Mycoplasma haemofelis

#!/usr/bin/env python3
from docx import Document
from docx.shared import Pt, Inches, RGBColor
from docx.enum.text import WD_ALIGN_PARAGRAPH
from docx.enum.table import WD_TABLE_ALIGNMENT
from docx.oxml.ns import qn
from docx.oxml import OxmlElement

DARK_BLUE = RGBColor(0x1F, 0x3A, 0x5F)
ACCENT = RGBColor(0x2E, 0x74, 0xB5)
GREY = RGBColor(0x59, 0x59, 0x59)

doc = Document()

# Base style
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style.font.name = "Calibri"
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def h2(text):
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def body(text, bold=False, italic=False):
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def bullet(text):
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def numbered(text):
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def note_box(text):
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    run = p.add_run("Clinical Note: " + text)
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    return p

# ===================== TITLE PAGE =====================
title = doc.add_paragraph()
title.alignment = WD_ALIGN_PARAGRAPH.CENTER
run = title.add_run("Feline Hemoplasmosis")
run.font.size = Pt(28)
run.font.bold = True
run.font.color.rgb = DARK_BLUE

sub = doc.add_paragraph()
sub.alignment = WD_ALIGN_PARAGRAPH.CENTER
run = sub.add_run("Clinical Reference Guide: Diagnosis and Management")
run.font.size = Pt(15)
run.font.color.rgb = ACCENT

sub2 = doc.add_paragraph()
sub2.alignment = WD_ALIGN_PARAGRAPH.CENTER
run = sub2.add_run("Mycoplasma haemofelis | 'Candidatus Mycoplasma haemominutum' | 'Candidatus Mycoplasma turicensis'")
run.font.size = Pt(11)
run.font.italic = True
run.font.color.rgb = GREY

doc.add_paragraph()
disclaimer = doc.add_paragraph()
disclaimer.alignment = WD_ALIGN_PARAGRAPH.CENTER
run = disclaimer.add_run("For use by veterinary professionals. Based on ABCD (European Advisory Board on Cat Diseases) "
                          "guidelines and current peer-reviewed veterinary literature. Not a substitute for clinical "
                          "judgement or up-to-date primary sources.")
run.font.size = Pt(9)
run.font.color.rgb = GREY

doc.add_page_break()

# ===================== TABLE OF CONTENTS (manual) =====================
h1("Contents")
toc_items = [
    "1. Overview and Etiology",
    "2. Transmission and Epidemiology",
    "3. Pathogenesis",
    "4. Clinical Presentation",
    "5. Differential Diagnosis",
    "6. Diagnostic Approach",
    "7. Treatment Protocols",
    "8. Monitoring, Prognosis and Relapse",
    "9. Prevention and Zoonotic Considerations",
    "10. Quick-Reference Summary Table",
    "11. Key References",
]
for item in toc_items:
    bullet(item)

doc.add_page_break()

# ===================== 1. OVERVIEW =====================
h1("1. Overview and Etiology")
body("Feline hemoplasmosis (formerly feline infectious anemia / hemobartonellosis) is caused by wall-less, "
     "epicellular bacteria of the genus Mycoplasma (hemotropic mycoplasmas, or 'hemoplasmas') that attach to the "
     "surface of feline erythrocytes. Three species are recognized in domestic cats:")

add_table(
    ["Species", "Former Name", "Pathogenicity", "Key Features"],
    [
        ["Mycoplasma haemofelis (Mhf)", "Haemobartonella felis, 'Ohio'/large-form strain",
         "High", "Most pathogenic; can cause severe, life-threatening hemolytic anemia in immunocompetent cats"],
        ["'Candidatus M. haemominutum' (CMhm)", "H. felis, 'California'/small-form strain",
         "Low", "Most prevalent hemoplasma worldwide; usually subclinical unless cat is immunocompromised or coinfected"],
        ["'Candidatus M. turicensis' (CMt)", "n/a",
         "Low-Moderate", "Less common; can cause disease in immunosuppressed or coinfected cats"],
    ],
)
doc.add_paragraph()
note_box("Species cannot be reliably distinguished on blood smear morphology alone. Species-specific PCR is "
         "required for definitive identification, and it matters clinically because M. haemofelis carries by far "
         "the highest risk of severe anemia and typically warrants more aggressive treatment.")

