A 2 year 3months old child has been presented with fever and vomiting

A 2 year 3months old child has been presented with fever and vomiting of 10days duration. O/E: GCS 10/15. He weighed 7kgs and height – 78cms. CNS examination revealed left 6th nerve palsy, a brisk knee reflex with extensor plantar reflex. Neck stiffness was present. a) What is the likely diagnosis? What are the points in favour of the diagnosis? b) How would you investigate this child? c) How would you manage this child?

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tuberculous meningitis child management anti-TB drugs dosage dexamethasone 2025 guidelines

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Clinical Case: 2-year 3-month-old child with fever, vomiting, altered consciousness, and meningismus

a) Likely Diagnosis and Points in Favour

Diagnosis: Tuberculous Meningitis (TBM)

Additional note - Nutritional status: Before addressing TBM, it is important to flag that this child weighs 7 kg at age 2 years 3 months (expected ~12-13 kg) and has a height of 78 cm (expected ~87 cm). This represents severe acute-on-chronic malnutrition (weight-for-height severely low, height-for-age stunted). Malnutrition is a major risk factor for TB and for severe CNS infections generally.

Points in Favour of TBM

Feature	Relevance
Subacute onset (10 days)	TBM characteristically presents over 5-30 days, unlike acute bacterial meningitis (hours to days). Average duration before diagnosis is ~12 days - this case fits exactly.
Fever	Universal in TBM. Typically low-grade and prolonged in TB.
Vomiting	Reflects raised intracranial pressure (ICP) - classic in TBM due to basilar exudate causing CSF flow obstruction.
GCS 10/15 (altered consciousness)	TBM causes encephalopathy. Patients present as lethargic, stuporous, or comatose; this child has significant depression of consciousness.
Left 6th (abducens) nerve palsy	TBM is predominantly a basal meningitis. The inflammatory exudate at the base of the brain preferentially involves cranial nerves III, IV, VI, and VII. The 6th nerve has the longest intracranial course and is most commonly affected. Cranial nerve palsies are a hallmark of TBM in children. The 6th nerve is also stretched in raised ICP as a "false localizing sign."
Brisk knee reflexes + extensor plantar response (upgoing Babinski)	These upper motor neuron (UMN) signs indicate corticospinal tract involvement - seen due to cerebral vasculitis, hydrocephalus, or direct parenchymal involvement. TBM causes arteritis of vessels at the base of the brain (internal capsule territory).
Neck stiffness (meningismus)	Direct evidence of meningeal irritation from subarachnoid space contamination.
Severe malnutrition	Both a risk factor for TB disease and for TBM specifically. TB is far more common in malnourished children with impaired cell-mediated immunity.
Age group (2 years)	TBM accounts for up to 10% of all TB cases in children, compared to ~1% in adults. Children under 5 are at highest risk of disseminated and CNS TB following primary infection.
Combination of basal signs + raised ICP + long duration	This triad (cranial nerve palsy + pyramidal signs + subacute course) is classical for TBM and should prompt immediate treatment even before microbiologic confirmation.

MRC (Medical Research Council) Staging - this child fits Stage II TBM (GCS 10, focal neurological signs present but patient not deeply comatose; contrast with Stage I - alert with no focal signs, and Stage III - comatose or severe deficits).

b) Investigation

Urgent/Immediate

1. Lumbar Puncture (LP) with CSF Analysis This is the cornerstone investigation. Perform after excluding papilledema and raised ICP on clinical grounds (or after CT if indicated - see below).

Expected CSF findings in TBM:

Parameter	Expected Finding
Opening pressure	Elevated
Appearance	Clear/xanthochromic, forms a cobweb clot on standing
WBC count	10-500 cells/µL (usually 100-500)
Cell type	Predominantly lymphocytes (65-75%); early disease may show polymorphs
Protein	Elevated >100 mg/dL (very high protein >500 mg/dL is poor prognostic sign)
Glucose	Low (CSF:serum glucose ratio <0.5; often <45 mg/dL) - but rarely <20 mg/dL
Acid-fast bacilli smear	Positive in only 10-20%
Culture for M. tuberculosis	Positive in 2-50%; takes 4-8 weeks; gold standard
CSF PCR (MTB)	Rapid; sensitivity 25-80%, specificity >95% - best available rapid test
Adenosine deaminase (ADA)	Elevated (>10 IU/L) - supports diagnosis

2. Neuroimaging - CT/MRI Brain

CT brain with contrast (before LP if papilledema, focal deficit, or clinical raised ICP concern): shows basal meningeal enhancement, hydrocephalus (communicating or obstructive), periventricular ooze, infarcts, tuberculomas
MRI brain is superior: better demonstrates basal exudate, vasculitic infarcts (internal capsule, basal ganglia), tuberculomas, and spinal involvement

3. Chest X-ray

50% of TBM patients have abnormal CXR; look for miliary mottling (1-2 mm nodules throughout both lung fields - "snowstorm" pattern), hilar lymphadenopathy, primary complex, consolidation. Miliary TB is strongly associated with TBM.

4. Tuberculin Skin Test (TST) / Mantoux

5 TU PPD intradermally; read at 48-72 hours; induration ≥10 mm (≥5 mm if malnourished/immunocompromised) is significant
May be negative in up to 50% of TBM cases (anergy from severe disease or malnutrition) - a negative result does not exclude TBM

5. Bacteriologic Investigations for MTB

Gastric aspirate (3 consecutive early-morning samples) - best non-invasive TB culture source in children who cannot expectorate
Sputum/bronchial lavage if possible
Blood culture (BACTEC) for mycobacteria in miliary/disseminated disease
Urine AFB and culture

6. Blood Investigations

Complete blood count (CBC): lymphocytosis, anemia of chronic disease
ESR: elevated
CRP: elevated
Serum electrolytes: hyponatremia from SIADH is common in TBM
Blood glucose (to compare with CSF glucose ratio)
Liver function tests (baseline before starting anti-TB drugs - isoniazid and rifampicin are hepatotoxic)
HIV serology (ELISA) - mandatory, as HIV dramatically worsens TBM prognosis
Blood urea, creatinine

7. GeneXpert MTB/RIF (Xpert Ultra) on CSF

WHO-recommended rapid molecular test; detects MTB and rifampicin resistance within 2 hours from CSF
Sensitivity ~50-60% on CSF but far faster than culture; should be sent on CSF whenever TBM is suspected

8. Ophthalmologic Examination

Fundoscopy: papilledema (raised ICP), choroid tubercles (pathognomonic of miliary TB - yellowish-white discrete lesions), optic atrophy

9. Anthropometric Assessment + Nutritional workup

Weight-for-height Z-score, MUAC, serum albumin - given the severe malnutrition in this child

c) Management

Management has three pillars: anti-TB chemotherapy, adjunctive corticosteroids, and supportive/general care. Neurosurgical involvement should be available.

