CNS Infections: Parasites & Fungi

CNS Infections: Parasites & Fungi

• This presentation discusses fungal and parasitic infections of the central nervous system (CNS).
• Key objectives are to describe types, compare meningitis, properties of etiological agents, diagnostic importance of CSF analysis, and epidemiological factors.

Terms Defined

• Meningitis can be acute, aseptic, or chronic.
• Encephalitis refers to brain inflammation, while myelitis involves spinal cord inflammation.
• Brain abscesses are localized infections within the brain tissue.

Chronic Meningitis

• Characterized by meningeal inflammation with cerebrospinal fluid (CSF) pleocytosis exceeding 4 weeks.
• Symptoms evolve over days or weeks, including headache and fever
• Nuchal rigidity may be subtle or absent.
• Can progress to seizures, mental status changes, confusion, hallucinations, focal neurologic deficits, hydrocephalus, and increased intracranial pressure.

Etiological Agents of Chronic Meningitis

• Fungal causes include: Aspergillus spp., Candida spp., Coccidioides spp., Cryptococcus spp., Histoplasma spp., Pseudallescheria spp., and Sporothrix spp.
• Parasitic causes include: Taenia solium and Angiostrongylus spp.

Fungal Chronic Meningitis: General Themes

• Often opportunistic, occurring in individuals with immune suppression or defects (CMI).
• Typically presents with moderate lymphocytic pleocytosis in the CSF.

Cryptococcus neoformans

• Presentation includes subacute meningoencephalitis, fever of unknown origin, and hydrocephalus.
• Diagnosis involves cryptococcal antigen latex agglutination and microscopy of India ink preparations, though the latter is less sensitive due to capsules.
• Treatment consists of amphotericin B plus flucytosine.

Coccidioides posadasii & C. immitis

• Manifests as erythema nodosum and hydrocephalus.
• Laboratory findings include CSF eosinophilia (in endemic areas) and complement-fixing antibodies (75-95% of cases).
• Cultures can be hazardous and are positive in 50% of cases.
• Treatment involves amphotericin B plus an azole.

Histoplasma capsulatum

• It is rare, with endemic regions in the Ohio River Valley.
• Presentation includes fever, oral lesions, hepatosplenomegaly, and hydrocephalus.
• Diagnosis through culture (27-65% of cases), Histoplasma polysaccharide antigen detection in urine, blood, or CSF (61% of patients), and visualization of yeast cells inside macrophages.
• Treatment is amphotericin B

Pseudallescheria spp. (P. boydii)

• This is a common fungal etiologic agent for mycetoma
• It can cause meningitis, meningoencephalitis, and brain abscesses
• Frequently observed in immunocompromised individuals but also seen in immunocompetent individuals
• Associated with polluted water, sewage, and swamps, as well as near-drowning victims.
• Resistant to Amphotericin B, but miconazole shows promise.

Parasitic Chronic Meningitis: Taenia solium

• Taenia solium is the pork tapeworm that causes neurocysticercosis
• It's endemic in Mexico, South America, and Asia
• Presentation includes seizures (most common), obstructive cysts leading to hydrocephalus, and space-occupying lesions
• Laboratory findings include calcified lesions on head CT and lymphocytic pleocytosis with eosinophils
• Treatment: Albendazole, steroids, analgesics, antiepileptic drugs, surgical resection/ ventricular shunts

Angiostrongylus cantonensis

• The rat lungworm (roundworm) is endemic to Asia and the Pacific Islands
• Acquired through ingestion of raw or inadequately cooked shellfish or snails.
• Incubation period is up to 1 year
• Presentation includes nausea, vomiting, neck stiffness, global headaches, and rash with pruritus.
• Diagnosis involves history (area and food) and CSF/peripheral eosinophilia
• Treatment: None, as it often resolves spontaneously.

Other Rare Causes

• Blastomycosis, Candida spp., paracoccidioidomycosis, phaeohyphomycosis, mucormycosis, actinomycosis, toxoplasmosis, Sporothrix schenckii, and Aspergillus spp. can lead to chronic meningitis.
• Usually cause abscesses, which may leak into the subarachnoid space to cause chronic meningitis

CNS Infection (Encephalitis)

• It is an inflammatory process in the brain
• Associated with clinical evidence of neurologic dysfunction
• Most challenging syndromes to diagnose
• Specific pathogen is identified in < 50% of cases
• Parasitic causes are less commonly identified, but are neurotropic and cause sporadic encephalitis and myelitis.

