Infectious Diseases II: Parasitic Infections PDF

PATHOLOGY | TRANS 4F LE Infectious Diseases II: Parasitic Infections DR. CARINA P. VILLAMAYOR, FPSP | Lecture Date (09...

PATHOLOGY | TRANS 4F LE Infectious Diseases II: Parasitic Infections DR. CARINA P. VILLAMAYOR, FPSP | Lecture Date (09/27/2024) | Version 1 01 OUTLINE → Describe the color of his urine I. Protozoa III. Review Questions ▪ Darkened urine A. Malaria IV. References → Is the history of travel significant? B. Babesiosis V. Formative quiz ▪ Yes, infectious diseases can be endemic. Malaria C. Leishmaniasis is prevalent in Palawan D. Trypanosomiasis → What do you see in his thick and thin smear? II. Metazoa ▪ Infected RBCs A. Strongyloidiasis B. Tapeworms ▪ Crescent-shaped gametocytes C. Trichinosis → What is your tentative diagnosis? D. Schistosomiasis ▪ The patient has malaria E. Lymphatic Filariasis F. Onchocerciasis Caused by Plasmodium sp. → Intracellular parasite Must Lecturer Book Previous Youtube → Transmitted by female Anopheles mosquito ❗️ Know 💬 📖 📋 Trans 🔺 Video Epidemiology → Worldwide infection: affects 500 million and kills more SUMMARY OF ABBREVIATIONS than 1 million people each year CO Class Officer → According to the World Health Organization, 90% of LEARNING OBJECTIVES deaths from malaria occur in sub-Saharan Africa ▪ leading cause of death in children below 5 years old. ✔ Classify parasites according to the division where it Anopheles mosquito is widely distributed throughout Asia, belongs. Africa, and Latin-America ✔ Specify the characteristic tropism of parasites as to the Conditions incompatible with parasite survival (provide primary organ affected. protection against malarial infection): ✔ Identify the disease and discuss the epidemiology of → G6PD deficiency these infectious agents. → Duffy negative inheritance - protect against P. vivax ✔ Demonstrate knowledge and understanding of → Hemoglobinopathies (Hb-SS) - protect against P. etio-pathogenesis of the infectious disease. falciparum ✔ Demonstrate knowledge and understanding of the pathology of the infectious disease by identifying and describing the gross lesion and microscopic findings. LIFE CYCLE OF MALARIA ✔ Evaluate the diagnostic procedures to be used given the expected results. I. PROTOZOA Protozoa → Unicellular → Eukaryotic Parasitic protozoa → Transmission: insects or by the fecal-oral route → Mainly reside in the blood or intestine of humans A. MALARIA CASE A 42-year-old reporter, fresh from doing a report in Palawan 3 weeks prior to consult, came back to Manila complaining of recurrent fevers, shaking chills and dark Figure 2. Life cycle of malaria[CDC] urine. He noted that he would experience shaking chills 1. Female Anopheles mosquito carry the infectious stage, and high grade fever every other day. He also had the sporozoites, in their salivary glands dizziness, headache and mild GI upset. His hemoglobin 2. Mosquito takes a blood meal causing the release of was 7.0 g/dL. His peripheral blood smear is shown. sporozoites into the human’s blood 3. Attach to and invade liver cells within minutes by binding to hepatocyte receptors for thrombospondin and properdin (both are serum proteins) 💬 4. Within hepatocytes, the parasites multiply rapidly to schizonts → This is the stage of the parasite that occurs in the 💬 liver → Schizonts rupture and enters the erythrocytic cycle Figure 1. Patient’s blood smear (L) and urine (R)[Lecture PPT] LE 1 TG 3 | Almeda, Alunday, Alvarez, C.L., Alvarez, TE | Ancheta AVPAA | Castro, Calpito PAGE 1 of 13 TRANS 1 C.A., Ancheta VPAA | Arcega, Cambas PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP → ❗️P. vivax, P. ovale: have tendency to form latent Blackwater fever hypnozoites in hepatocytes → cause relapses → Described as sudden massive intravascular hemolysis ❗ 5. Release of as much as 30,000 merozoites (asexual, with resultant hemoglobinuria 💬 haploid forms) upon hepatocyte rupture. Infect erythrocytes of all ages, heavy parasitemia is 6. Immature trophozoites mature in the RBCs. Some possible trophozoites may develop into mature male and female Diagnosis gametocytes. → Small ring forms, applique forms, double nuclear dots → Gametocytes are ingested by mosquitoes and go → Multiply parasitization of RBCs through the sporogonic cycle in the vector. → Heavy parasitemia is possible due to it being able to HALLMARK SYMPTOMS affect all erythrocyte ages ❗️Recurrent chills and fever → Crescent-shaped (or banana-shaped) gametocyte → (+) Schizonts in peripheral blood (not usually seen) is → Correspond to synchronized rupture of RBCs and a grave prognosis release of merozoites Anemia → Secondary to RBC destruction Splenomegaly Joint pain Table 1. Symptom comparison of malaria from Plasmodium