{
  "filename": "fbsf_pathophysiology_schematic.png",
  "iteration": 3,
  "description": "Mechanistic schematic of Flea-Borne Spotted Fever (R. felis) pathophysiology synthesizing Iterations 1-3 findings",
  "timestamp": "2026-09-28 13:31:24",
  "code": "\nimport matplotlib.pyplot as plt\nfrom matplotlib.patches import FancyBboxPatch, FancyArrowPatch\nimport matplotlib.patches as mpatches\n\nfig, ax = plt.subplots(figsize=(13, 9))\nax.set_xlim(0,10); ax.set_ylim(0,10); ax.axis('off')\nax.set_title(\"Flea-Borne Spotted Fever (Rickettsia felis): Integrated Pathophysiology\",\n             fontsize=15, fontweight='bold')\n\ndef box(x,y,w,h,text,color):\n    ax.add_patch(FancyBboxPatch((x,y),w,h,boxstyle=\"round,pad=0.05\",\n                 linewidth=1.3,edgecolor='black',facecolor=color,alpha=0.9))\n    ax.text(x+w/2,y+h/2,text,ha='center',va='center',fontsize=9,wrap=True)\n\ndef arrow(x1,y1,x2,y2):\n    ax.add_patch(FancyArrowPatch((x1,y1),(x2,y2),arrowstyle='-|>',\n                 mutation_scale=18,linewidth=1.8,color='dimgray'))\n\n# Stage 1: transmission/inoculation\nbox(0.3,8.3,3.0,1.2,\"1. TRANSMISSION\\nCat flea Ctenocephalides felis\\n(mosquitoes potential)\\n\u2192 dermal inoculation\",'#cfe8f3')\n# Stage 2: entry\nbox(3.7,8.3,3.0,1.2,\"2. ENDOTHELIAL ENTRY\\nOmpB\u2013Annexin A2 adhesion\\nFGFR1 / heparan sulfate\\ninternalization\",'#d5e8d4')\n# Stage 3: intracellular\nbox(7.1,8.3,2.7,1.2,\"3. INTRACELLULAR\\nphagosomal escape\\n(patatin phospholipase)\\nRickA actin motility, mTOR\",'#d5e8d4')\n# Stage 4 survival\nbox(7.1,6.3,2.7,1.4,\"4. SURVIVAL\\nNF-\u03baB blocks apoptosis\\n(masks caspase-8/9/3)\\n\u2192 replication & cell-to-cell spread\\nAdr1/2 complement evasion\",'#ffe6cc')\n# Stage 5 dissemination\nbox(3.7,6.3,3.0,1.4,\"5. DISSEMINATION\\nhematogenous spread to\\nmicrovascular endothelium\\n(skin, brain, lung, liver)\",'#cfe8f3')\n# Stage 6 vascular injury\nbox(0.3,6.3,3.0,1.4,\"6. VASCULAR INJURY\\n\u2191permeability, edema\\nROS/oxidative injury\\nprocoagulant: TXA2, thrombin\\nvasculitis, microthrombi\",'#f8cecc')\n# Stage 7 inflammation\nbox(0.3,4.0,4.4,1.6,\"7. INFLAMMATION (effector phase)\\nEndothelium+macrophage cytokines:\\nIL-8, IP-10/CXCL10, MCP-1, MIP-1\u03b1, VEGF, IL-1\u03b2, IL-6\\nRecruit leukocytes \u2192 amplify permeability\",'#fff2cc')\n# Stage 8 protective immunity\nbox(5.1,4.0,4.6,1.6,\"8. PROTECTIVE IMMUNITY\\nNK + CD8 T cells; IFN-\u03b3 clears bacteria;\\nperforin prevents thrombosis\\nDeficit \u2192 severe/thrombotic disease\",'#e1d5e7')\n# Stage 9 clinical\nbox(0.3,1.8,4.4,1.6,\"9. CLINICAL PHENOTYPE\\nFever, headache, maculopapular rash,\\n\u00b1eschar; transaminitis, thrombocytopenia\\nComplications: CNS meningoencephalitis,\\npleural effusion, multi-organ failure\",'#f8cecc')\n# Stage 10 treatment\nbox(5.1,1.8,4.6,1.6,\"10. TREATMENT\\nDoxycycline (1st-line, urgent)\\nAlt: azithromycin, rifampicin,\\nfluoroquinolones\\nDx: IFA seroconversion, qPCR skin/eschar\",'#d5e8d4')\n\n# arrows\narrow(3.3,8.9,3.7,8.9)\narrow(6.7,8.9,7.1,8.9)\narrow(8.45,8.3,8.45,7.7)\narrow(7.1,7.0,6.7,7.0)\narrow(3.7,7.0,3.3,7.0)\narrow(1.8,6.3,1.8,5.6)   # vascular -> inflammation\narrow(4.7,4.8,5.1,4.8)   # inflammation <-> immunity\narrow(2.5,4.0,2.5,3.4)   # inflammation -> clinical\narrow(4.7,2.6,5.1,2.6)   # clinical -> treatment\n\nax.text(5,0.5,\"Core mechanism: endothelial-targeted infection \u2192 vasculitis via oxidative + procoagulant injury and chemokine-driven permeability\",\n        ha='center',fontsize=10,style='italic')\nplt.tight_layout()\nplt.savefig('fbsf_pathophysiology_schematic.png',dpi=140,bbox_inches='tight')\nprint(\"Schematic saved. Findings integrated across 10 stages.\")\n"
}