01Approach to the Critical Patient/attcp40

Immediate priorities

›Hemodynamic and fluid status

›Severe dehydration from profuse watery diarrhea

›SBP <90 mmHg or MAP <65 mmHg

›Tachycardia >100 bpm

›Initiate IV fluid resuscitation with isotonic crystalloid if hemodynamically unstable

›30 ml/kg bolus for shock physiology

›Reassess volume status after each bolus

›Electrolyte derangements from high-volume stool losses

›Hyponatraemia, hypokalaemia, metabolic acidosis

›Altered mental status triage

›New confusion or focal deficits — consider CNS microsporidiosis (E. cuniculi, Trachipleistophora)

›Emergent CT head to exclude mass lesion or bleed

›MRI brain with contrast if CT non-diagnostic

›Seizure activity — neurology consult and seizure precautions

›Benzodiazepine for active seizure

›Immune status rapid assessment

›CD4 <100 cells/mm³ — highest risk for disseminated disease

›ART non-adherence as precipitant

›Concurrent opportunistic infections common

Key decision points

›Disseminated vs localized disease

›Intestinal-only — most common; outpatient management if tolerating PO

›Stool special stains or PCR to confirm

›Disseminated — multi-organ involvement requires inpatient evaluation

›Encephalitis, hepatitis, nephritis, myositis

›Ocular — urgent ophthalmology consultation for keratoconjunctivitis

›Risk of corneal perforation in immunocompetent hosts with stromal keratitis

02History/hx62

Presenting symptoms

›Diarrheal illness characterization

›Watery, non-bloody, intermittent or continuous

›Volume and frequency per day

›Duration >2 weeks raises suspicion for microsporidiosis

›Associated GI symptoms

›Crampy abdominal pain

›Nausea and vomiting

›Bloating and steatorrhea (malabsorption pattern)

›Weight loss and wasting

›Quantify kilograms lost and timeframe

›Failure to thrive in pediatric patients

›Fever pattern

›Typically absent in microsporidiosis

›Fever suggests co-infection or alternative diagnosis

›CMV colitis, MAC, bacterial superinfection

›Extra-intestinal symptoms

›Ocular symptoms (keratoconjunctivitis)

›Eye redness, tearing, photophobia, foreign body sensation

›Blurred vision or visual loss

›Respiratory symptoms (E. hellem, E. cuniculi)

›Cough, dyspnea, sinusitis

›Neurologic symptoms (E. cuniculi, Trachipleistophora)

›Headache, confusion, seizures

›Musculoskeletal symptoms (Pleistophora, Anncaliia, Trachipleistophora)

›Proximal muscle pain and weakness (myositis)

›Genitourinary symptoms (E. hellem)

›Dysuria, urinary frequency

03Physical Exam/exam55

Vitals and hemodynamic status

›Vital sign pattern

›Temperature

›Afebrile typical of intestinal microsporidiosis

›Fever suggests co-infection or disseminated disease

›Heart rate

›Tachycardia as dehydration marker

›>100 bpm warrants IV fluid assessment

›Blood pressure

›Orthostatic changes indicating significant volume depletion

›SBP <90 mmHg — shock protocol

›Weight

›Compare to previous documented weight

›>10% loss over 1 month indicates severe wasting

General and nutritional status

›Appearance and nutritional assessment

›Cachexia and muscle wasting

›Temporal wasting, loss of fat pads

›Proximal muscle weakness

›Dehydration signs

›Dry mucous membranes

›Poor skin turgor

›Sunken eyes

Abdominal exam

›Abdominal findings

›Bowel sounds

›Hyperactive (diarrheal state)

›Palpation

04Differential Diagnosis/ddx38

Cannot-miss diagnoses in immunocompromised hosts

›Cryptosporidiosis (ICD-10: A07.2)

›Watery diarrhea, acid-fast positive oocysts on stool

›Often co-occurs with microsporidiosis

›Distinguish by modified acid-fast vs modified trichrome stain

›CD4 <50 cells/mm³ increases severity

›CMV colitis (ICD-10: B25.1)

›Bloody diarrhea in advanced AIDS

›Colonoscopy with biopsy required — owl-eye inclusions

›CMV antigenemia or PCR in blood

›Mycobacterium avium complex (ICD-10: A31.2)

›Diarrhea with systemic symptoms, fever, sweats, weight loss

›Blood cultures for mycobacteria

›LDH and alkaline phosphatase often elevated

›Cystoisospora belli (ICD-10: A07.3)