spp. P. falciparum P. vivax, P.ovale, P. malariae Severe malaria Low levels of parasitemia High levels of Mild anemia parasitemia Splenic rupture* Figure 3. Plasmodium falciparum in blood[Lecture PPT] Severe anemia Nephrotic syndrome* Cerebral symptoms Plasmodium vivax Renal failure Most widely disseminated and prevalent malaria infection Pulmonary edema worldwide Death → Found in tropical and temperate zones *Rare instances → Most common species in the Philippines along with P. falciparum Table 2. Fever recurrence according to species. Repeated exoerythrocytic development in the liver Fever Can cause relapses years after the initial infection Species Type Occurrence → Because of renewed exoerythrocytic and erythrocytic P. falciparum Malignant Tertian Every 48 hours schizogony from the latent hepatic sporozoites called Malaria ❗️ hypnozoites P. vivax Benign Tertian Every 48 hours Infect young erythrocytes (reticulocytes) Malaria Duffy negative inheritance confers immunity from P. P. ovale Ovale Malaria Every 48 hours vivax infection P. malariae Quartan Malaria Every 72 hours Diagnosis → Single large ring succeeded by amoeboid form in pale large red cell DIAGNOSING MALARIA → (+) Schuffner’s dots ▪ Condensed hemoglobin Through thin and thick smear ▪ Found in invaded RBC → Thin smear: for species identification → Only reticulocytes invaded → Thick smear for presence detection → Round gametocyte More than 1 trophozoite within a single RBC indicates a high probability of malaria Plasmodium falciparum → 💬 Most likely to be fatal Notorious for causing fatal parasitemia. The patients usually succumb to a lot of parasites within their system. Occur in tropical areas worldwide → Most common species/endemic in the Philippines, along Figure 4. Plasmodium vivax in blood[Lecture PPT] with P. vivax Plasmodium ovale Hemoglobinopathies (Hb-SS or sickle cell disease) Least frequent malarial infection protect against P. falciparum malaria Found in Western Africa, India, South America Causes the following: Disease relapses may occur weeks to months following → Cerebral malaria ❗️ subsidence of previous attacks via hypnozoites ▪ Blockage of brain vessels by RBCs, Plasmodium Infect young erythrocytes (reticulocytes) 💬 organisms, and hemosiderin pigment Diagnosis ▪ P. falciparum is the only species that causes this → Single compact ring like the trophozoite of P. malariae disease → (+) Large pale RBC with Schuffner’s dots like P. vivax ▪ May be oval and fimbriated PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 2 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP Figure 5. Plasmodium ovale in blood[Lecture PPT] Plasmodium malariae Occurs worldwide (+) Recrudescence Figure 8. Malignant cerebral malaria with (+) pinpoint → Recurrence due to increased numbers of persisting hemorrhages[Lecture PPT] blood stage forms to clinically detectable levels, not from persisting liver forms ❗️ → May be observed in P. falciparum as well Infect older erythrocytes Diagnosis → Single large compact ring in “basket” or “band” forms → Schizont with 6-12 merozoites around a central pigment ▪ Schizonts described as “fruit pie” or “daisy head” Figure 9. (L) Blood vessels plugged with parasitized RBCs causing pinpoint hemorrhages. (R) P. falciparum infected RBCs marginating within a capillary in cerebral malaria[Lecture PPT] B. BABESIOSIS Figure 6. Plasmodium malariae in blood[Lecture PPT] PATHOLOGY OF MALARIA LIVER IN MALARIA Progressively enlarged and pigmented → Kupffer cells: heavily laden with malarial pigment, parasites, and cellular debris → Parenchymal cells: some pigment also present → Phagocytic cells: pigmented and may be found dispersed throughout the bone marrow, lymph nodes, subcutaneous tissue, and lungs Figure 10. Pathogenesis of Babesiosis[Lecture PPT] ❗️Etiologicagent: Babesia microti and Babesia divergens → Malaria-like protozoans Reservoir: White footed mouse (B. microti) ❗ Mode of Transmission → Bite of deer ticks ▪ same deer ticks that carry Lyme disease and granulocytic ehrlichiosis → Blood transfusion Figure 7. Liver infected with malaria[Lecture PPT] ▪ B. microti survives in refrigerated blood ▪ Can cause transfusion-related infection MALIGNANT CEREBRAL MALARIA PATHOGENESIS OF BABESIOSIS (+) Pinpoint hemorrhages over the cerebrum ▪ Brain vessels clogged with parasitized RBCs ❗️ Babesiosis parasitizes red blood cells Causes fever and hemolytic anemia ▪ Poor perfusion Mild symptoms In severe hypoxia, patients succumb to ischemia and → Exception: debilitated or splenectomized individuals infarction who may develop severe and fatal parasitemia Fatal cases: Shock and hypoxia, jaundice, hepatic necrosis, acute renal tubular necrosis, adult respiratory distress syndrome, erythrophagocytosis, visceral