01Approach to the Critical Patient/attcp60

Immediate priorities

›Airway and breathing threats

›Hypoxemia from ARDS

›SpO2 < 90% on room air

›PaO2 < 60 mmHg

›Altered mental status with aspiration risk

›GCS < 13

›If unable to protect airway, proceed to definitive airway control

›Respiratory failure pattern

›Bilateral infiltrates with refractory hypoxemia

›Rising PaCO2 with fatigue

›Circulation and hemolytic crisis threats

›Shock physiology

›SBP < 90 mmHg

›MAP < 65 mmHg

›Severe hemolytic anemia markers

›Hemoglobin < 7 g/dL equivalent (< 4.3 mmol/L)

›Markedly elevated LDH and indirect bilirubin

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

›Class I recommendation

›Source control and blood smear simultaneously

›Parasitemia severity classification

›Mild-moderate: parasitemia < 4%, no organ dysfunction

›Outpatient treatment candidate if immunocompetent

›Oral antiparasitic regimen appropriate

›Severe: parasitemia 5–10% with organ injury or hemoglobin < 4.3 mmol/L

›Hospitalization required

›IV antiparasitic regimen

02History/hx56

Presentation pattern

›Core syndrome

›Fever

›Intermittent high fever

›Rigors and drenching night sweats

›Constitutional symptoms

›Fatigue and malaise preceding fever by days

›Myalgia and arthralgia

›Hemolysis symptoms

›Dark urine (hemoglobinuria)

›Jaundice

›Exposure and onset

›Tick exposure history

›Outdoor activity in endemic area (Northeast or Upper Midwest US)

›Peak season May through September

›Most patients do not recall the tick bite

›Onset timing

›Symptoms begin 1–4 weeks after tick bite

›Transfusion-transmitted cases 1–9 weeks (up to 6 months) after transfusion

Risk factors

›High-risk host features

›Asplenia or prior splenectomy

›Strongest risk factor for severe disease

›Life-threatening even with low parasitemia

›Immunosuppression

›B-cell lymphoma or rituximab therapy

›Solid organ or stem cell transplant

›HIV with low CD4 count

03Physical Exam/exam58

Vitals and general

›Stability snapshot

›Temperature

›High intermittent fever typical

›Hypothermia as severe sepsis marker in elderly

›Heart rate

›Tachycardia from fever and anemia

›Persistent tachycardia despite antipyretics suggests severe hemolysis

›Blood pressure

›SBP < 90 mmHg indicates severe or septic shock

›MAP < 65 mmHg triggers vasopressor consideration

›Oxygen saturation

›Room air value essential

›SpO2 < 90% requires immediate oxygen and ARDS evaluation

›General appearance

›Diaphoretic and ill-appearing

›Severity correlates with degree of hemolysis

›Pallor from hemolytic anemia

HEENT and abdominal exam

›HEENT findings

›Scleral icterus

›Indirect hyperbilirubinemia from hemolysis

›Severity correlates with degree of hemolysis

›Conjunctival pallor

›Hemolytic anemia marker

›Absent erythema migrans rash

›Abdominal exam

›Splenomegaly

04Differential Diagnosis/ddx43

Life-threatening mimics

›Hematologic emergencies

›Malaria (Plasmodium falciparum)

›ICD-10 B50.9

›Most important mimic; ring forms similar on smear

›Distinguish by pigment deposits, schizonts, gametocytes present in malaria

›Travel to malaria-endemic region outside US

›Thrombotic thrombocytopenic purpura

›ICD-10 M31.1

›Schistocytes on smear, ADAMTS13 activity markedly low

›No parasitemia

›Hemolytic uremic syndrome

›ICD-10 D59.3

›Diarrheal prodrome, schistocytes, renal failure

›No parasitemia

Tick-borne coinfections

›Other tick-borne diseases

›Anaplasmosis (human granulocytic anaplasmosis)

›ICD-10 A77.49

›Morulae in neutrophils on smear

›Leukopenia more prominent

›Coinfection rate approximately 20% in endemic areas

›Lyme disease

›ICD-10 A69.20

›Erythema migrans rash distinguishes

›Approximately 20% coinfection rate with babesiosis

›Ehrlichiosis

›ICD-10 A77.40

05Laboratory Tests/lt65

Core diagnostic labs

›Peripheral blood smear

›Gold standard for rapid diagnosis

›Giemsa or Wright stain required

›Request manual (non-automated) review explicitly

›Key findings

›Intraerythrocytic ring forms

›Maltese cross (tetrad) configuration — pathognomonic for Babesia, infrequently seen

