The Daily Differential — Monday, April 27, 2026

2 of 5

Critical Parasitic Infections

Severe parasitic disease is easy to miss in non-endemic settings, especially when travel history is not obtained. The highest-risk missed diagnosis is...

At the Bedside

In the ED, focus on severe malaria first whenever a patient has fever plus recent travel to a malaria-endemic area or immigration from an endemic region.

High-risk parasitic emergencies to know
Severe falciparum malaria
Cerebral malaria
Babesiosis with hemolysis
Strongyloides hyperinfection/dissemination, especially after steroids
Neurocysticercosis causing seizures or hydrocephalus
Amebic liver abscess or fulminant colitis
Schistosomiasis is less often an ED critical illness but can present with severe complications

Initial evaluation
Travel/residence history, immunocompromise, HIV, pregnancy, steroid exposure
Vitals, mental status, seizure activity, jaundice, respiratory distress, signs of shock
CBC, CMP, LFTs, bilirubin, creatinine, glucose, lactate, coagulation studies
Thick and thin smears for malaria; repeat if initial smear negative but suspicion remains
Rapid malaria antigen test if available, but microscopy still matters
Hemolysis labs when babesiosis suspected: LDH, haptoglobin, retic count
Blood gas if severe illness; type and screen if hemolysis significant
CT/MRI brain if focal deficits, hydrocephalus concern, or seizure workup in neurocysticercosis
Stool ova/parasites are rarely immediately helpful for unstable presentations

Severe malaria red flags
Altered mental status, coma, seizures
Severe anemia, hemoglobinuria
Renal failure
Acidosis, hypoglycemia
ARDS/pulmonary edema
Shock
High parasitemia
Jaundice with end-organ dysfunction

ED management of severe malaria
Immediate ID/ICU involvement
Start IV artesunate as soon as available; if not immediately available, initiate alternative therapy per CDC/institutional pathway and obtain artesunate urgently
Manage complications:
Dextrose for hypoglycemia
Blood products for severe anemia
Renal support for AKI
Seizure control
Careful fluids; avoid worsening pulmonary edema
Serial smears/parasitemia assessment
Exchange transfusion is now rarely used and specialist-guided

Babesiosis
Similar to malaria on smear, but no travel to malaria region may be a clue; think tick exposure or asplenia
Severe disease may cause hemolytic anemia, thrombocytopenia, organ failure
Treat severe disease with azithromycin + atovaquone in many cases; clindamycin + quinine for severe/intolerant situations in some protocols; exchange transfusion may be indicated in severe parasitemia — specialist-guided

Strongyloides hyperinfection
Consider in patients from endemic regions with steroids/immunosuppression, GI symptoms, pulmonary symptoms, gram-negative sepsis, or eosinophilia that may disappear in severe disease
Early ivermectin is key; broad-spectrum antibiotics often needed for translocated enteric bacteremia

Neurocysticercosis
New seizure in immigrant/traveler from endemic area
Stabilize seizure first
CT may show calcified or cystic lesions; MRI better later
Antiparasitic therapy is not always started in the ED and may worsen inflammation; neurology/ID input important
Steroids and antiepileptics often precede antiparasitic therapy

Amebic liver abscess
Fever, RUQ pain, hepatomegaly, travel or origin from endemic region
Ultrasound/CT can identify abscess
Metronidazole or tinidazole is standard tissue therapy; luminal agent needed later, usually outpatient/inpatient consultant-directed

Disposition
Severe malaria, babesiosis with organ dysfunction, strongyloides hyperinfection, CNS parasitic disease, and amoebic complications require admission
ICU for altered mentation, severe anemia/hemolysis, shock, respiratory failure, or cerebral disease

A Classic Presentation

A 31-year-old man presents with fever, confusion, and dark urine 5 days after returning from Nigeria. He is febrile, tachycardic, mildly hypotensive, icteric, and intermittently somnolent. Labs show thrombocytopenia, hemoglobin 8.2 g/dL, creatinine 2.1 mg/dL, total bilirubin 5.6 mg/dL, and glucose 48 mg/dL. Thick and thin smears reveal Plasmodium falciparum with high parasitemia. In the ED, he receives dextrose, cautious resuscitation, ICU admission, and emergent IV artesunate with serial smears and complication management for severe malaria.

