A 63-year-old man with non-Hodgkin lymphoma is brought to the emergency department because of fever and confusion that have progressively worsened over the past 3 days. He also has a 3-day history of loose stools. He returned from France 2 weeks ago where he stayed in the countryside and ate typical French cuisine, including frog, snail, and various homemade cheeses. His last chemotherapy cycle was 3 weeks ago. He is oriented to person but not to place or time. His temperature is 39.5°C (103.1°F), pulse is 110/min, and blood pressure is 100/60 mm Hg. Examination shows cervical and axillary lymphadenopathy. The lungs are clear to auscultation. There is involuntary flexion of the bilateral hips and knees with passive flexion of the neck. Neurologic examination shows no focal findings. Laboratory studies show: Hemoglobin 9.3 g/dL Leukocyte count 3600/mm3 Platelet count 151,000/mm3 Serum Na+ 134 mEq/L Cl- 103 mEq/L K+ 3.7 mEq/L Glucose 102 mg/dL Creatinine 1.3 mg/dL A lumbar puncture is performed. Cerebrospinal fluid analysis shows a leukocyte count of 1200/mm3 (76% segmented neutrophils, 24% lymphocytes), a protein concentration of 113 mg/dL, and a glucose concentration of 21 mg/dL. The results of blood cultures are pending. Which of the following is the most appropriate initial pharmacotherapy?

Vancomycin, ampicillin, and cefepime

Ampicillin, gentamicin, and dexamethasone

A 44-year-old man is brought to the emergency department by his daughter for a 1-week history of right leg weakness, unsteady gait, and multiple falls. During the past 6 months, he has become more forgetful and has sometimes lost his way along familiar routes. He has been having difficulties operating simple kitchen appliances such as the dishwasher and coffee maker. He has recently become increasingly paranoid, agitated, and restless. He has HIV, hypertension, and type 2 diabetes mellitus. His last visit to a physician was more than 2 years ago, and he has been noncompliant with his medications. His temperature is 37.2°C (99.0°F), blood pressure is 152/68 mm Hg, pulse is 98/min, and respiratory rate is 14/min. He is somnolent and slightly confused. He is oriented to person, but not place or time. There is mild lymphadenopathy in the cervical, axillary, and inguinal areas. Neurological examination shows right lower extremity weakness with normal tone and no other focal deficits. Laboratory studies show: Hemoglobin 9.2 g/dL Leukocyte count 3,600/mm3 Platelet count 140,000/mm3 CD4+ count 56/µL HIV viral load > 100,000 copies/mL Serum Cryptococcal antigen Negative Toxplasma gondii IgG Positive An MRI of the brain is shown below. Which of the following is the most likely diagnosis?

Progressive multifocal leukoencephalopathy

Cryptococcal meningoencephalitis

A 33-year-old man is brought into the emergency department with fever, lethargy, and confusion. He is a cachectic man in acute distress, unable to respond to questions or follow commands. His friend confides that the patient has been sexually active with multiple male partners and was diagnosed with HIV several months ago, but was lost to follow up. Based on prior records, his most recent CD4 count was 65 cells/uL. Which of the following is the most appropriate next step in management?

Recheck CD4 and HIV viral load serologies

Neurological exam with fundoscopy

A 3-day-old female newborn delivered vaginally at 36 weeks to a 27-year-old woman has generalized convulsions lasting 3 minutes. Prior to the event, she was lethargic and had difficulty feeding. The infant has two healthy older siblings and the mother's immunizations are up-to-date. The infant appears icteric. The infant's weight and length are at the 5th percentile, and her head circumference is at the 99th percentile for gestational age. There are several purpura of the skin. Ocular examination shows posterior uveitis. Cranial ultrasonography shows ventricular dilatation, as well as hyperechoic foci within the cortex, basal ganglia, and periventricular region. Which of the following is the most likely diagnosis?

Congenital Toxoplasma gondii infection

Congenital parvovirus infection

Congenital Treponema pallidum infection

Congenital cytomegalovirus infection

A 2-day old male newborn delivered vaginally at 36 weeks to a 29-year-old woman, gravida 3, para 2, has generalized convulsions lasting 2 minutes. Previous to the event, he had difficulty feeding and was lethargic. Pregnancy and delivery were uncomplicated. Apgar scores were 7 and 8 at 1 and 5 minutes, respectively. Pregnancy and delivery of the mother's first 2 children were also uncomplicated. Medications of the mother include folic acid and a multivitamin. The mother's immunizations are up-to-date. The infant appears icteric. His vital signs are within normal limits. The infant's weight and length are at the 5th percentile, and his head circumference at the 99th percentile for gestational age. There are several purpura of the skin. Ocular examination shows posterior uveitis. The patient does not pass his auditory screening tests. Cranial ultrasonography shows ventricular dilatation, as well as hyperechoic foci within the cortex, basal ganglia, and periventricular region. Which of the following is the most likely diagnosis?

Congenital parvovirus infection

A pathologist receives a patient sample for analysis. Cells in the sample are first labeled with fluorescent antibodies and then passed across a laser beam in a single file of particles. The light scatter and fluorescent intensity of the particles are plotted on a graph; this information is used to characterize the sample. This laboratory method would be most useful to establish the diagnosis of a patient with which of the following?

