01Approach to the Critical Patient/attcp74

Immediate priorities

›Airway and breathing threats

›Respiratory failure from pulmonary hyperinfection

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›ARDS pattern infiltrates

›Diffuse bilateral ground-glass opacities

›Larval migration through pulmonary vasculature

›If respiratory failure, early intubation planning

›Avoid delay in hypoxemic patient

›Lung-protective ventilation for ARDS

›Circulation and sepsis threats

›Septic shock from enteric bacterial translocation

›SBP < 90 mmHg

›MAP < 65 mmHg

›Gram-negative bacteremia in 40% of hyperinfection cases

›Enteric organisms breach bowel wall with larvae

›Lactate >= 2 mmol/l indicates tissue hypoperfusion

›If septic shock, broad-spectrum antibiotics within 1 hour

›Cover enteric Gram-negatives and anaerobes

›Piperacillin-tazobactam or meropenem first-line

›Neurologic threats

›CNS dissemination with meningitis or brain abscess

›Altered mental status in hyperinfection

›Neck stiffness or photophobia

›Enteric bacterial meningitis carrying extremely high mortality

›Larvae carry gut flora through meninges

›LP after imaging if clinically stable

02History/hx73

Presenting symptoms

›Gastrointestinal symptoms

›Diarrhea — often bloody or watery

›May be profuse in hyperinfection

›Alternating with constipation in chronic disease

›Abdominal pain

›Diffuse or periumbilical

›Mimics acute abdomen with ileus or obstruction

›Nausea, vomiting, anorexia, weight loss

›Malnutrition is both risk factor and consequence

›Malabsorption from mucosal invasion

›Pulmonary symptoms

›Cough

›May be productive with larvae-laden sputum

›Hemoptysis in severe pulmonary hyperinfection

›Dyspnea and wheezing

›Löffler-like syndrome from larval migration

›ARDS pattern in severe cases

›Dermatologic symptoms

›Larva currens — pathognomonic migratory serpiginous urticaria

›Perianal, buttocks, and lower abdomen distribution

›Moves rapidly (centimeters per hour) unlike cutaneous larva migrans

›Pruritus ani

›Perianal pruritus from larval migration

Epidemiologic history

›Geographic exposure

›Tropics and subtropics — highest endemicity

›Sub-Saharan Africa, Southeast Asia, Latin America

03Physical Exam/exam59

Vital signs and general

›Vital sign patterns

›Fever

›Present in 50-70% of hyperinfection cases

›Hypothermia in severe septic shock

›Tachycardia and hypotension

›Septic shock physiology

›HR > 100 bpm as early sepsis sign

›Tachypnea and hypoxia

›SpO2 monitoring

›Respiratory rate as marker of severity

›General appearance

›Degree of distress and toxicity

›Diaphoresis, pallor, altered mentation

›Cachexia and malnutrition signs

Abdominal exam

›Abdominal findings

›Diffuse tenderness

›Peritoneal signs if bowel perforation

›Rigidity indicating surgical emergency

›Bowel sounds

›Absent sounds suggesting ileus

›High-pitched sounds with obstruction

›Hepatomegaly

›Hepatic involvement in disseminated disease

›Liver tenderness on palpation

›Rectal exam

›Perianal erythema and excoriation

04Differential Diagnosis/ddx55

Life-threatening mimics

›Sepsis and bacteremia from other sources

›ICD-10: A41.9 — Sepsis, unspecified organism

›Distinguish by larvae on stool/sputum exam

›Eosinophilia suggests parasitic etiology if present

