# Clinical Cases: Parasites - Protozoa

## Case 1: Cerebral Malaria

### Presentation
A 32-year-old woman presents with high fever, severe headache, and altered mental status. She returned 10 days ago from a 3-week trip to rural Kenya where she was doing volunteer work. She took mefloquine prophylaxis but admits to missing several doses. She has had 4 days of fever with rigors and now cannot be roused easily. Vital signs: temperature 40.2°C, heart rate 120 bpm, blood pressure 90/60 mmHg. She opens her eyes to voice but is disoriented and follows commands inconsistently. Peripheral blood smear shows intraerythrocytic ring forms with multiple rings per cell and parasitemia of 15%. Rapid diagnostic test is positive for Plasmodium falciparum.

### Clinical Image
![P. falciparum on blood smear](image_01.png)
*Peripheral blood smear demonstrating Plasmodium falciparum infection with characteristic small ring forms, multiple rings per red blood cell, and high parasitemia - features associated with severe malaria.*

**Image Source**: Lecture image - malaria parasitology

### Questions

1. **What is the diagnosis, and which Plasmodium species is responsible?**

2. **Why is this species associated with severe disease, particularly cerebral malaria?**

3. **What is the appropriate management for severe malaria?**

4. **How could this case have been prevented?**

### Answers

1. **Diagnosis and species**: This is **severe malaria** with cerebral involvement caused by **Plasmodium falciparum**. The diagnosis is based on travel to an endemic area, fever with altered consciousness, and peripheral smear showing P. falciparum (characterized by small ring forms, multiple rings per RBC, and high parasitemia). P. falciparum causes the vast majority of malaria deaths and is the only species that commonly causes cerebral malaria.

2. **Why P. falciparum causes severe disease**: P. falciparum has unique pathogenic features:
   - **Cytoadherence**: Infected RBCs express PfEMP1 surface protein that binds to endothelial receptors (ICAM-1, CD36), causing **sequestration** in microvasculature
   - **Cerebral malaria**: Sequestration in cerebral capillaries causes microvascular obstruction, hypoxia, and blood-brain barrier disruption
   - **High parasitemia**: Unlike other species that prefer reticulocytes or older RBCs, P. falciparum invades RBCs of all ages, enabling massive parasite loads
   - **Rosetting**: Infected RBCs adhere to uninfected RBCs, worsening obstruction
   - **No hypnozoite stage** (unlike P. vivax and P. ovale), but severe acute illness

3. **Management of severe malaria**:
   - **Intravenous artesunate** is the treatment of choice (superior to quinine)
   - Dose: 2.4 mg/kg IV at 0, 12, 24 hours, then daily until oral therapy tolerated
   - **Exchange transfusion** considered for parasitemia >10% with severe disease
   - Transition to oral artemisinin-combination therapy (ACT) when able
   - **Supportive care**: ICU monitoring, seizure prophylaxis if cerebral involvement, correct hypoglycemia, treat secondary infections
   - Monitor for delayed hemolysis after artesunate therapy

4. **Prevention strategies**:
   - **Chemoprophylaxis adherence**: This patient's missed doses likely contributed to breakthrough infection. Options include atovaquone-proguanil (Malarone), doxycycline, or mefloquine depending on resistance patterns
   - **Mosquito avoidance**: DEET-containing repellents, permethrin-treated clothing and bed nets, avoiding outdoor exposure at dusk/dawn (peak Anopheles feeding)
   - **Awareness**: Seek medical attention for any fever within 3 months of travel to endemic area
   - Prophylaxis must be continued after leaving endemic area (duration varies by drug)

---

## Case 2: Giardiasis

### Presentation
A 28-year-old man presents with 3 weeks of bloating, foul-smelling diarrhea, and excessive flatulence. He recently returned from a backpacking trip in Colorado where he drank water from mountain streams. His stools are pale, greasy, and float. He has lost 8 pounds. He denies fever, blood in stool, or tenesmus. Physical examination is notable for diffuse abdominal distension and hyperactive bowel sounds. Stool ova and parasite examination reveals oval cysts with multiple nuclei.

### Clinical Image
![Giardia trophozoite and cyst](image_02.png)
*Microscopic appearance of Giardia lamblia: (A) Trophozoite showing characteristic "face-like" appearance with two nuclei and flagella, (B) Cyst form with multiple nuclei seen on stool O&P examination.*

**Image Source**: Lecture image - Giardia morphology

### Questions

1. **What is the diagnosis, and how was this infection acquired?**

2. **Why does this organism cause steatorrhea and malabsorption?**

3. **What diagnostic tests are available for this infection?**

4. **What is the appropriate treatment?**

### Answers

1. **Diagnosis and transmission**: This is **giardiasis** caused by **Giardia lamblia** (also called G. intestinalis or G. duodenalis). The infection was acquired through consumption of fecally contaminated water from mountain streams - the classic "hiker's diarrhea" or "beaver fever." Giardia cysts are hardy and survive in cold mountain water; beavers and other animals serve as reservoirs. Giardia is also a common cause of waterborne outbreaks and daycare-associated diarrhea.

