/spleen (also oral swab for PCR)",
    "• CBC: thrombocytopenia + elevated liver enzymes + DIC picture",
    "• BSL-4 required for all culture work!"
], shade_rgb="D6E4F0")

# Treatment
add_heading(doc, "TREATMENT", level=3)
add_bullet(doc, "PRIMARY: Aggressive supportive care")
add_bullet(doc, "IV fluids (Lactated Ringer's preferred over Normal Saline) — volumes can be 10L/day!", bold_prefix="  • ")
add_bullet(doc, "Vasopressors for shock, O2 therapy, analgesics, antipyretics, nutritional support", bold_prefix="  • ")
add_bullet(doc, "Treat secondary infections (antibiotics covering GI flora — translocation risk)", bold_prefix="  • ")
add_bullet(doc, "SPECIFIC antivirals:")
add_bullet(doc, "Atoltivimab + Maftivimab + Odesivimab (Inmazeb) — FDA-approved monoclonal antibody cocktail (2020), for Zaire ebolavirus", bold_prefix="  • ")
add_bullet(doc, "Ansuvimab (Ebanga) — FDA-approved single monoclonal antibody (2020)", bold_prefix="  • ")
add_bullet(doc, "Remdesivir — used in some outbreaks (investigational for EVD)", bold_prefix="  • ")

add_heading(doc, "PREVENTION & CONTROL", level=3)
add_bullet(doc, "VACCINE: rVSV-ZEBOV (Ervebo) — FDA/EMA approved live-attenuated vaccine for Zaire ebolavirus; used in ring vaccination strategy")
add_bullet(doc, "ISOLATION: strict contact/droplet precautions; PPE for all HCW")
add_bullet(doc, "SAFE BURIAL practices (virus survives in corpses!)")
add_bullet(doc, "Contact tracing + 21-day monitoring period")
add_bullet(doc, "Avoid bushmeat consumption in outbreak areas")
add_bullet(doc, "No airborne precautions needed in routine care (not airborne virus)")

# Memory Story for Ebola
add_memory_box(doc, [
    "",
    "THE STORY OF 'EBOLA IN THE JUNGLE'",
    "",
    "A hunter in DRC (Congo) catches a BAT 🦇 and eats it for dinner.",
    "After 8–10 days: FEVER, headache, body aches — looks like malaria (always rule out malaria first!)",
    "Days 3–7: He can't stop VOMITING and DIARRHEA (10 litres a day! — his body is flooding out)",
    "Days 7–10: He starts BLEEDING — nose, gums, GI tract. The virus has destroyed his clotting!",
    "His family nurses him → they get it too. The hospital gets it. This is how 28,000 got infected.",
    "",
    "MNEMONIC: 'FILOVIRUS FIGHTS FAST'",
    "  F = Filoviridae family",
    "  I = Isolated in BSL-4",
    "  L = Long filamentous shape (shepherd's crook on EM)",
    "  O = Outbreak amplified by funerals & hospitals",
    "  V = Viremia detectable Day 3 by RT-PCR",
    "  I = Incubation 2–21 days (average 8–10)",
    "  R = Reservoir = Fruit bats (suspected)",
    "  U = Untreated CFR = 25–90%",
    "  S = Semen persistence 3–9 months!",
    "",
    "LAB MNEMONIC: 'RAVIS = Rule out, Antigen RDT, Virus isolation (BSL-4), IHC (post-mortem), Serology'",
    "  R = rRT-PCR first-line, A = Antigen ELISA / OraQuick RDT",
    "  V = Vero cell culture (BSL-4 only), I = IHC on post-mortem tissue",
    "  S = Serology (IgM/IgG ELISA) for survivors",
    "",
    "THE '3 PHASES' HOOK: DRY → WET → BLOODY",
    "  Dry = flu-like, Wet = diarrhea/vomiting, Bloody = hemorrhage"
])

add_page_break(doc)

# ══════════════════════════════════════════════════════════════════════════════
#  QUICK COMPARISON TABLE (Exam favourite!)
# ══════════════════════════════════════════════════════════════════════════════
add_heading(doc, "QUICK COMPARISON TABLE", level=1, color=(0,70,127), center=True)
add_heading(doc, "(KFD vs. Chikungunya vs. Ebola — Exam Gold!)", level=2, color=(180,40,40), center=True)
add_separator(doc)