Study Directive

Memorize WHO/CDC severe malaria criteria and be able to name 6 without looking.
Practice asking a 20-second travel history on every fever patient this week.
Review malaria smear terminology: rings, parasitemia, thick vs thin smear purpose.
Build a differential for “seizure in immigrant patient” that includes neurocysticercosis, malaria, toxoplasmosis, and cryptococcus.
Do 10 parasitology board questions focused on severe malaria and babesiosis.

Key Medications

IV artesunate for severe malaria:* 2.4 mg/kg IV at 0, 12, and 24 hours, then q24h until able to transition to oral therapy
Atovaquone-proguanil:* dosing depends on weight/formulation and indication; commonly used for uncomplicated malaria, not as sole therapy for severe malaria — check reference
Azithromycin for babesiosis combination therapy:* 500–1000 mg PO/IV on day 1, then 250–1000 mg daily depending on regimen — meaningful variability; check reference
Atovaquone for babesiosis:* 750 mg PO q12h with food
Clindamycin for severe babesiosis alternative regimen:* 600 mg IV q6h or 300–600 mg IV q6–8h depending on protocol — check reference
Quinine:* dosing varies and adverse effects are common — check reference before use
Ivermectin for strongyloides:* 200 mcg/kg PO daily; duration depends on hyperinfection/dissemination severity — specialist-guided
Albendazole for neurocysticercosis:* regimen varies by lesion burden and is often not started independently in the ED — check reference
Dexamethasone for neurocysticercosis-associated cerebral edema:* common regimens vary; use specialist guidance
Metronidazole for amoebic liver abscess:* 500–750 mg PO/IV q8h for 7–10 days, followed by a luminal agent directed by consultant/team

High-Yield Pearls

Severe malaria kills through microvascular sequestration of parasitized RBCs, leading to cerebral dysfunction, acidosis, renal failure, and shock.
In strongyloides hyperinfection, steroids can trigger explosive autoinfection and gram-negative sepsis.
Babesia can resemble malaria on smear, but travel history and the absence of malarial exposure help differentiate.

Board Question

A 27-year-old woman presents with fever and confusion after returning from Sierra Leone. Labs show thrombocytopenia, AKI, and hypoglycemia. Blood smear confirms Plasmodium falciparum. What is the most appropriate treatment?

AOral chloroquine
BOral metronidazole
CIV artesunate
DAlbendazole Correct answer:
CIV artesunate Explanation: Severe falciparum malaria requires parenteral therapy, and IV artesunate is the treatment of choice. Chloroquine resistance is common and oral therapy is not appropriate in severe disease.

3 of 5

Croup

Croup is common, but severe upper airway obstruction can deteriorate quickly. The key ED skill is identifying the child who needs immediate nebulized...

At the Bedside

Croup is viral laryngotracheitis causing barky cough, hoarseness, and inspiratory stridor, usually in children 6 months to 3 years.

Typical presentation
Barking cough
Hoarse voice
Inspiratory stridor
Low-grade fever, URI prodrome
Worse at night

Assess severity
Mild: barky cough, no stridor at rest
Moderate: stridor at rest, mild-moderate retractions, no marked distress
Severe: prominent stridor at rest, significant retractions, agitation or lethargy
Impending respiratory failure: decreased stridor due to poor air movement, cyanosis, altered mental status, fatigue

Immediate approach
Keep child calm; avoid unnecessary agitation
Allow position of comfort with caregiver
Do not force invasive oral exam if epiglottitis/bacterial tracheitis is possible
Pulse ox; oxygen if hypoxemic or severe distress
Clinical diagnosis in most cases; imaging rarely needed

When to reconsider the diagnosis
Toxic appearance, high fever, drooling, tripod position -> think epiglottitis
Copious secretions, toxic child, poor response to epi -> bacterial tracheitis
Sudden onset/choking -> foreign body
Unilateral findings -> foreign body or abscess
Recurrent/atypical age -> airway anomaly

Testing
Usually none
Neck radiographs are not routinely required
Viral testing rarely changes ED care
If severe/atypical and alternative diagnosis suspected, involve airway experts before imaging/procedures

Treatment
Dexamethasone for all severities unless truly minimal disease and reliable follow-up; benefits onset within hours and reduces return visits
Nebulized epinephrine for stridor at rest or moderate-severe croup
Humidified air is low-risk but not a definitive evidence-based therapy
Reassess after epinephrine for work of breathing, stridor, and need for repeat dosing
Rarely, heliox or advanced airway management if failing