1. Anti-TB Chemotherapy

For CNS TB (TBM/miliary) in children under 15 years, current guidelines (WHO 2024/2025; NDoH 2024) recommend:

Intensive phase (2 months) - 4 drugs:

Drug	Dose	Route
Isoniazid (H)	15-20 mg/kg/day (max 450 mg)	Oral
Rifampicin (R)	22.5-30 mg/kg/day (max 900 mg)	Oral
Pyrazinamide (Z)	35-45 mg/kg/day (max 2 g)	Oral
Ethionamide (Eto)	17.5-22.5 mg/kg/day (max 1 g)	Oral (preferred 4th drug for CNS TB - better CNS penetration than ethambutol)

Why ethionamide over ethambutol? Ethambutol has poor CSF penetration once meningeal inflammation resolves. Ethionamide penetrates the CNS well. Some centers use fluoroquinolones (levofloxacin) as the 4th drug - also excellent CNS penetration and preferred in MDR-TB. Per Medscape/ATS guidelines, the preferred pediatric regimen is INH + RIF + PZA + ethionamide (or aminoglycoside) intensively.

Continuation phase (7-10 months) - 2 drugs:

Isoniazid + Rifampicin (daily)
Total duration: 9-12 months for TBM (vs. 6 months for pulmonary TB)

Current 2025 guidelines per ATS/CDC/ERS/IDSA 2025 guideline update support this extended duration for CNS disease. The SURE trial (ongoing, 2025) is evaluating whether 6 months of intensified treatment may be sufficient in children.

Pyridoxine (Vitamin B6): 5-10 mg/day orally - given with isoniazid to prevent isoniazid-induced peripheral neuropathy.

2. Adjunctive Corticosteroids (MANDATORY in TBM)

A systematic review and meta-analysis shows corticosteroids reduce TBM mortality by ~25% - Murray & Nadel's Textbook of Respiratory Medicine, p.1199.

Dexamethasone is preferred (better CNS penetration than prednisolone):

Per MSF Medical Guidelines:

Child: Dexamethasone 0.6 mg/kg/day IV/PO once daily for 4 weeks, then taper off over 4 weeks (total 8 weeks)

For this child (7 kg): ~4 mg/day dexamethasone for 4 weeks, then gradual taper.

Give IV initially if the child cannot take oral medications; switch to oral when improving.

3. Supportive and General Management

Immediate:

Secure IV access; monitor vitals continuously (GCS, BP, pulse, SpO2, temperature)
Nursed 30° head elevation to reduce ICP
Strict fluid balance - fluid restrict to 2/3 maintenance if SIADH suspected (hyponatremia is common)
Serum electrolytes monitoring every 12-24 hours; treat hyponatremia cautiously (gradual correction)
Nasogastric tube if GCS <10 or unable to feed safely
Bladder catheterization for strict urine output monitoring
DVT prophylaxis is not applicable at this age

Raised ICP management:

Mannitol 0.25-0.5 g/kg IV over 20-30 min if signs of acute herniation (unequal pupils, Cushing's triad)
Elevate head of bed; avoid neck flexion
Hyperventilation (target pCO2 35 mmHg) if mechanically ventilated and herniation imminent

Seizure management:

UMN signs and altered consciousness in TBM predispose to seizures
Prophylactic anticonvulsants are not routinely given but treat active seizures with lorazepam 0.1 mg/kg IV, followed by phenobarbitone (10-20 mg/kg loading)
EEG if subclinical seizures suspected

Nutritional rehabilitation:

This child has severe malnutrition - a significant additional concern
Therapeutic feeding (F75 initially, then F100 or ready-to-use therapeutic food per SAM protocol)
Monitor for refeeding syndrome
Vitamin A supplementation (200,000 IU single dose given severe malnutrition)

Hydrocephalus:

Monitor clinically (increasing head circumference, worsening GCS, sunset sign)
CT brain if clinical deterioration
Refer neurosurgery if communicating hydrocephalus - serial LPs can temporarily reduce CSF pressure; obstructive hydrocephalus requires VP shunt or external ventricular drain

Contact tracing and source case:

Screen all household contacts for TB
Identify the index/source case (usually an adult with active pulmonary TB in the household)

Monitoring on anti-TB drugs:

LFTs at baseline, 2 weeks, then monthly (hepatotoxicity from INH + RIF + PZA)
Visual acuity if ethambutol is used instead of ethionamide
CBC for anemia

Outcome counseling:

TBM is one of the most severe forms of TB - mortality ~25-50% even with treatment
Survivors carry significant morbidity: epilepsy, motor deficits, intellectual disability, hydrocephalus, visual/hearing impairment
Stage II TBM (as in this child) has a better prognosis than Stage III

Key References:

Murray & Nadel's Textbook of Respiratory Medicine, Central Nervous System Tuberculosis, pp. 1199-1200
Plum and Posner's Diagnosis and Treatment of Stupor and Coma, Tuberculous Meningitis, p. 421
ROSEN's Emergency Medicine, Tuberculous Meningitis
WHO/NDoH 2024 Paediatric TB guidelines (via TB Think Tank, 2025)
ATS/CDC/ERS/IDSA 2025 Clinical Practice Guideline on TB Treatment
MSF Medical Guidelines - Adjunctive corticosteroids in TBM

Create a summary guide on CSF interpretation in meningitis differentials

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Running Command

mkdir -p /tmp/workspace/csf-guide && ls /tmp/workspace/csf-guide/

Writing File

~/csf-guide/build_csf_guide.py

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

# ── Colour palette ──────────────────────────────────────────────────────────
NAVY       = HexColor("#1A2E4A")
BLUE       = HexColor("#1F6FBF")
LIGHT_BLUE = HexColor("#D6E8F7")
TEAL       = HexColor("#0D7C7C")
TEAL_LIGHT = HexColor("#D0F0F0")
RED        = HexColor("#C0392B")
RED_LIGHT  = HexColor("#FADBD8")
AMBER      = HexColor("#D68910")
AMBER_LIGHT= HexColor("#FCF3CF")
GREEN      = HexColor("#1E8449")
GREEN_LIGHT= HexColor("#D5F5E3")
PURPLE     = HexColor("#6C3483")
PURPLE_LIGHT=HexColor("#E8DAEF")
GREY_LIGHT = HexColor("#F2F4F4")
GREY_MID   = HexColor("#BFC9CA")
GREY_DARK  = HexColor("#5D6D7E")
WHITE      = white
BLACK      = black

