Central nervous system infections Notes


Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Central nervous system infections essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Central nervous system infections:


Naegleria fowleri (Primary amebic meningoencephalitis)

Toxoplasma gondii (Toxoplasmosis)

NOTES NOTES CENTRAL NERVOUS SYSTEM INFECTIONS MICROBE OVERVIEW PATHOLOGY & CAUSES ▪ Rare infections of central nervous system (CNS) by ameba, parasites RISK FACTORS ▪ Immunosuppression (Acanthamoeba, Toxoplasmosis gondii), immersion in infested water (Naegleria fowleri) SIGNS & SYMPTOMS ▪ Fever, headache, seizures, focal neurological signs, mental status change DIAGNOSIS LAB RESULTS ▪ Presence of infectious agent via microscopy, culture, polymerase chain reaction (PCR), presence of specific antibodies Granulomatous amebic encephalitis ▫ Brain biopsy: trophozoites in perivascular space and thick walled cysts, PCR/DNA probes may show Acanthamoeba Primary amoebic meningoencephalitis ▪ Lumbar puncture ▫ CSF microscopy: motile amebae/ fluorescent antibody staining ▫ CSF PCR: Naegleria fowleri DNA ▫ CSF culture: Naegleria fowleri can be grown on nonnutrient agar coated with Escherichia coli Toxoplasmosis ▪ PCR (blood, CSF): Toxoplasma gondii DNA (inactive cysts may evade detection) ▪ Antibody titres ▫ IgG: evidence of current/previous infection ▫ IgM: occur in weeks after initial infection ▫ Antibody avidity testing: affinity for antigen increases with duration of infection ▪ Sabin–Feldman dye test: high titers → acute infection ▪ Tissue biopsy: tachyzoites in tissues/ smears TREATMENT MEDICATIONS ▪ Antifungal, antiparasitic agents OSMOSIS.ORG 353
ACANTHAMOEBA osmosis.org/learn/acanthamoeba PATHOLOGY & CAUSES Genus of amebae ▪ Single-celled eukaryotes ▪ Environmentally ubiquitous organisms ▫ Acanthamoeba spp. isolated from soil, air, fresh water, sewage, seawater, chlorinated swimming pools, domestic tap water, bottled water, hospitals, airconditioning units, contact lens cases ▪ Life stages ▫ Metabolically active trophozoite ▫ Dormant stress resistant cyst ▪ Generally free living bacterivores, can cause human infection (acanthamebiasis) Granulomatous amoebic encephalitis ▪ Infection associated with immunosuppression (e.g. diabetes, HIV/AIDS, hematological malignancy, malnutrition, hepatic cirrhosis, chronic renal failure, systemic lupus, chemotherapy) ▪ Parasite enters body through cuts in skin/ inhalation → hematogenous spread to CNS → invasion of connective tissue → inflammatory response → neuronal damage Endosymbiosis, secondary infection ▪ Several human pathogens infect, replicate within Acanthamoeba ▫ Legionella pneumophila, Pseudomonas aeruginosa, some strains of E. coli, Staphylococcus aureus ▪ Replication inside Acanthamoeba → enhanced growth in human macrophages, increased antibiotic resistance → more virulent, fulminant infections SIGNS & SYMPTOMS ▪ Fever, headache, seizures, focal neurological signs (e.g. cranial nerve palsies), mental status change (e.g. 354 OSMOSIS.ORG confusion), sepsis → progressive worsening over weeks/months → death DIAGNOSIS DIAGNOSTIC IMAGING Brain CT/MRI ▪ Meningeal exudate, pseudotumoral lesions, multiple space-occupying lesions with ring enhancement LAB RESULTS Lumbar puncture ▪ Often contraindicated due to risk of herniation associated with mass lesions ▪ Analytical findings generally nonspecific ▫ Intermediate elevations in white blood cell count, elevated protein, decreased glucose levels ▪ Giemsa staining, microscopy ▫ Trophozoites Tissue biopsy ▪ Brain biopsy ▫ Trophozoites in perivascular space, thick-walled cysts on light microscopy; PCR/DNA probes may reveal Acanthamoeba ▫ Immunocompetent host: granulomatous lesions ▫ Severely immunosuppressed host: insufficient CD+ve T-cells to mount granulomatous response → perivascular cuffing with amoebae in necrotic tissue ▪ If other organs involved (e.g. skin, conjunctiva, lungs) ▫ Trophozoites