add_lab_table(doc, [
    ["Causative agent",     "KFD virus (Flavivirus)", "Chikungunya virus (Alphavirus)", "Ebola virus (Filovirus)"],
    ["Family",             "Flaviviridae",            "Togaviridae",                    "Filoviridae"],
    ["Genome",             "ssRNA (+)",                "ssRNA (+)",                      "ssRNA (-)"],
    ["Vector",             "Haemaphysalis ticks",      "Aedes aegypti/albopictus",       "None (direct contact)"],
    ["Reservoir",          "Rodents (rats, squirrels)", "Humans (epidemic) / Primates",  "Fruit bats (suspected)"],
    ["Amplifying host",    "Monkeys (die from it)",    "Humans",                         "Non-human primates"],
    ["Incubation",         "3–8 days",                 "4–7 days",                       "2–21 days (avg 8–10)"],
    ["Key clinical sign",  "Biphasic fever + hemorrhage + meningitis (Phase 2)", "Arthralgia (hallmark) + rash", "Wet diarrhea/vomiting + hemorrhage + multiorgan failure"],
    ["CFR",                "5–10%",                    "Very rare (near 0%)",            "25–90% (avg ~50%)"],
    ["Lab test (acute)",   "RT-PCR + HI/CF serology",  "RT-PCR (Day 1–7), then IgM ELISA", "rRT-PCR (Day 3+) + Antigen ELISA"],
    ["Virus isolation",    "Suckling mice / Vero (BSL-3)", "Suckling mice / Vero (BSL-2)", "Vero E6 cells (BSL-4 ONLY)"],
    ["Specific CBC",       "Leukopenia + thrombocytopenia", "Lymphopenia + thrombocytopenia", "Thrombocytopenia + elevated LFT + DIC"],
    ["Vaccine",            "Killed KFD vaccine",       "None",                           "rVSV-ZEBOV (Ervebo) — live-attenuated"],
    ["Treatment",          "Supportive",               "Paracetamol/NSAIDs (no aspirin)", "Supportive + Inmazeb/Ebanga (mAbs)"],
    ["Notifiable disease", "Yes (India)",               "Yes (India)",                   "Yes (International quarantine disease)"],
    ["H2H transmission",   "NO",                        "No (except blood/vertical)",    "YES (major feature — contact with fluids)"],
    ["BSL required",       "BSL-3",                    "BSL-2",                          "BSL-4"]
], ["Parameter", "KFD", "Chikungunya", "Ebola"])

# Final Exam Tips Box
add_heading(doc, "EXAM TIPS & IMPORTANT ONE-LINERS", level=2, color=(0,70,127))
add_shaded_box(doc, "Must-Know for Dr. MGR University Exams", [
    "1. KFD: First recognized in SHIMOGA (Karnataka), 1957 — called 'Monkey Disease'",
    "2. KFD: Vector = Haemaphysalis spinigera (nymphal stage bites humans)",
    "3. KFD: Man is DEAD-END / INCIDENTAL host — no human-to-human transmission",
    "4. KFD: Biphasic illness — Phase 2 = meningitic phase (after 7–21 days of remission)",
    "5. KFD: CFR = 5–10% | Vaccine: Killed vaccine available",
    "6. Chikungunya: Alphavirus | Togaviridae — remember: 'ALPHA TOGA'",
    "7. Chikungunya: Hallmark = ARTHRALGIA persisting months to years",
    "8. Chikungunya: Aedes bites DAYTIME (why bednet is less useful!)",
    "9. Chikungunya: RT-PCR = Day 1–7 | IgM ELISA = After Day 7",
    "10. Chikungunya: PRNT = gold standard serology (discriminates from Mayaro, O'nyong-nyong)",
    "11. Ebola: Filovirus | BSL-4 | Filamentous 'shepherd's crook' on EM",
    "12. Ebola: Reservoir = fruit bats | Amplification = person-to-person via body fluids",
    "13. Ebola: Semen persistence = 3–9 MONTHS post-recovery (important for sexual transmission!)",
    "14. Ebola: rRT-PCR = test of choice | OraQuick RDT = all results PRESUMPTIVE",
    "15. Ebola: If sample taken <3 days onset → need 2 negative PCRs ≥48 hrs apart to rule out",
    "16. Ebola: Vaccine = rVSV-ZEBOV (Ervebo) | Treatment mAbs = Inmazeb + Ebanga (FDA-approved)",
    "17. All 3 diseases: Virus isolation uses VERO CELLS or suckling mice",
    "18. All 3 diseases: RT-PCR is the BEST early/acute phase diagnostic test",
    "19. DIFFERENTIAL: Malaria MUST always be ruled out first in any tropical hemorrhagic fever!",
    "20. KFD + Ebola = Viral Hemorrhagic Fevers | Chikungunya = Arboviral fever (not primarily hemorrhagic)"
])

doc.save("/tmp/workspace/microbiology-answers/Microbiology_Answersheet_KFD_Chikungunya_Ebola.docx")
print("Document created successfully!")