›Spontaneous bacterial peritonitis

›Ascites with fever and peritoneal signs

›Paracentesis distinguishes

›Bacterial meningitis from other causes

›ICD-10: G00.9 — Bacterial meningitis, unspecified

›CSF larvae diagnostic for Strongyloides

›Enteric organisms on CSF culture should raise suspicion

›ARDS from other causes

›ICD-10: J80 — Acute respiratory distress syndrome

›BAL larvae distinguish pulmonary hyperinfection

›Consider alongside pneumonia and aspiration

Gastrointestinal mimics

›Inflammatory bowel disease

›ICD-10: K51.9 — Ulcerative colitis, unspecified

›Bloody diarrhea overlap

›Biopsy may reveal larvae in mucosa

›ICD-10: K50.9 — Crohn's disease, unspecified

›Transmural involvement mimics

›Immunosuppression for IBD can trigger hyperinfection

›Intestinal obstruction

›ICD-10: K56.60 — Unspecified intestinal obstruction

›Ileus from bowel wall invasion

›Imaging may show thickened bowel wall

05Laboratory Tests/lt90

Complete blood count

›White blood cell count

›Leukocytosis typical in hyperinfection

›Left shift indicating bacterial co-infection

›Leukopenia in overwhelming sepsis — poor prognostic sign

›Eosinophil count — critical pitfall

›Eosinophilia absent in 70-100% of hyperinfection

›Normal eosinophil count does NOT rule out disease

›Eosinophilia when present is protective (lower mortality)

›Hemoglobin and platelets

›Anemia from GI blood loss

›Iron deficiency pattern with chronic disease

›Normocytic in acute blood loss

›Thrombocytopenia

›DIC complication

›Sepsis-related consumptive process

Metabolic and organ function panels

›Comprehensive metabolic panel

›Hypoalbuminemia

›Protein-losing enteropathy

›Marker of malnutrition severity

›Elevated transaminases

›Hepatic involvement in disseminated disease

›Sepsis-related hepatic dysfunction

›Electrolyte abnormalities

›Hyponatremia with SIADH from CNS disease

›Hypokalemia from diarrhea losses

›Renal function

›Creatinine and BUN for AKI

›Sepsis-associated renal failure

›Contrast consideration for imaging

›Urinalysis

›Larvae in urine in disseminated disease (rare)

›Hematuria and pyuria in renal involvement

Inflammatory and sepsis markers

›Lactate

›Serum lactate for tissue perfusion

›>= 2 mmol/l — sepsis concern

›>= 4 mmol/l — septic shock threshold

›Serial lactate clearance

›Repeat at 2 hours after resuscitation

›Failure to clear portends poor prognosis

›Procalcitonin and CRP

›Procalcitonin elevation with bacterial co-infection

›Guides antibiotic duration

›High levels with Gram-negative bacteremia

›CRP — nonspecific but markers disease activity

›Useful for treatment response monitoring

Coagulation panel

›DIC screen

›PT, PTT, INR

›Prolonged in coagulopathy

›Fibrinogen consumption in DIC

›D-dimer

›Elevated in DIC and PE

›Context-dependent interpretation

›Fibrinogen

›Low fibrinogen confirms consumptive DIC

›Replace with cryoprecipitate if bleeding

Microbiological workup

›Blood cultures

›Two sets before antibiotics

›Enteric organisms — E. coli, Klebsiella, Enterococcus

›Gram-negative bacteremia in ~40% of hyperinfection

›Follow to clearance with serial cultures

›Duration of bacteremia guides antibiotic course

›Stool examination

›Stool ova and parasites — look for filariform larvae

›Single stool sensitivity low (~30%)

