Parasites I

Neglected Tropical Diseases

Tropical infections endemic in low-income populations

Most prevalent neglected tropical disease

Soil Nematodes (3 Diseases)

Parasitism

Symbiotic relationship that benefits one organism while harming the host

Biological Parasite

Organism that grows, feeds, and is sheltered in/on a host organism (harming the host)

Medical Parasite

Organism that causes disease in humans not including fungi, viruses, bacteria

Endoparasite

Infection inside the host

Ectoparasite

Infestation on the surface of the host

Lumenal Parasite

Parasite found in the intestines or urogenital tract; opposite to blood/tissue parasite

Host

Exploited partner in a parasitic relationship

Definitive Host

• Host in which the obligate sexual stage of parasite’s life cycle occurs

Examples of Definitive Hosts

• Humans and beef tape worm

• Mosquitoes and malaria

Intermediate Host

Host in which non-sexual reproduction/development occurs

Examples of Intermediate Host

• Cows and beef tape worm

• Humans and malaria

Incidental Host

Host that isn’t needed for the parasite’s life cycle (common in zoonoses)

Example of Intermediate Host

Humans and Toxoplasma

Reservoir

Animal hosts that maintain natural parasite cycle in the wild

Example of a Reservoir

Beaver and Giardia

Transmission

Mode by which infection is spread between or within a host

Direct Transmission

Infection is spread via exchange of bodily fluids (Trichomonas)

Ingestive Transmission

Oral infection by dormant cyst or egg in food/environment (Giardia/Tapeworm)

Protozoan Cyst

• Environmentally stable, non-replicating form involved in fecal/oral transmission (Giardia, Toxoplasma, Entamoeba)

• Slow, replicating tissue form (Toxoplasma)

Helminth Cytst

Dormant, juvenile (larvae) form in host tissue; undercooked meat (Tapeworm)

Egg

Product of sexual reproduction by adult worms; single pre-larval form, fecal/oral (Trichuris - Whipworm; Ascaris - Roundworm)

Invasive Transmission

Infection spread by direct penetration of skin (Schistosoma/Hookworm)

Vector Transmission

Infection spreads in active, non-replicating form by blood-sucking arthropod (Mosquitos)

Maternal Transmission

Trans-placental spread of infection from mother to fetus (vertical)

Vector

Host species that transmits an infectious form of a parasite to another host

Biological Vector

Essential for the life cycle of a parasite

Phoretic/Mechanical Vector

A host that transmits a parasite without being essential to its life cycle

Epidemiology

Study of factors/conditions that control the spread of disease

Geographic Distribution

Maximum global extent of a disease no matter intensity

Prevalence

Disease intensity in an area (% susceptible); sporadic, endemic, epidemic

Incidence

New infections in a population in a given time

What is the challenge in giving drug therapies for parasites?

They use the same pathways as human cells; like chemotherapy

Which are the hardest organisms to treat?

Protozoa; most similar to human cells = lethal and rapid drug resistance

Parasites Associated with HIV

1. Toxoplasma gondii

2. Cryptosporidium hominis

Trichomoniasis

Sexually transmitted infection caused by Trichomonas vaginalis in the urogenital tract; common in women

T. vaginalis Life Cycle

Single stage that includes trophozoite and no cyst stage; reliant on human

Symptoms of Trichomoniasis in Women

• Vaginitis: burning and itching

• Inflammation

• Frothy, fishy discharge

Symptoms of Trichomoniasis in Men

• Often asymptomatic

• Infection of urethra and prostate

• Mild discharge

Does infection with T. vaginalis provide immunity?

No, an infection may still develop again

Giardiasis

GI infection (intestinal) caused by Giardia lamblia spread by the fecal/oral route; direct transmission via anal sex

Life Cycle of G. lamblia

1. Cyst is ingested by human

2. Excystation → Trophozoite in the intestines

3. Replication by binary fission

4. Encystation for excretion into environment

Symptoms of Giardiasis

• Non-bloody diarrhea, flatulence, cramps, nausea

• Onset of 2 weeks, can be acute or chronic

• Malabsorption Syndrome

Is reinfection with G. lamblia possible?