Pancytopenia and deep vein thrombosis with intermittent hemoglobinuria

Ventricular septal defect and facial dysmorphism with low T-lymphocyte count

Painless generalized lymphadenopathy with monomorphic cells and interspersed benign histiocytes on histology

Multiple opportunistic infections with decreased CD4 counts

Vesicular lesions with dermatomal distribution and dendritic corneal ulcers

A 28-year-old female in the 2nd trimester of pregnancy is diagnosed with primary Toxoplasma gondii infection. Her physician fears that the fetus may be infected in utero. Which of the following are associated with T. gondii infection in neonates?

Hydrocephalus, chorioretinitis, intracranial calcifications

Hutchinson’s teeth, saddle nose, short maxilla

Deafness, seizures, petechial rash

Patent ductus arteriosus, cataracts, deafness

Temporal encephalitis, vesicular lesions

Toxoplasma gondii for USMLE Step 3: High-Yield Microbiology Lessons

Toxo Overview - The Cunning Cat Parasite

Obligate intracellular, zoonotic protozoan with a worldwide distribution.
Definitive host: Felines (cats) are the sole host for sexual reproduction.
Transmission forms & routes:
- Oocysts: Ingested from soil or water contaminated with cat feces.
- Bradyzoites: Tissue cysts consumed in undercooked/raw meat (esp. pork, lamb).
- Tachyzoites: Active, replicating form; responsible for vertical (transplacental) transmission.

Toxoplasma gondii life cycle in humans and animals

⭐ In immunocompromised patients (e.g., HIV with CD4 < 100), reactivation is common, classically causing multiple ring-enhancing brain lesions.

Transmission & Lifecycle - From Cat to Human

Toxoplasma gondii life cycle with cat and human hosts

Definitive Host: Cat. Oocysts are shed in feces.
Intermediate Hosts: Humans, livestock, rodents.
Human Infection Routes:
- Ingesting oocysts from contaminated water, soil, or cat litter.
- Ingesting tissue cysts (bradyzoites) in undercooked meat.
- Transplacental (congenital) transmission.

⭐ Risk of congenital transmission ↑ with gestational age (highest in 3rd trimester), but disease severity is greatest if infection occurs in the 1st trimester.

Clinical Syndromes - Brain, Eyes, & Baby

Immunocompromised (AIDS, CD4 < 100)
- Toxoplasmic Encephalitis (TE): Headache, confusion, fever, focal deficits, seizures.
- Imaging: Multiple ring-enhancing lesions on CT/MRI.
Immunocompetent & Congenital
- Chorioretinitis: Most common manifestation.
- Eye pain, floaters, vision loss. Fundoscopy shows "headlights in the fog."
- Often a reactivation of a congenital infection.
Congenital (Transplacental)
- Classic Triad: Chorioretinitis, hydrocephalus, and intracranial calcifications.
- Risk of transmission ↑ with gestational age, but severity ↓.

⭐ In AIDS patients, Toxoplasmic Encephalitis is the most common cause of a CNS mass lesion.

Diagnosis - Spotting the Intruder

Serology: Primary method. Detects anti-Toxoplasma IgG & IgM antibodies. IgM indicates recent infection.
Imaging (Immunocompromised): CT or MRI of the brain reveals multiple, ring-enhancing lesions, often with a predilection for the basal ganglia.
Definitive Diagnosis: Brain biopsy showing tachyzoites is the gold standard but reserved for unclear cases.
Congenital: PCR analysis of amniotic fluid.

Brain MRI showing ring-enhancing lesions in toxoplasmosis

⭐ In HIV patients, the presence of ring-enhancing lesions on brain imaging is most commonly caused by toxoplasmosis, especially with a CD4 count < 100 cells/μL.

Treatment & Prevention - The Toxo Takedown

Primary Regimen (Immunocompromised & Severe Disease):
- Pyrimethamine + Sulfadiazine
- Plus Leucovorin (folinic acid) to prevent hematologic toxicity.
Alternative: TMP-SMX (especially for prophylaxis), or regimens with Clindamycin/Atovaquone.
Prophylaxis (e.g., HIV):
- Initiate when CD4 count < 100 cells/μL.
- TMP-SMX is the preferred agent.
General Prevention:
- Thoroughly cook meat to kill cysts.
- Pregnant women should avoid contact with cat feces (litter boxes).

⭐ Leucovorin rescue is essential; it bypasses the dihydrofolate reductase (DHFR) block in human cells, preventing myelosuppression, but not in the parasite.

High‑Yield Points - ⚡ Biggest Takeaways

Key transmission routes: cat feces (oocysts), undercooked meat (cysts), or transplacental (tachyzoites).

Classic triad of congenital toxoplasmosis: chorioretinitis, hydrocephalus, and intracranial calcifications.

In immunocompromised patients (AIDS < 100 CD4), presents with multiple ring-enhancing brain lesions.

Diagnosis is confirmed with serology or PCR.

Prophylaxis and treatment rely on pyrimethamine and sulfadiazine (plus leucovorin).

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