L18 Protozoan Infections

Eukaryotic Diseases: Protozoan Infections

Introduction to Protists

  • Reading Assignments: Chapters 11.3-11.4, 18.6, 21.5, 24.6

  • Outline of Today’s Lecture:

    • Introduction to Protists

    • Pathogenesis of Plasmodium (malaria)

    • Pathogenesis of Trypanosoma (sleeping sickness and Chagas’ disease)

    • Amoebic Pathogenesis of Naegleria fowleri

Overview of Medically Relevant Eukaryotic Microbes

  • Categories:

    • Fungi

    • Protists

    • Algae

    • Protozoa

    • Alveolates

    • Trypanosomes

    • Amoebas

    • Invertebrate parasites

    • Helminths

    • Arthropods

General Characteristics of Organisms

Algae

  • Key Roles:

    • Major carbon fixers

    • Oxygen producers

  • Features:

    • Conduct photosynthesis using chloroplasts

    • Usually motile via pairs of flagella

    • May exist as single cells or in forms like filaments and sheets (e.g., kelp)

    • Extremely rarely cause human pathogenesis

  • Types of Algae:

    1. Green algae

    2. Red algae

    3. Brown algae

Protozoa

  • Definition: Protozoa = “first animals”

  • Characteristics:

    • Mostly single-celled

    • Motile

    • Can be free-living or parasitic

    • Feeding: Heterotrophic predators ingest other microorganisms, organic tissues, and debris

  • Types of Protozoa:

    1. Alveolates

    2. Trypanosomes

    3. Amoebas

Alveolates

  • Characteristics:

    • Mostly single-celled

    • Possess a complex outer covering known as the cortex

    • Cortex consists of alveoli (flattened sacs of fluid) for protection and structure

    • Utilize flagella for whiplike motion

    • Some are covered in cilia for mobility and prey capture

    • Some species exhibit photosynthetic abilities

  • Human Pathogens Example: Plasmodium causing malaria

Trypanosomes

  • Definition:

    • Single-celled obligate parasites

    • Characterized by a single flagellum for motility

    • Exhibit complex parasitic life cycles with multiple developmental forms in hosts

  • Serious Human Pathogens:

    • African sleeping sickness

    • Chagas’ disease

    • Leishmaniasis

Amoebas

  • Definition:

    • Single-celled heterotrophs

  • Characteristics:

    • Possess pseudopodia (extensions of cytoplasm for motility)

    • Consume bacteria, other protists, and small invertebrates

    • Can exist in multiple life stages for transmission and metabolism

    • Mostly free-living, but some are opportunistic pathogens (e.g., Naegleria fowleri)

Mechanisms Used by Protozoa for Pathogenesis

  • Direct Cell Damage:

    • Protozoan cells inflict damage directly

  • Immune Evasion Strategies:

    • Antigenic Masking/Mimicry:

    • Protozoa coat themselves in host proteins preventing immune detection

    • Antigenic Variation:

    • Surface antigens are frequently altered to evade immune response

    • Intracellular Growth:

    • Protozoa grow within specific host cell types

    • Immunosuppression:

    • Alter production of signaling molecules to keep immune cells inactive

    • Complex Life Cycles:

    • Involves different life stages for specific functions, including intracellular proliferation and transmission

Protozoan Pathogens and Associated Diseases

  • Common habitats: Protozoa are widespread in the environment and often spread via arthropod vectors.

  • Potential Infections:

    • Eye Infections: Keratitis (e.g., Acanthamoeba)

    • Systemic Infections:

    • Malaria (Plasmodium)

    • Babesiosis (Babesia)

    • Chagas’ disease (Trypanosoma)

    • Leishmaniasis (Leishmania)

    • Toxoplasmosis (Toxoplasma)

    • Neurological Infections:

    • Sleeping sickness (Trypanosoma)

    • Toxoplasmosis (Toxoplasma)

    • Brain-eating amoebas

    • Gastrointestinal Infections:

    • Traveler’s diarrhea (Giardia)

    • Amebic dysentery

    • Reproductive Tract Infections:

    • Trichomoniasis (Trichomonas)

Pathogenesis of Plasmodium (Malaria)

General Characteristics

  • Definition: An intracellular, parasitic alveolate

  • Life Cycle:

    • Two main hosts with complex life cycles:

    • Sexual Cycle: In mosquitoes (the definitive/primary host)

    • Asexual Cycle: In humans (the intermediate host)

  • Transmission: Via mosquito bite

  • Species That Cause Malaria:

    • Plasmodium falciparum

    • Plasmodium malariae

    • Plasmodium vivax

    • Plasmodium ovale

Life Cycle of Plasmodium in Humans

  • In Mosquitoes (Sexual Cycle):