›Limitation

›Insensitive at low parasitemia; PCR if high suspicion with negative smear

›Babesia PCR

›More sensitive than smear at low parasitemia

›Real-time or 18S rRNA RT-PCR

›Species identification capability (B. microti vs B. duncani vs B. divergens)

›Recommended if smear negative with strong clinical suspicion

›IDSA 2020 guideline recommendation

›Also useful for treatment response monitoring

›Parasitemia quantification

›Critical for severity stratification and exchange transfusion decision

›Report as percentage of infected red blood cells

›Recheck every 12–24 hours until < 1%

Hemolysis and organ function labs

›Hemolysis panel

›Complete blood count

›Hemolytic anemia (often normocytic)

›Thrombocytopenia very common

›Leukopenia or normal WBC (leukocytosis uncommon)

›LDH

06Diagnostic Tests/dt71

Scoring Systems

›Severity stratification

›Parasitemia percentage — primary severity marker

›< 4%: mild-moderate, outpatient candidate if immunocompetent

›5–10% with organ injury: severe, hospitalization required

›> 10%: life-threatening, ICU, exchange transfusion consideration

›SOFA score

›Used to define acute organ injury in severe babesiosis

›Score >= 2 indicates organ dysfunction

›Guides ICU admission decision

›IDSA 2020 severity criteria

›Severe hemolytic anemia: hemoglobin < 4.3 mmol/L

›Thrombocytopenia: platelets < 40 × 10^9/L

›Elevated total bilirubin > 3× ULN

›Evidence of ARDS, DIC, renal failure, hepatic failure

›Exchange transfusion thresholds

›Absolute threshold: parasitemia > 10%

›STOP-BABESIOSIS 2026 study data

›Nearly 5-fold lower adjusted risk of in-hospital death or 30-day readmission with exchange transfusion (3.6% vs 9.8%, aOR 0.22)

›Relative threshold: parasitemia 5–10% with acute organ injury

›Severe hemolytic anemia (hemoglobin < 4.3 mmol/L and LDH > 3× ULN)

›Infectious diseases and hematology consultation

MRI

›MRI role in babesiosis

›Limited acute utility

›Not a first-line diagnostic modality

›Availability constraints in acute setting

›Specific indications

07Disposition/dispo49

Admission and ICU criteria

›Admission indications

›Parasitemia >= 4%

›IV antiparasitic therapy required

›Serial smear monitoring inpatient

›Hemodynamic instability

›SBP < 90 mmHg

›Lactate >= 2 mmol/L with infection concern

›Significant hemolytic anemia

›Hemoglobin requiring transfusion support

›Rapidly rising LDH and bilirubin trend

›Immunocompromised host

›Asplenia, transplant, rituximab, HIV with low CD4

›Extended treatment course required

›Inability to tolerate oral medications

›Persistent vomiting

›Encephalopathy affecting compliance

›ICU admission indications

›Parasitemia > 10%

›Exchange transfusion planning

›Continuous monitoring

›ARDS or respiratory failure

›Ventilatory support need

›HFNC with rising oxygen requirement

›Septic shock

›Vasopressor requirement

›Lactate >= 4 mmol/L

›DIC with active bleeding

08Treatment/t89

Antiparasitic therapy — mild to moderate

›Preferred first-line regimen

›Atovaquone 750 mg PO every 12 hours

›Must be taken with fatty meal for adequate absorption

›Duration 7–10 days for immunocompetent

›Azithromycin 500 mg PO on day 1, then 250 mg PO daily

›Duration 7–10 days for immunocompetent

›Combination with atovaquone is Class I recommendation per IDSA 2020

›Alternative regimen (more adverse effects)

›Clindamycin 600 mg PO every 8 hours

›Duration 7–10 days

›Higher GI adverse effect rate

›Quinine sulfate 650 mg PO every 8 hours

›Duration 7–10 days

›Cinchonism risk: tinnitus, GI upset, headache

›Monitor for QT prolongation with quinine

›Quinidine IV no longer available in the US

Antiparasitic therapy — severe inpatient

›Preferred inpatient regimen

›Atovaquone 750 mg PO every 12 hours

›Continue PO even in hospitalized patients if tolerated

›With fatty meal or enteral fat if via feeding tube

›Azithromycin 500 mg IV every 24 hours

›Step down to oral when clinically improving

›Total duration 7–10 days for immunocompetent

›Combination is Class I recommendation per IDSA 2020

›Alternative severe regimen

›Clindamycin 600 mg IV every 6 hours

›Switch to oral clindamycin when tolerating PO

›C. difficile risk counseling

›Quinine sulfate 650 mg PO every 8 hours

›Cardiac monitoring for QT prolongation

›Tinnitus and cinchonism monitoring

Exchange transfusion

›Indications

›Absolute: parasitemia > 10%

›STOP-BABESIOSIS 2026: exchange transfusion reduced adjusted risk of in-hospital death or 30-day readmission (3.6% vs 9.8%, aOR 0.22)