›Serial exams x3-7 improve yield significantly

›Agar plate culture — most sensitive stool method

›Sensitivity ~89%

›Requires fresh stool and 48-72 hours incubation

›Baermann concentration technique

›Improved sensitivity over direct smear

›Better for larvae with low motility

›Serology

›Strongyloides IgG ELISA

›Sensitivity 75-94% in immunocompetent hosts

›Reduced to 43-68% in immunocompromised — major limitation

›Cannot be used alone to rule out disease

›HTLV-1 serology

›Essential in all hyperinfection cases

›Guides prognosis and secondary prophylaxis planning

›Other specimens

›Sputum examination

›Larvae identifiable in respiratory secretions

›Induced sputum increases yield

›CSF analysis

›If meningitis suspected — LP after imaging

›Larvae and enteric organisms may be identified

›Stool PCR

›Available in specialized centers

›Sensitivity ~62%, specificity ~95%

›Useful when other methods negative

06Diagnostic Tests/dt87

Scoring Systems

›Severity stratification

›No validated scoring system specific to Strongyloides hyperinfection

›SOFA score for organ dysfunction in septic hyperinfection

›APACHE II for ICU prognostication

›WHO classification of strongyloidiasis

›Chronic uncomplicated: eosinophilia, minor GI symptoms

›Hyperinfection: massive larval burden, systemic spread

›Disseminated: larvae beyond GI tract and lungs

›Severity predictors from meta-analysis data

›Corticosteroid use — strongest predictor of severe disease

›Absence of eosinophilia — associated with increased mortality

›Septic shock — mortality approaches 100% without treatment

›ICD-10 coding

›B78.0 — Intestinal strongyloidiasis

›Chronic or limited GI disease

›B78.1 — Cutaneous strongyloidiasis

›Larva currens predominant presentation

›B78.7 — Disseminated strongyloidiasis

›Larvae beyond GI tract and lungs

›B78.9 — Strongyloidiasis, unspecified

›Use when syndrome not fully characterized

MRI

›Brain MRI indications

›CNS dissemination evaluation

›Altered mental status in hyperinfection

›Suspected brain abscess or meningitis

›Findings in CNS strongyloidiasis

›Multiple enhancing lesions on contrast T1

›Leptomeningeal enhancement in meningitis

›Abscess formation with rim enhancement

›Abdominal MRI

›Bowel wall assessment

›Thickening from mucosal invasion

›Superior soft tissue contrast vs CT

›Used when CT contrast contraindicated

›Hepatic involvement

›Focal hepatic lesions in disseminated disease

›MRI superior for characterization

CT

›CT chest indications and findings

›Pulmonary hyperinfection pattern

›Diffuse bilateral ground-glass opacities

›Consolidation in secondary bacterial pneumonia

›Centrilobular nodules from larval migration

›ARDS pattern

›Bilateral airspace disease

›Pleural effusions

›Sensitivity for pulmonary involvement

›High sensitivity for detecting infiltrates

›Not specific — cannot distinguish from other causes

›CT abdomen and pelvis

›Bowel findings

›Bowel wall thickening — duodenum and jejunum predominant

›Ileus pattern with air-fluid levels

›Pneumatosis intestinalis in severe mucosal injury

›Mesenteric changes

›Mesenteric lymphadenopathy

›Ascites from protein loss or peritonitis

›Hepatosplenic findings

›Hepatomegaly

›Splenomegaly in HTLV-1 co-infected patients

›CT head

›CNS dissemination evaluation

›Initial imaging before LP if meningismus

›Abscess or edema pattern

›Findings

›Hypodense lesions in brain abscess

›Cerebral edema in severe meningitis

Ultrasound

›Abdominal ultrasound

›Hepatic assessment

›Hepatomegaly with echogenic changes

›Periportal thickening in hepatic involvement

›Ascites detection

›Free fluid in peritoneum

›Guide diagnostic paracentesis if needed

