W5: Parasite lecture

General Characteristics of Parasites

  • Biological Classification: Parasites are Eukaryotes, characterized by large cells and an extensive genome protected from excessive mutation levels.

  • Lifestyle Classifications:  

    • Obligate Parasites: Entirely dependent on the host for their life cycle.

    • Facultative Parasites: Can live independently but may resort to parasitism under specific conditions.

    • Endoparasites: Reside within the host's body.

    • Ectoparasites: Reside on the external surface of the host.

  • Transmission and Life Cycles:  

    • Usually not airborne.

    • Commonly utilize invertebrate animal vectors (e.g., insects, snails).

    • Direct Parasites: Involve a single host.

    • Indirect Parasites: Involve multiple hosts in the life cycle.

  • Management Challenges:

    • Prevention and containment are typically easier than for viruses and bacteria.

    • Treatment is problematic because parasites are eukaryotes; shared biological pathways mean drugs often impact the host's physiology.

Global Prevalence and Transmission Dynamics

  • Epidemiological Comparison:  

    • Bacteria: 37% of diseases, 48% of outbreaks, 54% of Emerging Infectious Diseases (EIDs).

    • Viruses: 33% of diseases, 40% of outbreaks, 25% of EIDs.

    • Parasites: 15% of diseases, 4% of outbreaks, 20% of EIDs.

  • Transmission Routes:

    • Vector-borne: Insect bites.  

    • Direct Vertebrate Contact: Transmission of eggs.

    • Fecal-Oral: Exposure to animal feces.

    • Dietary: Consumption of raw meat, raw fish, and contaminated fruits or vegetables.

    • Waterborne: Contaminated water sources.

    • Medical/Congenital: Blood transfusions and maternal (vertical) transmission.

Pharmacological Treatments and Mechanisms

  • Drug Targets: Because hosts and parasites share similar genes, drugs must target specific metabolic or cellular differences.

  • Specific Antiprotozoal and Antifungal Drugs:

    • Benznidazole and Nifurtimox: Used for Trypanosoma; generate radical species that damage DNA and cellular machinery.

    • Systemic Corticosteroids: Used for many parasites as hormone mediators; provide anti-inflammatory, immunosuppressive, anti-proliferative, and vaso-constrictive effects.     

    • Miconazole: Used for fungi; inhibits the cytochrome P450 enzyme (Note: Animals possess an equivalent enzyme, P451).

    • Pyrimethamine: Used for Plasmodium, Toxoplasma, and Cystoisospora; inhibits dihydrofolate reductase.

Neglected Parasitic Zoonoses and Economic Impact

  • Characteristics: Significant morbidity in rural populations, under-reported, and neglected by funding agencies. Predominantly found in tropical regions.

  • Geographic Distribution:

    • Latin America: Chagas disease (Trypanosoma cruzi).  

    • Asia, Africa, and Latin America: Echinococcosis and Taeniasis (Taenia solium).    

    • Asia and Africa: Leishmaniasis.   

    • Africa: Cysticercosis and Trematodiasis.

  • Economic Burden: Total cost is up to $15 billion, which is lower than microbial or viral zoonoses. Specific costs include:

    • Malaria: >12 billion in direct costs.

    • African Trypanosomiasis: $3-5 billion.

    • Soil-transmitted Helminths: 4141 million per year in Latin America and the Caribbean.

    • Schistosomiasis: $2.7 million in Cambodia.

Protozoal Zoonoses: Biology and Key Diseases

  • General Biology: Unicellular, ranging from 1mm to several mm. Can be free-living (water/soil) or parasitic. Mobile organisms with sexual or asexual (binary fission) reproduction. Most sexual species have two-stage life cycles (proliferating and resting).

  • African Sleeping Sickness (Trypanosomiasis):

    • Agent: Trypanosoma brucei (Vector: Tsetse flies).

    • Reservoirs: Antelopes, cattle, camels, and horses.

    • Symptoms: High fever, nausea, erythematous plaque formation; causes approximately $9,000 deaths per year.