›Exchange approximately 2.5× patient red blood cell volume

›Relative: parasitemia 5–10% with severe complications

›Acute organ injury (AKI, hepatic failure, ARDS)

›Severe hemolytic anemia (hemoglobin < 4.3 mmol/L and LDH > 3× ULN)

›Procedure targets

›Target >= 90% reduction in parasitemia

›Repeat smear immediately after procedure

›Additional exchange if parasitemia remains elevated

›Transfusion medicine and hematology consultation mandatory

›Coordinate with infectious diseases

›ICU monitoring during procedure

›Continuation of antiparasitic therapy

›Do not stop antiparasitic medications during exchange transfusion

›Continue atovaquone plus azithromycin throughout

›Antiparasitic therapy reduces residual infected cells

Immunocompromised extended therapy

›Prolonged treatment protocol

›Duration >= 6 weeks total

›Including at least 2 final weeks with consistently negative blood smears

›IDSA 2020 Class I recommendation

›Azithromycin dose consideration

›500–1000 mg per day (higher range for severely immunocompromised)

›Monitor for azithromycin-associated QT prolongation

›Reduce immunosuppression when clinically feasible

›Delay elective rituximab or anti-cytokine therapy

›Coordinate with rheumatology or oncology

›Relapse monitoring

›Serial blood smears every 2 weeks

›Relapse rate high in B-cell lymphoma and rituximab-treated patients

›Positive PCR alone after smear clearance does not indicate treatment failure in immunocompetent

Coinfection treatment

›Empirical doxycycline addition

›Indication: suspected Lyme disease or anaplasmosis coinfection

›Approximately 20% coinfection rate in endemic areas

›Add if clinical features of Lyme or HGA present

›Doxycycline 100 mg PO or IV every 12 hours

›Duration 10–14 days for anaplasmosis

›Duration per Lyme disease guidelines if confirmed

›IDSA 2020 recommendation for coinfection testing and empirical treatment in endemic regions

Supportive care

›Hemodynamic support

›IV fluid resuscitation for septic physiology

›Crystalloid 30 mL/kg initial bolus for septic shock

›Reassess after each bolus with lactate and clinical response

›Vasopressors for refractory hypotension

›Norepinephrine 0.01–3 mcg/kg/min

›Titrate to MAP >= 65 mmHg

›Transfusion support

›Packed red blood cells for symptomatic severe anemia

›Threshold hemoglobin < 4.3 mmol/L (7 g/dL) in stable patients

›Higher threshold with cardiac or respiratory compromise

›Platelets and FFP if DIC with active bleeding

›Platelet target > 50 × 10^9/L for active bleeding

›Fibrinogen replacement if < 1.5 g/L

›Tick bite management

›Remove any attached ticks with fine-tipped tweezers

›Grasp close to skin and pull upward steadily

›Do not twist or jerk

09Special Populations/sp71

Pregnancy

›Pregnancy-specific considerations

›Increased susceptibility to severe disease

›Physiologic immunomodulation of pregnancy

›Impaired splenic clearance function

›Vertical transmission risk

›Perinatal transmission documented

›Neonatal babesiosis can be asymptomatic to life-threatening

›Maternal oxygenation goals

›Maintain SpO2 >= 95% when feasible

›Fetal monitoring when viable gestation

›Treatment in pregnancy

›Preferred: atovaquone plus azithromycin

›Limited human safety data but considered safer than clindamycin plus quinine

›Discuss risk-benefit with maternal-fetal medicine

›Quinine cautions in pregnancy

›Avoid in first trimester (teratogenicity concerns)

