THE THE PATHOLOGY OF PATHOLOGY OF

PARASITIC PARASITIC INFECTIONSINFECTIONS

Prof. Dr. Ferda ÖzkanProf. Dr. Ferda Özkan

GOALGOAL

To learn the pathologic effects of To learn the pathologic effects of the parasitic infections. the parasitic infections.

Luminal protozoaLuminal protozoa

Amebiasis Amebic meningoencephalitis Cryptosporidiosis Giardiasis Trichomoniasis

AMEBIASIS This is infestation / infection with Entamoeba histolytica, primarily a colonic disease. Patients have acute or chronic diarrhea (amebic dysentery)– Many years may elapse between inoculation

and symptomatic disease.

Usually the amoeba is a commensal, and symptoms are unusual. Around 40 million people become seriously sick each year.

Ingested cysts (the form able to survive in the outside world) are activated in the stomach, releasing active trophozoites. The colon (especially the right side; cecum and ascending colon) is affected. The amoebas penetrate the crypts, burrow down, stop at the muscularis mucosa, and spread out; the undermining creates the Erlenmeyer flask ulcer. Eventually the mucosa sloughs, and diarrhea becomes severe. The ulcers are full of fibrin and debris as well as amoebas without any inflammatory response. Sometimes there is a profusion of granulation tissue, simulating a tumor (amoeboma). Rarely, the bowel perforates.

Complications:– Liver abscess: Amoebas penetrate

vessels and are drained to the liver, where abscesses are really expanding areas of necrosis without a significant inflammatory response.

– Systemic dissemination: They may become superinfected by bacteria, rupture into the peritoneum, pericardium, pleura, or wherever, and/or spread by the bloodstream to the lungs or brain.

AMEBIASIAMEBIASISS

AMEBIC MENINGOENCEPHALITIS Naegleria fowleri live especially in the

warmer states. The amoebas enter CNS through the

nasal mucosa, cribriform plate, and first cranial nerves.

Around a week after exposure, they produce a purulent, necrotizing, hemorrhagic infection of the brain and its coverings.

CRYPTOSPORIDIOSIS This newly-discovered but common disease produces outbreaks of mild, self-limited diarrhea, especially in children. The acid-fast organism, Cryptosporodium, is a common veterinary pathogen and veterinary commensal. The microrganisms are located in the brush border of the gut and enjoy the free food. Acid-fast staining of the stool shows the cyst stage. It can be fatal in a malnourished child. And AIDS and AIDS-related complex patients get a longstanding diarrhea which can also be fatal.

CRYPTOSPORIDIOSISCRYPTOSPORIDIOSIS

GIARDIASIS Giardia lamblia, an intestinal flagellate

which affects various wild animals, can be acquired from drinking stream-water (Colorado), drinking tap-water .

Giardia concentrates in the duodenum and sends cysts out in the stool.

Most giardia infestations never become symptomatic. Sometimes causes indigestion, diarrhea, and even malabsorption, by coating the gut and damaging the villi.

Low IgA, general hypogammaglobulinemia, or immunosuppression makes giardia infection more severe.

TRICHOMONIASIS Infection of the vagina or male genital tract

with Trichomonas vaginalis. This 15 micron flagellate is a very annoying, though

nonlethal, sexually-transmitted pathogen. Most patients who harbor trichomonas are not

symptomatic. The agent is best-known for producing vaginitis

in women during reproductive years. Men get urethritis and prostatitis. In both sexes, itching, burning, and discharge

are seen. The discharge in vaginitis is scanty and frothy, and often malodorous; it is usually not purulent.

Clinically called strawberry vagina.

Blood and tissue protozoaBlood and tissue protozoa

Malaria African trypanosomiasis

MALARIA

Infection with any of four different species of Plasmodia, causing periodic paroxysms of chills, fever and sweating, anemia, and splenomegaly.This disease causes tremendous morbidity, especially among young children, especially in the poor nations of Africa and Asia. – At least 1 million kids die of malaria every year just

in Africa.