›Watery diarrhea with eosinophilia

›Acid-fast oocysts on stool — larger than Cryptosporidium

›Responds to TMP-SMX

Other important differentials

›Giardiasis (ICD-10: A07.1)

›Bloating, steatorrhea, foul-smelling stool

›Trophozoites or cysts on stool O&P

›Stool ELISA high sensitivity

›Cyclospora cayetanensis (ICD-10: A07.89)

›Prolonged watery diarrhea with travel history

›Modified acid-fast — variable staining, spherical oocysts

›HIV enteropathy (ICD-10: K52.89)

›Diagnosis of exclusion — all infectious causes excluded

05Laboratory Tests/lt49

Stool diagnostic tests

›Modified trichrome stain (Weber's stain) — primary diagnostic stain

›Spores appear pink-red with equatorial belt-like stripe on green background

›Specificity 100%

›Sensitivity lower than PCR — operator-dependent

›Must be specifically requested; not included in standard O&P

›1-3 stool specimens increase yield

›Calcofluor white (fluorescent brighteners)

›Most sensitive screening stain — spores fluoresce bright blue/white

›Uvitex 2B alternative — equivalent sensitivity

›False positives from yeast possible

›Requires fluorescence microscope

›Stool PCR

›Highest sensitivity (100%) and specificity (97.9%)

›Enables species identification — critical for treatment selection

›Available at CDC and reference laboratories

›16S-like rRNA gene target for Encephalitozoon spp.

›Preferred when modified trichrome negative but clinical suspicion high

Blood and urine tests

›CD4 count and HIV viral load

›CD4 <100 cells/mm³ — clinical threshold for microsporidiosis susceptibility

›CD4 >200 cells/mm³ sustained — target for treatment discontinuation

›Viral load guides ART optimization decisions

›Basic metabolic panel

›Electrolytes — Na, K, Cl, HCO3 for diarrheal derangements

›Hyponatraemia common

›Metabolic acidosis from bicarbonate losses

›BUN and creatinine — dehydration and nephritis (E. hellem)

06Diagnostic Tests/dt65

Scoring Systems

›Severity stratification for microsporidiosis

›Mild — intermittent diarrhea, adequate oral intake, stable weight

›Outpatient management with close follow-up

›Moderate — persistent diarrhea with dehydration, electrolyte abnormalities, weight loss

›IV fluid resuscitation, consider observation or short admission

›Severe — disseminated disease, wasting syndrome, encephalitis, cholangitis, hemodynamic instability

›Inpatient admission required

›Infectious disease, neurology, or GI consultation

›IDSA severity criteria for infectious diarrhea (Shane et al. 2017)

›Hospitalization warranted for severe dehydration, altered mental status, or immune compromise with systemic features

›Applies to microsporidiosis management decisions

MRI

›MRI brain with gadolinium

›Indications

›Altered mental status, new seizures, focal neurologic deficits

›Suspected CNS microsporidiosis (E. cuniculi, Trachipleistophora)

›Expected findings in CNS microsporidiosis

›Granulomatous encephalitis — multifocal T2 hyperintense white matter lesions

›Punctate enhancement pattern with gadolinium

›Hydrocephalus in severe cases

›Trachipleistophora encephalitis — may mimic toxoplasmosis or PML

›CSF PCR and brain biopsy may be required for definitive diagnosis

›MRCP (magnetic resonance cholangiopancreatography)

›Indications

›Suspected biliary microsporidiosis (E. bieneusi cholangiopathy)

›RUQ pain with elevated ALP in AIDS patient

›Expected findings

07Disposition/dispo36

Admission criteria

›Indications for hospital admission

›Severe dehydration — unable to maintain oral hydration

›IV fluid resuscitation required

›Electrolyte derangements requiring IV correction

›Hemodynamic instability

›SBP <90 mmHg or MAP <65 mmHg

›ICU-level care for septic shock

›Inability to tolerate oral medications or intake

›Required for PO antiparasitic therapy

›Disseminated disease — multi-organ involvement

›Encephalitis, hepatitis, nephritis, myositis

›Specialist input required

›Severe malnutrition or wasting requiring inpatient nutritional support

›TPN consideration if enteral route not feasible

›Diagnostic uncertainty requiring inpatient workup

›Stool PCR pending, empiric therapy initiated

Discharge criteria

›Criteria for safe discharge

›Hemodynamically stable

›Tolerating oral fluids without ongoing volume losses exceeding intake

›Electrolytes corrected

›Oral electrolyte replacement feasible

›Tolerating oral antiparasitic medications and ART

›Reliable outpatient follow-up arranged

›Infectious disease within 1-2 weeks

›Stool re-examination scheduled

08Treatment/t64

Initial stabilization

›Fluid and electrolyte resuscitation

›IV isotonic crystalloid for hemodynamic compromise

›Normal saline or lactated Ringer's 30 ml/kg bolus

›Reassess after each 500 ml aliquot

›Oral rehydration with electrolyte-containing solutions for mild-moderate dehydration