  • Chagas Disease (American Trypanosomiasis):  

    • Agent: Trypanosoma cruzi (Euglenoid).  

    • Vector: Triatomine ("kissing bug," "assassin bug," or "vampire bug"). Resistance to insecticides is reported in South America.  

    • Morphology:

      • The replicating epimastigotte form in culture (Giemsa stain).

      • Trypomastigote in a peripheral blood smear from a patient with acute Chagas disease

      • Nest of amastigotes within a cardiac myocyte in a patient with chronic Chagas disease (hematoxylin and eosin stain)

    • Reservoirs: Raccoons, opossums, armadillos, foxes, domestic pigs, and cats.

    • Impact: 6 million infected, 12,000 deaths per year. Up to 45% develop heart disease (severe myocarditis). Oral and blood transmission reported in Canada, Australia, and Europe.

  • Leishmaniasis:

    • Agent: Leishmania infantum (Visceral) and Leishmania major (Cutaneous).

    • Vector: Sandflies.

    • Forms: Zoonotic Cutaneous Leishmaniasis (ZCL) (bumps to open sores) and Zoonotic Visceral Leishmaniasis (ZVL) (weight loss, anemia, enlarged spleen/liver; fatal if untreated).

    • Reservoir host:

      • ZCL: Rodents

      • ZVL: Domestic and wild mammals including cats and foxes

    • Impact: 20,000-30,000 deaths

    • Prevalence: BOTH ENDEMIC, ZCL(SE Europe, C/S America): $600,000 to $1 million new cases/year; ZVL(E Africa, India, and Brazil): 360 million people at risk of infection.

  • Toxoplasmosis:

    • Agent: Toxoplasma gondii (Apicomplexan).

    • Prevalence: Infects 10-90% of the global population (roughly half the world). Often asymptomatic in adults, low death toll

    • Reservoirs: Pigs, sheep, goats, poultry, and rabbits.

    • Behavioral Modification: T. gondii alters rodent behaviour to increase predation by cats.

    • Congenital Risks: Maternal transmission leads to miscarriage or neurologic symptoms in infants.

    • Symptoms: Lymphadenopathy, fever, malaise

  • Malaria:

    • Zoonotic Species: Plasmodium knowlesi - only species classified as a zoonotic disease

    • Vector: Anopheles mosquito.

    • Emerging species: P. simium and P. brasilianum in South America.

    • Hosts: 30 primate species; 250 non-human vertebrate species total.

    • Pathology: Infects RBCs; accumulates in liver and brain. 3.4 billion people at risk.

    • Treatment: Vaccines currently under development. Antimalarial drug exist and are successful although come with important side effects. Resistance to these drugs is in the increase

Fungal and Mycotic Zoonoses

  • Scope: Over 1 billion people affected, with 1 million deaths annually.

  • Primary Colonization: Mostly skin (dermatomycoses), but lung infections are common and potentially lethal.

  • Significant Pathogens:

    • Candida auris: Highly drug-resistant; spreading in US hospitals/nursing homes.

    • Cryptococcus gattii: Causes lung infections and meningitis (Pacific Northwest).

    • Aspergillosis: Linked to environmental exposure. Climate change (warmer temperatures) is expected to expose 9 million more people in Europe by 2100.

  • Histoplasmosis (Cave Disease):

    • Agent: Histoplasma capsulatum.

    • Transmission: Inhaling spores from bat or bird droppings.

    • Diagnosis: Often misdiagnosed as tuberculosis. Fatal if untreated.

    • Treatments: Itraconazole (side effects: heart/liver failure) and Amphotericin B (high toxicity, organ damage).

Helminth (Parasitic Worm) Zoonoses

  • Classification: Polyphyletic group including Platyhelminths (tapeworms, flukes) and Nematodes (roundworms, hookworms).

  • Schistosomiasis (Blood Flukes):

    • Agent: Schistosoma sp. (Trematode).

    • Vector: Freshwater snails.