The WHO rates malaria as the world's worst primary health problem.

Plasmodia are intracellular parasites carried by female Anopheles mosquitoes.The four important Plasmodium species are P. falciparum, P. vivax, P. ovale, and P. malariae. – P. falciparum and, more recently, P.

vivax have become increasingly resistant to antimalarial drugs.

Humans are the intermediate host.

Massive hemolysis correlates with the paroxysms of fever, chilling.Organisms in the liver can cause hepatomegaly. The spleen is generally enlarged (splenomegaly), often huge and fibrotic in falciparum malaria. The phagocytic cells are infected, and (especially the RES cells) contain the Prussian-blue negative, brown-black iron pigment of malaria (hemozoin pigment) ; formation of this pigment is likely to deplete marrow iron stores.

In malignant malaria (P. falciparum), there is plugging of brain vessels by parasitized red cells each cell containing a sigle dot of hemozoin pigment. There are ring hemorrhages that are related to local hypoxia. "Blackwater fever" (usually seen in falciparum malaria) results from vigorous hemolysis, and renal failure resulting from hemoglobinuria. – Intravascular hemolysis,– Hemoglobinemia,– Hemoglobinuria.

RBCs containing P. falciparum schizonts adhere to vascular endothelium, obstructing small blood vessels and causing tissue anoxia in various organs. Patients with cerebral malaria may develop symptoms ranging from irritability to coma; respiratory distress syndrome, diarrhea, icterus, epigastric tenderness, retinal hemorrhages, algid malaria (a shocklike syndrome), and severe thrombocytopenia also occur.

Renal disease may result from volume depletion, the plugging of blood vessels, immune complex deposition, or blackwater fever.

P. vivax and P. ovale rarely compromise the function of vital organs. Mortality is rare and is mostly due to splenic rupture or uncontrolled hyperparasitemia in asplenic persons.

MalariaMalaria

Grossly, sections of the brain in cases of CNS Grossly, sections of the brain in cases of CNS malaria show a characteristic grayish malaria show a characteristic grayish

discoloration of the cortexdiscoloration of the cortex

OOrganisms rganisms showing showing brown-to-black pigmentationbrown-to-black pigmentation lining the inside wall of blood vessels, capillary lining the inside wall of blood vessels, capillary

congestion, and perivascular hemorrhagescongestion, and perivascular hemorrhages..

Intracellular protozoaIntracellular protozoa

ToxoplasmosisChagas's disease Leishmaniasis

TOXOPLASMOSIS (Toxoplasma gondii)

Infection with Toxoplasma gondii, causing a spectrum of manifestations ranging from asymptomatic benign lymphadenopathy to life-threatening CNS disease, chorioretinitis, and mental retardation.Toxoplasma gondii is an ubiquitous protozoan parasite of birds and mammals (particularly the cats).– Eggs (oocysts) are shed in cat feces, and if

ingested, can infect most mammals.

– This obligate intracellular parasite invades and multiplies asexually within the cytoplasm of any nucleated cell.

Small crescentic "tachyzoites" (3-6 ) may be seen, and so can "cysts" (loaded host cells) full of "bradyzoites". The human infection, which is very common worldwide is caught from cat droppings or eating raw meat from an incidentally-infected animal, or by transmission across the placenta.

Toxoplasma organisms infecting a human host can only complete their life cycle if the human is eaten by a cat, lion, tiger, etc. They would prefer to infect mice. The human response to toxoplasmosis varies with age and immune status. Adults with normal immunity suffer only a mild, infectious-mononucleosis-like illness. In fetuses, newborns, or the (even mildly) immunocompromised, toxoplasmosis is a devastating infection, capable of severely damaging the eyes and brain. The process continues following birth, and it's wise to screen newborns for it.