hemorrhage PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 3 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP DIAGNOSIS ▪ Contain a single mitochondria with DNA massed into Blood smear morphology: maltese crosses or tetrads a unique sub-organelle called Kinetoplast → Dividing form; characteristic of babesia → Amastigotes proliferate within macrophages → Resembles P. falciparum ring stages, but lacks → Dying macrophages release progeny amastigotes that hemozoin can infect additional macrophages: Tetrad formation in thin blood smear: dividing form ▪ Promastigote - develops and lives extracellularly in characteristic of Babesia the sandfly vector ▪ Amastigote - multiplies intracellularly in host macrophages VISCERAL LEISHMANIASIS ❗️Etiologic agent: L. donovani ❗️Parasites invade macrophages through the mononuclear phagocyte system → Infected phagocytic cells crowd the bone marrow; may be found in the lungs, GIT, kidneys, pancreas, and testes Figure 11. The thin blood smear showing tetrad Severe systemic infection formation[Lecture PPT] → Hepatosplenomegaly, lymphadenopathy, weight loss, C. LEISHMANIASIS pancytopenia, myalgia, fever Chronic inflammatory disease of skin, mucous → Advanced leishmaniasis can progress with fatal membranes, and viscera secondary bacterial infections and hemorrhages related → Endemic: Middle East, South Asia, Africa, Latin America to thrombocytopenia → Epidemic: Sudan, India, Bangladesh, Brazil May be accompanied by Kala-azar (black fever in Hindi) ▪ Visceral leishmaniasis → Skin hyperpigmentation in South Asian ancestry Etiologic agent: obligate intracellular, kinetoplast ❗️ containing (kinetoplastid) protozoan parasite ❗️ Transmission: bite of infected Sandflies Infective stages: → Promastigote stage: Infective stage to man ▪ From sandfly to man ▪ Develops and lives extracellularly in sandfly vector → Amastigote stage: Infective stage to sandfly Figure 13. (Left) Giemsa-stained tissue scraping of ▪ From man to sandfly Leishmania spp. amastigotes; (Middle) Smear of a biopsy ▪ Multiplies intracellularly in host macrophages taken from a skin lesion; (Right) Intact macrophage is Reservoirs: mammals (e.g. rodents, dogs, foxes) filled with amastigotes[Lecture PPT] LIFE CYCLE OF LEISHMANIA SPP. CUTANEOUS LEISHMANIASIS ❗️Etiologic agents: L. major, L. mexicana, & L. braziliensis Mild localized disease of skin ulcers (Tropical sore) on exposed skin → Begin as itching papules surrounded by induration → Shallow, expanding ulcers with heaped-up borders ❗️ Heals by involution in 6 to 18 months without treatment ❗️ Histologic lesion: Granuloma Pathologic appearance: Purple edematous plaque with central necrotic crust Figure 12. Life cycle of Leishmania spp.[CDC] Upon biting infected humans or animals, sandflies ingest macrophages containing amastigotes → Amastigotes differentiate into promastigotes → Promastigotes multiply within the sandfly digestive Figure 14. (L) Skin ulcer; (R) Purple Edematous Plaque on tract and migrate to the salivary gland for transmission the right cheek in Bites from infected sand flies infect humans by releasing Cutaneous Leishmaniasis for 5 months [Lecture PPT] the slender and flagellated promastigotes into the dermis → Sandfly saliva potentiates parasite infectivity MUCOCUTANEOUS LEISHMANIASIS → Promastigotes are phagocytosed by macrophages → The acidity of the phagolysosome induces promastigote ❗️Etiologic agents: L. braziliensis Also called “Espundia” transformation into round amastigotes without flagella Lesions are progressive and highly destructive PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 4 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP Moist, ulcerating or non-ulcerating lesions in the Symptoms: intermittent fever, progressive brain ❗️ nasopharyngeal areas are grossly disfiguring Microscopically: mixed inflammatory infiltrate of plasma 📋 dysfunction (sleeping sickness), and death Splenomegaly, lymphadenopathy, cachexia ❗️ cells, lymphocytes, and parasite-containing macrophages Pathologic findings → Later stages of tissue inflammation: granulomatous with → Chancre less parasites; lesions remit and scar ▪ Large, rubbery, red chancre at insect bite → Reactivation may occur after long intervals through ▪ Large numbers of parasites surrounded by dense, unexplained mechanisms predominantly mononuclear inflammatory infiltrate → Splenomegaly and lymphadenopathy with chronicity ▪ Due to to infiltration of lymphocytes, plasma cells, and macrophages filled with dead parasite ▪ Chronic disease leads to progressive cachexia → When devoid of energy and normal mentation, patients waste away Figure 15. Mixed Inflammatory Infiltrate of Parasite-Containing Macrophages, Lymphocytes, and