    • Pathology:

      • Eggs shed from infected humans in feces of urine

      • Eggs hatch and release miracidia

      • Miracidia penetrates small tissue of snails

      • Sporocysts develop in snail (successive generations)

      • Free-swimming cercariae released from snail into water

      • Cercariae penetrate human skin

      • Cercariae lose tails during penetration and become schistosomulae

      • Circulation

      • Migration to portal blood in liver and maturation into adults

      • paired adult worms migrate to mesenteric venules of bowel/rectum, laying eggs that circulate to liver and shed into stools/ venous plexus of bladder; eggs shed in urine

    • Emerging Zoonotic Form: Hybrids in West Africa between S. haematobium (human) and S. bovis or S. curassoni (livestock). NEGLECTED TROPICAL DISEASE

    • Treatment: Praziquantel (mechanism not fully understood).

    • 250,000 infected humans and 20,000 deaths

    • Symptoms: Headache, fatigue, abdominal pain, hives. 90% of all patients have abdominal pain. Long term infection may lead to liver damage, kidney failure, infertility, or bladder cancer. Can cause developmental issues in children

  • Fasciolosis (Liver Fluke):

    • Agent: Fasciola hepatica.

    • Transmission: Watercress or undercooked meat consumption.

    • Pathology: Similar life cycle and freshwater snail as intermediate host.

    • Characteristics: Hard to detect; includes diploid and triploid specimens reproducing parthenogenetically. Emerging resistance to Triclabendazole (treatment drug).

  • Tapeworms (Platyhelminths) (Cestoda):

    • Morphology: 1mm to 20m; no gut; uses a scolex (head) and bothria (sucking cups) for attachment; hermaphroditic.

      • all species are parasitic

    • Specific Diseases:

      • Coenurosis: Taenia multiceps/serialis (dogs as intermediate hosts, sheep/rabbits in cycle).  

      • Cysticercosis: Taenia solium (pork tapeworm); invades muscles, eyes, and CNS.

      • Echinococcosis (Hydatidosis): Echinococcus granulosus (dogs to humans; cattle/swine/kangaroos as intermediate hosts). Found in every continent apart from Antarctica. 1 million people affected. Found in 8,000-year-old human remains. Infects the liver

  • Roundworms (Nematodes):

    • Toxocariasis: Toxocara canis/cati from canid and cat feces. Infects 5% of EU/USA population. 5% of cases result in permanent sight loss.

    • Ancylostoma ceylanicum: Endemic to SE Asia and Australia; Hosts include dogs, cats, hamsters, and humans. Long term effects causes delayed development in children and increased mortality in pregnant women and infants.

      • Classified as re-emerging but neglected parasitic zoonosis

Management and Factors of Emergence

  • Emergence Factors:

    • Climate Change: Higher temperatures accelerate parasite development and vector multiplication.

    • Changes in location: movement of animals brings new parasites; emerging new infections and diseases

    • Biodiversity Changes: Increases risk of drug-resistant strains.

    • Host Concentration: Modulates the speed of infection spread.

    • Wildlife Reservoirs: Wild rodents act as "hyper reservoirs" for multiple zoonoses.

  • One Health Initiative: WHO pilot programs integrating targeted chemotherapy in high-prevalence areas with community education and environmental monitoring.



Prevention

  • Easily preventable with proper sanitation and hygiene

  • most are easily cured with proper medication

  • but most are in tropical/poorer areas, that suffer with socio-economic problems to tackle the issue of prevention and management. Also creates a lack of cases reported, preventing needed monitoring.

  • With intense tourism and globalisation, likelihood of spread

Therapeutic Use of Parasitic Zoonoses

  • Cancer Treatment: Plasmodium induces an innate immune response and lowers angiogenesis (vessel formation). Combined with gemcitabine, it has shown synergistic inhibitory effects on tumor growth and metastasis in murine lung cancer models.

  • Helminthic Therapy: Using flatworms/trematodes to treat autoimmune disorders (Crohn's, Ulcerative colitis, Coeliac disease, MS, Asthma) by lowering the host's immune response.

    • limited side effects observed