OUTPUT = "/tmp/workspace/csf-guide/CSF_Interpretation_Guide.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    leftMargin=1.8*cm, rightMargin=1.8*cm,
    topMargin=2*cm, bottomMargin=2*cm,
    title="CSF Interpretation in Meningitis Differentials",
    author="Orris Medical Education",
)

W, H = A4
CONTENT_W = W - 3.6*cm   # usable width

styles = getSampleStyleSheet()

# ── Custom paragraph styles ─────────────────────────────────────────────────
def S(name, **kw):
    return ParagraphStyle(name, **kw)

sTitle = S("sTitle", fontName="Helvetica-Bold", fontSize=22,
           textColor=WHITE, alignment=TA_CENTER, leading=28)
sSubtitle = S("sSubtitle", fontName="Helvetica", fontSize=12,
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sTag = S("sTag", fontName="Helvetica-Bold", fontSize=9,
         textColor=AMBER, alignment=TA_CENTER)

sH1 = S("sH1", fontName="Helvetica-Bold", fontSize=14,
        textColor=WHITE, leading=18)
sH2 = S("sH2", fontName="Helvetica-Bold", fontSize=12,
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sH3 = S("sH3", fontName="Helvetica-Bold", fontSize=10,
        textColor=TEAL, leading=14)

sBody = S("sBody", fontName="Helvetica", fontSize=9,
          textColor=HexColor("#2C3E50"), leading=13, spaceAfter=3,
          alignment=TA_JUSTIFY)
sBullet = S("sBullet", fontName="Helvetica", fontSize=9,
            textColor=HexColor("#2C3E50"), leading=13,
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sNote = S("sNote", fontName="Helvetica-Oblique", fontSize=8,
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sTableH = S("sTableH", fontName="Helvetica-Bold", fontSize=8,
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sTableCell = S("sTableCell", fontName="Helvetica", fontSize=8,
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sTableCellL = S("sTableCellL", fontName="Helvetica", fontSize=8,
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sTableCellB = S("sTableCellB", fontName="Helvetica-Bold", fontSize=8,
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sCellNote = S("sCellNote", fontName="Helvetica-Oblique", fontSize=7,
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sCaption = S("sCaption", fontName="Helvetica-Oblique", fontSize=7.5,
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sRef = S("sRef", fontName="Helvetica-Oblique", fontSize=7,
         textColor=GREY_DARK, leading=10, spaceAfter=1)

# ── Helper flowables ─────────────────────────────────────────────────────────
def rule(color=BLUE, thickness=1.5, space=6):
    return HRFlowable(width="100%", thickness=thickness, color=color,
                      spaceAfter=space, spaceBefore=space)

def section_header(text, color=BLUE):
    tbl = Table([[Paragraph(text, sH1)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("ROUNDEDCORNERS", [5,5,5,5]),
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        ("LEFTPADDING", (0,0), (-1,-1), 12),
        ("RIGHTPADDING", (0,0), (-1,-1), 12),
    ]))
    return tbl

def info_box(text, bg=LIGHT_BLUE, border=BLUE):
    tbl = Table([[Paragraph(text, sBody)]], colWidths=[CONTENT_W])
    tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), bg),
        ("BOX", (0,0), (-1,-1), 1.2, border),
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        ("BOTTOMPADDING", (0,0), (-1,-1), 7),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
    ]))
    return tbl

def bullet(text):
    return Paragraph(f"\u2022  {text}", sBullet)

story = []

# ════════════════════════════════════════════════════════════════════════════
# PAGE 1 – TITLE BANNER
# ════════════════════════════════════════════════════════════════════════════
banner = Table(
    [[Paragraph("CSF Interpretation in Meningitis", sTitle)],
     [Paragraph("A Differential Diagnosis Guide for Medical Students", sSubtitle)],
     [Spacer(1, 6)],
     [Paragraph("Orris Medical Education  •  August 2026", sTag)]],
    colWidths=[CONTENT_W]
)
banner.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), NAVY),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING", (0,0), (-1,-1), 16),
    ("RIGHTPADDING", (0,0), (-1,-1), 16),
    ("ROUNDEDCORNERS", [8,8,8,8]),
]))
story += [banner, Spacer(1, 10)]

# ── INTRODUCTION BOX ───────────────────────────────────────────────────────
story += [
    section_header("Why CSF Analysis Matters"),
    Spacer(1, 6),
    Paragraph(
        "Cerebrospinal fluid (CSF) analysis via lumbar puncture is the cornerstone investigation "
        "in any patient with suspected meningitis. The pattern of abnormalities — opening pressure, "
        "cell count and differential, protein, and glucose — reliably distinguishes the four major "
        "categories of meningitis and guides urgent empiric treatment, often before culture results "
        "are available. This guide summarises normal CSF values, the classic profiles of each "
        "meningitis type, and the key investigations and clinical pearls for each.",
        sBody),
    Spacer(1, 6),
]

# ── NORMAL CSF VALUES BOX ──────────────────────────────────────────────────
story += [
    Paragraph("Normal CSF Reference Values (Adult)", sH2),
]

normal_data = [
    [Paragraph("Parameter", sTableH),
     Paragraph("Normal Range", sTableH),
     Paragraph("Clinical Note", sTableH)],
    [Paragraph("Opening Pressure", sTableCellL),
     Paragraph("70–180 mm H₂O", sTableCell),
     Paragraph("Measured with patient lateral decubitus; >200 = raised ICP", sTableCellL)],
    [Paragraph("Appearance", sTableCellL),
     Paragraph("Clear, colourless", sTableCell),
     Paragraph("Xanthochromia → SAH or high protein; turbidity → infection", sTableCellL)],
    [Paragraph("WBC count", sTableCellL),
     Paragraph("0–5 cells/µL", sTableCell),
     Paragraph("Predominantly lymphocytes in adults", sTableCellL)],
    [Paragraph("RBC", sTableCellL),
     Paragraph("0 (non-traumatic)", sTableCell),
     Paragraph("Traumatic tap → correct WBC by 1 WBC per 700 RBC", sTableCellL)],
    [Paragraph("Glucose", sTableCellL),
     Paragraph("50–75 mg/dL  (2.8–4.2 mmol/L)", sTableCell),
     Paragraph("CSF:serum ratio >0.6 is normal; always send paired serum glucose", sTableCellL)],
    [Paragraph("Protein", sTableCellL),
     Paragraph("15–45 mg/dL  (0.15–0.45 g/L)", sTableCell),
     Paragraph("Elevated with BBB disruption, infection, or malignancy", sTableCellL)],
    [Paragraph("Gram stain / Culture", sTableCellL),
     Paragraph("Negative", sTableCell),
     Paragraph("Any positive is abnormal", sTableCellL)],
]