# ===================== 2. TRANSMISSION =====================
h1("2. Transmission and Epidemiology")
h2("Routes of Transmission")
bullet("Cat bite wounds / aggressive interactions - strongly associated epidemiologically with M. haemofelis transmission (blood-to-blood transfer via saliva)")
bullet("Fleas (Ctenocephalides felis) - long suspected vector; DNA has been detected in fleas, but recent systematic review/meta-analysis data suggest flea-borne transmission may be less significant than historically assumed, likely reflecting surface contamination rather than true biological transmission (Moore et al., 2024)")
bullet("Ticks - possible but unproven vector role")
bullet("Blood transfusion from an infected (including subclinically infected) donor cat")
bullet("Vertical transmission (queen to kitten) - reported, mechanism not fully defined")
h2("Risk Factors")
bullet("Male sex, outdoor/unrestricted access, non-pedigree breed")
bullet("Older age (more associated with CMhm prevalence)")
bullet("Concurrent FeLV and/or FIV infection")
bullet("History of cat fights or bite wounds")
bullet("Multi-cat households and shelters (higher exposure risk)")

# ===================== 3. PATHOGENESIS =====================
h1("3. Pathogenesis")
body("Hemoplasmas attach to the external surface of the erythrocyte membrane. They do not lyse cells directly; "
     "instead, attachment alters red cell membrane antigens and structure, which triggers immune-mediated "
     "recognition and removal of parasitized (and sometimes non-parasitized) erythrocytes, principally by "
     "extravascular hemolysis (splenic macrophage phagocytosis and sequestration).")
bullet("Bacteremia is cyclical - parasitemia waxes and wanes over hours to days, which affects the sensitivity of blood smear examination and even PCR at a single time point")
bullet("Severity of anemia depends more on the host immune response and strain factors than on organism burden alone")
bullet("Splenectomized cats and those with FeLV/FIV coinfection are prone to more severe, harder-to-control disease")
bullet("A positive direct Coombs' test can occur secondary to hemoplasma infection because of immune-mediated red cell injury - this does not necessarily indicate primary immune-mediated hemolytic anemia (IMHA)")
bullet("Rare severe complications reported include hemophagocytic syndrome")

# ===================== 4. CLINICAL PRESENTATION =====================
h1("4. Clinical Presentation")
h2("M. haemofelis (acute disease)")
bullet("Lethargy, weakness, anorexia, weight loss")
bullet("Pale mucous membranes +/- icterus")
bullet("Tachycardia, tachypnea, +/- systolic heart murmur (secondary to anemia)")
bullet("Splenomegaly")
bullet("Intermittent pyrexia, often correlating with peaks in bacteremia")
bullet("Occasionally acute collapse due to severe, rapidly progressive anemia")
h2("CMhm / CMt (typically subclinical or mild)")
bullet("Most infections are asymptomatic chronic carrier states")
bullet("Clinical disease is largely restricted to immunocompromised cats, those coinfected with FeLV/FIV, or cats coinfected with multiple hemoplasma species")
note_box("Chronic M. haemofelis carriers exist and typically show no significant anemia; conversely, acute infection "
         "in an immunocompetent cat can be severe. Clinical course does not always correlate simply with species.")