Airway planning
If worsening despite treatment, call anesthesia/ENT early
Intubation is uncommon but should be controlled and performed by the most experienced clinician
Use a smaller-than-age-predicted endotracheal tube because of subglottic narrowing

Disposition
Discharge: improved after dexamethasone, no stridor at rest, minimal work of breathing, tolerating PO, reliable caregivers
Observe/admit: recurrent stridor after epinephrine, persistent moderate symptoms, need for repeated epi, poor intake/dehydration, unreliable follow-up
ICU: severe/refractory symptoms, escalating epinephrine requirement, impending respiratory failure, intubation

A Classic Presentation

A 2-year-old boy is brought in at 1 AM with a barking cough and noisy breathing. He had rhinorrhea earlier in the day and now has inspiratory stridor at rest with mild subcostal retractions but is alert and consolable. Oxygen saturation is 97% on room air. He is kept on his mother’s lap, given dexamethasone 0.6 mg/kg PO and nebulized racemic epinephrine, and reassessed over the next few hours. His stridor at rest resolves, work of breathing normalizes, and he is discharged with return precautions.

Study Directive

Memorize the treatment threshold: stridor at rest = nebulized epinephrine + dexamethasone.
Practice differentiating croup, epiglottitis, bacterial tracheitis, and foreign body in a four-column note from memory.
Review pediatric airway sizing and write down the “use a smaller tube in subglottic edema” rule.
Do 5 pediatric airway simulation stems and make a disposition decision for each.
Teach a junior learner the difference between croup and bronchiolitis in under 2 minutes.

Key Medications

Dexamethasone:* 0.6 mg/kg PO/IM/IV once (common max 10–16 mg depending on protocol; many EDs use max 10 mg)
Lower doses such as 0.15–0.3 mg/kg may be used in some settings, but 0.6 mg/kg remains standard
Racemic epinephrine 2.25%:* 0.5 mL nebulized diluted in 2.5–3 mL NS
L-epinephrine (1 mg/mL, 1:1000):* 5 mL nebulized is a commonly used equivalent alternative
Heliox:* no universal ED dose; delivered as a gas mixture when available in severe cases — institution-specific

High-Yield Pearls

Croup is a subglottic process; this is why the child is hoarse and may have a classic steeple sign, though imaging is rarely needed.
Nebulized epinephrine works quickly via alpha-mediated vasoconstriction of airway mucosa but wears off, so observation matters.
A calm child with stridor is safer than a frightened child with the same anatomy; agitation worsens dynamic obstruction.

Board Question

A 20-month-old child presents with barky cough and inspiratory stridor at rest. He is afebrile, non-toxic appearing, and has mild retractions. Which is the best next step?

AImmediate lateral neck radiograph
BDexamethasone only, then discharge immediately
CNebulized epinephrine plus dexamethasone
DEmergent intubation Correct answer:
CNebulized epinephrine plus dexamethasone Explanation: Stridor at rest indicates at least moderate croup. Nebulized epinephrine provides rapid temporary improvement, while dexamethasone reduces ongoing airway edema and relapse.

4 of 5

Cytomegalovirus

CMV is usually mild or silent in immunocompetent patients, but in advanced HIV, transplant recipients, and other immunosuppressed patients it can cause...

At the Bedside

In the ED, CMV matters most in immunocompromised patients.

Who gets severe disease?
Advanced HIV/AIDS, especially very low CD4 counts
Solid organ or stem cell transplant recipients
Patients on significant immunosuppression

Presentations to recognize
CMV retinitis: floaters, blurry vision, visual field defects, painless visual loss
CMV colitis: abdominal pain, diarrhea, hematochezia, fever
CMV esophagitis: odynophagia/dysphagia in advanced HIV
CMV pneumonitis: dyspnea/hypoxemia in transplant patients
CMV encephalitis/polyradiculopathy: AMS, weakness, urinary retention, neuropathic symptoms
Mononucleosis-like syndrome in immunocompetent adults: fever, malaise, atypical lymphocytes, heterophile-negative mono picture

Assessment
ABCs, sepsis screen, hydration
Detailed immune status: HIV history, transplant meds, steroid use
Focused eye exam in any visual complaint:
Visual acuity
Pupils
Confrontation fields
Funduscopic exam if possible
GI/volume status in severe diarrhea
Neuro exam if weakness or encephalopathy

