Pathogenesis of Parasitic Disease PDF

Chapter 77.82 Pathogenesis of Parasitic Disease Protozoan & helminthic disease – is highly variable – organisms themselves are not highly virulent – Unlike many bacterial and viral parasitic infections are often chronic, lasting months to years – severity of illness depe...

Chapter 77.82 Pathogenesis of Parasitic Disease Protozoan & helminthic disease – is highly variable – organisms themselves are not highly virulent – Unlike many bacterial and viral parasitic infections are often chronic, lasting months to years – severity of illness dependent on – the dose and the # of organisms acquired over time – virtually always acquired from an exogenous source – acquired via the bites of arthropod vectors  Factors Associated with Parasite Pathogenicity Factors – Infective dose and exposure – Penetration of anatomic barriers – Attachment – Replication – Cell and tissue damage – Disruption, evasion, and inactivation of host defenses  Parasite Ports of Entry Route Examples Ingestion Giardia spp., Entamoeba histolytica, Cryptosporidium spp., cestodes, nematodes Direct Penetration Arthropod bite Malaria, Babesia spp., filaria, Leishmania spp., trypanosomes Transplacental penetration Toxoplasma gondii Organism-directed penetration Hookworm, Strongyloides spp., schistosomes  Immunopathologic Reactions to Parasitic Disease Reaction Mechanism Result Example Type 1: anaphylactic Antigen + IgE antibody Anaphylactic shock, Helminth infection, attached to most cells: bronchospasm, local African histamine release inflammation trypanosomiasis Type 2: cytotoxic Antibody + antigen on Lysis of cell-bearing Trypanosoma cruzi cell surface: microbial antigens infection complement activation or antibody-dependent Type 3: Antibody +cellular cytotoxicity Inflammation and tissue Malaria, immune extracellular antigen damage; complex deposition in schistosomiasis, complex complex glomeruli, joints, skin vessels, trypanosomiasis brain; glomerulonephritis, and vasculitis Type 4: cell- Sensitized T-cell Inflammation, mononuclear Leishmaniasis, mediated reaction with antigen, accumulation, macrophage schistosomiasis, (delayed) liberation of activation; tissue damage trypanosomiasis lymphokines, triggered cytotoxicity  Microbial Interference with or Avoidance of Immune Defenses Type of Interference Mechanism Examples Antigenic variation Variation of surface antigens African trypanosomes, within the host Plasmodium spp., Babesia spp., Giardia spp. Molecular mimicry Microbial antigens mimicking Plasmodium spp., host antigens, leading to poor trypanosomes, schistosomes antibody response Concealment of antigenic site Acquisition of coating of host Hydatid cyst, filaria, (masking) molecules schistosomes, trypanosomes Intracellular location Failure to display microbial Plasmodium spp. (RBC), antigen on host cell surface trypanosomes,Leishmania Inhibition of phagolysosomal Trypanosoma cruzi fusion pp., Toxoplasma spp. Immunosuppression degradation of immunoglobulins Trypanosomes, Plasmodium spp.; schistosomes  Laboratory Methods for Diagnosing Parasitic Disease Macroscopic examination: Wet mount , Permanent stains – Stool concentrates Serologic examination : Antibody response & Antigen detection Nucleic acid hybridization – Probes and amplification techniques , Detection – Identification Culture Animal inoculation Xenodiagnosis :exposing a parasite-free normal host to the parasite and then examining the host for parasites  Chapter 81 Intestinal and Urogenital Protozoa Protozoa may colonize and infect the – oropharynx, duodenum and small bowel, colon, and urogenital tract of humans – Amebae, flagellates; ciliate, coccidian, or microsporidian parasites – These organisms are transmitted by the fecal-oral route In the United States outbreaks of diarrhea caused by Giardia or Cryptosporidium species The spread – be controlled in part by improved sanitation and by chlorination and filtration of water supplies  Life cycle of Entamoeba histolytica Intestinal amebiasis develop clinical symptoms related to the localized tissue destruction in the large intestine The main source of water and food contamination is the asymptomatic carrier who passes cysts The prevalence of infection in the United States is 1% to 2% Patients infected with E. histolytica pass noninfectious trophozoites and the infectious cysts in their stools cysts can be transmitted by oral-anal sexual practices, with amebiasis prevalent in homosexual populations. Direct trophozoite transmission in sexual encounters can produce cutaneous amebiasis Treatment The identification of E. histolytica trophozoites Acute