# ===================== 5. DIFFERENTIAL DIAGNOSIS =====================
h1("5. Differential Diagnosis")
body("Hemoplasmosis should be considered in any cat presenting with regenerative (occasionally non-regenerative) "
     "anemia, particularly with concurrent pyrexia. Other differentials to exclude or consider concurrently:")
bullet("Primary immune-mediated hemolytic anemia (IMHA)")
bullet("Secondary IMHA (drug-induced, neoplasia-associated, other infection-associated)")
bullet("Cytauxzoonosis")
bullet("Feline leukemia virus (FeLV) - associated bone marrow disease/anemia")
bullet("Babesiosis (regional)")
bullet("Heinz body hemolytic anemia (oxidative injury, e.g., onions, propofol, certain drugs)")
bullet("Hypophosphatemia-associated hemolysis")
bullet("Inherited red cell disorders (e.g., pyruvate kinase deficiency)")
bullet("Blood loss anemia (GI bleeding, trauma, coagulopathy)")

# ===================== 6. DIAGNOSTIC APPROACH =====================
h1("6. Diagnostic Approach")
h2("Step 1: Confirm and characterize the anemia")
bullet("CBC with reticulocyte count, blood smear review, total solids/albumin, globulin")
bullet("Assess regenerative status; hemoplasmosis usually produces a regenerative anemia unless very acute or peracute")

h2("Step 2: Blood smear examination")
bullet("Fresh, well-prepared, thinly spread blood smear stained with Wright-Giemsa or a rapid Romanowsky stain")
bullet("Organisms appear as small basophilic cocci, rings, or rod-shaped structures on the RBC surface")
bullet("Sensitivity is LOW: parasitemia is cyclical, often intermittent and low-grade; artefacts (stain precipitate, Howell-Jolly bodies) commonly cause false positives")
note_box("A negative blood smear does NOT rule out hemoplasma infection. Do not rely on smear alone for diagnosis or to exclude disease.")

h2("Step 3: Molecular testing (diagnostic test of choice)")
bullet("Real-time quantitative PCR (qPCR) on EDTA blood - sensitive, specific, and species-discriminating")
bullet("Allows quantification of bacterial load, useful for monitoring response to treatment and confirming clearance")
bullet("Because subclinical carriage exists (especially CMhm), a positive PCR does not by itself confirm that the organism is the cause of the presenting anemia - always interpret alongside CBC, clinical signs, and exclusion of other causes")

h2("Step 4: Concurrent testing")
bullet("FeLV/FIV testing - common co-infections and important prognostic/management factors")
bullet("Direct Coombs' test if primary IMHA is suspected as an alternative or concurrent diagnosis")
bullet("Consider testing for other regional vector-borne pathogens if travel/geographic history warrants")

h2("Diagnostic Algorithm Summary")
add_table(
    ["Finding", "Interpretation / Next Step"],
    [
        ["Regenerative anemia + fever + positive PCR (Mhf)", "Diagnosis of clinical hemoplasmosis supported - treat"],
        ["Positive PCR, no anemia, no clinical signs", "Subclinical carrier - treatment generally NOT recommended"],
        ["Negative smear, high clinical suspicion", "Proceed to PCR - do not rely on smear alone"],
        ["Positive Coombs' + positive hemoplasma PCR", "Treat infection first; reserve corticosteroids only if anemia persists despite adequate antibiotic therapy and diagnosis remains uncertain"],
        ["Non-regenerative anemia", "Investigate marrow disease, FeLV, chronic disease - hemoplasmosis less likely sole cause"],
    ],
)

# ===================== 7. TREATMENT =====================
h1("7. Treatment Protocols")
h2("General Principles (per ABCD guidelines)")
bullet("Treat cats with clinical signs and clinicopathological abnormalities consistent with hemoplasmosis")
bullet("Treatment of healthy, subclinically infected cats is NOT recommended, regardless of species detected")
bullet("Consider treating asymptomatic M. haemofelis-positive cats in specific situations (e.g., risk of recrudescence, planned immunosuppression, blood donor screening, risk to other cats/household)")