Workup
CBC, CMP, LFTs
HIV testing/CD4/viral load if undiagnosed or out of care, usually inpatient but should be initiated if needed
CMV viral load/PCR is useful in some contexts but does not replace tissue diagnosis for many organ-specific diseases
Ophthalmology exam is critical for retinitis
CT abdomen/pelvis if severe colitis complications suspected
CXR/CT chest in pulmonary complaints
MRI/spine imaging and LP if CNS disease suspected, with consultant guidance

ED management
Stabilize organ-specific complications: fluids, pain control, transfusion if severe bleeding, oxygen
If CMV retinitis is suspected, obtain urgent ophthalmology; treatment delay risks permanent vision loss
In critically ill immunocompromised patients with likely CMV organ disease, early antiviral therapy is specialist-guided and often started on admission
Distinguish CMV from other opportunistic infections:
HIV patient with headache/AMS -> cryptococcus, toxoplasmosis, CNS lymphoma also high on list
HIV patient with odynophagia -> Candida and HSV also common
HIV patient with dyspnea -> PJP, bacterial pneumonia, TB also considered

Disposition
Admit if organ-invasive disease is suspected, inability to tolerate PO, vision-threatening disease, severe diarrhea/dehydration, hypoxemia, CNS symptoms, or major immunosuppression
Outpatient management may be reasonable for well-appearing immunocompetent mono-like illness after excluding emergencies

A Classic Presentation

A 39-year-old man with untreated HIV presents with 2 weeks of blurry vision and floaters in the right eye. He denies eye pain. Visual acuity is reduced, and funduscopic exam shows patchy retinal whitening with hemorrhages. He is hemodynamically stable but appears chronically ill and reports weight loss. The ED team suspects CMV retinitis, obtains urgent ophthalmology consultation, sends HIV-related labs, and admits him for antiviral therapy planning and comprehensive opportunistic infection evaluation.

Study Directive

Memorize 4 CMV organ syndromes: retinitis, colitis, esophagitis, pneumonitis.
Compare CMV retinitis, HSV keratitis, retinal detachment, and endophthalmitis in a quick visual complaint differential.
Review which opportunistic infections cluster by CD4 count, especially CMV, cryptococcus, toxoplasmosis, and PJP.
Practice a fundoscopy review session or image drill focused on CMV retinitis.
Write down the difference between PCR positivity and tissue-invasive disease for CMV.

Key Medications

Ganciclovir:* 5 mg/kg IV q12h for induction in many severe CMV infections; renal adjustment required
Valganciclovir:* 900 mg PO BID for induction in selected stable patients with non-CNS disease such as some retinitis cases; renal adjustment required
Foscarnet:* dosing varies by indication/renal function and toxicity profile is significant — check reference
Cidofovir:* rarely ED-initiated; dosing and prehydration/probenecid protocols vary — check reference

High-Yield Pearls

CMV retinitis often progresses along retinal vessels, producing the classic “pizza pie” or hemorrhagic necrotizing retinitis appearance.
CMV disease severity is driven by impaired cell-mediated immunity; this is why advanced HIV and transplant patients are highest risk.
A heterophile-negative mono-like syndrome with atypical lymphocytes can be CMV in immunocompetent adults, but that is rarely the ED emergency.

Board Question

A patient with advanced AIDS presents with painless progressive visual loss and floaters. Funduscopic examination reveals fluffy yellow-white perivascular retinal lesions with hemorrhage. Which diagnosis is most likely?

AAcute angle-closure glaucoma
BCMV retinitis
COptic neuritis
DBacterial conjunctivitis Correct answer:
BCMV retinitis Explanation: CMV retinitis classically causes painless visual changes with hemorrhagic retinal lesions in severely immunocompromised patients. It is vision-threatening and requires urgent specialty involvement and antiviral therapy.

5 of 5

Diphtheria

Diphtheria is rare in vaccinated populations, but it is a true airway and toxin-mediated emergency. Missing it risks sudden airway compromise, myocarditis,...

At the Bedside

Consider diphtheria in an under-immunized patient with sore throat, low-grade fever, toxic appearance, cervical adenopathy/swelling, and a gray pharyngeal pseudomembrane.

