Introduction to Immunology and Parasitology

Parasitology

• Parasitology: the study of parasites, their hosts, and the relationships between them
• Medical parasitology: focuses on parasites that affect humans and their medical significance

Symbiosis

• Symbiosis: the living together of unlike organisms that involve protection or other advantages to one or both organisms
• Types of symbiosis:
  • Mutualism: both organisms benefit
  • Commensalism: one organism benefits, the other is not affected

Parasitism

• Parasitism: one organism lives on or in another, depending on the latter for its survival, usually at the expense of the host
• Types of parasites:
  • Obligate parasites: require a host to complete their life cycle
  • Facultative parasites: can exist in a free-living state or become parasitic when needed
  • Accidental or incidental parasites: establish themselves in a host where they do not normally live
  • Spurious parasites: free-living organisms that pass through the digestive tract without infecting the host

Hosts

• Definitive or final host: the host in which the parasite attains sexual maturity
• Intermediate host: harbors the asexual or larval stage of the parasite
• Paratenic host: the parasite does not develop further, but remains alive and can infect another susceptible host

Vectors

• Vectors: responsible for transmitting parasites from one host to another

Modes of Transmission

• Foodborne
• Skin penetration
• Bites of arthropod vectors
• Congenital transmission
• Inhalation of airborne eggs
• Sexual intercourse

Life Cycle

• Refers to the development of a parasite in its earliest form and its survival and development in the outside environment and within a host
• May be simple or complex, involving one or multiple hosts

Epidemiology

• Study of the occurrence and distribution of disease in human populations and communities
• Important indicators:
  • Prevalence: the number of cases of a disease present in a population at a given time
  • Incidence: the number of new cases that develop in a period of time

Control, Prevention, and Treatment

• Preventive control measures: designed to break the transmission cycle
• Treatment options: antiparasitic medications and therapies

Zoonotic Parasites

• Diseases passed from animals to humans or vice versa
• Examples:
  • Trypanosoma cruzi (Chagas disease)
  • Babesia ( protozoa found in RBC)
  • Leishmania (vector-borne parasite)
  • Giardia (waterborne parasite)
  • Cryptosporidium (waterborne parasite)

Protozoan Infections

• Entamoeba histolytica (amoeboisis)
• Acanthamoeba (free-living pathogenic amoeba)
• Naegleria (free-living pathogenic amoeba)
• Giardia lamblia (intestinal parasitic protozoan)
• Trichomonas vaginalis (parasitic protozoan)

Malaria

• Caused by Plasmodium (carried by Anopheles mosquito)
• Major symptoms:
  • Unarousable coma
  • Acidemia/acidosis
  • Severe normochromic normocytic anemia
  • Renal failure
  • Pulmonary edema/ARDS
• Diagnosis:
  • Peripheral blood smears
  • Rapid diagnostic tests
  • ELISA
• Treatment:
  • Artemisinin-based combination therapy
  • Atovaquone-proguanil
  • Chloroquine
  • Primaquine

Leishmaniasis

• Caused by diploid protozoa (vector: sandfly)
• Pathogenesis and clinical manifestations:
  • Cutaneous leishmaniasis
  • Diffuse cutaneous leishmaniasis
  • Mucocutaneous leishmaniasis
  • Visceral leishmaniasis

Coccidians

• Spore-forming, single-celled obligate intracellular protozoa
• Members of Phylum Apicomplexa
• Infect intestinal tract of invertebrates and vertebrates including humans

Cryptosporidium

• All stages of development are completed in the gastrointestinal tract of the host
• Oocysts are infectious and can be passed out in feces
• Diagnosis:
  • Stool examination
  • Indirect fluorescent antibody
  • Enzyme immunoassay
  • DNA probes
  • Acid-fast staining

Toxoplasmosis

• Caused by Toxoplasma gondii (coccidian)
• Infective stages: tachyzoites, bradyzoites, and oocysts
• Life cycle: schizogony, gametogony, and sporogony in intestinal epithelium
• Pathogenesis and clinical manifestations:
  • Encephalitis
  • Myocarditis
  • Pneumonia
  • Hepatitis
  • Splenomegaly
  • Stillbirth and abortion### Sarcosporidiosis or Sarcocystosis