Plasma Cells Figure 17. (L) Chancre in African Trypanosomiasis (R) Thin blood smears showing Trypanosoma brucei spp. DIFFUSE CUTANEOUS LEISHMANIASIS AMERICAN TRYPANOSOMIASIS ❗️ Rare form of dermal infection Also known as Chagas disease Etiologic agent: Trypanosoma cruzi ❗️ → In Ethiopia, East Africa, Central and South America ❗️ Begins as a single skin nodule and continues → Kinetoplastid, intracellular protozoan Transmission: bite of Kissing bugs (Triatomids) ❗️ spreading until entire body is covered by nodular lesions Microscopically: aggregates of foamy macrophages → Hide in the cracks of loosely constructed houses, feed stuffed with Leishmania on the sleeping inhabitants and pass the parasites in the feces → Infectious parasites enter the host through damaged skin or through mucous membranes → Infect animals (cats, dogs, rodents) Occurs rarely in the United States and Mexico but is more ❗️ common in South America, particularly Brazil Histologic appearance: C-shaped trypomastigote → “C for T. cruzi and Chagas disease” ❗️ → With large terminal kinetoplast Characteristic lesion: Chagoma → Transient, erythematous nodule at site of skin entry Figure 16. (L) Nodular Lesions in DIffuse Cutaneous Leishmaniasis (R) Foamy Histiocyte Aggregates Filled with Leishmania spp. D. TRYPANOSOMIASIS AFRICAN TRYPANOSOMIASIS Also known as Sleeping Sickness Figure 18. Triatomine bug (Kissing bug) vector of T. cruzi ❗️ Etiologic agents: kinetoplastid, extracellular protozoans Trypanosoma brucei rhodesiense (East Africa) ACUTE CHAGAS DISEASE ❗️ → Often acute and virulent In rare cases: high parasitemia, fever, progressive cardiac Trypanosoma brucei gambiense (West Africa) dilatation and failure, lymphadenopathy, splenomegaly ❗️ → Often chronic Mild in most cases Transmission: bite of Tsetse fly (genus Glossina) Primarily affects the heart and in endemic areas → Transmit African Trypanosoma to humans either from Major cause of sudden death due to cardiac arrhythmias. the reservoir of parasites found in: Cardiac damage results from direct invasion of myocardial ▪ T. brucei rhodesiense: Wild and domestic animals cells by the organisms and the subsequent inflammation ▪ T. brucei gambiense: From other humans → Within the fly, the parasites multiply in the stomach and CHRONIC CHAGAS DISEASE then in the salivary glands before developing into Occurs 5-15 years after initial infection non-dividing trypomastigotes, which are transmitted to Two main mechanisms of cardiac damage: humans and animals. → First, presence of persistent parasites leads to continued immune response with striking inflammatory PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 5 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP infiltration of the myocardium, even if scant organisms are → Female worms reside in the mucosa of the small present intestine where they produce eggs asexually → Second, parasites may induce an autoimmune Most of the larva are passed out the stool into the soil ❗️ response such that antibodies and T cells that recognize Causes diarrhea, bloating and malabsorption parasite proteins cross-react with host myocardial cells, Autoinfection nerve cells, and extracellular proteins such as laminin → S. stercoralis larvae hatched in the gut invade colonic mucosa to reinitiate infection → Immunocompromised patients, especially those on prolonged corticosteroid therapy, can have uncontrolled autoinfection leading to very high worm burden. Figure 19. Chronic Chagas disease[Lecture PPT] Both mechanisms cause damage to the following structures: → Myocardial cells and Conductance pathways ▪ Dilated cardiomyopathy and cardiac arrhythmias → Myenteric plexus ▪ Dilation of the colon (megacolon) and esophagus Figure 22. Strongyloides Mode of Transmission PATHOLOGIC FINDINGS IN STRONGYLOIDIASIS Diagnostic tests: → Stool Examination → Duodenal lavage Mild strongyloidiasis → Larvae are mainly present in duodenal crypts but not seen in underlying tissue → Eosinophil-rich infiltrate in the lamina propria with Figure 20. (L) Trypanosoma differentiated by T. cruzi mucosal edema C-shaped trypomastigote with large subterminal kinetoplast Hyperinfection of Strongyloides stercoralis results in: (R) Giemsa-stained thin smear, C-shaped T. cruzi → Invasion of larvae into the colonic submucosa, trypomastigote lymphatics, and blood vessels, with an associated mononuclear infiltrate → Presence of many adult worms, larvae, and eggs in the crypts of the duodenum and ileum Figure 21. T. cruzi (L) amastigotes in heart tissue; (R) amastigotes transforming into trypomastigotes in heart tissue II. METAZOA Figure 23. Longitudinal section of Strongyloides stercoralis Multicellular, eukaryotic organisms from an Intestinal Biopsy