infection: and cysts in stools and trophozoites in tissue metronidazole, followed by iodoquinol, is diagnostic of amebic infection diloxanide furoate, or paromomycin  Entameoba histolytica* Entameoba coli Size (diameter, μm) Trophozoite 12-50 μm 20-30 μm Cyst 10-20 μm 10-30 μm Pattern of peripheral nuclear Fine, dispersed ring Coarse, clumped chromatin Karyosome Central, sharp Eccentric, coarse Ingested erythrocytes Present Absent Cyst Structure No. of nuclei 1-4 1-8 Chromatoidal bars Rounded ends Splintered, frayed ends (A): Entamoeba histolytica trophozoite (B): cyst : Trophozoites are motile and vary in size from 12 to 60 μm (average, 15 to 30 μm). The single nucleus in the cell is round with a central dot (karyosome) and an even distribution of chromatin granules around the nuclear membrane. Ingested erythrocytes may be in the cytoplasm. The cysts are smaller (10 to 20 μm, with an average size of 15 to 20 μm) and contain one to four nuclei (usually four). Round chromatoidal bars may be in the cytoplasm.  Flagellates The flagellates of clinical significance include – Giardia lamblia (duodenalis/intestinalis) has trophozoites and cyst forms – Dientamoeba fragilis: No cyst form – Trichomonas vaginalis: No cyst form Diseases – primarily the result of mechanical irritation and inflammation – For example, G. lamblia attaches to the intestinal villi with an adhesive disk, resulting in localized tissue damage Life cycle of Giardia lamblia Infection with G. lamblia is initiated by ingestion of 10 to cysts The trophozoites can attach to the intestinal villi by a prominent ventral sucking disk spread of disease beyond the gastrointestinal tract is very rare person-to-person spread by the fecal-oral or oral-anal route. The cyst stage is resistant to chlorine concentrations (1 to 2 parts per million) used in most water-treatment facilities Infection with G. lamblia is initiated by ingestion of cysts Giardia lamblia trophozoite (A) and cyst (B). Trophozoites are 9 to 12 μm long and 5 to 15 μm wide. Flagella are present, as are two nuclei with large central karyosomes, a large ventral sucking disk for attachment of the flagellate to the intestinal villi, and two oblong parabasal bodies below the nuclei. The morphology gives the appearance that the trophozoites are looking back at the viewer. Cysts are smaller-8 to 12 μm long and 7 to 10 μm wide. Nuclei and parabasal bodies  Giardia lamblia (duodenalis) trophozoite (A) and cyst (B). Flagella, two nuclei with large central karyosomes are present. A large ventral sucking disk for attachment of the flagellate to the intestinal villi, and two oblong parabasal bodies below the nuclei. Four nuclei and four parabasal bodies are present Life cycle of Trichomonas vaginalis This parasite has worldwide distribution, with sexual intercourse as the primary mode of transmission Rarely: by fomites (toilet articles, clothing) of trophozoites Infants through the mother's infected birth canal Diagnosis The microscopic examination of vaginal or urethral discharge for characteristic trophozoites is the diagnostic method of choice. Stained (Giemsa, Papanicolaou) Culturing the organism (93% sensitivity) or using monoclonal fluorescent antibody staining (86% sensitivity). A nucleic acid probe assay is also available commercially. Serologic tests may be useful in epidemiologic surveillance.  T. vaginalis is not an intestinal protozoan but rather the cause of urogenital infections Prevalence in developed countries is 5% to 20% in women and 2% to 10% in men. Most infected women are asymptomatic or have a scant, watery vaginal discharge Treatment The drug of choice is metronidazole. No cyct form More recently, tinidazole has received U.S. Food and Drug Administration The flagella and a short, undulating (FDA) approval for treatment of membrane are present at one side, and an trichomoniasis Personal hygiene, axostyle extends through the center of the avoidance of shared toilet articles and clothing, and safe sexual practices are parasite important preventive actions Life cycle of Balantidium coli Balantidium coli : the only member of the ciliate group that is pathogenic for humans. Disease produced by B. coli is similar to amebiasis Symptomatic disease is characterized by abdominal pain and tenderness, tenesmus, nausea, anorexia, and watery stools with blood and pus Microscopic examination of feces for trophozoites and cysts is performed Treatment tetracycline; iodoquinol and metronidazole are alternative antimicrobials  Sporozoa or Coccidia Sporozoa – constitute a very large group called Apicomplexa or Coccidia – Are intestinal parasites and others