col_w = [CONTENT_W*0.22, CONTENT_W*0.28, CONTENT_W*0.50]
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t_normal.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), NAVY),
    ("BACKGROUND", (0,1), (-1,1), GREY_LIGHT),
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    ("BACKGROUND", (0,3), (-1,3), GREY_LIGHT),
    ("BACKGROUND", (0,4), (-1,4), WHITE),
    ("BACKGROUND", (0,5), (-1,5), GREY_LIGHT),
    ("BACKGROUND", (0,6), (-1,6), WHITE),
    ("BACKGROUND", (0,7), (-1,7), GREY_LIGHT),
    ("GRID", (0,0), (-1,-1), 0.5, GREY_MID),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 7),
    ("RIGHTPADDING", (0,0), (-1,-1), 7),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
]))
story += [t_normal, Spacer(1, 4),
          Paragraph("Note: Neonates and young infants have higher normal WBC and protein — always use age-adjusted reference ranges.", sNote),
          Spacer(1, 10)]

# ════════════════════════════════════════════════════════════════════════════
# MASTER COMPARISON TABLE
# ════════════════════════════════════════════════════════════════════════════
story += [
    section_header("Master CSF Profile Comparison", NAVY),
    Spacer(1, 8),
]

# Column headers
hdrs = ["Parameter", "Normal", "Bacterial", "Viral (Aseptic)", "Tuberculous", "Cryptococcal/Fungal"]
hdr_row = [Paragraph(h, sTableH) for h in hdrs]

cw = [CONTENT_W*0.18, CONTENT_W*0.10, CONTENT_W*0.155, CONTENT_W*0.155, CONTENT_W*0.155, CONTENT_W*0.155]

rows = [
    ["Opening\nPressure",      "< 180\nmm H₂O",   "↑↑\n200–500",       "↑ or normal\n<200",  "↑\n200–400",       "↑↑↑\nOften >400"],
    ["Appearance",             "Clear",             "Turbid/\nPurulent",  "Clear",              "Clear/ slight\nturbid", "Clear"],
    ["WBC (/µL)",              "0–5",               "100–5000\n(up to 10 000)", "10–1000",     "50–300",           "20–500"],
    ["Predominant\nCell Type", "Lymphocyte",        "Neutrophils\n(PMN)", "Lymphocytes",        "Lymphocytes\n(early: PMN)", "Lymphocytes"],
    ["Protein\n(mg/dL)",       "15–45",             "100–500",            "50–100",             "50–300",           ">45\n(often 100–500)"],
    ["Glucose\n(mg/dL)",       "50–75",             "< 40\n(<45% serum)", "Normal\n(40–80)",    "< 45\n(low)",      "< 40\n(very low)"],
    ["CSF:Serum\nGlucose",     "> 0.6",             "< 0.4",              "Normal\n≥ 0.6",      "< 0.5",            "< 0.4"],
    ["Gram Stain",             "Negative",          "Positive\n>60%",     "Negative",           "Negative",         "Negative"],
    ["Key Special\nTest",      "—",                 "Culture\n(>80%+)\nBlood culture", "Virus-specific\nPCR", "AFB smear/\nCulture/PCR\nADA", "India ink\nCryptococcal\nAntigen (CrAg)"],
    ["Cobweb Clot",            "Absent",            "Absent",             "Absent",             "Present\n(classic!)", "Absent"],
]

data = [hdr_row]

# row backgrounds alternating; special colour for critical cells
row_bgs = [GREY_LIGHT, WHITE] * 10

for i, row in enumerate(rows):
    cells = [Paragraph(row[0], sTableCellB)]
    for val in row[1:]:
        cells.append(Paragraph(val, sTableCell))
    data.append(cells)

master_tbl = Table(data, colWidths=cw, repeatRows=1)

ts = TableStyle([
    # Header row
    ("BACKGROUND", (0,0), (-1,0), NAVY),
    ("GRID", (0,0), (-1,-1), 0.4, GREY_MID),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 5),
    ("RIGHTPADDING", (0,0), (-1,-1), 5),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
    # Alternating rows
    *[("BACKGROUND", (0,i+1), (-1,i+1), row_bgs[i]) for i in range(len(rows))],
    # Colour-code critical values
    # Bacterial – glucose very low (row 5, col 2), PMN (row 3, col 2)
    ("BACKGROUND", (2,6), (2,6), RED_LIGHT),   # glucose
    ("BACKGROUND", (2,4), (2,4), RED_LIGHT),   # PMN
    ("BACKGROUND", (2,5), (2,5), RED_LIGHT),   # protein high
    # Viral – glucose normal (row 5, col 3)
    ("BACKGROUND", (3,6), (3,6), GREEN_LIGHT),
    # TBM – cobweb (row 9, col 4)
    ("BACKGROUND", (4,10), (4,10), AMBER_LIGHT),
    # Crypto – very high pressure
    ("BACKGROUND", (5,1), (5,1), PURPLE_LIGHT),
    ("BACKGROUND", (5,6), (5,6), PURPLE_LIGHT),
])
master_tbl.setStyle(ts)
story += [master_tbl, Spacer(1, 5),
          Paragraph("Sources: Washington Manual of Medical Therapeutics; Harrison's Principles of Internal Medicine 22e; Harriet Lane Handbook 23e.", sCaption),
          Spacer(1, 10)]

# ════════════════════════════════════════════════════════════════════════════
# PAGE 2 – INDIVIDUAL PROFILES
# ════════════════════════════════════════════════════════════════════════════
story.append(PageBreak())
story += [section_header("Individual Profiles — Key Features & Investigations"), Spacer(1, 8)]

# ── helper: profile card ──────────────────────────────────────────────────
def profile_card(title, color, light, lines, investigations, pearls):
    inner = []
    inner.append(Paragraph(title, S("ph", fontName="Helvetica-Bold", fontSize=11,
                                    textColor=color, leading=14, spaceAfter=3)))
    inner.append(rule(color, 1))
    for k, v in lines:
        inner.append(Paragraph(f"<b>{k}:</b>  {v}", sBody))
    inner.append(Spacer(1, 4))
    inner.append(Paragraph("Key Investigations", S("pi", fontName="Helvetica-Bold",
                                                    fontSize=9, textColor=GREY_DARK)))
    for inv in investigations:
        inner.append(bullet(inv))
    inner.append(Spacer(1, 4))
    inner.append(Paragraph("Clinical Pearls", S("pi2", fontName="Helvetica-Bold",
                                                  fontSize=9, textColor=GREY_DARK)))
    for p in pearls:
        inner.append(bullet(p))
    card = Table([[inner]], colWidths=[CONTENT_W])
    card.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), light),
        ("BOX", (0,0), (-1,-1), 1.5, color),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
        ("RIGHTPADDING", (0,0), (-1,-1), 10),
        ("TOPPADDING", (0,0), (-1,-1), 8),
        ("BOTTOMPADDING", (0,0), (-1,-1), 8),
    ]))
    return card