›WHO ORS formula preferred

›Potassium replacement for hypokalaemia

›IV KCl 10 mmol/hr via peripheral IV if K <3.0 mmol/l

›Symptomatic management

›Loperamide 4 mg PO initial dose, then 2 mg after each loose stool

›Maximum 16 mg/day

›Avoid in suspected invasive diarrhea or toxic colitis

›Nutritional supplementation

›High-calorie, high-protein diet to counteract malabsorption and wasting

›Enteral nutrition via NG tube if oral intake inadequate

Antiretroviral therapy — cornerstone of management

›ART initiation or optimization in HIV patients

›Immune reconstitution is the primary driver of clearance

›CD4 recovery to >200 cells/mm³ leads to symptom resolution in most patients

›Symptom improvement typically within 1 month of effective ART

›Organism eradication by approximately 6 months of sustained ART

›Defer to HIV/ID specialist for ART selection

›Drug interactions with albendazole and itraconazole considered

›IRIS (immune reconstitution inflammatory syndrome) monitoring required

Antiparasitic therapy — species-guided

›Encephalitozoon spp. (intestinalis, hellem, cuniculi) — first-line

›Albendazole 400 mg PO BID

›Minimum 14 days; continue until CD4 >200 cells/mm³ sustained for ≥3 months and symptoms resolved

›Mechanism: tubulin polymerization inhibition

›Monitoring: LFTs (hepatotoxicity), CBC (bone marrow suppression rare)

›Class I recommendation based on evidence and expert consensus

›Enterocytozoon bieneusi — ART plus adjunctive agent

›ART optimization — primary treatment

›Albendazole has limited efficacy against E. bieneusi

›Fumagillin 60 mg/day PO (if available)

›Effective for E. bieneusi; unavailable for systemic use in the US

›Monitoring: CBC every 1-2 weeks — dose-dependent thrombocytopenia

›Contraindicated in pregnancy (antiangiogenic mechanism)

›Nitazoxanide 500 mg PO BID for ≥14 days — alternative

›Reasonable alternative if fumagillin unavailable

›Limited efficacy when CD4 <100 cells/mm³

›Take with food to improve absorption and reduce GI adverse effects

›Trachipleistophora and Anncaliia (disseminated) — combination therapy

›Itraconazole 400 mg/day PO plus albendazole 400 mg PO BID

›Continue until sustained immune reconstitution achieved

›Itraconazole QT prolongation risk — baseline ECG recommended

›Drug interactions: itraconazole inhibits CYP3A4 — review ART for interactions

›Vittaforma corneae — limited data

›ART plus fumagillin if available

Ocular microsporidiosis treatment

›Keratoconjunctivitis (E. hellem, E. cuniculi, E. intestinalis)

›Topical fumagillin eye drops 70 mcg/ml

›2 drops every 2 hours for 4 days, then QID

›Investigational in US — compounding pharmacy required

›Combined with oral albendazole for non-E. bieneusi species

›ART optimization in HIV patients — immune reconstitution reduces ocular disease

›Stromal keratitis in immunocompetent hosts

›Topical fumagillin

›Ophthalmology surgical evaluation — corneal perforation risk

›Penetrating keratoplasty for severe cases

Ineffective treatments to avoid

›Metronidazole — not active in vitro or in animal models

›Should not be used for microsporidiosis

›Atovaquone — not active; should not be used

Secondary prophylaxis

›Albendazole 400 mg PO BID as maintenance prophylaxis

›Continue until CD4 >200 cells/mm³ sustained for ≥3 months after ART initiation

›Discontinue when immune reconstitution confirmed

›Risk of relapse if CD4 falls below threshold again

09Special Populations/sp62

Pregnancy

›Medication safety in pregnancy

›Albendazole — avoid in first trimester

›Teratogenic in animal models; limited human data

›Use only if benefit outweighs risk in second or third trimester

›If used, folic acid supplementation recommended

›Systemic fumagillin — contraindicated in pregnancy

›Antiangiogenic mechanism poses fetal vascular risk

›Nitazoxanide — limited safety data in pregnancy

›Category B; use with caution

›Itraconazole — avoid in pregnancy

›Teratogenic in animal studies

›Management approach in pregnancy

›Supportive care prioritized — IV fluids, nutritional support

›Dehydration and malnutrition pose independent fetal risk

›ART optimization — safest primary intervention in HIV-positive pregnant patients