• Caused by intracellular protozoa that infect humans and animals worldwide • Life cycle: • Merozoites penetrate muscle cells • Developed merozoites can be ingested by humans through raw or improperly cooked meat • Passed into the intestine, causing damage through circulation to different parts of the body • Fertilization occurs, and the parasite exits the host • Sporocysts and oocysts are passed through feces • If stages are in soil, and animals feed on sporocysts, the parasite ruptures and enters endothelial cells, undergoing schizogony and merozoites penetrate muscle cells • Affects animal movement • Pathogenesis and clinical manifestations: • Invasive forms: vasculitis, myositis, and may involve various tissues • Intestinal form: nausea, abdominal pain, diarrhea • Other symptoms: anorexia, nausea, abdominal pain, diarrhea, vomiting, tachycardia

Babesia spp. (Hemolytic Parasite)

• Caused by hemolytic parasite, causing babesiosis • Life cycle: • Mammalian hosts: merogony in RBC • Tick vector: gamogony in gut and epithelium • Sporogony accompanied by multiple fission in various cells and organs, forming sporokinetes and infective sporozoites • Merozoites form tetrads, transferred via blood transfusion • Within the tick: • Picks up through blood meal and ingests gametes • Gamete fertilization occurs, and enter salivary gland (sporogony), producing sporozoites • Injected into human or rat host

Liver Flukes (Fasciola spp.)

• Large digenetic trematodes found in liver and biliary passages of humans and ruminants • Life cycle: • Metacercaria exists in duodenum or jejunum • Release juvenile fluke that penetrate intestinal wall until peritoneal cavity • Wander until reaching the capsule of Glisson (outer layer of liver) and enter liver • Unembryonated egg carried by bile through sphincter of Oddi into intestine • Eggs mature in water (9-15 days) and transform into miracidium • Miracidium will look for its first intermediate host (snail) • Life cycle in snail: • Miracidium turns into sporocyst, then 1-2 generations of redia, producing cercaria • Cercariae will leave (5-6 weeks at night) and attach to aquatic plants to become metacercariae • Pathogenesis: • Acute stage: asymptomatic, dyspepsia, fever, RUQ abdominal pain, sudden onset of fever, hepatomegaly, marked eosinophilia • Chronic stage: asymptomatic, worm obstruction may stimulate inflammation of biliary epithelium, causing fibrosis, atrophy of liver parenchyma, and periductal cirrhosis • Ectopic sites of parasite migration: lungs, subcutaneous tissue, brain, orbit • Unusual form of fascioliasis: ingestion of raw Fasciola-infected liver, causing hemorrhagic nasopharyngitis and dysphagia

Clonorchis sinensis (Oriental Liver Fluke)

• Located in bile duct and gallbladder of humans and fish-eating mammals • Mode of transmission: ingestion of metacercaria present in infected raw or undercooked fish • Excyst in duodenum, and young flukes proceed to ampulla of Vater to common bile duct • Adult worms attach to bile duct mucosa by their suckers, embedding without forming a permanent epithelial lining ulcer • Eggs move to intestine together with bile, then wait to be excreted out of the body • Miracidium hatches after eggs are ingested by the first intermediate host (snail) • Pathogenesis: • Phases: desquamation of epithelial cells, hyperplasia and desquamation of epithelial cells, and adenomatous tissue formation • Light infection: asymptomatic, nonspecific clinical signs • Moderate infection: fever, diarrhea, inappetence, rash, edema, night blindness, swollen abdomen, hepatomegaly • Heavy infection: acute pain in RUQ of the digestive system • Chronic stages: liver malfunction, and more severe late complications

Lung Fluke (Paragonimus spp.)

• Adult stage: 7.5-12mm x 4-6mm, reddish-brown, with a tegument covered in scale-like spines • Adult worms reside in lungs, encapsulated in pairs by granuloma • Eggs are trapped by surrounding tissues, but can escape through air passages, and are swallowed and packed through the alimentary canal, then out of feces • Miracidia develop into sporocysts, then redia, then cercaria inside the snail • Cercariae enter the second intermediate host (mountain crab) • DH eats mountain crab, and worms excyst in duodenum, penetrate intestine, and embed in abdominal wall • Pathogenesis: • Larvae migrate for 1 week • Adult worms induce an inflammatory granulomatous response in lungs, generating a fibrous cyst • Symptoms: asymptomatic, chronic cough, hemoptysis, chest pain, dyspnea, low-grade fever, fatigue, generalized myalgia, and chronic bronchiectasis • Manifestations: cutaneous paragonimiasis, cerebral paragonimiasis (most severe)

Blood Fluke (Schistosoma spp.)