with the blood and tissue parasites – the existence of asexual (schizogony) and sexual (gametogony) reproduction The intestinal Sporozoa Cystoisospora (formerly Isospora), Sarcocystis, Cryptosporidium, and Cyclospora species The blood and tissue parasites – Plasmodium species, Leishmania species and Trypanosoma species Life cycle of Cystoisospora (formerly Isospora) species. Cystoisospora species in patients with acquired immunodeficiency syndrome (AIDS). Infection with this organism follows ingestion of contaminated food or water or oral-anal sexual contact. self- limiting enterocolitis characterized by watery diarrhea without blood Oocyst of Cystoisospora belli containing two sporoblasts. A, Wet mount. B, Acid-fast stain. Oocysts are ovoid (approximately 25 μm long and 15 μm wide) with tapering ends Life cycle of Cryptosporidium species Cystoisospora species cause infection in the deep intracellular invasion observed but Cryptosporidium organisms are found just within the brush border of the intestinal epithelium Infection is reported in a wide variety of animals, including mammals, reptiles, and fish Cryptosporidium may be detected in large numbers in unconcentrated stool specimens obtained from immunocompromised individuals with diarrhea Treatment No broadly effective therapy has been developed for managing Cryptosporidium infections in immunocompromised patients Acid-fast stained Cryptosporidium oocysts (approximately 5 to 7 μm in diameter)  Chapter 82 Blood and Tissue Protozoa Medically Important Blood and Tissue Protozoa – Plasmodium species – Babesia species – Toxoplasma species – Sarcocystis species – Acanthamoeba species – Balamuthia species – Naegleria species – Leishmania species – Trypanosoma species  Plasmodium species and malaria Plasmodia are coccidian or sporozoan parasites of blood cells The five species of plasmodia that infect humans are P. falciparum, P. knowlesi, P. vivax, P. ovale, and P. malariae – they require two hosts the mosquito for the sexual reproductive stages humans and other animals for the asexual reproductive stages Malaria – accounts for 1-5 billion febrile episodes – 1 to 3 million deaths annually, (85% in Africa) Life cycle of Plasmodium species Anopheles mosquito introduces infectious plasmodia sporozoites into circulatory system The sporozoites are taken into the liver, where asexual reproduction (schizogony) occurs This phase of growth is termed the exoerythrocytic cycle and lasts 8 to 25 days Rupture of liver liberating the plasmodia (termed merozoites entering initiating the erythrocytic cycle.  Malaria lifecycle Human infection is initiated – bite of an Anopheles mosquito-introduce sporozoites by saliva into the circulatory system – The sporozoites are carried to the parenchymal cells of the liver, where asexual reproduction (schizogony) occurs-exoerythrocytic cycle 8 to 25 days. Some species (e.g., P. vivax, P. ovale) can establish a dormant hepatic phase in which the sporozoites (called hypnozoites or sleeping forms) do not divide The presence of these viable plasmodia can lead to the relapse of infections months to years after the initial clinical disease (relapsing malaria) Rupture of the hepatocytes releases-merozoites -which in turn enter into erythrocytes, thus initiating the erythrocytic cycle Increased numbers of rupturing erythrocytes liberate merozoites, Toxic cellular debris and hemoglobin, into the circulation. Together these produce the typical pattern of chills, fever, and malarial rigors.  Plasmodium species P. vivax is selective and invades only young, immature erythrocytes containing the Duffy blood group antigen – infected red blood cells are usually enlarged and contain numerous pink granules or Schüffner dots, – the trophozoite is ring shaped but amoeboid in appearance, more mature trophozoites and erythrocytic schizonts containing up to 24 merozoites are present, and the gametocytes are round. – The mature schizonts often contain golden-brown hemozoin pigment granules (malarial pigment) These characteristics are helpful in identifying the specific plasmodial species, which is important for the treatment of malaria  Human Malarial Parasites Parasite Disease Plasmodium vivax Benign tertian or vivax malaria P. ovale Benign tertian or ovale malaria P. malariae Quartan or malarial malaria P. falciparum Malignant tertian or falciparum malaria  Diagnosis and treatment Microscopic examination of thick and thin films of blood – identifying the specific species responsible for disease. Serologic procedures are available – primarily for epidemiologic surveys Treatment – is based on the history regarding