12-2-09 Parasitology I (Introduction to parasites) Starting points: Incidence of parasitic infections has actually increased in recent years due

to immunosuppression from the AIDS epidemic. Many parasitic infections are zoonotic, or passed from animals to humans. The human disease may or may not resemble the disease in the animal host. Parasites go through several developmental stages that bear little resemblance to one another. Each has its distinct structure and biochemical/antigenic composition. Ex: Toxoplasma gondii is an intestinal coccidian in cats, but localizes in deep tissues (as a different form) in humans Parasitic infections tend to be chronic, lasting months to years. Repeated exposure to the same parasite will result in ever-increasing parasite burden. The duration of exposure and inoculum size greatly determine disease-causing potential. 1. Explain basic terminology, such as the difference between infection and infestation, and definitive host and intermediary host. Where parasites do their dirty work: Infection refers to a parasite present in the internal organs or tissues. Most common routes of infection include oral and penetration through the skin. Parasites that cause infection are called endoparasites. Infestation refers to a parasite that exists externally on hair, skin, or clothing. Such parasites are called ectoparasites. Three types of hosts: Definitive hosts are where parasites undergo sexual reproduction Intermediate hosts are where parasites undergo a larval stage of reproduction, but do not undergo sexual reproduction Parentic hosts are where parasites simply pass through and do not undergo sexual reproduction or larval development Note: Parasites are particularly adept ad avoiding host defense mechanisms. How parasites cause damage: 1. toxic products like hydrolytic enzymes 2. mechanical damage like blockage of internal organs, migration through tissue, and pressure atrophy 3. immunopathology like autoimmune/hypersensitivity reactions and fibrosis Parasite pathogenesis: parasites either develop rapid infection with quick mortality N. fowleri causing primary amoebic meningoencephalitis

P. jiroweci causing pneumocystosis Or develop chronically and do not cause problems unless they are left untreated Moreover, it is possible for severe sensitization reactions to occur when worms and/or larvae die in the host. Consequently, drugs used to treat worms may have a toxic effect by proviking such hypersensitivity reactions when killing the parasite.

Time course of parasite infection: Incubation period: time between acquisition of parasite and appearance of symptoms. Highly variable. Prepatent period: time between acquisition of parasite and shedding of eggs, larvae, or microfilia. Patent period: tie during which the diagnostic stages are shed (does not necessarily correlate with symptoms). 2. Name representative protozoan parasites according to their main localization in patients (intestinal protozoa, urogenital protozoa, blood, and tissue parasites). Note: protozoa are unicellular eukaryotes. All higher animals are infected with one or more species, indicating that many protozoa are commensals. Protozoa pass through several life stages: Trophozoites: protozoa that are parasitic, actively feeding and multiplying. Subdivided in amastigote, promastigote, epimastigote, and trypomastigote; tachyzoite and bradyzoite in T. gondii. Cysts: protozoa that have a protective membrane or thickened wall A single protozoan in a host has the potential to produce an immense population in the host, especially if s/he is immunocompromised. Think malaria, which results from only a few sporozoites of Plasmodium falciparum from the Anopheles mosquito. Protozoa based on localization in people: Intestinal protozoa: Entamoeba histolytica, Giardia lamblia, Cryptosporidium Urogenital protozoa: Trichomonas vaginalis Free-living amoeba: Naegleria fowleri, Acanthamoeba (which is transmsitted in contact lens solution, resulting in corneal ulcers) Intestinal coccidium: Toxoplasma gondii (parasitizes cats and is transmitted congenitally, via uncooked meat, or cat fecal matter to pet owners) Extracellular protozoan: Pneumocystis jiroveci (causes bilateral diffuse pneumonitis in immunocompromised patients with no discernable disease in healthy individuals) Hemoflaggelates: Trypanosoma cruzi (Chagas Disease), Trypansoma brucei (Sleeping Sickness), Leishmania (Cutaneous/Mucocuteaneous and Visceral Leishmaniasis known as Kala-Azar)) Malaria: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale In healthy people, Pneumocystis jiroveci, Toxoplasma gondii, and Cryptosporidium have no effect; consequently, the healthy serve as carriers for these protozoa, which can kill AIDS patients.