›Consult HIV/ID specialist and maternal-fetal medicine

›Ophthalmology referral for ocular disease

›Topical therapy safer than systemic

›Perinatal transmission

›Vertical transmission has been reported

›Neonatal microsporidiosis documented

Geriatric

›Age-specific risk factors

›Age ≥60 years — independent risk factor for microsporidiosis

›Immune senescence reduces clearance

›Polypharmacy — drug interaction risk

›Albendazole: CYP induction may reduce efficacy of concurrent medications

10Background/b74

Epidemiology

›Disease burden and prevalence

›Prevalence in HIV-infected patients with diarrhea: 7-50% depending on geographic region and CD4 level

›Higher in sub-Saharan Africa, South and Southeast Asia

›E. bieneusi accounts for approximately 90% of human gastrointestinal cases

›E. intestinalis accounts for approximately 8-10% of intestinal cases

›Immunocompetent host infection underrecognized

›Self-limited traveler's diarrhea in returning travelers

›Keratoconjunctivitis in contact lens wearers

›Organ transplant recipients — increasing incidence as transplantation expands

›Latent donor-derived transmission documented

›Transmission routes

›Waterborne — primary route; spores resistant to standard chlorination

›Boiling or UV treatment required to inactivate

›Foodborne — fecal contamination of produce and water sources

›Zoonotic — over 150 species identified; >180 animal hosts documented

›Nosocomial transmission possible among severely immunocompromised patients

›Vertical (perinatal) transmission documented

›Morbidity and mortality

›Significant mortality in profoundly immunosuppressed patients without ART

›Wasting syndrome, cholangiopathy, and encephalitis drive mortality

›Era of effective ART — dramatic decline in incidence and mortality from microsporidiosis

Pathophysiology

›Organism classification

›Obligate intracellular, spore-forming organisms

›Formerly classified as protozoa — genomic analysis reclassified as fungi-related (Fungi-like Microsporidia)

›Over 200 species identified; approximately 17 species infect humans

›Spore structure — unique polar tube (filament) mechanism

›Spore germinates and extrudes polar tube into host cell

›Sporoplasm injected directly into host cell cytoplasm

›Host cell invasion

›Polar tube penetration bypasses endocytosis

›Direct injection of sporoplasm into epithelial cell cytoplasm

›Merocytes proliferate intracellularly

›Villous atrophy and crypt hyperplasia in small intestine

›Malabsorption from mucosal destruction

›Watery diarrhea from osmotic and secretory mechanisms

›Immune evasion

›Intracellular lifecycle largely protected from humoral immunity

›CD4+ T-cell response critical for clearance

›CD4 <100 cells/mm³ — loss of immune control enables dissemination

›Spores environmentally resilient

›Resistant to chlorine, survive in soil and water for months

›Organ-specific pathophysiology by species

›E. bieneusi — enterocyte tropism; biliary epithelium involvement causes cholangiopathy

›Cannot be grown in culture; diagnosis relies on microscopy and PCR

›Encephalitozoon spp. — broader cell tropism (enterocytes, macrophages, hepatocytes, renal tubular cells, neurons)

›Disseminated disease pattern

›Trachipleistophora — skeletal and cardiac muscle tropism; CNS granulomas

Therapeutic Considerations

›Species identification drives treatment selection

›E. bieneusi vs Encephalitozoon spp. distinction is critical

›Albendazole effective for Encephalitozoon spp. — NOT for E. bieneusi

›PCR speciation required for optimal antiparasitic selection

›Empiric albendazole pending speciation reasonable for most immunocompromised patients

