7.3 Fungal & Parasitic Infections

7.3 Fungal & Parasitic Infections

Why This Matters for the PANCE

Fungal and parasitic diseases represent opportunistic and travel-related infections that frequently appear on the PANCE. Questions focus on identifying classic exposure histories (e.g., bird/bat droppings for histoplasmosis and cryptococcosis, wilderness streams for giardiasis, mosquito bites for malaria) and selecting the correct diagnostic tests (such as CSF antigen tests or thick and thin blood smears). Management details—especially G6PD screening prior to malaria therapy and the specific mechanisms of action of anti-parasitic agents—are high-yield testing targets.

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Candidiasis

Pathophysiology & Clinical Presentations

Candida albicans is an opportunistic yeast that is part of the normal human microflora of the GI tract and vagina. Pathologic overgrowth occurs when the local environment is altered (e.g., broad-spectrum antibiotic use, inhaled corticosteroids) or systemic immunity is impaired (e.g., uncontrolled diabetes, HIV, chemotherapy).

• Mucosal Candidiasis (Oral Thrush): Presents as creamy white, curd-like patches on the tongue and buccal mucosa. Classic Sign: These patches scrape off easily, leaving an erythematous, bleeding mucosal surface. This is a critical distinction from Oral Hairy Leukoplakia (caused by EBV), which cannot be scraped off. A KOH preparation reveals characteristic pseudohyphae and budding yeast. Treatment consists of topical antifungal therapy like Nystatin swish and swallow or clotrimazole troches.
• Esophageal Candidiasis: Presents with retrosternal chest pain and significant odynophagia (painful swallowing). This is considered an AIDS-defining illness and typically occurs when the CD4 count falls below 100 cells/uL. Endoscopy shows white plaques lining the esophageal mucosa. Treatment requires systemic therapy, most commonly Oral Fluconazole (200-400 mg daily).
• Vulvovaginal Candidiasis: Manifests with intense vulvar pruritus, vaginal burning, and a thick, white, curd-like ("cottage cheese") discharge. Unlike bacterial vaginosis or trichomoniasis, the vaginal pH remains normal (< 4.5). KOH prep shows pseudohyphae. Treatment typically involves single-dose Oral Fluconazole (150 mg) or topical azole creams.
• Cutaneous Candidiasis (Intertrigo): Appears as macerated, beefy red plaques localized in warm, moist skin folds (axillae, groin, under breasts), often characterized by surrounding satellite pustules or macules. Treatment involves keeping the area dry and applying topical nystatin, miconazole, or clotrimazole.
• Systemic Candidiasis (Candidemia): Most common in ICU patients with central venous catheters or those on broad-spectrum antibiotics. It requires prompt diagnosis via blood cultures and treatment with an echinocandin (like Caspofungin or Micafungin) until sensitivities are known.

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Cryptococcosis

Pathophysiology & Workup

Cryptococcus neoformans is an encapsulated, budding yeast universally found in soil contaminated with pigeon or bird droppings. The primary route of infection is inhalation of aerosolized spores. In healthy individuals, it may cause a mild, self-limited pulmonary infection. However, in severely immunocompromised patients, particularly those with AIDS and a CD4 count < 100 cells/uL, it frequently disseminates via the bloodstream to cause subacute cryptococcal meningitis. Symptoms often present insidiously over weeks, including headache, low-grade fever, lethargy, altered mental status, and occasionally cranial nerve palsies. Classic meningeal signs (nuchal rigidity) may be absent due to a blunted inflammatory response.