# 1. Bacterial Meningitis
story.append(KeepTogether([
    profile_card(
        "1.  Bacterial Meningitis",
        RED, RED_LIGHT,
        [
            ("Onset", "Acute — hours to 1–2 days"),
            ("Opening pressure", "↑↑ 200–500 mm H₂O"),
            ("WBC", "100–5,000 /µL, predominantly neutrophils (PMN >80%)"),
            ("Protein", "100–500 mg/dL"),
            ("Glucose", "<40 mg/dL; CSF:serum ratio <0.4 — hypoglycorrhachia"),
            ("Appearance", "Turbid or frankly purulent; may be haemorrhagic"),
        ],
        [
            "Gram stain of CSF (positive >60%) — do immediately",
            "CSF culture and sensitivity (positive >80%) — gold standard",
            "Blood cultures x2 before antibiotics",
            "CRP, procalcitonin, FBC, U&E",
            "CT brain before LP if papilledema, focal deficit, or GCS <15",
            "Multiplex PCR panel (BioFire/FilmArray) for rapid pathogen ID",
            "Lactate >3.5 mmol/L in CSF suggests bacterial aetiology",
        ],
        [
            "Common organisms: N. meningitidis (purpuric rash!), S. pneumoniae, H. influenzae, Group B Strep (neonates), Listeria (elderly/immunocompromised)",
            "Do NOT delay antibiotics to await CT/LP if clinically deteriorating",
            "Petechial/purpuric rash + fever = N. meningitidis until proven otherwise — give IV benzylpenicillin immediately",
            "Empiric treatment: Ceftriaxone 2g IV q12h + Vancomycin; add Ampicillin if >50 yrs or immunocompromised (Listeria cover)",
            "Adjunctive Dexamethasone 0.15 mg/kg q6h for 4 days reduces mortality and hearing loss",
        ]
    ),
    Spacer(1, 8)
]))

# 2. Viral Meningitis
story.append(KeepTogether([
    profile_card(
        "2.  Viral (Aseptic) Meningitis",
        GREEN, GREEN_LIGHT,
        [
            ("Onset", "Subacute — 1–7 days"),
            ("Opening pressure", "Normal or mildly elevated"),
            ("WBC", "10–1,000 /µL, predominantly lymphocytes"),
            ("Protein", "50–100 mg/dL (mildly elevated)"),
            ("Glucose", "Normal (40–80 mg/dL); CSF:serum ratio ≥0.6"),
            ("Appearance", "Clear"),
        ],
        [
            "CSF PCR panel: Enterovirus (most common), HSV-1 & 2, VZV, CMV, EBV",
            "HSV PCR — sensitivity 96%, specificity 99% (after 72h of symptoms)",
            "Serum and CSF serology for arbovirus (West Nile, Japanese encephalitis)",
            "MRI brain with FLAIR/DWI if encephalitis suspected (HSV: temporal lobe changes)",
            "EEG if seizures or encephalitis (HSV: periodic lateralised discharges)",
            "Serum and throat/rectal swabs for enterovirus PCR",
        ],
        [
            "\"Lymphocytic pleocytosis with normal glucose\" is the viral meningitis fingerprint",
            "Most common cause: Enteroviruses (Coxsackievirus, Echovirus)",
            "HSV-2 is the most common cause of viral meningitis in adults; HSV-1 causes encephalitis",
            "Early viral meningitis may show PMN predominance — repeat LP in 12–24h will show shift to lymphocytes",
            "Important: low glucose with lymphocytic pleocytosis = THINK TB or Fungal, NOT viral",
            "Management: usually supportive; Acyclovir 10 mg/kg IV q8h if HSV suspected",
        ]
    ),
    Spacer(1, 8)
]))

# 3. Tuberculous Meningitis
story.append(KeepTogether([
    profile_card(
        "3.  Tuberculous Meningitis (TBM)",
        AMBER, AMBER_LIGHT,
        [
            ("Onset", "Subacute to chronic — days to weeks (avg 12 days before diagnosis)"),
            ("Opening pressure", "↑ 200–400 mm H₂O"),
            ("WBC", "50–300 /µL, predominantly lymphocytes (early: PMN then shifts)"),
            ("Protein", "50–300 mg/dL; very high protein (>500) = poor prognosis"),
            ("Glucose", "<45 mg/dL; low but rarely <20 mg/dL; CSF:serum <0.5"),
            ("Appearance", "Clear; forms a cobweb/pellicle clot on standing — classic sign"),
            ("ADA", "Elevated (>10 IU/L) — supports diagnosis"),
        ],
        [
            "AFB smear (Ziehl-Neelsen stain): positive in only 10–20%; yield improves with large-volume or repeat LP",
            "CSF culture for M. tuberculosis: gold standard but takes 4–8 weeks",
            "CSF PCR (GeneXpert Ultra on CSF): rapid, sensitivity ~50–60%, specificity >95%",
            "CSF ADA: elevation supports TBM",
            "Chest X-ray: miliary shadowing, hilar lymphadenopathy, primary complex",
            "CT/MRI brain: basal meningeal enhancement, hydrocephalus, vasculitic infarcts, tuberculomas",
            "Mantoux/TST: may be negative (anergy) in up to 50% of TBM cases",
            "Gastric aspirate x3 (children who cannot expectorate): AFB smear and culture",
        ],
        [
            "Location of inflammation: BASE of brain → cranial nerve palsies (III, VI most common)",
            "Triad: subacute onset + cranial nerve palsies + lymphocytic CSF with low glucose = TBM",
            "Cobweb clot and very high protein = poor prognostic markers",
            "MRC Staging: Stage I (alert, no deficit) → Stage II (focal signs/altered consciousness) → Stage III (coma)",
            "Treatment: 2 months HRZE + 7–10 months HR; Dexamethasone adjunct reduces mortality by 25%",
            "Risk factors: malnutrition, HIV, young children (<5 yrs), immunocompromise",
        ]
    ),
    Spacer(1, 8)
]))