More on Chagas Disease Cause: Trypanosoma cruzi Life cycle: amastigotes divide intracellularly into pseudocysts pseudocysts release non-dividing trypomastigotes into the blood bugs take up trypomastigotes; within the bug, trypomastigotes become epimastigotes epimastigotes reproduce to form infective metacyclic trypomastigoes, which are expelled into feces to enter a new host through skin abrasions pathogenesis: inflammation elicited by pseudocyts causes myocarditis and destruction of PNS ganglia, mainly in the heart and myenteric plexus. Autoimmune reaction may also develop. Clinical symptoms: fever, edema, lymphadenopathy, tachycardia, heart enlargement, myocarditis, megaesophagus, megacolon Diagnosis: Chagas has a pretty clear clinical picture; direct demonstration of parasites or serologic tests are definitive Treatment: can only treat Chagas in the acute phase More on Sleeping Sickness Cause: Trypanosoma brucei Life cycle: Trypomastigotes multiply in blood Trypomastigotes are ingested by the tsetse fly, within which they multiply within the salivary glands to infect a new host when the fly bites Pathogenesis: autoimmune inflammation causes CNS demyelination. Parasite also causes immunosuppression, which facilitates secondary infections. Clinical symptoms: chancre, fever, headache, lymphadenopathy, meningoencephalitis, somnolence, death Diagnosis: sampling blood, lymph nodes and CSF and inoculating lab animals; serologic tests Treatment: pentadimine, serologic drugs More on Cutaneous/Mucocutaneous Leishmaniasis Cause: Leishmania sp. Life cycle: Amastigotes divide in host macrophages and other reticuloendothelial cells A sand fly ingests the amastigotes, which multiply into promastigotes Promastigotes migrate to the probsiscus of the sand fly to infect the next host Pathogenesis: lymphatic and hematogenous spread; severity depends on the Leishmania species and immunity of the host Clinical symptoms: skin/mucosal lesions with ulceration; lesions can be self-healing or chronic, localized or spreading Diagnosis: scrapings from lesions; serologic and skin tests Treatment: organic pentavalent antimonials and amphotericin B More on Visceral Leishmaniasis (Kala-Azar)

Cause: Leishmania sp. Pathogenesis: parasite invades reticuloendothelial cells of the liver, spleen, BM, lymph nodes, causing histiocytic hyperplasia and hypertrophy. Hematopoeitic tissues become replaced by macrophages. Clinical symptoms: often self-limiting, but can also be fatal; hepatosplenomegaly, lymphadenopathy, anemia, leucopenia, emaciation Diagnosis: culture parasites from BM and spleen samples; serologic tests Treatment: organic pentavalent antimonials and pentamidine

More on Malaria: Most common cause: Plasmodium falciparum (most dangerous of all the plasmodia) Life cycle: Sporozoites in salivary glands of Anopheles mosquitos are injected into the human host The sporozoites invade liver parenchymal cells, where they mature into liverstage schizonts, which burst to release tons of merozoites, which infect rbcs Within the rbc, the merozoite becomes either a gametocytes or an erythrocytic schizont Gametocytes are the sexual stage that is infectious to the mosquito; upon ingestion, the gametocytes evolve in the mosquito gut into gametes, which undergo fertilization and mature into sporozoites Schizonts are clusters of merozoites, and rupture of a shizont releases merozoites to infect other rbcs Pathogenesis: fever/chills (due to shizoint rbc rupture), sweating, headache, weakness note how malarial symptoms mimic those of a viral infection. Later severe disease presents as anemia, renal failure, multisystem failure, and an abnormal level of consciousness. Diagnosis: blood smear to ID plasmodia Treatment: resistance to chloroquinones!; use mefloquine, pyerimethamine/sufadoxine (Fansidar), quinine, quinidine, halofantrine, artemisinin derivatives. 3. Understand frequently used methods for the diagnosis of parasitic infections. See above (lots of culturing to demonstrate existence of parasites, serologic tests)