• Diagnostics:
  • Lumbar Puncture (LP): The most critical diagnostic step. A key finding is a markedly elevated opening pressure, often exceeding 250 mm H2O.
  • CSF Analysis: India Ink staining of the CSF is a rapid, classic diagnostic test showing encapsulated yeast cells surrounded by a clear halo. However, the Cryptococcal Antigen (CrAg) lateral flow assay or enzyme immunoassay is the diagnostic test of choice due to its extreme sensitivity and specificity (> 95%) in both serum and CSF.
• Management: Treatment is rigorous and typically divided into three phases:
  • Induction Therapy: IV Amphotericin B PLUS oral Flucytosine for a minimum of 2 weeks (or until CSF cultures are sterile). This aggressively reduces the fungal burden.
  • Consolidation Therapy: Oral Fluconazole (400 mg daily) for 8 weeks.
  • Maintenance Therapy: Oral Fluconazole (200 mg daily) for at least 12 months, or until the patient's CD4 count has recovered above 100 cells/uL on antiretroviral therapy (ART) for several months.
  • Managing Elevated ICP: Markedly elevated intracranial pressure must be managed aggressively to prevent blindness and brain herniation. This usually requires serial large-volume lumbar punctures or placement of a lumbar drain if pressures consistently exceed 250 mm H2O.

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Histoplasmosis

Clinical Presentation & Diagnostics

Histoplasma capsulatum is a dimorphic fungus that is strongly endemic to the Ohio, Mississippi, and Missouri River Valleys. It thrives in damp soil heavily enriched with nitrogen from bird or bat droppings. Classic exposure scenarios heavily tested on the PANCE include cleaning chicken coops, exploring caves (spelunking), excavating soil, or renovating old barns. Infection occurs via inhalation of microconidia. The majority of immunocompetent individuals remain asymptomatic or develop a mild, self-limiting flu-like illness. However, in immunocompromised hosts (especially those with CD4 counts < 150 cells/uL), the fungus disseminates widely. Disseminated histoplasmosis presents with fever, marked weight loss, generalized lymphadenopathy, hepatosplenomegaly, pancytopenia (due to bone marrow suppression), and painful mucocutaneous oral ulcers.

• Diagnostics:
  • Radiography: Chest X-rays may show focal infiltrates, hilar or mediastinal lymphadenopathy, or diffuse reticulonodular patterns resembling miliary TB. Over time, healed lesions may calcify.
  • Antigen Testing: The Urinary and Serum Histoplasma Antigen assay via enzyme immunoassay (EIA) is the most rapid and sensitive method for diagnosing acute and disseminated disease.
  • Histopathology/Biopsy: Tissue biopsy (e.g., from bone marrow or a lymph node) stained with silver or Giemsa will reveal the classic appearance of small, oval intracellular yeast cells packed within macrophages.
• Management:
  • Mild-to-Moderate Disease: Most immunocompetent patients require no therapy. For symptomatic pulmonary disease, Oral Itraconazole is administered for 6 to 12 weeks.
  • Severe/Disseminated Disease: Requires admission and initiation of IV Liposomal Amphotericin B for 1 to 2 weeks, followed by a prolonged step-down course of Oral Itraconazole for at least 12 months to prevent relapse.

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Malaria

Pathophysiology & Workup

Malaria is a severe febrile illness caused by protozoan parasites of the genus Plasmodium and transmitted by the bite of an infected female Anopheles mosquito. The major species affecting humans are P. falciparum, P. vivax, P. ovale, and P. malariae. The malarial life cycle is highly tested: Mosquitoes inject sporozoites into the bloodstream, which travel to the liver. There, they mature and multiply, bursting hepatic cells to release merozoites. These merozoites invade red blood cells, developing into trophozoites, which replicate and eventually rupture the RBCs, releasing more merozoites. This synchronous RBC lysis is what triggers the classic malarial paroxysms.