# 4. Cryptococcal / Fungal Meningitis
story.append(KeepTogether([
    profile_card(
        "4.  Cryptococcal / Fungal Meningitis",
        PURPLE, PURPLE_LIGHT,
        [
            ("Onset", "Subacute to chronic — days to weeks"),
            ("Opening pressure", "↑↑↑ markedly elevated (often >400 mm H₂O) — most distinctive feature"),
            ("WBC", "20–500 /µL, predominantly lymphocytes; may be very low in HIV"),
            ("Protein", ">45 mg/dL; often 100–500 mg/dL"),
            ("Glucose", "<40 mg/dL; very low; CSF:serum ratio <0.4"),
            ("Appearance", "Clear; India ink stain shows encapsulated yeasts"),
        ],
        [
            "India ink stain of CSF: yeast cells with wide polysaccharide capsule",
            "Serum and CSF Cryptococcal antigen (CrAg): highly sensitive (>93%) and specific",
            "Fungal culture of CSF: definitive (C. neoformans most common)",
            "Blood cultures: often positive in HIV patients with cryptococcaemia",
            "HIV test: cryptococcal meningitis is AIDS-defining (CD4 usually <100)",
            "Urine LF-LAM (Lateral Flow Assay) in HIV patients",
            "CT/MRI brain: dilated Virchow-Robin spaces, cryptococcomas",
        ],
        [
            "Very high opening pressure is the hallmark — therapeutic LP to drain CSF may be life-saving",
            "In HIV+ patients, cell count may be paradoxically low (poor immune response)",
            "Two-phase treatment: Amphotericin B + Flucytosine x2 weeks (induction) → Fluconazole (consolidation then maintenance)",
            "Corticosteroids are NOT beneficial in cryptococcal meningitis (unlike bacterial and TBM)",
            "Other fungi: Aspergillus, Candida (in immunocompromised, post-neurosurgery), Histoplasma (AIDS)",
        ]
    ),
    Spacer(1, 8)
]))

# ════════════════════════════════════════════════════════════════════════════
# PAGE 3 – DECISION ALGORITHM + SPECIAL TESTS + PITFALLS
# ════════════════════════════════════════════════════════════════════════════
story.append(PageBreak())
story += [section_header("Diagnostic Algorithm — Step-by-Step Approach", TEAL), Spacer(1, 8)]

algo_steps = [
    ("Step 1", "Clinically suspect meningitis",
     "Fever + headache + neck stiffness (Kernig's/Brudzinski's) + photophobia. ±  altered consciousness, cranial nerve palsies, seizures, rash."),
    ("Step 2", "Assess for LP safety",
     "Check for: papilledema, focal neurological deficit, GCS <13, immunocompromise, new-onset seizures. If any present → CT brain FIRST before LP. Do not delay antibiotics."),
    ("Step 3", "Lumbar puncture — send CSF for:",
     "Opening pressure • Appearance • Cell count + differential • Glucose (+ simultaneous serum glucose) • Protein • Gram stain & culture • PCR panel • Specialised tests (AFB, India ink, CrAg, ADA) as indicated."),
    ("Step 4", "Interpret the opening pressure",
     "Normal (<180) → viral likely. Elevated (200–500) → bacterial or TBM. Markedly elevated (>400) → think Cryptococcal meningitis."),
    ("Step 5", "Look at the cell type",
     "PMN (neutrophil) predominance → Bacterial (or very early viral/TBM). Lymphocyte predominance → Viral, TBM, or Fungal."),
    ("Step 6", "Interpret the glucose",
     "Normal glucose + lymphocytes = Viral meningitis. Low glucose + lymphocytes = TBM or Cryptococcal. Low glucose + neutrophils = Bacterial meningitis."),
    ("Step 7", "Protein level",
     "Mildly elevated (50–100) → viral. Moderately elevated (100–300) → TBM/Cryptococcal. Markedly elevated (>300–500) → Bacterial or severe TBM."),
    ("Step 8", "Targeted investigations",
     "Gram stain → Bacterial. AFB smear/PCR/ADA → TBM. India ink/CrAg → Cryptococcal. Virus PCR → Viral."),
]

for step, heading, detail in algo_steps:
    row = Table([[
        Table([[Paragraph(step, S("as", fontName="Helvetica-Bold", fontSize=8,
                                  textColor=WHITE, alignment=TA_CENTER))]],
              colWidths=[1.5*cm]),
        Table([[Paragraph(f"<b>{heading}</b>", sH3),
                Paragraph(detail, sBody)]], colWidths=[CONTENT_W - 1.5*cm - 0.3*cm])
    ]], colWidths=[1.5*cm, CONTENT_W - 1.5*cm])
    row.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (0,0), TEAL),
        ("BACKGROUND", (1,0), (1,0), TEAL_LIGHT),
        ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
        ("TOPPADDING", (0,0), (-1,-1), 5),
        ("BOTTOMPADDING", (0,0), (-1,-1), 5),
        ("LEFTPADDING", (0,0), (0,0), 4),
        ("LEFTPADDING", (1,0), (1,0), 8),
        ("RIGHTPADDING", (0,0), (-1,-1), 8),
        ("BOX", (0,0), (-1,-1), 0.5, GREY_MID),
    ]))
    story += [row, Spacer(1, 3)]

story += [Spacer(1, 10)]

# ── SPECIAL TESTS TABLE ──────────────────────────────────────────────────
story += [section_header("Special & Confirmatory CSF Tests", BLUE), Spacer(1, 6)]