Acute toxoplasmosis may mimic infectious mononucleosis with lymphadenopathy, fever, malaise, myalgia, hepatosplenomegaly, and pharyngitis.A severe disseminated form characterized by pneumonitis, myocarditis, meningoencephalitis, polymyositis, diffuse maculopapular rash, high fevers, chills has been described. Acute fulminating disease is uncommon.

Toxoplasmosis in immunocompromised patients can cause severe disease. – Clinically apparent toxoplasmosis develops in

30 to 40% of AIDS patients, in whom disease is more often due to reactivation of a preexisting latent infection than to newly acquired infection.

– Most patients with AIDS and toxoplasmosis develop life-threatening encephalitis or meningoencephalitis; myocarditis, pneumonitis, orchitis, involvement of other organs, and disseminated disease are much less common.

Congenital toxoplasmosis usually results from a primary (and often asymptomatic) acute infection acquired by the mother during pregnancy. – Women infected before conception ordinarily

do not transmit toxoplasmosis to the fetus, unless the infection is reactivated during pregnancy by immunosuppression.

– The risk of transplacental infection increases from 15% to 30 to 60% for maternal infections acquired in the 1st, 2nd, or 3rd trimester of gestation, respectively.

Most cases of ocular toxoplasmosis result from congenital infection that is reactivated later (often in the 2nd and 3rd decades) in life. – Focal necrotizing retinitis and a

secondary granulomatous inflammation of the choroid occur.

– Relapses of chorioretinitis are common and may lead to ocular pain, blurred vision, and sometimes blindness.

ToxoplasmosisToxoplasmosis

In this gross photo of a case of congenital In this gross photo of a case of congenital toxoplasmosis, you can appreciate the devastating toxoplasmosis, you can appreciate the devastating nature of the disease. The brain shows asymmetric nature of the disease. The brain shows asymmetric areas of cortical atrophy and profound destructionareas of cortical atrophy and profound destruction

WWidespread destruction characterized by foci of idespread destruction characterized by foci of calcification (the white lesions) distributed in the calcification (the white lesions) distributed in the

cortex. cortex.

Microscopically, the organisms may be Microscopically, the organisms may be found in histiocytes or lying free in the found in histiocytes or lying free in the

tissue within large capsulestissue within large capsules..

Chagas's disease (American trypanosomiasis)

Infection with Trypanosoma cruzi, causing chronic cardiomyopathy, megaesophagus, or megacolon.Trypanosoma cruzi is carried by the reduviid "kissing bug” (triatomidae), which infests poor homes in much of Latin America; its range extends into South Texas.Natural reservoirs exist among armadillos, dogs and other wildlife.

Following inoculation, there is likely to be inflammation of the eye and lymphadenopathy on the same side (Ramona's sign), followed in a few weeks by systemic signs. In the human, the trypanosome appears in the blood.

In both acute and chronic forms, death results from cardiac involvement (arrhythmias, failure). However, brain involvement and esophageal paralysis (mega esophagus) and colonic paralysis (megacolon) are also important. The latter result from neuron damage and are not reversible. The disease can pass to the unborn child, producing brain damage or abortion.

Charles Darwin was attacked in South America. His cardiomyopathy may have been chronic Chagas's disease.

Leishmaniasis Infections with related species of Leishmania, causing visceral, cutaneous, or mucocutaneous disease.Leishmania: a small (1-5 micron) protozoan which is endemic in wild animals.They look like two blue dots. They are carried by sand-flies (Phlebotomus) species, and all have important animal reservoirs.

Visceral Leishmaniasis (Kala-azar; black

fever) is caused by parasites of the L. donovani complex, and involves massive infiltration of RES (spleen, liver, nodes, marrow), and hematopoiesis eventually fails.Often the spleen reaches gigantic size (up to 3 kg). – The spleen with infected macrophages, accompanied

by marked plasmacytosis, obscures the organ’s normal architecture.

Phagocytic cells crowd in bone marrow and may also be found in the lungs, GI tract, pancreas, testes, and other organs. – The tissue reaction becomes granulomatous by time.