Contracted via: B. TAPEWORMS (CESTODES) → Consumption of the parasite in undercooked meat → Direct invasion through the skin or via insect bites ❗️Etiologic agents: Taenia solium & Echinococcus Diagnosed by microscopic identification of larvae or ova in granulosus excretions or tissues, and by serology → Cestode parasites that cause Cysticercosis and Hydatid Disease respectively. A. STRONGYLOIDIASIS ❗️Etiologic agent: Strongyloides stercoralis → Both are caused by larvae that develop after ingestion of tapeworm eggs. → Inhabit the soil as adult worms Have a complex life cycle which requires: → Infect human when larvae penetrate the skin → Definitive host - Sexual maturity After skin penetration, they travel in the circulation to the → Intermediate host - Worm does not reach sexual ❗️ lungs and up to the trachea where they are swallowed. maturity Parthenogenesis PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 6 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP CYSTICERCOSIS Figure 25. Larval T. solium Cyst in a Right Frontal Lobe ❗️Etiologic agent: Taenia solium (pork tapeworm) Lesion. Note the invaginated scolex w/ hooklets and clear cyst fluid Mode of transmission (2 types): a. Ingestion of undercooked pork containing cysticerci (larval cysts) → Cysticerci attach to the intestinal wall → Develop into adult tapeworms → Can grow many meters in length → Cause mild abdominal symptoms → Parasite life cycle is completed in this mode of infection and cysticercosis does NOT develop → Can live in the body for years Figure 26. HPO of Cysticercus Cysts b. Ingestion/consumption of food or water contaminated with human feces (with Taenia Rice grain calcifications solium eggs) → Larvae infiltrating skeletal muscles → The intermediate host (usually pig) ingest food or water with Taenia ova → Within the GIT, ova will develop into larvae and penetrate the gut wall → Dissemination through the bloodstream and encyst in many organs (brain, muscle, skin, and heart) to cause cysticercosis. → Adult tapeworms are not produced in this mode 💬 of infection since encysted larval cysts cannot develop into adults; permanently in the larval 💬 stage → This second mode of transmission causes the Figure 27. T. solium larvae infiltrating the leg muscles true development of cysticercosis HYDATID DISEASE PATHOLOGIC FINDINGS OF CYSTICERCOSIS Neurocysticercosis → Larva encyst in the brain → Cerebral symptoms depend on the location of the cysts: ▪ Intraparenchymal ▪ Attached to the arachnoid ▪ Freely floating in the ventricular system Figure 24. Neurocysticercosis[Lecture PPT] Figure 28.Hydatid disease[Lecture PPT] → Cysts are ovoid and white to opalescent, often ❗️Etiologic agent: Echinococcus granulosus Definitive host: dogs grape-sized, and contain an invaginated scolex with Intermediate host: sheep (usual), humans (accidental) hooklets that are bathed in clear cyst fluid Humans are accidental intermediate hosts, infected by → The cysticercus cyst wall is more than 100 μm thick, ingestion of food contaminated with ova from dogs or foxes rich in glycoproteins, and evokes little host reaction Ingestion of Echinococcus ova which hatch in the when intact duodenum; invade the liver, lungs, bones → When cysts degenerate, there is inflammation, followed They lodge within the capillaries where they incite an by focal scarring, and calcifications inflammatory reaction composed of mononuclear leukocytes and eosinophils Many larvae are destroyed, but some encyst → Cysts progressively increase in size and reach up to 10 cm in 5 years PATHOLOGIC FINDINGS OF HYDATID DISEASE The hydatid cyst has an inner, nucleated germinative cell layer and an outer opaque, non-nucleated layer These are all located within an opalescent fluid PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 7 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP Hydatid cysts may contain degenerating scolices of the LIFE CYCLE OF T. SPIRALIS worm which may produce a fine, sand-like sediment called hydatid sand Figure 32. Trichinosis pathogenesis[Lecture PPT] Begins at the intestines and ends in the muscles as Figure 29. Brood Capsule Containing Scolices in a humans are considered as dead-end hosts. Hydatid Cyst Removed from Lung Tissue In the gut, the larvae develop into adults where they mate and release larvae. These larvae travel through the bloodstream and penetrate muscle cells. Less commonly, they can go to the heart, lungs, and brain. PATHOLOGIC FINDINGS IN TRICHINOSIS Heart → Patchy interstitial myocarditis (eosinophils & giant cells) ▪ Can lead to scarring → Larvae in the heart do not encyst and are difficult to identify (die and disappear) Figure 30. Protoscoleces of Adult Tapeworms (L) Hydatid Lungs Cyst (R) → Larvae