›Reserve for refractory or life-threatening disease

›Exchange transfusion considerations

›Apply same parasitemia thresholds as non-pregnant

›Coordinated obstetric and hematology management

›Imaging in pregnancy

›CXR with shielding when clinically indicated

›ARDS diagnosis should not be delayed

›CT only when benefit outweighs radiation risk

›Ultrasound preferred for abdominal evaluation

›Splenic assessment without radiation

Geriatric

›Older adult features

›Atypical presentation

›Afebrile infection possible despite significant parasitemia

›Delirium or functional decline as primary presenting symptom

›Higher severity risk

›Median age of severe cases approximately 71 years

›Reduced splenic reserve and immune senescence

›Comorbidity burden

›Chronic renal insufficiency increases AKI risk

›Cardiac disease increases hemolysis tolerance impairment

›Management modifications

›Drug adverse effect vigilance

›Quinine cinchonism symptoms more pronounced

›QT prolongation risk higher with polypharmacy

›Azithromycin dose adjustment not routinely required but monitor

›Renal dosing adjustment

›Atovaquone not renally cleared — no adjustment needed

›Monitor creatinine closely during therapy

›Disposition bias toward admission

›Frailty and limited functional reserve

›Falls risk with severe fatigue and anemia

›Limited home monitoring capacity

Pediatrics

›Pediatric epidemiology and severity

›Generally milder disease in immunocompetent children

›Severe disease rare in previously healthy children

›Neonates at higher risk for severe disease

›Asplenic children at extreme risk

›Same life-threatening severity risk as adults

›Aggressive early treatment

›Transfusion-transmitted neonatal babesiosis

›May present asymptomatically or with jaundice and anemia

›Blood transfusion history in neonate critical to elicit

›Pediatric treatment dosing

›Atovaquone 20 mg/kg PO every 12 hours (maximum 750 mg per dose)

›With fatty meal or full-fat milk

›Duration 7–10 days for immunocompetent

›Azithromycin 12 mg/kg on day 1 (maximum 500 mg), then 6 mg/kg daily (maximum 250 mg)

›Duration 7–10 days for immunocompetent

›Clindamycin alternative: 20–40 mg/kg per day divided every 8 hours (maximum 600 mg per dose)

›Quinine sulfate 8 mg/kg every 8 hours (maximum 650 mg per dose)

›QT monitoring required

›Pediatric exchange transfusion thresholds

›Same parasitemia thresholds as adults

›> 10% parasitemia or 5–10% with organ injury

›Pediatric hematology and infectious diseases consultation mandatory

10Background/b89

Epidemiology

›Incidence and geography

›Endemic regions — northeastern and upper midwestern United States

›Primary states: Massachusetts, Connecticut, Rhode Island, New York, New Jersey, Minnesota, Wisconsin

›Incidence sharply increasing in recent years (MMWR 2023 data)

›Transmission routes

›Primary: Ixodes scapularis (black-legged deer tick) bite

›Blood transfusion — leading cause of transfusion-transmitted parasitic infection in US

›Organ transplantation (rare)

›Perinatal (rare)

›Seasonal peak: May through September

›Nymph stage of Ixodes scapularis most common transmitter

›Very small size (< 2 mm) — often unnoticed

›Burden and outcomes

›Approximately 25% of adult infections asymptomatic

›Higher asymptomatic rate in children

›Seroprevalence in endemic areas significantly exceeds reported cases

›Hospitalized patient mortality 2.8–8.8%

›Up to 20% in immunocompromised patients

›Transfusion-transmitted cases approximately 20% fatality rate

›Babesiosis is nationally notifiable in the United States

›Reported cases increasing annually per CDC data

›Underreporting likely significant

Pathophysiology

›Parasite biology

›Causative agents — intraerythrocytic protozoa of genus Babesia

›B. microti — predominant US species

›B. duncani — West Coast cases, potentially more virulent

›B. divergens — European cases, severe hemolysis

›Life cycle and red cell invasion

›Tick inoculates sporozoites into blood

›Sporozoites invade red blood cells and multiply asexually

›Merozoites released upon red cell lysis — reinvade new RBCs

›Maltese cross (tetrad) form

›Pathognomonic for Babesia species

›Results from division of merozoites within RBC

›Infrequently seen on smear

›Hemolytic mechanisms

›Intravascular hemolysis

›Direct RBC lysis by merozoite egress

›Immune-mediated hemolysis from RBC surface modification

›Hemoglobinuria from free hemoglobin in urine

›Splenic role

›Spleen clears infected RBCs via filtration

›Asplenic patients lose primary clearance mechanism — fulminant hemolysis

›Functional asplenia (sickle cell, chronic disease) confers similar risk

›Organ injury mechanisms

›Anemia-mediated injury

›Reduced oxygen delivery to tissues

›Cardiac and renal hypoperfusion

›Inflammatory cascade

›Cytokine release from hemolysis and parasitemia

›ARDS, DIC, multi-organ failure in severe disease

›Thrombocytopenia mechanism

›Splenic sequestration

›Immune destruction of platelets

›DIC consumption

Therapeutic Considerations

›Antiparasitic selection principles

›Atovaquone mechanism

›Inhibits mitochondrial electron transport in Babesia

›Must be combined with azithromycin to prevent resistance

›Absorption requires dietary fat — non-negotiable administration requirement

›Azithromycin mechanism

›Protein synthesis inhibition

›Synergistic with atovaquone against B. microti

›Clindamycin plus quinine alternative

›Higher adverse effect burden (cinchonism, GI intolerance)