    • Parasitic gametes (haploid) ingested during mosquito feeding

    • Gametes unite in the midgut, forming infectious sporozoites (diploid)

    • Sporozoites transmitted to humans via mosquito saliva during feeding

  • In Humans (Asexual Cycle):

    • Sporozoites travel through the bloodstream to the liver

    • Undergo cell division yielding merozoites that infect red blood cells

    • Reproduction leads to high concentrations of parasites and subsequent hemolysis (destruction of red blood cells)

Malaria's Impact

  • Global Significance: Most devastating infectious disease on Earth

  • Statistical Data:

    • Estimated infections per year: 200-300 million

    • Death toll: 1-3 million annually (predominantly children)

  • Symptoms Due to RBC Lysis:

    • High fevers

    • Anemia

    • Reduced oxygen levels

    • Impaired neurological function

    • Potential for death

  • Vaccine Research: Research ongoing for malaria vaccines

Cyclical Nature of Malaria Infections

  • Infection Cycles: Continuous cycles of parasite dissemination and RBC destruction (hemolysis)

  • Antigenic Variation: Parasites alter surface proteins to escape the immune response

  • Fever Stages:

    • Cold Stage: Lasting 30-60 minutes

    • Hot Stage: Lasting 2-6 hours, with temperatures rising up to 105°F

    • Sweating Stage: Lasting 2-4 hours

  • Linkage: Synchronized bursts of RBCs contribute to recurrent symptoms

Pathogenesis of Trypanosoma

General Characteristics

  • Classification: Unicellular and flagellated parasites

  • Features:

    • Exist as extracellular parasites

    • Multiple species that infect various host organisms

    • Transmission vectors involve multiple arthropods

Immune Evasion Mechanism

  • Variant Surface Glycoprotein (VSG) Expression:

    • Trypanosomes evade the immune system by constantly switching forms of VSG

    • Each variant governs surface expression, necessitating the need for diverse VSG genes

    • Only one version of VSG is expressed at any time, complicating vaccine development

Diseases Caused by Trypanosomes

  1. African Sleeping Sickness (Trypanosoma brucei)

    • Prevalence in sub-Saharan Africa (approximately 10,000 cases per year)

    • Wild and domestic animal reservoirs

    • Transmission via tsetse flies through blood-feeding

    • Systemic illness affecting various organs and the central nervous system

    • Symptoms include disrupted sleep patterns, tremors, aphasia, shuffling gait, leading to eventual coma and death

  2. Chagas’ Disease (Trypanosoma cruzi)

    • Common in Central and South America

    • Wild and domestic animal reservoirs

    • Transmitted via triatomine bugs during blood feeding

    • Leads to systemic infection, attacking various organs

    • Mucosal irritation or cardiac complications can arise chronic in nature

Amoebic Pathogenesis of Naegleria fowleri

General Characteristics

  • Definition: Single-celled amoeba, commonly referred to as “brain-eating amoeba”

  • Habitat: Free-living in warm, freshwater environments such as lakes, pools, and aquaria

  • Feeding and Temperature: Optimal growth at approximately 107°F (42°C)

  • Disease Potential: Can cause severe central nervous system (CNS) infections

Life Cycle of Naegleria fowleri

  • Life Stages:

    1. Cyst: Resistant to adverse conditions

    2. Trophozoite: Infectious stage that travels through the olfactory nerve to the brain; actively feeding form

    3. Flagellate: Can transition from the flagellate form, typically in response to environmental changes, but does not contribute extensively to pathogenesis leading to infection

Pathology of Naegleria fowleri

  • Meningoencephalitis:

    • Trophozoites penetrate the blood-brain barrier and begin to consume brain tissue

    • Symptoms include severe headache, nausea, and stiff neck

    • Death typically occurs within 14 days of exposure

    • Detection of trophozoites in cerebrospinal fluid (CSF) is a dire prognostic indicator

    • Rarity of infections: Approximately 154 known cases since 2000, averaging 5-10 per year over the last decade

Summary of Key Lecture Points

  • Protists Classification:

    • Include algae (photosynthetic autotrophs) and protozoa (heterotrophic predators) such as amoebas, alveolates, and trypanosomes

  • Pathogenic Mechanisms: Protozoan pathogens exploit complex multi-host life cycles and diverse immune evasion strategies

  • Plasmodium: Transmitted by mosquitoes; uses an erythrocytic life cycle to cause malaria, a severe disease

  • Trypanosomes: Utilized by various insects; employ VSG variation to avoid immune detection while causing serious diseases such as sleeping sickness and Chagas’ disease

  • Naegleria fowleri: Has three distinct life stages that permit it to cause serious CNS infections