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Overview: When Single-Celled Eukaryotes Cause Disease
Protists are mostly single-celled, eukaryotic organisms. Some live harmlessly or even beneficially in the environment or in other organisms; others can cause serious diseases in humans. As eukaryotes, parasitic protists are more similar to our own cells than bacteria are. This has two important consequences:
- They often have complex life cycles with several stages, sometimes involving different hosts.
- It is harder to find drugs that kill them without also harming human cells.
In this chapter we focus on protists that live as parasites in or on humans and act as pathogens.
General Features of Protist Pathogens
Modes of Life and Transmission
Pathogenic protists can be:
- Intracellular parasites – they live inside human cells (e.g., malaria parasites in red blood cells).
- Extracellular parasites – they live in body fluids or tissues outside cells (e.g., many intestinal amoebae).
- Tissue parasites – they inhabit specific organs such as liver, brain, or heart.
Typical transmission routes include:
- Vector-borne (through blood-feeding arthropods)
- Example: mosquitoes transmitting malaria parasites.
- Example: tsetse flies transmitting African trypanosomes.
- Fecal–oral (ingestion of cysts or oocysts)
- Via contaminated water, food, or dirty hands.
- Important in intestinal protozoan infections.
- Direct contact or oral–oral
- Less common but possible for some species in close-contact settings.
Infectious Stages: Cysts, Oocysts, Trophozoites
Many protists form specialized stages that allow survival outside the body:
- Cysts
- Thick-walled, resistant forms, usually passed with feces.
- Survive drying, stomach acid, and environmental stress.
- Infect new hosts when ingested (e.g., cysts of Giardia or Entamoeba).
- Oocysts
- A special type of encysted stage produced after sexual reproduction in some groups (e.g., Plasmodium, Toxoplasma).
- Often require a period of maturation in the environment or in a vector.
- Trophozoites
- Active, feeding, multiplying forms inside the host.
- Generally fragile and cannot survive long outside the body.
Understanding which stage is infectious is crucial for prevention and diagnosis.
Main Groups of Protist Pathogens
Amoebae
Amoebae move and feed by extending cell projections called pseudopodia. Most free-living amoebae are harmless, but some are parasitic.
Intestinal Amoebae: Example *Entamoeba histolytica*
- Transmission
- Ingestion of mature cysts in contaminated water, food, or via unwashed hands.
- Infection site
- Large intestine.
- Disease
- Amoebiasis (amoebic dysentery): can range from mild diarrhea to severe bloody diarrhea and abdominal pain.
- In some cases, amoebae invade the intestinal wall, enter the bloodstream, and cause liver abscesses and other extraintestinal disease.
- Pathogenesis
- Trophozoites adhere to the intestinal mucosa and secrete substances that damage tissue.
- This leads to ulcer formation and bleeding.
Other amoebae, such as Naegleria fowleri and Acanthamoeba spp., are free-living but can, under rare circumstances, invade humans:
- Naegleria fowleri can cause rapidly fatal brain infection after contaminated water enters the nose.
- Acanthamoeba can cause eye infections (keratitis) and, in immunocompromised patients, disseminated disease.
Flagellates
Flagellates move with one or more whip-like flagella. Several important human parasites belong to this group.
Intestinal Flagellates: Example *Giardia duodenalis* (also *G. lamblia*)
- Transmission
- Fecal–oral: ingestion of cysts in contaminated water, food, or via person-to-person contact (e.g., in daycare centers).
- Cysts are highly infectious; only a few may be needed to cause disease.
- Infection site
- Upper small intestine.
- Disease
- Giardiasis: causes watery, often foul-smelling diarrhea, abdominal cramps, bloating, and malabsorption.
- Can be acute or chronic, sometimes leading to weight loss.
- Pathogenesis
- Trophozoites attach to the intestinal mucosa but usually do not invade it.
- They interfere with nutrient absorption, especially fats.
Blood and Tissue Flagellates: *Trypanosoma* and *Leishmania*
These are mainly vector-borne parasites with complex life cycles.
African Trypanosomes: Sleeping Sickness
- Species
- Trypanosoma brucei gambiense (West and Central Africa).
- Trypanosoma brucei rhodesiense (East and Southern Africa).
- Transmission
- Bite of infected tsetse flies.
- Infection site
- First in blood and lymph, later in the central nervous system.
- Disease
- African sleeping sickness:
- Early stage: fever, headache, joint pain, swollen lymph nodes.