Classic features
Gradual sore throat, malaise, low-grade fever
Gray/white adherent pseudomembrane in pharynx/tonsils/nasopharynx
Bleeding when membrane is disturbed
“Bull neck” from cervical soft tissue swelling/adenopathy
Hoarseness, stridor, respiratory distress if laryngeal involvement
Toxin complications: myocarditis, arrhythmias, heart block, neuropathy

Initial ED priorities
Airway assessment first
Place on droplet and contact precautions per local policy
Avoid aggressive manipulation of the pharynx if airway is tenuous
Notify public health/infection prevention early
Consult ENT/anesthesia if any concern for impending obstruction

Workup
Diagnosis is largely clinical in the ED
CBC, CMP
EKG for conduction abnormalities
Troponin if myocarditis suspected
Obtain swab/culture/PCR per local public health guidance, but do not delay treatment for testing
CXR if lower airway involvement suspected
Evaluate vaccination status and close contacts

Treatment
Diphtheria antitoxin as soon as possible after specialist/public health coordination; neutralizes unbound toxin only
Antibiotics to eradicate organism and reduce transmission
Airway support; intubation/tracheostomy may be needed in advanced obstruction
Continuous cardiac monitoring if significant illness due to myocarditis risk
Admit all suspected respiratory diphtheria

Disposition
ICU if airway compromise, pseudomembrane extension, myocarditis, arrhythmia, weakness/neuropathy, or toxic appearance
Public health coordination for isolation, contact management, and immunization issues is mandatory

A Classic Presentation

A 7-year-old under-immunized child presents with sore throat, muffled voice, and progressive neck swelling. He is febrile to 38.2°C, tachycardic, and has inspiratory stridor. Oropharyngeal exam reveals a thick gray adherent tonsillopharyngeal membrane with scant bleeding after minimal contact. The ED team places him in isolation, avoids repeated throat manipulation, initiates airway planning with ENT/anesthesia, contacts public health for urgent diphtheria antitoxin access, starts antibiotics, obtains an ECG, and admits him to the ICU.

Study Directive

Memorize the triad: pseudomembrane, bull neck, myocarditis risk.
Draw the diphtheria toxin mechanism from memory: ADP-ribosylation of EF-2 -> blocked protein synthesis.
Review isolation steps and who to call first in a suspected rare public-health infection at your institution.
Practice differentiating diphtheria from peritonsillar abscess, epiglottitis, and bacterial tracheitis.
Read one brief guideline summary on antitoxin access and contact prophylaxis workflow.

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Mechanism Pearl of the Day: Several of today’s highest-stakes diseases cause severe illness not just by organism burden, but by how they injure tissue: mucor through angioinvasion and necrosis, malaria through microvascular sequestration, croup through subglottic mucosal edema, CMV through failure of cell-mediated immune control, and diphtheria through toxin-mediated inhibition of protein synthesis.

Key Medications

Diphtheria antitoxin:* dose depends on disease site, duration, and severity; availability is public-health controlled and dosing varies — consult CDC/public health/institutional protocol immediately
Erythromycin:* 500 mg IV/PO q6h or 250–500 mg PO q6h depending on formulation/severity — check current protocol
Penicillin G:* dosing varies by formulation/severity; commonly specialist/public health guided — check reference
Benzathine penicillin G:* may be used in some eradication regimens; dose varies — check reference
Tdap/Td booster:* indicated because infection does not reliably confer immunity; follow current immunization guidance

High-Yield Pearls

The pseudomembrane is adherent because of toxin-induced necrosis and fibrinous exudate; forceful removal can provoke bleeding and worsen airway compromise.
Cardiac toxicity from diphtheria can present days after throat symptoms begin; obtain an ECG early.
Diphtheria toxin inactivates EF-2, halting protein synthesis and causing local necrosis plus systemic myocarditis/neuropathy.

Board Question

A child with incomplete immunizations presents with sore throat, cervical swelling, and an adherent gray pharyngeal membrane. What is the most important next step in management?

AWait for culture confirmation before treatment
BRemove the membrane to improve symptoms
CAdminister diphtheria antitoxin and antibiotics promptly
DTreat with oseltamivir Correct answer:
CAdminister diphtheria antitoxin and antibiotics promptly Explanation: Diphtheria is a clinical diagnosis in the ED, and treatment should not await culture confirmation. Antitoxin neutralizes circulating unbound toxin, while antibiotics reduce organism burden and transmission.

TheDaily Differential

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