travel to endemic areas Chloroquine drug of choice but Chloroquine-resistant strains of P. falciparum are present in all areas of endemicity (Africa, Southeast Asia, South America) P. vivax infection – a combination of supportive measures and chemotherapy – Bed rest, relief of fever and headache, regulation of fluid balance – blood transfusion are supportive therapies Plasmodium vivax ring forms and young trophozoites. Note the multiple stages of the parasite (rings and trophozoite) seen in the peripheral blood smear, the enlarged parasitized erythrocytes, and the presence of Schüffner's dots with the trophozoite form. These are characteristic of P. vivax infections Plasmodium vivax ring forms with double chromatin dots. This feature is more reminiscent of Plasmodium falciparum than P. vivax. P. vivax rings have a large quantity of cytoplasm and a large chromatin dot, as well as occasional pseudopods. The red blood cells are normal, up to 1.5 times normal size, round, and contain fine Schüffners dots. Ring forms of Plasmodium falciparum. Note the multiple ring forms within the individual erythrocytes, which is characteristic of this organism. Ring forms of Plasmodium falciparum. Note the multiple ring forms and appliqué (accolé) forms within the individual erythrocytes, which is characteristic of this organism. Mature gametocyte of Plasmodium falciparum. The presence of this sausage-shaped form is diagnostic of P. falciparum malaria  Human Malarial Parasites Plasmodium vivax Benign tertian malaria P. ovale Benign tertian or ovale malaria P. malariae Quartan or malarial malaria P. falciparum Malignant tertian (36 to 48 h) malaria, P. knowlesi Simian malaria or quotidian malaria The incubation period of P. falciparum is the shortest of all the plasmodia, ranging from 7 to 10 days Trophozoite stages and schizonts of P. falciparum are rarely in blood films Peripheral blood smears of P. falciparum malaria have young ring forms and rarely gametocytes Infected RBCs do not enlarge and become distorted as they do with P. vivax and P. ovale Occasionally, reddish granules known as Maurer dots are observed in P. falciparum P. falciparum, similar to P. knowlesi and P. malariae- No hypnozoites in the liver Relapses from the liver are not known to occur Schistosoma mansoni egg. These eggs are 115 to 175 μm long and 45 to 70 μm wide, contain a miracidium, and are enclosed in a thin shell with a prominent lateral spine. Life cycle of Toxoplasma gondii A protozoa commonly found in cat feces and undercooked meat. Pregnant women should avoid coming in contact with cat litter boxes Cyst of T. gondii in tissue. Hundreds of organisms may be present in the cyst, which may become active and initiate disease with decreased host immunity (e.g., immunosuppression in transplant patients and in diseases such as AIDS).  Leishmaniasis in Humans arasite Disease Geographic Distribution L. donovani Visceral leishmaniasis Africa, Asia Mucocutaneous leishmaniasis Cutaneous leishmaniasis Dermal leishmanoid L. tropica Cutaneous leishmaniasis Afghanistan, India, Turkey, Visceral leishmaniasis (rare) former USSR, Middle East, Africa, India L. major Cutaneous leishmaniasis Middle East, Afghanistan, Africa, former USSR L. aethiopica Cutaneous leishmaniasis Ethiopia, Kenya, Yemen, former Diffuse cutaneous leishmaniasis USSR Mucocutaneous leishmaniasis L. mexicana Cutaneous leishmaniasis Texas, Belize, Guatemala, Diffuse cutaneous leishmaniasis Mexico L. braziliensis Cutaneous leishmaniasis Central and South America Mucocutaneous leishmaniasis Life cycle of Leishmania species Amastigotes in clinical specimens or the promastigotes in culture Demonstration of the amastigotes in properly stained smears cultures of ulcer tissue determines Treatment Pentavalent antimonial compound sodium stibogluconate (Pentostam) Giemsa-stained amastigotes (Leishman-Donovan bodies) of L. donovani present in a touch preparation of spleen. A small, dark- staining kinetoplast can be seen next to the spherical nucleus in some parasites  Trypanasomes Parasite Vector Disease Trypanosoma brucei Tsetse fly African trypanosomiasis gambiense and T. b. (sleeping sickness) rhodesiense Trypanosoma cruzi Reduviids American trypanosomiasis (Chagas disease) The infective stage of the organism is the trypomastigote present in the salivary glands of transmitting tsetse flies The life cycle of T. b. rhodesiense is similar to that of T. b. gambiense (see with both trypomastigote and epimastigote stages and transmission by tsetse flies Life cycle of Trypanosoma brucei Trypomastigote stage of Trypanosoma brucei gambiense in a blood smear Organisms can be demonstrated in thick and thin blood films, in concentrated anticoagulated blood preparations, and in aspirations from lymph nodes and concentrated spinal fluid Treatment Suramin is the drug of choice for treating the acute blood and lymphatic stages of the disease, with pentamidine as an alternative.  