h2("First-Line Antibiotic Therapy")
add_table(
    ["Drug", "Dose", "Duration", "Notes"],
    [
        ["Doxycycline", "5-10 mg/kg PO once or twice daily (commonly 5 mg/kg BID)", "2-4 weeks (up to 28 days)",
         "First-line; effective for reducing clinical signs and bacterial load; complete bacteremia clearance not guaranteed (~1/3 of cats clear with doxycycline alone)"],
        ["Marbofloxacin", "2 mg/kg PO once daily", "2-4 weeks",
         "Used as follow-on if bacteremia persists after doxycycline, or as alternative if doxycycline not tolerated"],
        ["Pradofloxacin", "As labeled (vet fluoroquinolone)", "2-4 weeks",
         "Shown effective experimentally against M. haemofelis; alternative fluoroquinolone option"],
        ["Enrofloxacin", "5 mg/kg PO once daily (use lowest effective dose)", "2-4 weeks",
         "Caution: retinal toxicity risk in cats at higher doses; use conservatively"],
    ],
)
note_box("Doxycycline can cause esophageal stricture in cats if tablets are not followed by food/water or a liquid "
         "formulation is not used - always chase tablets with food or water, or use a liquid/compounded formulation.")

h2("Sequential / Combination Protocol for Refractory Bacteremia")
body("A controlled study demonstrated that a sequential protocol of doxycycline followed by marbofloxacin achieved "
     "complete clearance of M. haemofelis bacteremia (confirmed by qPCR) in chronically infected cats, with no "
     "reactivation even after immunosuppressive corticosteroid challenge. Roughly a third of cats cleared with "
     "doxycycline alone and did not require the second-line fluoroquinolone.")
numbered("Start doxycycline (5 mg/kg BID PO) for up to 28 days")
numbered("Recheck qPCR blood load after completion")
numbered("If bacteremia persists, follow with a course of marbofloxacin")
numbered("A treatment-free interval between courses does not appear to worsen outcome")

h2("Adjunctive / Supportive Care")
bullet("IV fluid therapy to correct dehydration and support perfusion")
bullet("Blood transfusion (packed red cells or fresh whole blood) for severe, life-threatening anemia (PCV typically <15 percent or clinical signs of hypoxia/collapse)")
bullet("Oxygen supplementation in severely anemic, dyspneic patients")
bullet("Nutritional support if anorexic")

h2("Role of Corticosteroids")
body("Corticosteroids are NOT routinely recommended. Even cats with a positive Coombs' test generally recover with "
     "antibiotic and supportive care alone. Immunosuppressive glucocorticoids have experimentally been shown to "
     "increase hemoplasma bacteremia and can reactivate subclinical infection.")
bullet("Reserve corticosteroids only for cats with a positive Coombs' test that fail to respond to appropriate antibiotic treatment alone, and where the diagnosis remains uncertain (possible concurrent primary IMHA)")

# ===================== 8. MONITORING / PROGNOSIS =====================
h1("8. Monitoring, Prognosis and Relapse")
h2("Prognosis")
bullet("Generally good with prompt, appropriate treatment")
bullet("Mortality can be high in severe, peracute M. haemofelis disease if treatment is delayed")
bullet("Albumin-to-globulin (A:G) ratio has been identified as a useful prognostic indicator for mortality (cut-off approximately 0.46; reported sensitivity ~92%, specificity ~88% in one study, Ider et al., 2024)")
bullet("Serum endothelin-1 and vascular endothelial growth factor-A concentrations have also been investigated as potential prognostic/severity biomarkers")

h2("Monitoring Response")
bullet("Serial PCV/hematocrit and clinical assessment during the acute phase")
bullet("Repeat qPCR at end of antibiotic course to assess bacteremia clearance, particularly for M. haemofelis or in cats where clearance is clinically important (e.g., blood donors, multi-cat households, immunosuppressed in-contact cats)")
bullet("Relapse can occur after apparent clinical resolution because the organism may persist in tissue sites (e.g., spleen) less accessible to antibiotics - ensure full treatment courses are completed even after clinical improvement")

# ===================== 9. PREVENTION =====================
h1("9. Prevention and Zoonotic Considerations")
h2("Prevention")
bullet("Routine, effective flea control (reduces potential vector-borne transmission risk)")
bullet("Minimize cat fight/bite exposure - neuter roaming males, reduce free-roaming outdoor access where feasible")
bullet("Screen blood donor cats by PCR for all three hemoplasma species prior to transfusion use")
bullet("Test-and-manage strategy in multi-cat households, particularly around new introductions")
h2("Zoonotic Risk")
body("Evidence for zoonotic transmission of feline hemoplasmas to humans is limited and remains controversial. "
     "Any theoretical risk is considered relevant mainly to severely immunocompromised owners, and this "
     "consideration may factor into decisions about pursuing complete bacteremia clearance in an infected "
     "household cat rather than driving routine practice for most patients.")