Yes, it’s possible to be reinfected but humoral immunity has been seen

Amebiasis

Infection caused by Entamoeba histolytica that is usually in the intestines but can be invasive

Transmission of E. histolytica

• Ingestive (fecal/oral)

• Direct (anal sex)

Amebiasis in the US

• Endemic because of poor hygiene and anal sex

• Epidemic due to poor water purification

Life Cycle of E. histolytica

1. Ingestion of cysts (fecal contamination)

2. Trophozoites form in colon

3. Cysts and Trophozoites excreted in feces

Possible Progression of Amebiasis

Asymptomatic/mild → Dysentery → Invasive

Symptoms of Amebiasis Carriers

Can be chronic for months, shedding cysts without symptoms

Symptoms of Amebiasis Dysentery

Bloody diarrhea, submucosal ulcers in colon

Symptoms of Invasive Amebiasis

Rare; spread to liver (HEPATIC), abscesses can be found all over (lung, brain, skin, anus, etc.)

Immunity and Amebiasis

Humoral immunity for invasive disease; acquired immunity possible in endemic areas

Types of Kinetoplastid Protozoa

1. Leishmania

2. Trypanosoma cruzi - Chagas disease

3. Trypanosoma brucei - African Sleeping Sickness

Leishmaniasis

Disease in the blood and tissues caused by vector-borne Leishmania

Vector for Leishmaniasis

Sandfly

Reservoir for Leishmaniasis

Domestic/wild animals

Life Cycle of Leishmaniasis

Cysts are ingested by sandflies, where they develop into infective forms before being transmitted to mammals

Types of Leishmaniasis Diseases

1. Cutaneous

2. Mucocutaneous

3. Visceral

Symptoms of Cutaneous Leishmaniasis

• Ulcer/sore at infection site; satellite lesions

• Amastigotes in lesion

• Healing leading to scarring

Symptoms of Mucocutaneous Leishmaniasis

• Metastasis after primary lesion heals

• Nasopharyngeal ulcers, amastogotes

• Immunity with chemotherapy

Symptoms of Visceral Leishmaniasis

• Spread to organs, normally without lesions

• Fever, wasting, hepatomegaly

• Immunity with chemotherapy

African Trypanosomiasis (African Sleeping Sickness)

Parasitic disease caused by T. brucei in the blood, lymphatics, and tissues spread by tsetse flies as a vector

Where is African Typanosomiasis found?

Only in the sub-Saharan as an endemic disease; epidemic in social turmoil

Life Cycle of T. brucei

1. Procyclic in the midgut of a Tsetse Fly

2. Metacyclic in salivary glands of Tsetse Fly

3. Long, slender → Short, stumpy in Mammal Blood

Symptoms of African Trypanosomiasis

• Self-healing chancre; dissemination

• Parasitemia with fever

• Lymphadenopathy (Winterbottom)

• CNS Infection (edema, sleepy, dementia)

• Death

How does T. brucei evade immune defense?

Antigenic Variation; changing antigens to cause parasitemia, halt it, then maximize transmissibility after peak of parasitemia

Virulence Factor of T. brucei

Variant Surface Glycoprotein (VSG): barrier covering surface

South American Trypanosomiasis - “Chagas Disease”

Intracellular vector-borne infection in blood, lymphatics, and tissue caused by Trypanosoma cruzi

Vector for South American Trypanosomiasis

Reduvid bugs

Where is South American Trypanosomiasis found?