›Reserve for refractory or atovaquone-intolerant cases

›Resistance emergence

›Azithromycin resistance reported in immunocompromised patients

›Dual resistance (atovaquone plus azithromycin) documented after prolonged therapy

›Relapse in immunocompromised — consider clinical infectious diseases guidance

›Exchange transfusion evidence

›STOP-BABESIOSIS 2026 (JAMA Internal Medicine)

›Multicenter study demonstrating exchange transfusion benefit in high parasitemia

›Nearly 5-fold lower adjusted risk of death or 30-day readmission (aOR 0.22)

›Targeted approximately 2.5× RBC volume exchange

›Mechanism of benefit

›Removes circulating infected RBCs rapidly

›Reduces parasite burden faster than antiparasitic alone

›Replaces hemolyzed RBCs simultaneously

›Prevention counseling

›DEET-based insect repellent on exposed skin

›Effective against Ixodes ticks

›Reapply per product instructions

›Permethrin-treated clothing

›Long-lasting tick repellent for fabric

›Shirts, pants, socks, shoes

›Daily tick checks after outdoor activity

›Inspect hairline, ears, axilla, groin, popliteal fossa

›Prompt removal within 24–36 hours reduces transmission risk

11Patient Discharge Instructions/pdi33

copy discharge instructions

›Babesiosis home care instructions

›Take all medications as prescribed

›Atovaquone (Mepron) must be taken with a fatty meal — eat cheese, peanut butter, or full-fat yogurt with each dose

›Azithromycin with or without food

›Complete the full course even if feeling better

›Rest and fluids

›Drink plenty of fluids to stay hydrated

›Avoid strenuous activity until cleared by your doctor

›Fatigue may last weeks to months — this is normal

›Tick prevention

›Use insect repellent with DEET when outdoors

›Wear long sleeves and pants in wooded or grassy areas

›Check your entire body for ticks after being outdoors

›Remove attached ticks promptly with fine-tipped tweezers

›Warning signs to return to ER

›Return immediately if you develop:

›Worsening fever or new chills after starting antibiotics

›Dark or tea-colored urine (sign of red blood cell destruction)

›Yellowing of your skin or eyes (jaundice)

›Shortness of breath or difficulty breathing

›Severe abdominal pain (may indicate splenic problem)

›Confusion, severe headache, or unusual drowsiness

›Bleeding that does not stop easily

›Signs of allergic reaction: rash, hives, swelling, difficulty swallowing

›Follow-up instructions

›See your doctor within 48–72 hours of discharge

›Repeat blood test to confirm parasite levels are dropping

12References/r32

Guidelines and key sources

›Primary guidelines

›IDSA 2020 Clinical Practice Guidelines on Diagnosis and Management of Babesiosis

›Krause PJ et al., Clinical Infectious Diseases 2021

›doi: 10.1093/cid/ciaa1216

›CDC Tickborne Diseases of the United States Reference Manual, 6th Edition (2022)

›Shadick NA, Maher N, Hoak D

›Covers tick prevention, recognition, and management

›IDSA/ASM Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases 2024 Update

›Miller JM et al., Clinical Infectious Diseases 2024

›doi: 10.1093/cid/ciae104

Landmark studies

›Key evidence

›STOP-BABESIOSIS Trial, JAMA Internal Medicine 2026

›Leaf DE, Monson AE et al.

›Exchange transfusion for severe babesiosis — multicenter data

›aOR 0.22 for in-hospital death or 30-day readmission with exchange transfusion

›Babesiosis-Related Sepsis: Am J Trop Med Hyg 2026

›Long J, Henao-Martinez AF et al.

›Multicenter retrospective global research network analysis

›Trends in Reported Babesiosis Cases 2011–2019, MMWR 2023

›Swanson M, Pickrel A, Williamson J, Montgomery S

›Increasing incidence in Northeast and Midwest

›Vannier E, Krause PJ — Human Babesiosis, NEJM 2012

›Comprehensive pathophysiology and clinical review

›Sanchez E et al., JAMA 2016 — Diagnosis, Treatment, and Prevention of Lyme Disease, Anaplasmosis, and Babesiosis review

Coding standards

›Diagnostic codes

Evidence & Review