- Late stage: parasites invade the brain, causing confusion, disturbances of sleep–wake cycles, behavioral changes, and coma.
- Biological features
- Trypanosomes constantly change their surface proteins (antigenic variation), helping them evade the immune system and cause chronic infection.
American Trypanosomes: Chagas Disease
- Species
- Trypanosoma cruzi.
- Transmission
- Via triatomine bugs (“kissing bugs”) that defecate near the bite wound; parasites in feces enter through skin breaks or mucous membranes.
- Also via blood transfusion, organ transplantation, or congenitally.
- Infection site
- Initially at the entry site and nearby lymph nodes; later heart muscle, digestive tract, and other tissues.
- Disease
- Chagas disease:
- Acute phase: often mild symptoms or fever; sometimes swelling at the entry site.
- Chronic phase: years later, heart failure, arrhythmias, enlargement of esophagus or colon (megaesophagus, megacolon).
- Tissue damage
- The parasite damages tissues directly and indirectly via inflammation.
*Leishmania* Species: Leishmaniases
- Transmission
- Bite of infected female sandflies.
- Infection site
- Inside certain white blood cells of the skin, mucous membranes, or internal organs.
- Main clinical forms
- Cutaneous leishmaniasis: skin ulcers.
- Mucocutaneous leishmaniasis: destruction of mucous membranes of nose, mouth, throat.
- Visceral leishmaniasis (kala-azar): infection of liver, spleen, bone marrow; leads to fever, weight loss, anemia, and enlarged organs.
- Risk factors
- Poverty, malnutrition, weakened immune system, and certain environmental conditions that favor sandflies.
Apicomplexa
Apicomplexans are a group of protists characterized by a set of organelles at one end (the apical complex) used to invade host cells. They are all parasitic.
Malaria Parasites: *Plasmodium* Species
- Species infecting humans
- Plasmodium falciparum (most dangerous),
- P. vivax,
- P. ovale,
- P. malariae,
- and occasionally P. knowlesi.
- Transmission
- Bite of infected female Anopheles mosquitoes.
- Infection site
- Initially liver cells, then red blood cells.
- Disease
- Malaria: periodic fevers, chills, anemia, and, in severe cases, organ failure and death.
- Biological features
- Complex life cycle alternating between human and mosquito.
- Asexual multiplication in humans causes cycles of red blood cell rupture, explaining periodic fever attacks.
- Sexual stages develop in mosquitoes, completing the cycle.
*Toxoplasma gondii*: Toxoplasmosis
- Transmission
- Ingestion of oocysts shed in the feces of infected cats (contaminated soil, vegetables, water).
- Consumption of tissue cysts in undercooked meat from infected animals.
- Congenital infection: from an infected mother to the fetus during pregnancy.
- Infection site
- Various tissues: muscle, brain, eye, and others.
- Disease
- In healthy individuals: often asymptomatic or mild flu-like illness.
- In immunocompromised persons (e.g., AIDS patients): severe disease with brain or eye involvement.
- In congenital infection: can lead to miscarriage, stillbirth, or severe damage to the nervous system and eyes.
- Persistence
- The parasite forms tissue cysts that can persist for life.
Intestinal Coccidia: *Cryptosporidium* and Others
- Species
- Cryptosporidium parvum, Cryptosporidium hominis, and related species.
- Transmission
- Fecal–oral via oocysts in contaminated drinking water, swimming pools, or food.
- Oocysts are highly resistant to many disinfectants, including standard chlorination.
- Infection site
- Small intestine.
- Disease
- Cryptosporidiosis: watery diarrhea, abdominal cramps, nausea.
- Self-limiting in many healthy individuals, but can be chronic and severe in immunocompromised patients.
Other intestinal apicomplexans, such as Cyclospora cayetanensis and Cystoisospora (Isospora) belli, also cause diarrheal illness, especially where sanitation is poor.
Typical Symptoms and Organ Systems Involved
Protist infections can affect many organs. Main patterns include:
- Intestinal infections
- Diarrhea (watery or bloody), abdominal pain, bloating, malabsorption, weight loss.
- Examples: Giardia, Entamoeba histolytica, Cryptosporidium.
- Blood and systemic infections
- Fever, anemia, enlarged liver and spleen, general malaise.
- Examples: Plasmodium, Leishmania, Trypanosoma spp.
- Neurological involvement
- Confusion, sleep disturbances, seizures, coma.
- Examples: African trypanosomiasis, severe cerebral malaria, rare amoebic encephalitis, severe toxoplasmosis.