›Bowel wall thickening

›Limited by ileus and bowel gas

›CT preferred for full abdominal assessment

›Point-of-care ultrasound

›Focused cardiac assessment

›IVC collapsibility for volume status

›Sepsis-associated cardiomyopathy

›Pleural assessment

›Pleural effusion detection

›Guide thoracentesis if indicated

›Transcranial Doppler

›Not routinely indicated

›MRI preferred for CNS assessment

›Consider in comatose patient if MRI unavailable

07Disposition/dispo47

ICU admission criteria

›All hyperinfection cases require ICU admission

›High mortality mandates intensive monitoring

›Case fatality rate 60-87% even with treatment

›Approaches 100% without treatment

›Hemodynamic monitoring requirements

›Arterial line for continuous blood pressure

›Central venous access for vasopressors

›Respiratory monitoring

›Serial ABGs and chest imaging

›Intubation readiness

›Mandatory consultations before admission

›Infectious disease consultation

›Treatment duration and monitoring guidance

›AST-IDCOP guideline adherence

›Critical care team for ICU management

›Ventilator management if ARDS develops

›Vasopressor titration

Transfer criteria

›Transfer triggers

›Lack of infectious disease specialist on-site

›Tropical medicine center preferred

›Parasitology specialist availability

›Surgical emergency requiring higher-level care

›Bowel perforation with peritonitis

›GI bleeding requiring endoscopic or surgical intervention

›CNS dissemination requiring neurosurgical consultation

›Brain abscess drainage

08Treatment/t97

Anthelmintic therapy

›Ivermectin — drug of choice

›Chronic strongyloidiasis dosing

›200 mcg/kg oral single dose

›Repeat at 2 weeks for increased efficacy

›Hyperinfection dosing

›200 mcg/kg orally once daily

›Continue until larvae cleared from all body fluids

›Then continue for minimum 7-14 additional days after clearance

›Route alternatives when oral absorption compromised

›Subcutaneous ivermectin — veterinary formulation, off-label

›Per-rectum ivermectin — off-label, used in ileus cases

›Transplant case series support non-oral routes

›Mechanism of action

›Glutamate-gated chloride channel agonist

›Causes paralysis and death of larvae and adult worms

›Does not reliably kill eggs — treatment must continue through cycles

›Albendazole — alternative or combination therapy

›Dosing

›400 mg orally twice daily for 10-14 days

›Can be combined with ivermectin for severe cases

›Role

›Second-line when ivermectin unavailable

›Combination therapy in refractory hyperinfection

›Less effective than ivermectin per Cochrane review

›Thiabendazole — historical alternative

›25 mg/kg twice daily for 5 days

›Higher toxicity profile — rarely used now

›Superseded by ivermectin and albendazole

›Emodepside — emerging agent

›Phase 2a trial data (2025) — promising efficacy

›Dose-ranging study vs ivermectin in Laos

›May offer alternative for ivermectin-resistant cases

›Not yet approved for human strongyloidiasis

›Investigational use only

Antibiotic therapy for bacterial co-infection

›Empiric broad-spectrum coverage

›First-line for septic shock

›Meropenem 1 g IV every 8 hours

›Covers enteric Gram-negatives, anaerobes, and ESBL producers

›Alternative

›Piperacillin-tazobactam 4.5 g IV every 6 hours

›Adequate coverage for most enteric pathogens

›De-escalation based on cultures

›Narrow spectrum once susceptibilities known

›Duration guided by source control and clinical response

›CNS bacterial meningitis coverage

›Ceftriaxone 2 g IV every 12 hours

›Gram-negative meningitis coverage

›Adjust based on CSF culture and susceptibilities

›Add metronidazole if enteric anaerobes suspected