C. TRICHINOSIS → Focal edema ❗️Etiologic agent: Trichinella spiralis → Hemorrhage → Eosinophilic infiltrate → A nematode parasite acquired by ingestion of larvae in undercooked infected meat from pigs, boars, and Striated Skeletal Muscle horses → T. spiralis coiled larvae become intracellular parasites ▪ These animals have been infected by eating T. ▪ Increase dramatically in size spiralis-infected rat or meat products. ▪ Modify host muscle cell (Nurse Cell) − Loses striations and gains a collagenous capsule − Develops a plexus of new blood vessels − Nurse cell-parasite complex is asymptomatic o Worm may persist for years before it dies and calcifies − Antibodies to larval antigens, which include an immunodominant carbohydrate epitope Tyvelose o Reduce reinfection o Useful for serodiagnosis of the disease ▪ Membrane-bound vacuoles within nurse cells ❗️ ▪ Mononuclear inflammatory cells (eosinophils) T. spiralis preferentially encyst in skeletal muscles with the richest blood supply (See figure 29) → Diaphragm, extraocular, deltoid, gastrocnemius, and intercostal muscles. Coiled T. spiralis larvae are ~1mm long → Surrounded by membrane-bound vacuoles within nurse cells, which in turn are → Surrounded by new blood vessels and an eosinophil-rich mononuclear cell infiltrate. ▪ Infiltrate is greatest around dying parasites, which Figure 31. Life Cycle of Trichinella spiralis[LecturePPT] calcify and leave behind characteristic scars for retrospective diagnosis of trichinosis. PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 8 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP ▪ Adult species reside in the superior mesenteric vein ▪ Diseases caused: − Hepatic granuloma and fibrosis leading to hepatic cirrhosis − Most deaths caused by hepatic cirrhosis − Predominantly affects the liver and gut → S. mansoni ▪ Found in Latin America, Africa, and the Middle East ▪ Adult species reside in the inferior mesenteric vein ▪ Diseases caused: − Hepatic granuloma and fibrosis leading to hepatic Figure 33. Coiled T. spiralis larva in skeletal muscle[Lecture cirrhosis → S. mekongi ▪ Found in East Asia ▪ Diseases caused: − Most death caused by hepatic cirrhosis − Predominantly affects the liver and gut Present as Obstructive Uropathy → S. haematobium ▪ Found in Africa ▪ Adult species reside in the venous plexus of the urinary bladder Figure 34. T. spiralis larva within skeletal muscle[Lecture ▪ Diseases caused: − Hematuria and granulomatous disease of the D. SCHISTOSOMIASIS bladder resulting in chronic obstructive uropathy CASE OVA MORPHOLOGY A 55-year-old male farmer from Leyte complains of Schistosoma may be speciated depending on the progressive ascites and diffuse RUQ tenderness. appearance of the ova → Size: 46-100 𝜇m → Shape: Ovoid, round, or pear-shaped → Color: Pale-yellow → Differentiated by the presence of a curved hook/spine ▪ S. japonicum: lateral knob ▪ S. mansoni: subterminal spine ▪ S. haematobium: terminal spine Figure 35. Histological Section of the Farmer’s Liver. [Lecture PPT] Diagnosis? Causative agent? → Schistosomiasis. S. japonicum Mode of transmission? → freshwater snails transmit the schistisome larvae (cercaria) → cercaria penetrate the skin → migrate through the peripheral circulation Figure 36. S. japonicum ova. [Lecture PPT] Gross and microscopic findings? → Grossly, there is pipestem fibrosis of the liver. → Microscopically, they appear as calcified ovoid structures. Schistosoma sp. Present as Hepatic Cirrhosis ❗️ → S. japonicum ▪ Oriental blood fluke ▪ Found in East Asia (China), Philippines, & Indonesia Figure 37. S. mansoni ova. [Lecture PPT] − Endemic in Mindoro, Leyte, Samar, Sorsogon, and Mindanao ▪ Lays 3x more eggs which hatch only in clean water and sufficient oxygen (500 - 2000 immature eggs/day) 💬 − Carrier: Oncomelania hupensis quadrasi snails o live in slow flowing, oxygenated water ways − Reside in the portal vein and its branches Figure 38. S. haematobium ova. [Lecture PPT] PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 9 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP PATHOGENESIS HEPATOSPLENIC SCHISTOSOMIASIS Acute Schistosomiasis also known as Katayama Fever Present with fever, myalgia, RUQ pain and tenderness, and hepatomegaly Due to host’s granulomatous reaction to eggs deposited in the liver and other organs Egg deposition commonly involves the liver, intestines, lungs, and CNS Figure 41. Hepatic Schistosomiasis. [Lecture PPT] PIPE-STEM FIBROSIS OF THE LIVER Characteristic pathology of schistosomiasis in the liver: pipe-stem fibrosis → Resembles the stem of an old clay pipe The fibrosis often obliterates the portal veins leading to: → Portal hypertension → Severe congestive splenomegaly → Esophageal varices → Ascites