Chapter 64 Central Nervous System Infections TREATMENT MEDICATIONS ▪ Current treatment regimes uncertain (based on in vitro studies, case reports) ▫ Antifungal, antiparasitic agents in combination ▫ Empiric antifungal regime: miltefosine, fluconazole, pentamidine isethionate +/- trimethoprim-sulfamethoxazole, metronidazole, macrolide antibiotic SURGERY ▪ Single cerebral lesions ▫ Surgical resection NAEGLERIA FOWLERI (PRIMARY AMEBIC MENINGOENCEPHALITIS) osmosis.org/learn/naegleria_fowleri PATHOLOGY & CAUSES ▪ Thermophilic, free-living ameba, found in bodies of warm (stagnant), freshwater TYPES ▪ Life cycle, three forms 1. Cyst ▫ Immotile, dormant, survival phase ▫ Smooth, single-layered cell wall with single nucleus, naturally resistant to environmental factors ▫ Formation of cysts induced by unfavorable conditions such as food shortage, overcrowding, desiccation, accumulation of waste products, cold temperatures (< 10° celsius) 2. Trophozoite (ameboid) ▫ Feeding, reproductive, infective phase ▫ Transformation into trophozoites occurs around 25° celsius ▫ Reproduction occurs via binary fission (single cell divides into two offspring), optimal temperature 42° celsius 3. Biflagellate (two flagella) ▫ Mobile, infective phase ▫ Pear-shaped body with two flagella ▫ Flagellate phase occurs when ameba encounters change in fluid ionic concentration → allows movement to suitable environment ▪ In human tissues Naegleria fowleri exists as ameboid trophozoite; flagellate form may be found in CSF/during initial nasal insufflation Primary amoebic meningoencephalitis ▪ AKA naegleriasis ▪ Rare infection, fatality rate > 95% ▪ Mechanism of entry ▫ Insufflated into sinuses during waterbased activities → attaches to olfactory epithelium → follows olfactory axon through cribiform plate → migration to olfactory bulbs → spread throughout brain → diffuse meningoencephalitis ▪ In tissues, Naegleria fowleri feeds via two mechanisms; feeding on neurological tissue → necrosis, bleeding ▫ Phagocytosis of red, white blood cells ▫ Piecemeal consumption of astrocytes, neurons via amoebostome (actin-rich sucking apparatus extended from cell surface) OSMOSIS.ORG 355
SIGNS & SYMPTOMS ▪ Symptoms appear 1–9 days after nasal exposure → death likely follows within two weeks ▪ Change in sensation of taste, smell; headache, fever, nausea, stiff neck, seizures, coma DIAGNOSIS DIAGNOSTIC IMAGING Brain imaging ▪ Initially unchanged ▫ Reveals associated complications Leptomeningeal enhancement, diffuse subarachnoid hemorrhage, oedema, hydrocephalus, multiple cerebral infarcts LAB RESULTS ▪ Lumbar puncture ▫ CSF microscopy: motile amebae/ fluorescent antibody staining ▫ CSF PCR: Naegleria fowleri DNA ▫ CSF culture: Naegleria fowleri can be grown on nonnutrient agar coated with E. coli → drop of CSF of infected individual added, incubated at 37° celsius; clearing of E. coli in thin tracks indicative of trophozoite feeding → likely infection TREATMENT MEDICATIONS: ▪ Amphotericin B +/- fluconazole ▪ Miltefosine TOXOPLASMA GONDII (TOXOPLASMOSIS) osmosis.org/learn/toxoplasma_gondii PATHOLOGY & CAUSES ▪ Obligate intracellular parasite capable of infecting nearly all warm-blooded animals ▫ Only definitive hosts: biological family Felidae (e.g. house cats) ▪ 30–50% of global population exposed, may be chronically infected Life cycle ▪ Sexual reproduction ▫ Consumes infected animal meal (e.g. mouse) → parasite survives transit through stomach → infects small intestinal epithelial cells → parasites undergo sexual development, reproduction → millions of thick-walled, zygote-containing, oocytes produced ▪ Felid shedding ▫ Infected epithelial cells rupture → 356 OSMOSIS.ORG release oocytes into intestinal lumen → shedding in feces → spread via soil, water, food ▫ Oocysts highly resilient; can survive, remain infective for months in cold, dry climates ▪ Infection of intermediate host ▫ Ingestion of oocysts by warm blooded animals (e.g. humans) → oocyst wall dissolved by proteolytic enzymes in stomach, small intestine → frees sporozoites from within oocyst → parasites invade intestinal epithelium, surrounding cells → differentiation into tachyzoites (motile, quickly-multiplying phase) ▪ Asexual reproduction in intermediate host ▫ Tachyzoites replicated inside specialized vacuoles until host cell dies, ruptures → release, hematogenous spread of tachyzoites to all tissues