›500 mg IV every 8 hours

›CNS penetration adequate

›Dexamethasone for bacterial meningitis — use with extreme caution

›May worsen Strongyloides hyperinfection

›Weigh benefit vs harm individually

Immunosuppression management

›Reduce or discontinue immunosuppression

›Corticosteroids — taper and discontinue if possible

›Critical step — reduces larval burden amplification

›Discuss with primary team managing underlying condition

›Transplant immunosuppression

›Balance rejection risk vs hyperinfection mortality

›Transplant team involvement mandatory

›Tacrolimus and mycophenolate dose reduction considered

›IRIS monitoring if rapid immunosuppression withdrawal

›Immune reconstitution inflammatory syndrome

›May paradoxically worsen symptoms transiently

Supportive care

›Fluid resuscitation

›Crystalloid bolus for sepsis and hypotension

›30 ml/kg initial bolus per Surviving Sepsis Campaign

›Reassess volume status after each bolus

›Vasopressor therapy for refractory hypotension

›Norepinephrine 0.01-3 mcg/kg/min — first-line vasopressor

›Vasopressin 0.03-0.04 units/min as second agent

›Respiratory support

›Supplemental oxygen titration

›Target SpO2 92-96%

›High-flow nasal cannula for moderate hypoxemia

›Mechanical ventilation for ARDS

›Lung-protective ventilation strategy

›Tidal volume 6 ml/kg ideal body weight

›PEEP titration per ARDSnet protocol

›Nutritional support

›NPO if ileus, obstruction, or hemodynamic instability

›Parenteral nutrition for disseminated disease with malabsorption

›Early enteral nutrition when gut function returns

›High protein, high calorie targets

›25-30 kcal/kg/day

›1.2-1.5 g protein/kg/day

Pre-treatment prophylaxis

›Screen at-risk patients before immunosuppression

›Stool exam and serology before corticosteroids or transplant

›All endemic region exposures require screening

›Empiric ivermectin if testing unavailable and urgency high

›WHO preventive chemotherapy recommendation

›Treatment of at-risk populations in endemic areas

›Pre-transplant screening mandatory per AST-IDCOP guidelines

›Post-COVID corticosteroid protocol

›Empiric ivermectin protocol implemented at some centers

›Demonstrated safety and efficacy in COVID-19 dexamethasone cohort

09Special Populations/sp68

Pregnancy

›Pregnancy considerations

›Ivermectin safety in pregnancy

›FDA Category C — limited human data

›Animal studies show embryotoxicity at high doses

›Generally avoided in first trimester if possible

›Risk-benefit in hyperinfection

›Maternal mortality from untreated hyperinfection is extremely high

›Ivermectin use justified when hyperinfection is life-threatening

›Consult maternal-fetal medicine and infectious disease

›Albendazole in pregnancy

›Teratogenic in animal studies

›Avoid in first trimester

›Use only if ivermectin unavailable and disease life-threatening

›Obstetric complications

›Vertical transmission rare but reported

›Larvae can cross placenta

›Neonatal strongyloidiasis documented

›Preterm labor risk with systemic illness

›Monitoring with obstetric team

›Fetal monitoring for compromised pregnancies

›Breastfeeding

›Ivermectin excreted in breast milk

›Pause breastfeeding during treatment if possible

Geriatric

›Age-related risk factors

›Higher prevalence of undiagnosed chronic infection

›Remote endemic area exposure decades prior

10Background/b81

Epidemiology

›Global burden

›Estimated 30-100 million infected worldwide

›Most asymptomatic chronic carriers

›Hyperinfection rare but catastrophic

›Endemic regions

›Tropics and subtropics — highest burden

›Sub-Saharan Africa, Southeast Asia, Central and South America

›Rural southeastern United States (Appalachia)