›E. bieneusi requires ART plus fumagillin or nitazoxanide

›Role of immune reconstitution

›ART-induced immune restoration leads to microsporidiosis resolution

›CD4 recovery >200 cells/mm³ allows antiparasitic discontinuation

›Primary goal of management in HIV patients

›IRIS risk after ART initiation

›Paradoxical worsening before improvement

›Usually self-limited; severe IRIS may require corticosteroids

›Treatment monitoring parameters

›Clinical response — stool frequency, weight

›Improvement expected within 2-4 weeks of effective therapy

›CBC monitoring on fumagillin — thrombocytopenia

›Every 1-2 weeks during therapy; dose reduction or discontinuation if platelets <100 x10⁹/l

›LFTs on albendazole — hepatotoxicity

›Baseline then every 4 weeks

›CD4 count trending

›Target >200 cells/mm³ for 3+ months before stopping maintenance therapy

›Fumagillin availability challenge

›Not commercially available for systemic use in the US

›Available in some European countries

›CDC consultation recommended for access

›Topical ophthalmic formulation via compounding pharmacy in US

11Patient Discharge Instructions/pdi37

copy discharge instructions

›Diagnosis and overview

›Microsporidiosis is an infection caused by microscopic fungal-related parasites called microsporidia

›Most common in people with weakened immune systems, especially low CD4 counts in HIV

›Spread through contaminated water, food, or contact with infected animals

›Medications — take as directed

›Albendazole — take with a fatty meal to improve absorption

›Do not skip doses — incomplete treatment can lead to relapse

›Report yellowing of skin or eyes (jaundice) to your doctor immediately

›Your HIV medications (ART) are the most important treatment

›ART helps your immune system recover, which is the main way this infection clears

›Do not stop taking ART for any reason without talking to your doctor

›If prescribed nitazoxanide — take with food

›Diet and hydration

›Drink plenty of fluids — water, oral rehydration solutions with electrolytes

›Sports drinks or oral rehydration sachets help replace lost salts

›High-calorie, high-protein foods to help regain weight

›Avoid untreated tap water if immune system is weakened

›Boiled or filtered water strongly recommended

›Prevention and hygiene

›Wash hands thoroughly after using the bathroom and before eating

›Avoid drinking from rivers, lakes, or streams

›Avoid contact with stool from animals if possible

›Contact lens wearers — inform your eye doctor about this infection

›Return to emergency department immediately for

›Inability to keep down any fluids for more than 8 hours

›Dizziness, fainting, or feeling very weak (signs of severe dehydration)

›Eye pain, redness, or new visual changes

12References/r20

Guidelines and key sources

›Han B, Pan G, Weiss LM. Microsporidiosis in Humans. Clinical Microbiology Reviews. 2021. PMID: 34190570

›Comprehensive review — organism biology, clinical manifestations, diagnosis, treatment

›Primary evidence source for species-specific treatment recommendations

›IDSA/HIVMA/OAC Guidelines for Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025

›Benson C, Brooks J, Dhanireddy S, et al.

›Available at: clinicalinfo.hiv.gov

›Covers treatment algorithms, ART interaction guidance, secondary prophylaxis thresholds

›DHHS/OAC Pediatric Guidelines for Prevention and Treatment of Opportunistic Infections in Children with HIV. 2025

›Kapogiannis BG, Yates F, Li W, et al.

›Pediatric dosing recommendations for albendazole and nitazoxanide

›Shane AL, Mody RK, Crump JA, et al. 2017 IDSA Clinical Practice Guidelines for Diagnosis and Management of Infectious Diarrhea. Clinical Infectious Diseases. 2017. PMC5850553

›Disposition and severity stratification criteria

›Weber R, Bryan RT. Microsporidial Infections in Immunodeficient and Immunocompetent Patients. Clinical Infectious Diseases. 1994. PMID: 7811872

›Early characterization of microsporidial staining methods and clinical spectrum

›Han B, Takvorian PM, Weiss LM. Invasion of Host Cells by Microsporidia. Frontiers in Microbiology. 2020. PMID: 32132983

›Polar tube invasion mechanism and intracellular lifecycle

›Didier ES et al. Comparison of Three Staining Methods for Detecting Microsporidia in Fluids. J Clin Microbiol. 1995. PMID: 8586689

›Comparative stain performance data including calcofluor white vs trichrome

›Pazmiño-Gómez BJ et al. Prevalence and Risk Factors of E. bieneusi and E. intestinalis Among PLHIV with Diarrhea. J Clin Medicine. 2025. PMID: 39860354

›Contemporary prevalence data; CD4 and age as independent risk factors

Evidence & Review

Evidence & Review