- Cardiac and digestive involvement
- Heart rhythm disorders, heart failure, esophageal or intestinal motility problems.
- Example: chronic Chagas disease (Trypanosoma cruzi).
- Ocular disease
- Inflammation of the eye, vision disturbances.
- Examples: ocular toxoplasmosis, Acanthamoeba keratitis.
Diagnosis of Protist Infections
Diagnosis relies on detecting the parasite or its effects. Common approaches include:
- Microscopic examination
- Direct observation of cysts, oocysts, or trophozoites in stool samples.
- Blood smears for malaria and blood trypanosomes.
- Tissue biopsies for certain tissue parasites.
- Antigen detection
- Rapid tests using antibodies that recognize parasite proteins (e.g., some malaria tests).
- Molecular methods
- PCR-based tests to detect parasite DNA or RNA in clinical samples; useful for precise species identification and for low-level infections.
- Serology
- Detection of specific antibodies in the blood; especially useful for chronic infections and for parasites that are difficult to find directly (e.g., Toxoplasma gondii, Trypanosoma cruzi).
- Imaging and clinical findings
- Ultrasound, X-ray, CT, or MRI may show damage to organs, supporting the diagnosis (e.g., liver abscesses, brain lesions).
Treatment Principles and Challenges
Treating protist infections involves several difficulties:
- Eukaryotic similarity
- Because protists share many cellular features with humans, drugs must be specific enough to harm parasites more than human cells, which limits options and can cause side effects.
- Multiple life stages
- Different stages of a parasite may respond differently to drugs; a drug effective against one stage (e.g., blood forms of malaria) may not eliminate others (e.g., liver or dormant stages).
- Drug resistance
- Many protist parasites, particularly Plasmodium falciparum, have evolved resistance to multiple drugs, complicating therapy.
Typical approaches:
- Use of antiprotozoal drugs tailored to the parasite species and disease form.
- Combination therapies to improve effectiveness and reduce resistance development (e.g., artemisinin-based combination therapy in malaria).
- Supportive therapy
- Rehydration in diarrheal diseases.
- Treatment of anemia, organ failure, or co-infections in severe systemic infections.
Prevention and Control
Because many protist infections are linked to environment, water, vectors, and hygiene, prevention focuses on:
Hygiene and Sanitation
- Safe drinking water (filtration, appropriate disinfection, boiling).
- Proper sewage disposal and fecal waste management.
- Handwashing with soap, especially after using the toilet and before handling food.
- Food hygiene: washing raw vegetables, cooking meat thoroughly, avoiding consumption of raw or undercooked meat from unknown sources.
Vector Control
For vector-borne protists:
- Mosquito control (for malaria and some other parasites)
- Elimination of breeding sites (standing water).
- Insecticide-treated bed nets.
- Indoor residual spraying with insecticides.
- Sandfly and kissing bug control
- Use of insecticide-treated materials, improved housing, bed nets, and environmental management.
Protection of Vulnerable Groups
- Pregnant women
- Special counseling about toxoplasmosis (e.g., handling cat litter, consuming raw meat) and malaria prevention in endemic regions.
- Immunocompromised individuals
- Avoidance of risky exposures (untreated water, contact with cat feces, travel to high-risk areas if possible).
- Travelers
- Information about malaria prophylaxis, mosquito protection, and food and water safety in endemic regions.
Surveillance and Public Health Measures
- Monitoring of drinking water quality.
- Reporting and controlling outbreaks of waterborne or foodborne protozoan infections.
- Screening of blood donors and organ donors for relevant parasites in regions where Chagas disease, malaria, or leishmaniasis occur.
Significance for Global Health
Protist pathogens play a major role in global disease burden:
- Malaria
- One of the most important infectious diseases worldwide, especially affecting children in tropical and subtropical regions.
- Leishmaniasis, Chagas disease, and human African trypanosomiasis
- Classified as “neglected tropical diseases”: they mainly affect poor populations and often receive less attention and fewer resources than their impact would warrant.
- Waterborne protozoan infections
- Outbreaks of giardiasis or cryptosporidiosis can occur even in industrialized countries if water treatment fails or is inadequate.
Because many of these diseases are linked to poverty, inadequate infrastructure, and environmental conditions, their control is as much a social and political challenge as a medical one. Understanding protists as pathogens helps to grasp why improvements in water supply, sanitation, housing, education, and vector control are central elements of disease prevention.