Endemic in SA (rural and urban); infected reduvids can be in the US

Life Cycle of T. cruzi

1. Reduvids feed on blood containing Trypomastigotes

2. Epimastigotes multiple in gut of reduvid

3. Metacyclic phase → passed in feces

4. Invade intracellularly as amastigotes

Symptoms of South American Trypanosomiasis

• Acute

  • Fever, chagoma (Romana’s sign); severe in children (death)

  • Trypomastigotes present

• Chronic

  • No circulating trypomastigotes; amastigotes present

  • Damage nerve/muscle cells of colon, heart, esophagus

  • Death from heart attack

  • Inflammation, autoimmunity

Important Apicomplexans

1. Toxoplasma gondii

2. Plasmodium spp

Characteristics of Apicomplexans

• Obligate intracellular

  • Apical intracellular organelles used for invasion

• Lifecycles alternate between:

  • Asexual (schizogony) and sexual (sporulation)

Where is the sexual cycle in Toxoplasma?

Felines

Where is the sexual cycle in Plasmodium?

Mosquitoes

Toxoplasmosis

Parasitic infection in tissue/blood caused by Toxoplasma gondii transmitted by ingestive or transplacental routes

Where is T. gondii found?

Worldwide; commonly in cat feces and undercooked meat

Natural Toxoplasma Life Cycle

1. Development of sporozoites in oocyst

2. Intermediate host (rat/mouse) ingests oocyst

3. Transmitted to definitive host (feline) where reproduction occurs

4. Shedding of oocyst

Incidental Toxoplasma Life Cycle

1. Oocyst consumed by animal

2. Human eats infected animal meat that is undercooked

Two Phases of Toxoplasma Infection

1. Tachyzoite (fast)

2. Bradyzoite (slow)

Tachyzoite Stage

• Rapid replication in acute infection

• Reactivate dormant cysts

• Can cross placenta

• Controlled by primary immune response (failure in immunocompromised)

Bradyzoite Stage

• Encysted slow growth (dormant)

• Source of reactivation

• Memory immune response control (not in immunocompromised)

How does a tachyzoite divide?

Endodyogeny: two daughter cells form inside a parent cell

Symptoms of Toxoplasmosis

• Initially asymptomatic

• Controlled by humoral immunity

  • Not for the immunodeficient (HIV), causes encephalitis and seizure

• Life-long latent infection

• Maternal primary infection causes in-utero infection

Malaria

Parasitic infection caused by Plasmodium in hepatocytes/erythrocytes transmitted by female mosquito vectors

Transmission of Malaria

• Female mosquito vector

• Congenital

• Needle sharing

What is the reservoir of Malaria?

Humans

Epidemiology of Malaria

• Cosmopolitan areas

• Children most risk for death

• Increasing drug resistance

• P. falciparum is biggest causative agent

Stages of Malaria Life Cycle

1. Erythrocyte Cycle (Asexual)

2. Sexual Cycle

3. Liver Cycle (Asexual)

Malaria Erythrocyte Cycle

Involved gamete → zygote → oocyst that is ingested by mosquito → sporozoite in salivary gland → transmitted to human → Hypnozoite in P. vivax and P. ovale only → Merozoites go to erythrocyte → release of gametocyte after rupture

Symptoms of Malaria

• Fever cycle, bursts of merozoites (P. falciparum has broad bursts)

• Anemia (erythrocyte destruction)

• Myalgia, splenomegaly

• Cerebral malaria (P. falciparum ONLY)

• Latent hepatic for P. vivax and P. ovale

Fever Cycles of Malaria

1. P. falciparum - Malignant Tertian

2. P. vivax/ovale - Tertian

3. P. malariae - Quartan

Identifying Feature of Human Malarias

• Banana-shaped gametocytes

• No trophozoites/schizonts

• RBC multiple ring stages

Malaria Immunity

Only temporary and slowly developed in endemic areas, reinfection is easy

Types of Platyhelminthes

1. Cestoda

2. Trematoda

Cestoda

• Tapeworms (flat, segmented - proglottid body)

  • Proglottids allow for hermaphroditic reproduction

• Nutrient absorption (no internal digestion)

• Attachment by scolex to host gut

• Transmit by larvae or egg (worse)

Trematoda

• Flukes in lungs, blood, liver

• Broad, flat bodies

• Simple digestion (one opening)

• Has intermediate hosts (snail)

• Invasive or ingestive