Schistosome eggs, diverted to the lung through portal collaterals, may produce granulomatous pulmonary arteritis with intimal hyperplasia, progressive arterial obstruction, and ultimately heart failure (cor pulmonale) Figure 39. Life Cycle Schistosoma spp. [Lecture PPT] Transmitted through freshwater snails in slow-moving → 💬 waters of tropical rivers, lakes, & irrigation ditches common in farming areas. Schistosome larvae (cercariae) swim through fresh water and penetrate human skin with the aid of proteolytic enzymes that degrade the keratinized layer of the skin Figure 42. Pipe-stem Fibrosis of the Liver. [Lecture PPT] Schistosomes migrate into the peripheral vasculature → travel to the lungs and heart → mature and mate in hepatic vessels → migrate out as male-female worm SCHISTOSOMA OVA IN THE LIVER pairs → settle in the portal or pelvic venous system Appear as calcified ovoid structures Females produce hundreds of eggs per day, around which Inflammatory patches or pseudopolyps form in the colon granulomas and fibrosis form The surface of the liver is bumpy, and cut surfaces reveal PATHOLOGIC FINDINGS granulomas and widespread fibrosis and portal enlargement without intervening regenerative nodules SCHISTOSOMA DERMATITIS Schistosoma Dermatitis: cercariae penetration in the skin Figure 43. Biopsy of Schistosoma in the Liver. [Lecture PPT] Figure 40. Schistosoma Dermatitis. [Lecture PPT] PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 10 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP E. LYMPHATIC FILARIASIS FILARIASIS OF THE LEG Etiologic agents: Massive edema and elephantiasis of the leg → Wuchereria bancrofti Chronic filariasis is characterized by persistent → Brugia malayi lymphedema of the extremities, scrotum, penis, or vulva Mosquito vector of W. bancrofti: Frequently theres is hydrocele and lymph node → Culex, Anopheles, Mansonia, Coquillettidia enlargement Mosquito vector of B. malayi: In severe and long-standing infections: → Culex, Anopheles, Mansonia → Chronically swollen legs may develop tough ❗️ Adult parasites found in lymphatics and lymph nodes subcutaneous fibrosis and epithelial hyperkeratosis, Microfilariae - diagnostic stage; found in the blood termed elephantiasis Reactions are caused by T cell response to parasites Elephantoid skin: Diseases caused by filariasis: → Dilation of the dermal lymphatics → Asymptomatic filaremia → Widespread lymphocytic infiltrates and focal cholesterol → Recurrent lymphadenitis deposits → Chronic lymphadenitis with swelling of the dependent → Epidermis is thickened and hyperkeratotic limb or scrotum Adult filarial worms (live, dead, or calcified) are present in → Tropical pulmonary eosinophilia the draining lymphatics or nodes, surrounded by: ▪ Involvement of lungs via microfilariae → Mild or no inflammation ▪ Marked by eosinophilia caused by TH2 responses → Intense eosinophilia with hemorrhage and fibrin and cytokine production (tropical eosinophilia) or by (recurrent filarial funiculoepididymitis) dead microfilariae surrounded by stellate, hyaline, → Granulomas eosinophilic precipitates embedded in small → Over time, the dilated lymphatics can develop polypoid epithelioid granulomas (Meyers-Kouwenaar bodies) infoldings ▪ Typically, these patients lack other manifestations of filarial disease Figure 46. Filariasis of the Leg. [Lecture PPT] FILARIASIS OF THE SCROTUM Hydrocele and lymph node enlargement In severe and long-lasting infections: → Chylous weeping of the scrotum may ensue In the testis, hydrocele fluid which often contains cholesterol crystals; red cells; and hemosiderin, induces thickening and calcification of the tunica vaginalis Figure 44. Life Cycle of W. bancrofti [Lecture PPT] PATHOLOGIC FINDINGS Diagnosis of filariasis depends on the nocturnal periodicity of the microfilariae found on the blood The blood for the thin and thick smear is collected between 10 PM to 2 AM to ensure optimum yield of the parasite Wuchereria bancrofti: → Microfilariae: appears sheathed, gently curved, with loosely packed nuclei not extended to the tip of the tail Brugia malayi: → Microfilariae: sheathed, tightly coiled, with packed nuclei Figure 47. Filariasis of the Scrotum. [Lecture PPT] Figure 45. W. bancrofti (L) and B. malayi (R) [Lecture PPT] Microfilariae is considered the diagnostic stage for filariasis PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 11 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP LYMPH NODE INVOLVEMENT RIVER BLINDNESS RESULTS FROM SCLEROSING KERATITIS Figure 48. B. malayi in Adult Lymph Node. [Lecture PPT] F. ONCHOCERCIASIS Figure 51. O. volvulus can cause river blindness. [Lecture PPT] ❗️ Etiologic agent: Onchocerca volvulus Also known as River Blindness