• Species Differences:
  • P. falciparum: Responsible for the most severe and fatal cases of malaria due to high parasitemia and microvascular sequestration (infected RBCs clumping and blocking capillaries). Complications include cerebral malaria, severe anemia, acute respiratory distress syndrome (ARDS), and dark hemoglobinuric urine ("blackwater fever"). Paroxysms often lack a clear cyclical pattern.
  • P. vivax and P. ovale: Cause "tertian" malaria, characterized by fever spikes every 48 hours. Crucially, they form dormant liver stages known as hypnozoites, which can reactivate months or years later causing clinical relapse.
  • P. malariae: Causes "quartan" malaria, with fever paroxysms every 72 hours.
• Diagnostics:
  • Microscopy: The absolute gold standard is the Giemsa-stained thick and thin blood smear. Thick smears allow for rapid detection of parasites, while thin smears are used for precise species identification and calculating the percentage of parasitemia. P. falciparum is characterized by delicate ring-form trophozoites within the RBC and distinct, large, banana- or crescent-shaped gametocytes.
• Management:
  • Uncomplicated Malaria: Regimens depend on regional resistance patterns. Chloroquine is the drug of choice in sensitive areas (e.g., parts of Central America and the Caribbean). In chloroquine-resistant regions, artemisinin-based combination therapies (ACTs) like Artemether-lumefantrine, or alternatives like Atovaquone-proguanil (Malarone), are used.
  • Severe Malaria: Requires aggressive inpatient management with IV Artesunate.
  • Hypnozoite Eradication: To prevent future relapses of P. vivax and P. ovale, the liver hypnozoites must be eradicated using Primaquine or Tafenoquine.
  • CRITICAL PANCE PEARL: You MUST screen all patients for Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency prior to administering primaquine or tafenoquine. These drugs induce oxidative stress, which can trigger massive, life-threatening acute hemolytic anemia in G6PD-deficient individuals.

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Giardiasis

Presentation & Management

Giardia duodenalis (also known as Giardia lamblia) is a flagellated, flagellated protozoan that represents a major cause of waterborne diarrheal disease worldwide. Transmission occurs via the fecal-oral route, most frequently by ingesting water contaminated with infectious Giardia cysts from wilderness streams, lakes, rivers, or poorly maintained wells. The cysts are remarkably hardy and are known for resisting standard water chlorination; they must be boiled or heavily filtered for safe consumption. Once ingested, the cysts excyst in the duodenum, releasing trophozoites that attach firmly to the upper intestinal mucosa using a ventral sucking disk. This attachment causes local inflammation and blunting of the microvilli, leading to a profound malabsorption of fats and carbohydrates.

• Clinical Presentation: Often referred to as "backpacker's diarrhea." After an incubation period of 1-2 weeks, patients present with profuse, watery, exceptionally foul-smelling, and greasy, floating stools (steatorrhea). Significant abdominal cramping, bloating, sulfuric belching, and flatulence are prominent. Unlike invasive bacterial pathogens, there is typically no fever, and no blood or mucus in the stool.
• Diagnostics:
  • Stool Antigen Assays: The ELISA or PCR for Giardia stool antigen is the diagnostic test of choice due to its high sensitivity and rapidity.
  • Microscopy: Stool Ova and Parasite (O&P) exams can visualize the classic pear-shaped, binucleated trophozoites with multiple flagella (often described as resembling a "falling leaf" when motile or an "old man's face" on stained slides). However, cyst shedding can be intermittent, making O&P less sensitive than antigen testing.
• Management:
  • Pharmacotherapy: The first-line treatments are nitroimidazole derivatives. Tinidazole (2 g single PO dose) is often preferred due to a higher cure rate and simpler dosing. Alternatively, Metronidazole (250 mg TID for 5-7 days) is highly effective. Nitazoxanide is an alternative option, particularly in pediatric patients.
  • PANCE Pearl (Disulfiram-Like Reaction): Patients prescribed metronidazole or tinidazole must be explicitly counseled to strictly avoid all alcohol consumption during the course of therapy and for at least 48 to 72 hours (4-5 days for tinidazole) after the last dose. Mixing these medications with alcohol causes a build-up of acetaldehyde, leading to a severe disulfiram-like reaction characterized by intense facial flushing, throbbing headache, severe nausea, voluminous vomiting, sweating, and tachycardia.