2. **Mechanism of steatorrhea and malabsorption**: Giardia causes malabsorption through multiple mechanisms:
   - **Mechanical blockade**: Trophozoites attach to the duodenal and jejunal brush border via a ventral sucking disk, physically covering the absorptive surface
   - **Microvillus damage**: Attachment causes blunting and shortening of microvilli
   - **Brush border enzyme deficiency**: Disruption of lactase and other enzymes causes secondary disaccharidase deficiencies
   - **Fat malabsorption**: Results in steatorrhea (fatty, foul-smelling, floating stools)
   - Notably, there is **no mucosal invasion**, hence no blood or leukocytes in stool

3. **Diagnostic tests**:
   - **Stool antigen testing** (EIA): Most commonly used; sensitive and specific
   - **Stool O&P examination**: Identifies cysts (and occasionally trophozoites); may require multiple samples due to intermittent shedding
   - **Stool PCR**: Highly sensitive
   - **String test (Enterotest)** or duodenal aspirate: Rarely needed, can identify trophozoites
   - Stool antigen testing has largely replaced microscopy as first-line

4. **Treatment**:
   - **First-line**: **Metronidazole** 250 mg three times daily for 5-7 days (or tinidazole single dose)
   - **Alternative**: Nitazoxanide (especially for children)
   - **Pregnancy**: Paromomycin (non-absorbable aminoglycoside)
   - Treatment failure may occur; retreatment with same or different agent
   - Lactose intolerance may persist for weeks after treatment; temporary dairy avoidance may help
   - Household contacts with symptoms should be tested and treated

---

## Case 3: Toxoplasmosis in Pregnancy

### Presentation
A 26-year-old pregnant woman at 14 weeks gestation is found to have Toxoplasma IgG and IgM antibodies positive on routine prenatal screening. She was seronegative at her first prenatal visit 8 weeks ago. She feels well with no symptoms. She has two cats at home and enjoys gardening. She recalls eating undercooked lamb at a dinner party about 6 weeks ago. She is very concerned about the effects on her baby.

### Clinical Image
![Toxoplasma lifecycle and congenital infection](image_03.png)
*Diagram illustrating Toxoplasma gondii life cycle with cats as definitive hosts, transmission routes to humans (undercooked meat, cat feces in soil), and potential consequences of congenital infection.*

**Image Source**: Lecture image - Toxoplasma transmission

### Questions

1. **What is the significance of seroconversion during pregnancy?**

2. **What are the potential consequences of congenital toxoplasmosis?**

3. **How should this patient be managed?**

4. **How could this infection have been prevented?**

### Answers

1. **Significance of seroconversion**: **Seroconversion during pregnancy** (converting from IgG-negative to positive) indicates **acute primary infection** during gestation. This carries significant risk of **vertical transmission** to the fetus. The timing of infection relative to gestational age determines outcomes:
   - **First trimester**: Lower transmission rate (10-15%) but more severe fetal effects
   - **Third trimester**: Higher transmission rate (60-70%) but often milder or subclinical fetal infection
   - Overall, earlier infection = more severe disease if transmitted

   A positive IgG with negative IgM in early pregnancy would indicate prior immunity and low risk.

2. **Consequences of congenital toxoplasmosis**: The classic triad is:
   - **Chorioretinitis**: Most common manifestation; may cause vision impairment
   - **Hydrocephalus**: From obstruction of the aqueduct of Sylvius
   - **Intracranial calcifications**: Diffuse, scattered pattern (contrast with CMV which shows periventricular calcifications)

   Other manifestations include hepatosplenomegaly, jaundice, seizures, and intellectual disability. Many congenitally infected infants are asymptomatic at birth but develop sequelae (especially chorioretinitis) later in life.

3. **Management approach**:
   - **Confirm acute infection**: IgG avidity testing (low avidity suggests recent infection), reference laboratory confirmation
   - **Amniocentesis**: PCR of amniotic fluid to determine if fetus is infected (usually performed after 18 weeks and at least 4 weeks after maternal infection)
   - **Treatment**:
     - If maternal infection confirmed but fetal infection not yet confirmed: **Spiramycin** to reduce transmission
     - If fetal infection confirmed: **Pyrimethamine + sulfadiazine + leucovorin** to reduce severity (after first trimester due to pyrimethamine teratogenicity)
   - **Serial fetal ultrasounds** to monitor for hydrocephalus, calcifications
   - Infectious disease and maternal-fetal medicine consultation

4. **Prevention**:
   - **Cook meat thoroughly** (tissue cysts killed at 67°C/153°F)
   - **Wash hands** after handling raw meat
   - **Avoid unpasteurized goat's milk**
   - **Wear gloves** when gardening or handling soil
   - **Cat litter precautions**: Have someone else change litter daily (oocysts require 1-5 days to sporulate and become infectious), or wear gloves; keep cats indoors
   - **Wash fruits and vegetables** thoroughly
   - Prenatal screening identifies susceptible women for counseling