• Embryonated egg from DH's stool will hatch into free-swimming miracidia in 2-4 hours in water • Miracidia infect snail IH and develop sporocysts • Sporocysts reproduce asexually, producing free-swimming cercariae • Cercariae penetrate DH's skin, lose tails, and transform to schistosomula • Schistosomula differentiate into male and female • Pathogenesis: • Swimmer's itch: cercarial penetration of skin with dermatitis and pruritus • Schistosomule migration: snail fever or katayama fever/syndrome • Chronic schistosomiasis: prolonged infection, liver cirrhosis, kidney damage, urinary bladder damage, and hepatosplenomegaly • 3 stages of clinical course of schistosomiasis infection: incubation, period of early egg deposition and extrusion, and period of tissue proliferation • Diagnosis: examination of stool and/or urine for ova, review of history of travel or residency history, and serological test for antischistosomal antibody • Treatment: praziquantel (most effective against adult worm)

Tapeworms (Phylum Nemathelminthes or Nematoda)

• General characteristics: elongated, cylindrical worms, frequently attenuated at both ends • Sexes are separate, male frequency being considerably smaller than female • Complete digestive tract • Free-living, with IH necessary for larval development of some forms • Intestinal and tissue-inhabiting species in humans • Two classes based on chemoreceptors: phasmidia (possess caudal chemoreceptors) and aphasmidia (lack caudal chemoreceptors)

Ascaris Lumbricoides

• Most common intestinal nematode • Also known as giant roundworm (most frequent in tropics) • Soil-transmitted helminth, meaning soil plays a major role in development and transmission • Epidemiology: 807 million to 1.2 billion people are infected • Mode of transmission: ingestion of embryonated egg/ova • Life cycle: direct (egg -> larva -> adult) • Diagnostic stages: ova/egg in stool, adult worm • Pathology: varying degrees of tissue reaction to invading larvae and intestinal irritation to adult • Pathogenesis: bowel obstruction with fever and malaise, vomiting, pneumonitis during larva migration to lungs, intestinal perforation, occlusion of appendix, lactose maldigestion or intolerance, eosinophilia during period of tissue migration, and increased IgG and IgE • Clinical manifestations: asymptomatic, abdominal discomfort, gut obstruction, impaired growth (children), and cough • Diagnostic tests: direct fecal smear, Kato technique or cellophane thick smear, Kato-Katz, concentration techniques, radiography, and cholangiograms • Treatment and prevention: albendazole and mebendazole### Treatment of Intestinal Nematodes

• Antidiarrheal and anthelminthic drugs are used to treat intestinal nematodes.
• Anthelminthic drugs include mebendazole and albendazole.
• Electrolyte replacement and a high protein diet are also recommended.

Dracunulus medinensis (Guinea Worm)

• The only helminthic parasite transmitted solely through water.
• Transmission occurs during drought when people are forced to drink from the same stagnant water supplies or pay for well water.
• Three conditions are required for the life cycle: skin contact with water, water containing appropriate microcrustacean (copepod), and water used for drinking.
• The parasite is believed to feed on blood due to the presence of dark brown gut material.
• Diagnosis is made from a local blister, worm, or larvae.
• The worm can be seen under the skin.
• Treatment involves drug therapy with metronidazole.
• Anti-inflammatory medication is used to help extract the adult worm.
• The worm is extracted by rolling it a few centimeters per day, which can take weeks or months.
• Exposing the area to cold water can help remove the worm faster.
• Infection does not provide immunity.

Trichinella spiralis (Muscle/Trichina Worm)

• A parasitic worm that infects carnivorous mammals, such as rats and swine fed uncooked garbage.
• Humans get infected from eating uncooked pork.
• The final host is swine, and the dead-end host is humans.
• The habitat is the small intestines (adult form) and striated muscles (larvae).
• The worm is whitish in color, measuring 1.5 x 3.5 mm by 0.04 to 0.06 mm.
• The male worm is 1.5 mm by 0.04 mm, with a single testis located near the posterior end of the body.
• The female worm measures 3.5 mm by 0.06 mm.