Microfilariae accumulate within eye chamber → → Due to the occurrence of blindness near the river where inflammation during degeneration → cause punctate black flies proliferate keratitis or small, fluffy corneal opacities → cause Transmitted by black flies (Simulium) sclerosing keratitis which opacifies cornea Location in the human host: ▪ Iridocyclotis Glaucoma: microfilariae in anterior → Adults: subcutaneous nodules chamber → Microfilariae: skin tissues ▪ Atrophy, Loss of Vision: involvement of choroid and Adult O. volvulus mate in the dermis, surrounded by a retina mixed infiltrate of host cells that produces a characteristic subcutaneous nodule called onchocercoma → Major pathologic process: release of large amounts of microfilariae by females into the skin and eye chambers Foci of epidermal atrophy and elastic fiber breakdown may alternate with areas of hyperkeratosis, hyperpigmentation with pigment incontinence, dermal atrophy, and fibrosis PATHOLOGIC FINDINGS LEOPARD, LIZARD, OR ELEPHANT SKIN Chronic, itchy dermatitis with focal darkening or loss of pigment and scaling Figure 52. (Top L and R) River Blindness; (Bottom) Adult Worm of O. Volvulus Obtained from Subcutaneous Nodules.[Lecture PPT] III. REVIEW QUESTIONS 1. [True/False] Ingestion of undercooked pork Figure 49. Onchocercal Lesion (L), Leopard Skin (R).[Lecture PPT] containing cysticerci or T. solium larva causes cysticercosis ONCHOCERCOMA a. True Subcutaneous nodule composed of a fibrous capsule b. False surrounding adult Onchocercus and a mixed inflammatory 2. What stage of erythrocytes does P. falciparum infect? infiltrate (fibrin, neutrophils, eosinophils, lymphocytes, and a. Proerythroblast giant cells) b. Polychromatophilic erythroblast c. None of the above d. All of the above 3. Unique characteristic of Babesiosis a. Tetrad formation in thin blood smear b. Abundance of eosinophils c. Hemozoin in thin blood smear d. Abundance of WBC ANS: 1. B. The second mode of transmission, which is the Figure 50. Cross-section of Onchocercoma containing adult ingestion of T. solium eggs, causes cysticercosis, not the O. volvulus (L) & Microfilariae from Skin Nodule (R).[Lecture PPT] ingestion of larva. PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 12 of 13 PATHOLOGY | LE 2 Infectious Diseases II: Parasitic Infections | Dr. Carina P. Villamayor, FPSP 2. D. All stages of the erythrocyte can be infected by P. IV. REFERENCES falciparum Asynchronous Session Lecture PPT - Dr. Carina P. Villamayor 3. A. Babesiosis is characterized by tetrad formation in the Robbins and Cotran Basic Pathology Synchronous Session thin blood smear or maltese crosses with the absence of hemozoin V. FORMATIVE QUIZ Question & Choices Answer & Rationale Schistosomiasis larvae (Cercariae) swim through the freshwater and penetrate human 1. Infective stage of Schistosomiasis Cercaria skin with the aid of proteolytic enzymes that degrade the keratinized layer 2. Characteristic of S. stercoralis to Female worms reside in the mucosa of the produce eggs asexually Parthenogenesis small intestine where they produce the eggs asexually Most common diagnostic test for protozoa and 3. Lab exam for diagnosis of Babesia metazoa; Blood smear for Babesiosis has Blood smear maltese crosses or tetrads The diagnosis of filariasis depends on the 4. Diagnostic stage of Filariasis Microfilaria nocturnal periodicity of the microfilariae found in the blood. Echinococcus granulosus has an inner, 5. Hydatid cyst Echinococcus granulosus nucleated germinative cell later and outer, opaque, non-nucleated layer. Allows the Candida to evade host immune responses; Able to shift between different 6. Ability of Candida to adapt to phenotypes and this ability involves Phenotypic switching changes in the environment coordinated regulation of phase-specific genes that allows it to adapt to changes in the environment C. gatti is more likely to cause infection in 7. Species of Cryptococcus seen in immunologically healthy or normal individuals; C. gatti immunologically normal patients Causes large masses in the lungs and mistaken as tumors 8. Benign tertian malaria P. vivax African trypanosomes are transmitted via the bite of an infected tsetse fly (genus Glossina) which can manifest as intermittent fever, 9. Sleeping sickness vector Tsetse fly splenomegaly, lymphadenopathy, progressive brain dysfunction (sleeping sickness), cachexia, and death Mucor spp. is the only fungal infection that can be transmitted via ingestion of spores that can 10. Fungal infection which can invade the Mucor spp. lead to GIT mucormycosis. Other primary sites GIT of invasion include the nasal sinuses (rhinocerebral mucormycosis) PATHOLOGY Infectious Diseases II: Parasitic Infections PAGE 13 of 13