# ===================== 10. SUMMARY TABLE =====================
h1("10. Quick-Reference Summary Table")
add_table(
    ["Parameter", "M. haemofelis", "Ca. M. haemominutum", "Ca. M. turicensis"],
    [
        ["Pathogenicity", "High", "Low", "Low-Moderate"],
        ["Typical presentation", "Acute hemolytic anemia, even in healthy cats", "Usually subclinical", "Usually subclinical"],
        ["Disease drivers", "Can occur in immunocompetent cats", "Immunosuppression, coinfection", "Immunosuppression, coinfection"],
        ["Treat if subclinical?", "Consider in select situations", "No", "No"],
        ["First-line treatment", "Doxycycline +/- marbofloxacin", "Doxycycline (if symptomatic)", "Doxycycline (if symptomatic)"],
        ["Diagnostic test of choice", "qPCR", "qPCR", "qPCR"],
    ],
)

# ===================== 11. REFERENCES =====================
h1("11. Key References")
refs = [
    "Tasker S, et al. Haemoplasmosis in cats: European guidelines from the ABCD on prevention and management. J Feline Med Surg. 2018;20:256-261. PMID: 29478400.",
    "ABCD (European Advisory Board on Cat Diseases). Guideline for Haemoplasmosis in Cats. abcdcatsvets.org (accessed 2025-2026 update, incorporating Ider et al. 2024 prognostic data).",
    "Novacco M, et al. Consecutive antibiotic treatment with doxycycline and marbofloxacin clears bacteremia in Mycoplasma haemofelis-infected cats. Vet Microbiol. 2018.",
    "Moore CO, Lashnits E, Lappin M, et al. A case of mistaken identity: a systematic review, meta-analysis, and reinvestigation of hemotropic Mycoplasma spp. infection in Ctenocephalides felis (cat flea). Parasit Vectors. 2024;PMID: 38720359.",
    "Strandberg NJ, Tang KM, Dos Santos AP. Hemophagocytic syndrome in a cat with Mycoplasma haemofelis infection. Vet Clin Pathol. 2023;PMID: 37025047.",
    "Tasker S. Haemotropic mycoplasmas: what's the real significance in cats? J Feline Med Surg. 2010;12:369-381.",
    "Dowers KL, Tasker S, Radecki SV, et al. Use of pradofloxacin to treat experimentally induced Mycoplasma haemofelis infection in cats. Am J Vet Res. 2009;70:105-111.",
    "Merck Veterinary Manual. Hemotropic Mycoplasma Infections in Animals. merckvetmanual.com.",
    "Clinician's Brief. Feline Hemoplasmosis. cliniciansbrief.com.",
    "VCA Animal Hospitals. Feline Hemotrophic Mycoplasmosis. vcahospitals.com.",
]
for r in refs:
    p = doc.add_paragraph(r, style="List Number")
    for run in p.runs:
        run.font.size = Pt(9.5)

# Footer note
doc.add_paragraph()
foot = doc.add_paragraph()
run = foot.add_run("Document generated as a clinical reference aid. Always confirm current dosing and protocols "
                    "against the latest ABCD guideline and product labeling before clinical use.")
run.italic = True
run.font.size = Pt(8.5)
run.font.color.rgb = GREY

doc.save("/tmp/workspace/feline-hemoplasma-guide/Feline_Hemoplasmosis_Clinical_Reference_Guide.docx")
print("Saved successfully")