spec_data = [
    [Paragraph("Test", sTableH), Paragraph("Meningitis Type", sTableH),
     Paragraph("Sensitivity", sTableH), Paragraph("Specificity", sTableH), Paragraph("Note", sTableH)],
    [Paragraph("Gram stain", sTableCellL), Paragraph("Bacterial", sTableCell),
     Paragraph(">60%", sTableCell), Paragraph("~97%", sTableCell),
     Paragraph("Yield reduced after antibiotics", sTableCellL)],
    [Paragraph("CSF culture", sTableCellL), Paragraph("Bacterial", sTableCell),
     Paragraph(">80%", sTableCell), Paragraph("~100%", sTableCell),
     Paragraph("Gold standard; antimicrobial sensitivities", sTableCellL)],
    [Paragraph("Blood culture", sTableCellL), Paragraph("Bacterial", sTableCell),
     Paragraph("~50%", sTableCell), Paragraph("High", sTableCell),
     Paragraph("Always collect before antibiotics", sTableCellL)],
    [Paragraph("Multiplex PCR\n(FilmArray/BioFire)", sTableCellL), Paragraph("Bacterial/Viral", sTableCell),
     Paragraph("~90%+", sTableCell), Paragraph("~97%", sTableCell),
     Paragraph("Rapid (1h); does not replace culture", sTableCellL)],
    [Paragraph("HSV PCR", sTableCellL), Paragraph("Viral (Encephalitis)", sTableCell),
     Paragraph("96%", sTableCell), Paragraph("99%", sTableCell),
     Paragraph("Best after 72h of symptoms and <7d of treatment", sTableCellL)],
    [Paragraph("Enterovirus PCR", sTableCellL), Paragraph("Viral", sTableCell),
     Paragraph("~86%", sTableCell), Paragraph("~97%", sTableCell),
     Paragraph("Most common cause of aseptic meningitis", sTableCellL)],
    [Paragraph("AFB smear\n(ZN stain)", sTableCellL), Paragraph("TBM", sTableCell),
     Paragraph("10–20%\n(↑60% with large vol)", sTableCell), Paragraph("High", sTableCell),
     Paragraph("Yield increases with volume and repeat sampling", sTableCellL)],
    [Paragraph("MTB culture", sTableCellL), Paragraph("TBM", sTableCell),
     Paragraph("~45%", sTableCell), Paragraph("~100%", sTableCell),
     Paragraph("Takes 4–8 weeks; gold standard for TBM", sTableCellL)],
    [Paragraph("GeneXpert Ultra\n(MTB PCR)", sTableCellL), Paragraph("TBM", sTableCell),
     Paragraph("~50–60%", sTableCell), Paragraph(">95%", sTableCell),
     Paragraph("WHO-endorsed; rapid (2h); detects rifampicin resistance", sTableCellL)],
    [Paragraph("ADA (adenosine\ndeaminase)", sTableCellL), Paragraph("TBM", sTableCell),
     Paragraph("~79%", sTableCell), Paragraph("~91%", sTableCell),
     Paragraph(">10 IU/L supports TBM; useful where PCR unavailable", sTableCellL)],
    [Paragraph("India ink stain", sTableCellL), Paragraph("Cryptococcal", sTableCell),
     Paragraph("~50%", sTableCell), Paragraph(">95%", sTableCell),
     Paragraph("Encapsulated yeast with halo; faster than culture", sTableCellL)],
    [Paragraph("CrAg (Cryptococcal\nAntigen)", sTableCellL), Paragraph("Cryptococcal", sTableCell),
     Paragraph(">93%", sTableCell), Paragraph(">97%", sTableCell),
     Paragraph("Serum CrAg highly sensitive; CSF CrAg confirms CNS disease", sTableCellL)],
    [Paragraph("CSF Lactate", sTableCellL), Paragraph("Bacterial", sTableCell),
     Paragraph("~93%", sTableCell), Paragraph("~96%", sTableCell),
     Paragraph(">3.5 mmol/L strongly suggests bacterial aetiology", sTableCellL)],
    [Paragraph("VDRL (CSF)", sTableCellL), Paragraph("Neurosyphilis", sTableCell),
     Paragraph("~50–70%", sTableCell), Paragraph("~99%", sTableCell),
     Paragraph("Insensitive but specific; send when syphilis suspected", sTableCellL)],
]

scw = [CONTENT_W*0.18, CONTENT_W*0.17, CONTENT_W*0.12, CONTENT_W*0.12, CONTENT_W*0.41]
spec_tbl = Table(spec_data, colWidths=scw, repeatRows=1)
spec_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,0), BLUE),
    ("ROWBACKGROUNDS", (0,1), (-1,-1), [GREY_LIGHT, WHITE]),
    ("GRID", (0,0), (-1,-1), 0.4, GREY_MID),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 6),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
]))
story += [spec_tbl, Spacer(1, 8)]

# ── PITFALLS BOX ─────────────────────────────────────────────────────────
story += [section_header("Common Pitfalls & Exam Tips", RED), Spacer(1, 6)]

pitfalls = [
    ("<b>Early viral meningitis may show PMN predominance</b> — repeat LP in 12–24h shows shift to lymphocytes. Do not label as bacterial without culture evidence.",),
    ("<b>Low glucose + lymphocytes ≠ viral meningitis</b> — this is TBM or Cryptococcal until proven otherwise. Viral meningitis has NORMAL glucose.",),
    ("<b>Negative Mantoux/TST does not exclude TBM</b> — up to 50% of TBM patients are anergic (especially malnourished children, HIV-positive patients).",),
    ("<b>Cryptococcal meningitis: very high opening pressure</b> — markedly elevated ICP is the most distinctive feature. Therapeutic LPs may be needed to prevent blindness.",),
    ("<b>Antibiotics before LP?</b> — if CT is needed first, or patient deteriorates: start IV antibiotics IMMEDIATELY. Do not allow waiting for LP to delay treatment.",),
    ("<b>Traumatic tap correction</b> — subtract 1 WBC for every 700 RBC. Do the same for protein (subtract 1 mg/dL per 1000 RBC).",),
    ("<b>Cobweb clot in CSF = TBM until proven otherwise</b> — due to very high fibrinogen and protein content.",),
    ("<b>Paediatric normal values differ</b> — neonates have higher baseline WBC (up to 30 cells) and protein. Always use age-adjusted ranges.",),
    ("<b>CSF:serum glucose ratio</b> is more reliable than absolute CSF glucose — always send paired serum glucose at time of LP.",),
    ("<b>CSF lactate >3.5 mmol/L</b> distinguishes bacterial from viral meningitis with >90% accuracy — especially useful when patient has received prior antibiotics.",),
]

pit_data = [[Paragraph(f"\u26a0  {p[0]}", sBullet)] for p in pitfalls]
pit_tbl = Table(pit_data, colWidths=[CONTENT_W])
pit_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), RED_LIGHT),
    ("BOX", (0,0), (-1,-1), 1.2, RED),
    ("TOPPADDING", (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING", (0,0), (-1,-1), 10),
    ("RIGHTPADDING", (0,0), (-1,-1), 10),
    ("GRID", (0,0), (-1,-1), 0.3, HexColor("#F1948A")),
]))
story += [pit_tbl, Spacer(1, 8)]