›US epidemiology

›Predominantly imported infection in immigrants and travelers

›Veteran populations with historical exposure

›Rising incidence with global migration

›Hyperinfection incidence

›1-2% of infected immunosuppressed patients develop hyperinfection

›Underestimated due to diagnostic challenges

›Corticosteroid use accounts for majority of cases

›Post-transplant incidence

›Highest risk in first 6 months post-transplant

›Donor-derived transmission median onset 13 weeks

›Mortality

›Case fatality rate 60-87% even with treatment

›Approaches 100% without anthelmintic therapy

›Presence of eosinophilia at presentation associated with lower mortality

Pathophysiology

›Life cycle and autoinfection

›Strongyloides stercoralis lifecycle

›Free-living: rhabditiform larvae in soil develop to filariform

›Filariform larvae penetrate intact human skin

›Migrate via bloodstream to lungs, then swallowed to GI tract

›Autoinfection cycle

›Rhabditiform larvae can transform to filariform within host

›Penetrate intestinal mucosa or perianal skin

›Cycle every approximately 2 weeks — allows indefinite persistence

›Normal immune control

›Th2 response and eosinophils contain larval burden

›IgE-mediated mechanisms limit autoinfection

›Hyperinfection mechanism

›Immunosuppression disrupts Th2 control

›Corticosteroids directly impair eosinophil function

›HTLV-1 skews Th1 response, abrogating Th2 protective immunity

›Accelerated autoinfection

›Massive larval proliferation overwhelms host defenses

›Larvae penetrate and disrupt bowel wall integrity

›Bacterial translocation

›Larvae carry gut flora through disrupted mucosa

›Enteric bacteria enter bloodstream and CSF

›Polymicrobial Gram-negative sepsis results

›Pulmonary hyperinfection

›Larvae traverse pulmonary vasculature

›Hemorrhagic alveolitis and inflammation

›Secondary bacterial pneumonia from seeding

Therapeutic Considerations

›Ivermectin mechanism and pharmacology

›Glutamate-gated chloride channel agonist

›Causes paralysis and death of parasites

›High affinity for invertebrate chloride channels

›Pharmacokinetics

›Peak serum concentration 4 hours after oral dose

›Half-life 12-16 hours

›Hepatic metabolism via CYP3A4

›Treatment duration controversy

›No RCT-level evidence for optimal hyperinfection duration

›Consensus: treat until larvae absent from all body fluids

›Minimum 7-14 days post-clearance

›Treatment failure and resistance

›Treatment failure mechanisms

›Impaired oral absorption in ileus — use alternative routes

›Inadequate duration — larvae in deep tissues may repopulate

›HTLV-1 impairs immune clearance despite drug effect

›Emerging resistance

›Anecdotal ivermectin resistance reports in humans

›Veterinary ivermectin resistance in animals well-documented

›Emodepside as alternative in development

›Preventive strategy

›Pre-immunosuppression screening

›Stool exam plus serology for all at-risk patients

›Empiric ivermectin if testing not feasible and urgency high

›AST-IDCOP guideline recommendation

›Screen all transplant candidates from endemic regions

›Treat with ivermectin before transplantation

›WHO preventive chemotherapy

›Mass drug administration in highly endemic settings

›Preventive chemotherapy review published Lancet Infect Dis 2025

11Patient Discharge Instructions/pdi49

copy discharge instructions

›Your diagnosis and condition

›You have been treated for Strongyloides — a parasitic infection

›This parasite lives in soil and enters through the skin

›In your case, the infection became serious and required hospitalization

›Your medication is very important

›Take all doses of your antiparasitic medication as prescribed

›Do not stop early even if you feel better

›Follow-up stool tests are required

›Stool samples check that the parasite is gone

›You will need tests at 2 weeks and 4 weeks after discharge

›Return to emergency department if you experience

›Worsening abdominal pain or cramping

›Especially if severe or associated with vomiting

›If you cannot keep food or water down

›Bloody diarrhea or black tarry stools

›This can mean GI bleeding

›Go to ER immediately

›Shortness of breath or new cough

›Especially coughing up blood

›Chest pain with breathing

›Fever above 38.3 degrees Celsius

›Especially with chills or shaking

›Severe headache, neck stiffness, or confusion

›These can be signs of spread to the brain

›Call 911 or go to ER immediately

›Skin rash that moves or spreads rapidly

›Especially around abdomen, buttocks, or thighs

12References/r41

Guidelines and key sources

›AST-IDCOP Guidelines — Parasitic infections in transplantation

›La Hoz RM, Morris MI et al. Clinical Transplantation 2019

›Strongyloides screening and management in transplant recipients

›Mandatory pre-transplant screening recommendation

›Abad CLR, Bhaimia E, Schuetz AN, Razonable RR. Clinical Transplantation 2022

›Comprehensive review of strongyloidiasis after solid organ and HSCT

›Cochrane Systematic Review

›Henriquez-Camacho C et al. Cochrane Database Syst Rev 2016

›Ivermectin versus albendazole or thiabendazole for S. stercoralis

›Ivermectin superior efficacy demonstrated

›WHO Guideline Review

›Lo NC, Addiss DG, Buonfrate D et al. Lancet Infect Dis 2025

›Review of WHO preventive chemotherapy for strongyloidiasis control

›Mass drug administration evidence base

Landmark studies and reviews

›Severe Strongyloidiasis Systematic Review

›Rojas OC, Montoya AM, Villanueva-Lozano H et al. Trans R Soc Trop Med Hyg 2023

›Meta-analysis of 339 severe cases

›Mortality 60-87% even with treatment

›Immunocompromised host review

›Keiser PB, Nutman TB. Clin Microbiol Rev 2004

›Strongyloides in immunocompromised population

›Pathophysiology and management review

›Czeresnia JM, Weiss LM. Lung 2022

›Comprehensive pulmonary and systemic manifestations review

›Outcomes data

›Henao-Martinez AF et al. Am J Trop Med Hyg 2024

Evidence & Review