Parasitic encephalitis

• Naegleria fowleri is a protozoan that causes amebic meningoencephalitis (PAM; Brain-eating disease), and has 100% mortality
• Entry: nose while swimming (not drinking)
• It is found in US freshwater in southern-tier states
• Thermophile (46oC)

Parasitic Encephalitis (N. fowleri)

• Symptoms displayed are altered level of consciousness, loss of the sense of smell
• Laboratory: Neutrophilic pleocytosis, Motile trophozoites on wet mount of warm CSF, Brain histopathology
• Epidemiology: Summer months, Children & adolescent boys at highest risk, Swimming in fresh water, & particularly water sports
• High mortality even with treatment, and Miltefosine shows promise

Parasitic encephalitis

• Balamuthia mandrillaris is a protozoan found in soil
• Its endemic central America
• Infection can occur via cuts and wounds on skin or through inhalation.
• Presentation similar to TB, Granulomatous Amebic Encephalitis": Subacute progressive disease with Space-occupying lesions, Cranial nerve palsies, Hydrocephalus
• Diagnosis via Serology (research laboratories), or Brain histopathology

Parasitic encephalitis (B. mandrillaris)

• High mortality and poor prognosis, with an 89% mortality rate.
• Slow progressive disease (2 years)
• Diagnosis via Lymphocyte pleocytosis and depressed glucose (confused with TB), Serology (Indirect immunofluorescence antibody), Brain histopathology, and Real-time PCR of brain tissue
• Treatment involves Sulfadiazine, a macrolide antibiotic (azithromycin or clarithromycin), rifampin, & fluconazole

Parasitic encephalitis

• Baylisascaris procyonis (Raccoon roundworm (helminthes)) is contracted by Ingesting infectious eggs (accidental ingestion of dust or dirt)
• Patients suffering from Pica/geophagia are high risk
• Diagnosis via Eosinophilic pleocytosis, Peripheral eosinophilia, Deep white matter abnormalities (MRI), and Serology on CSF/serum (CDC)
• Epidemiology: Infected raccoons in the mid-Atlantic, northeastern & Midwestern states & parts of California
• Treatment: albendazole

Parasitic encephalitis

• Gnathostoma spp. (round worm)
• Eating undercooked or raw freshwater fish, eels, frogs, birds, & reptiles can cause infections
• Primarily in tropical and subtropical areas (Thailand, Japan)
• Larvae Moves under skin to brain
• Diagnosis: Microscopic ID of larvae in tissue or ELISA
• Treatment: Albendazole & ivermectin for skin infection, None for CNS infection

Brain Abscesses

• Are more common in males (2-3x) and also occur in young children and adults over 60
• Predisposing conditions includes Otitis media or mastoiditis
• Mostly bacterial in etiology
• Parasites that can cause brain abscess: Taenia solium (cysticercosis)Entamoeba histolytica, Schistosoma japonicum, or Paragonimus spp.
• Fungi when immunocompromised: Aspergillus spp. are especially common in patients who have bone marrow & transplants, T-cell immunity defects (including AIDS patients) are predisposed to Cryptococcus neoformans, Neutropenia patients predisposed to Aspergillus, Mucor, & Candida

Brain Abscesses

• Clinical manifestations are largely due to presence of space-occupying lesions
• Most common symptoms: Headache (75% of patients), Altered mental status, Focal neurologic findings (especially hemiparesis) (>60%), Fever (50%), Nausea & vomiting (25–50%), Seizures (generalized; 30%), or Other signs/symptoms depending on the abscess stage, size & anatomic location
• Diagnosis via Peripheral leukocytosis (40% normal), Low serum Na+ (ADH), Platelet counts may be high or low, Elevated erythrocyte sedimentation rate, orElevated CRP

Entamoeba histolytica

• Predominantly a GI disease, with brain abscesses being a less common manifestation
• Diagnosis: serology & PCR of brain abscess aspirate or CSF
• Treatment: Metronidazole or tinidazole (followed by paromomycin or iodoquinol)

Schistosoma japonicum

• A.k.a. bilharzia or Blood fluke
• Not found in the US (careful review of travel & residence history)
• 2nd in impact after malaria (> 200 million)
• Most devastating parasitic disease: Lives in freshwater snails (skin), most pathogenic spp. (produce up to 3,000 eggs/day)
• Diagnosis via Microscopic examination of eggs, ELISA for anti-schistosomal Abs, granuloma formation in brain
• Treatment: praziquantel

Paragonimus spp.

• A Lung fluke (flat worm) caused by consuming Ingestion of raw or undercooked crab or crayfish
• Rare in US (multiple cases in Midwest; eating raw crayfish on river raft trips in Missouri)
• P. kellicotti (midwestern & southern US in crayfish)
• Symptoms similar to TB
• Diagnosis is made via Microscopic examination of eggs or by detection of a Peripheral eosinophilia
• Praziquantel is effective