# ════════════════════════════════════════════════════════════════════════════
# PAGE 4 – QUICK REFERENCE CARD + REFERENCES
# ════════════════════════════════════════════════════════════════════════════
story.append(PageBreak())
story += [section_header("Quick Reference Pocket Card", NAVY), Spacer(1, 8)]

qr_headers = ["", "Bacterial", "Viral", "TBM", "Cryptococcal"]
qr_rows = [
    ["Onset",     "Hours–1d",   "1–7d",   "Days–weeks",  "Days–weeks"],
    ["Pressure",  "↑↑",         "N/↑",    "↑",           "↑↑↑"],
    ["Cells",     "PMN 100–5000","Lymph 10–1000", "Lymph 50–300", "Lymph 20–500"],
    ["Protein",   "100–500",    "50–100", "50–300",       ">45–500"],
    ["Glucose",   "<40 ↓↓",     "Normal", "<45 ↓",        "<40 ↓↓"],
    ["Appearance","Turbid",     "Clear",  "Clear/cobweb",  "Clear"],
    ["Key test",  "Gram/Culture","Virus PCR","AFB/PCR/ADA","India ink/CrAg"],
    ["Rx",        "Ceftriaxone\n+Vancomycin\n+Dexa","Supportive\n±Acyclovir","HRZE x2m\n+HR x7-10m\n+Dexa","AmphB+5FC\nthen Flucon"],
]

qr_col_colors = [NAVY, RED, GREEN, AMBER, PURPLE]
qr_light = [GREY_LIGHT, RED_LIGHT, GREEN_LIGHT, AMBER_LIGHT, PURPLE_LIGHT]

qr_header_row = [Paragraph(h, sTableH) for h in qr_headers]
qr_data = [qr_header_row]
for row in qr_rows:
    cells = [Paragraph(row[0], sTableCellB)]
    for v in row[1:]:
        cells.append(Paragraph(v, sTableCell))
    qr_data.append(cells)

qr_cw = [CONTENT_W*0.14] + [CONTENT_W*0.215]*4
qr_tbl = Table(qr_data, colWidths=qr_cw, repeatRows=1)
ts2 = TableStyle([
    ("BACKGROUND", (0,0), (0,0), NAVY),
    ("BACKGROUND", (1,0), (1,0), RED),
    ("BACKGROUND", (2,0), (2,0), GREEN),
    ("BACKGROUND", (3,0), (3,0), AMBER),
    ("BACKGROUND", (4,0), (4,0), PURPLE),
    ("GRID", (0,0), (-1,-1), 0.5, GREY_MID),
    ("TOPPADDING", (0,0), (-1,-1), 6),
    ("BOTTOMPADDING", (0,0), (-1,-1), 6),
    ("LEFTPADDING", (0,0), (-1,-1), 6),
    ("RIGHTPADDING", (0,0), (-1,-1), 6),
    ("VALIGN", (0,0), (-1,-1), "MIDDLE"),
])
for r_idx in range(1, len(qr_rows)+1):
    ts2.add("BACKGROUND", (1, r_idx), (1, r_idx), RED_LIGHT if r_idx%2 else HexColor("#FDFEFE"))
    ts2.add("BACKGROUND", (2, r_idx), (2, r_idx), GREEN_LIGHT if r_idx%2 else HexColor("#FDFEFE"))
    ts2.add("BACKGROUND", (3, r_idx), (3, r_idx), AMBER_LIGHT if r_idx%2 else HexColor("#FDFEFE"))
    ts2.add("BACKGROUND", (4, r_idx), (4, r_idx), PURPLE_LIGHT if r_idx%2 else HexColor("#FDFEFE"))
    ts2.add("BACKGROUND", (0, r_idx), (0, r_idx), GREY_LIGHT if r_idx%2 else WHITE)
qr_tbl.setStyle(ts2)
story += [qr_tbl, Spacer(1, 4),
          Paragraph("Rx = first-line empiric treatment. H=Isoniazid, R=Rifampicin, Z=Pyrazinamide, E=Ethambutol. AmphB=Amphotericin B, 5FC=Flucytosine, Flucon=Fluconazole. Dexa=Dexamethasone.", sCaption),
          Spacer(1, 12)]

# ── REFERENCES ────────────────────────────────────────────────────────────
story += [rule(GREY_MID), Paragraph("References", sH2)]
refs = [
    "Washington Manual of Medical Therapeutics — Typical CSF Findings in Meningitis Table",
    "Harrison's Principles of Internal Medicine 22e (2025, McGraw Hill) — Table 143-2: CSF Abnormalities in Bacterial Meningitis",
    "Harriet Lane Handbook 23e (Johns Hopkins) — Table 17.8: CSF Analysis in Suspected Meningitis",
    "Murray & Nadel's Textbook of Respiratory Medicine — Central Nervous System Tuberculosis, pp.1199–1200",
    "Plum and Posner's Diagnosis and Treatment of Stupor and Coma — Tuberculous Meningitis, p.421",
    "ROSEN's Emergency Medicine — Tuberculous & Cryptococcal Meningitis",
    "Frameworks for Internal Medicine — Meningitis Chapter",
    "Tintinalli's Emergency Medicine — Laboratory Testing in Meningitis",
    "WHO 2024/2025 Consolidated Guidelines on Tuberculosis — Treatment and Care (Module 4)",
    "MSF Medical Guidelines — Adjunctive Corticosteroids in TB (dexamethasone dosing)",
]
for r in refs:
    story.append(Paragraph(f"\u2022  {r}", sRef))

story += [Spacer(1, 6), rule(GREY_MID),
          Paragraph("Produced by Orris Medical Education  •  August 2026  •  For educational use only. Not a substitute for clinical judgement.", sCaption)]

doc.build(story)
print("PDF generated:", OUTPUT)

Running Command

cd /tmp/workspace/csf-guide && python build_csf_guide.py 2>&1

Running Command

ls -lh /tmp/workspace/csf-guide/CSF_Interpretation_Guide.pdf

Your PDF guide is ready for download:

CSF Interpretation Guide

PDF Document · PDF

Here is what the guide contains across 4 pages:

Page 1 — Foundations

Normal CSF reference values table (pressure, appearance, WBC, RBC, glucose, protein) with age-specific notes
Master comparison table across all four meningitis types (Bacterial, Viral, TBM, Cryptococcal) with colour-coded critical values

Page 2 — Individual Profiles

Four colour-coded profile cards (Red = Bacterial, Green = Viral, Amber = TBM, Purple = Cryptococcal) each covering: onset, opening pressure, WBC, protein, glucose, appearance, key investigations, and clinical pearls

Page 3 — Decision Tools

8-step diagnostic algorithm (from suspecting meningitis to targeted investigations)
Special and confirmatory tests table with sensitivity/specificity data (Gram stain, HSV PCR, AFB smear, GeneXpert, ADA, India ink, CrAg, CSF lactate, VDRL)
Common pitfalls and exam tips box (10 high-yield points)

Page 4 — Quick Reference

Compact pocket card covering all four types with onset, pressure, cells, protein, glucose, appearance, key test, and first-line treatment
Full reference list from Harrison's, Washington Manual, Harriet Lane Handbook, Murray & Nadel, and current WHO/MSF guidelines

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