Chap 83 Nematodes The most easily recognized form of intestinal parasite because of their large size and cylindric, unsegmented bodies; hence the common name roundworms Adult Ascaris lumbricoides  Nematodes of Medical Importance Parasite Common Name Disease Enterobius vermicularis Pinworm Enterobiasis Ascaris lumbricoides Roundworm Ascariasis Toxocara canis Dog ascaris Visceral larva migrans Toxocara cati Cat ascaris Visceral larva migrans Baylisascaris procyonis Raccoon ascaris Neural larva migrans Trichuris trichiura Whipworm Trichuriasis Ancylostoma duodenale Old World hookworm Hookworm infection Necator americanus New World hookworm Hookworm infection Ancylostoma braziliense Dog or cat hookworm Cutaneous larva migrans Strongyloides stercoralis Threadworm Strongyloidiasis Trichinella spiralis Pork worm Trichinosis Wuchereria bancrofti Bancroft filaria Filariasis Brugia malayi Malayan filaria Filariasis Loa loa African eye worm Loiasis Mansonella species Filariasis Onchocerca volvulus Onchocerciasis, river blindness Dirofilaria immitis Dog heartworm Dirofilariasis Dracunculus medinensis Guinea worm Dracunculosis Enterobius vermicularis egg. The thin-walled diagnosis involves use of an anal swab with eggs are 50 to 60 × 20 to 30 μm, ovoid, and flattened a sticky surface that picks up the eggs on one side (not because children sit on them, but this is an easy way to correlate the egg morphology with the epidemiology of the disease). The drug of choice is albendazole or mebendazole  Chap 84 Trematodes The trematodes (flukes) – are members of the Platyhelminthes and are generally flat, fleshy, leaf- shaped worms equipped with two muscular suckers Most flukes are hermaphroditic, with both male and female reproductive organs in a single body Trematode Common Name Intermediate Host Biologic Vector Reservoir Host Fasciolopsis buski Giant intestinal Snail Water plants (e.g., Pigs, dogs, rabbits, fluke water chestnuts) humans Fasciola hepatica Sheep liver fluke Snail Water plants (e.g., Sheep, cattle, watercress) humans Opisthorchis Chinese liver fluke Snail, freshwater Uncooked fish Dogs, cats, humans (Clonorchis) fish sinensis Paragonimus Lung fluke Snail, freshwater Uncooked crabs, Pigs, monkeys, westermani crabs, crayfish crayfish humans Schistosoma Blood fluke Snail None Primates, rodents, species domestic pets, livestock, humans  Laboratory diagnosis Stool examination reveals the large, golden, bile-stained eggs with an operculum on the top Adult Fasciolopsis buski (natural size) Fasciolopsis buski egg, 130 to 150 μm long and 65 to 90 μm wide, with a thin operculum at one end. Adult Fasciolopsis buski (natural size) Commonly called the sheep liver fluke, F. hepatica is a parasite of herbivores (particularly sheep and cattle) and humans. A number of liver flukes are recognized, and detected in the feces of patients Schistosomiasis is a major parasitic infection of tropical areas, with some 200 million infections worldwide The three schistosomes most frequently associated with human disease are Schistosoma mansoni Schistosoma japonicum Schistosoma haematobium The disease called schistosomiasis, or bilharziasis or snail fever differ from other flukes: they are male and female rather than hermaphroditic, and their eggs do not have an operculum Living male and female Schistosoma mansoni. The slender female (right) is normally seen within the gynecophoral groove of the male (left) are obligate intravascular parasites and are not found in cavities, ducts, and other tissues. The infective forms are skin- penetrating cercariae liberated from snails, and these differ from other flukes in that they are not eaten on vegetation, in fish, or in crustaceans. The diagnosis of schistosomiasis is usually established by the demonstration of characteristic eggs in feces Schistosoma mansoni egg. These eggs are Schistosoma japonicum egg. These eggs are 115 to 175 μm long and 45 to 70 μm wide, smaller than those of Schistosoma mansoni (70 to contain a miracidium, and are enclosed in a 100 μm long and 55 to 65 μm wide) and have a thin shell with a prominent lateral spine spine that is inconspicuous Schistosoma haematobium egg. These eggs are similar in size to those of Schistosoma mansoni but can be differentiated by the presence of a terminal, rather than lateral, spine.