Week 32 - CNS infections

CNS Infections

  • CNS infections can occur when pathogens breach the blood-brain barrier.

  • Toxin-borne infections can also affect the central nervous system (CNS).

Tetanus

Etiology

  • Caused by Clostridium tetani, a spore-forming bacterium.

  • Releases neurotoxins acting on the central nervous system:

    • Tetanolysin: Hemolysin that lyses red blood cells.

    • Tetanospasmin: An extremely potent neurotoxin.

  • Transmission occurs through wound contamination, burns, or needles.

  • Neurotoxins are delivered via blood and lymphatics to nerves, blocking release of inhibitory mediators at spinal synapses, leading to excessive motor neuron activity.

Epidemiology

  • In 2015, tetanus infection through umbilical cord stump resulted in 34,000 newborn deaths worldwide.

Clinical Features

  • Incubation period: Ranges from 3 to 21 days.

  • Symptoms include:

    • Exaggerated reflexes

    • Muscle rigidity

    • Uncontrolled muscle spasms

    • Lockjaw (trismus)

    • Dysphagia (difficulty swallowing), giving a sneering appearance.

    • Respiratory failure can occur.

Identification and Treatment

  • Identification:

    • Gram stain reveals a “drumstick” bacillus.

    • Cultured on blood agar.

  • Treatment includes:

    • Wound excision to remove infected tissue.

    • Antibiotic therapy.

    • Muscle relaxants.

    • Administration of human tetanus immunoglobulins (IgG).

  • Vaccines are available with boosters for those at risk of infection.

Parasite Infections

  • Infection by parasites entering the brain is extremely fatal.

  • Case example:

    • Toxoplasma gondii: A protozoan that forms tissue cysts in the brain.

African Sleeping Sickness

  • The World Health Organization (WHO) estimates a higher real incidence of infection, closer to 30,000 cases per year.

Trypanosomiasis

  • Caused by three species:

    • Trypanosoma brucei gambiense

    • Trypanosoma brucei rhodesiense

    • Trypanosoma cruzi (responsible for Chagas disease).

  • Differences exist in:

    • Vector of transmission.

    • Localization of the parasite.

    • Effects on the immune system.

Trypanosoma brucei gambiense Infection

  • Transmitted by the Tsetse fly (a vector-borne disease).

  • After the infected bite, parasites replicate in the bloodstream.

  • If untreated, they may travel to the CNS.

  • Symptoms of sleeping sickness include:

    • Personality changes.

    • Altered biological clock.

    • Confusion, slurred speech, seizures.

    • Difficulty walking and talking.

  • Infection can be asymptomatic for prolonged periods.

Trypanosome Transmission

  • Besides Tsetse fly bites, transmission can occur via:

    • Mother-to-child through the placenta.

    • Contaminated needles.

    • Sexual contact.

  • Two-stage infection process:

    1. Haemolymphatic stage: Initial multiplication in subcutaneous tissues and bloodstream.

    2. Neurological stage: Parasite crosses the blood-brain barrier.

    • Openings in endothelial cells allow trypanosomes to enter.

    • Parasites may use strategies involving white blood cells to cross tight junctions.

Trypanosome Lifecycle

  1. Initial infection occurs when a Tsetse fly delivers trypomastigotes into the bloodstream.

  2. Parasites differentiate into long slender forms to establish a bloodstream infection.

  3. Eventually invade extravascular tissues, including the CNS.

  4. When a Tsetse fly feeds on an infected host, it ingests parasites with the blood meal.

  5. Parasites undergo transformation into procyclic trypomastigotes, establishing a midgut infection in the fly.

  6. They migrate to the salivary glands for completion of the life cycle.

Epidemiology and Clinical Features

  • Sleeping sickness threatens approximately 60 million people in epidemic regions of Africa.

  • Trypanosoma brucei can survive undetected due to antigenic variation with around 900 different surface glycoprotein genes.

  • Lesions in the hypothalamus affect sleep and wake regulation.

Identification and Treatment

  • Requires skilled microscopy for parasite identification in body fluids or tissues.

  • A rapid anti-trypanosomal antibody test may be used.

  • Treatment is complex due to variations in disease stage and type of trypanosome, often utilizing the antimicrobial Pentamidine.

Summary

  • Overview of CNS infections caused by a variety of pathogens:

    • Bacterial: Neisseria meningitidis (meningitis).

    • Fungal: Cryptococcus neoformans.

    • Viruses: Rabies, herpes simplex virus encephalitis.

    • Parasites: African sleeping sickness (Trypanosoma brucei).