Chapter 64 Central Nervous System Infections ▪ Formation of tissue cysts ▫ Host immune response → tachyzoite conversion → bradyzoites (semidormant, slowly dividing stage) → inside host cells known as tissue cysts → can form in any organ; predominantly brain, eyes, striated muscle (including cardiac muscle) ▫ Consumption of tissue cysts in meat from infected animal ▫ Primary means of infection (e.g. pork, lamb) ▫ Tissue cysts maintained in host tissue for remainder of life via periodic cyst rupture, re-encysting RISK FACTORS ▪ Consumption of raw/undercooked meat; ingestion of contaminated water, soil/ vegetables; previous blood transfusion/ organ transplant; transplacental transmission COMPLICATIONS ▪ Toxoplasmic chorioretinitis ▫ AKA ocular toxoplasmosis ▫ Common cause of posterior segment infection ▫ Majority of cases acquired; also strongly associated with congenital infection SIGNS & SYMPTOMS ▪ Initial infection (immunocompetent host) ▫ Mild flu-like symptoms (e.g. swollen lymph nodes, headache, fever, fatigue, muscle aches, pains) ▪ Congenital infection ▫ Chorioretinitis (unilateral decrease in visual acuity), hydrocephalus, seizures, lymphadenopathy, hepatosplenomegaly ▪ Chronic/latent infection ▫ Asymptomatic in healthy hosts ▪ Immunocompromised host ▫ Active infection (toxoplasmosis) ▫ Headache, confusion, poor coordination, seizures, cough, dyspnea ▫ Reactivation of latent infection: worsening of immunosuppression due to progression of underlying disease (e.g. HIV/AIDS, iatrogenic immunosuppression) → loss of immune balance → progression to active infection DIAGNOSIS DIAGNOSTIC IMAGING CT scan with contrast ▪ Multiple 1–3 cm hypodense regions with nodular/ring enhancement predominantly in basal ganglia, corticomedullary junction T2 weighted MRI ▪ Iso/hyper-intense lesions surrounded by perilesional edema Fundoscopy ▪ Toxoplasmic chorioretinitis ▫ Unifocal area of acute-onset inflammation adjacent to old chorioretinal scar Figure 8.1 A histological section of the cerebrum demonstrating cerebral toxoplasmosis. There are bradyzoites present and a mixed inflammatory infiltrate which includes eosinophils. LAB RESULTS PCR (blood, CSF) ▪ Toxoplasma gondii DNA (inactive cysts may evade detection) Antibody titres ▪ IgG (persist for life) OSMOSIS.ORG 357
▫ Evidence of current/previous infection ▪ IgM (acute infection) ▫ Occur in weeks after initial infection, remain detectable for months ▫ Antibody avidity testing may clarify nature of infection; early toxoplasmaspecific IgG has low affinity for toxoplasma antigen; affinity increases with duration of infection ▪ Sabin–Feldman dye test ▫ Requires specialised laboratories (live Toxoplasma gondii required); high titers → acute infection ▫ Patient serum treated with Toxoplasma trophozoites + complement, incubated → methylene blue added (membrane stain) → if anti-toxoplasma antibodies present, complement facilitates lysis of parasite membrane → no staining of lysed membrane ▫ No antibodies in serum → intact membranes → membrane stained blue under microscopy ▪ Tissue (brain/lymph node/muscle) biopsy ▫ Tachyzoites (acute infection) may be demonstrated in tissues/smears Figure 8.2 An MRI scan of the head in the axial plane demonstrating cerebral toxoplasmosis. There are numerous peripherally enhancing nodules in the basal ganglia. 358 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Prevention ▫ Trimethoprim/sulfamethoxazole ▪ Acute infection ▫ Antimalarials: pyrimethamine ▫ Antibiotics: sulfadiazine with pyrimethamine, clindamycin, spiramycin ▪ Latent infection ▫ Cysts not sufficiently penetrated by traditional therapy ▫ Atovaquone (antimalarial) +/clindamycin (lincomycin antibiotic) ▪ Toxoplasmic chorioretinitis ▫ Sight-threatening lesions ▫ Triple therapy: pyrimethamine, sulfadiazine, folinic acid ▫ Mono-antibiotic therapy: trimethoprimsulfamethoxazole, clindamycin, spiramycin

Osmosis High-Yield Notes

This Osmosis High-Yield Note provides an overview of Central nervous system infections essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Central nervous system infections by visiting the associated Learn Page.