There is hyperpigmentation of the skinIn the kidneys, immune complex deposition and mesangial proliferation are sometimes observed, and in advanced cases amyloid deposition is frequent.Leishmania donovani is an intracellular parasite. – There are half a million cases of this dread

disease yearly, most of then in India or South America.

Cutaneous leishmaniasis – The oriental or tropical sore, the Delhi or

aleppo boil, the uta or chiclero ulcer, and forest yaws.

The causative agents are – L. major and L. tropica in southern

Europe, Asia and Africa; – L. mexicana complex in Mexico and

Central and South America; – L. braziliensis complex in Central and

South America.

Cutaneous leishmaniasis is a mild, self-healing lesion in warm countries. Eventually, the organisms are controlled by granuloma formation. Mucocutaneous leishmaniasis is common in South America and Middle East.The pathology is primarily chronic, non-healing ulcers. Diffuse cutaneous leishmaniasis occurs when there is extreme T-cell dysfunction, and look clinically much like lepromatous leprosy.

Sore is single and is usually located on exposed parts of the body. – After a long incubation period, it

begins as an itching papule suroounded by induration.

This turns into a shallow, slowly expanding ulcer with irregular borders. Most lesions involute within 6 months without requiring treatment.

Mucocutaneous Leishmaniasis

Mucocutaneous leishmaniasis is caused mainly by L. viannia braziliensis. A primary cutaneous ulcer appears, and closely resembles lesions of simple cutaneous leishmaniasis. However, mucocutaneous leishmaniasis can metastasize to nasopharyngeal tissues.– Gross mutilations of the nose and palate may

occur and require reconstructive surgery.

LeishmaniasisLeishmaniasis

HELMINTICHELMINTIC DISEASES DISEASES

In the following infestations, peripheral blood eosinophilia can be a helpful tipoff, but it is not very sensitive and not very specific: Ascariasis Filariasis Onchocerciasis Strongyloidiasis Trichinosis Visceral larva migrans

NematodeNematode (Roundworm) (Roundworm) InfectionsInfections

AscariasisAscariasis

Estimates suggest that 1 in 4 of the world’s population, or more than 1 billion people, are infected with the intestinal roundworm Ascaris lumbricoides. The vast majority of infected people are asymptomatic. Patients who are newly infected may have pulmonary symptoms (eg, cough, wheezing) and eosinophilia due to larval migration through the lungs.

The adult A. lumbricoides is a large, cream-colored worm.Ascaris lumbricoides is the largest roundworm: – Adult males are 15-30 cm in length, and adult

females are 20-35 cm in length. – Adult females lay about 200,000 eggs per day,

making diagnosis by stool examination easy.

Larvae hatch from ingested eggs in the stomach, small larvae that promptly penetrate the intestinal wall, travel through the lungs, are coughed up and swallowed, and settle in the gut.

Ascariasis causes three kinds of problems: – 1. Everyone is allergic to ascaris worm,

and these organisms can cause dyspnea as they pass through the lungs.

– 2. Infection with A lumbricoides is very rarely fatal, but death may occur because of mechanical intestinal obstruction.

– 3. Excited worms can plug a bile duct, perforate the appendix, pierce the bowel, and so forth.

Whipworm InfectionWhipworm Infectionss

TRICHURIASIS (Trichocephaliasis)Infection with Trichuris trichiura, causing abdominal pain and diarrhea.

Generally-harmless little (5 cm) worm has no tissue phase. Adult whiplike worms embed their heads into the superficial mucosa of the colon and caecum. Its eggs are ingested with fecal contamination. Heavy infections occur under conditions of poor sanitation, and can be fatal.

PinwormPinworm infections infections

Enterobiasis (oxyuriasis) Enterobius vermicularis is a small (1 cm) worm which causes night-itch when the female worm migrates to the anal skin for nightly egg-laying.

Unlike most roundworms, the life-cycle is entirely within the intestine. The infection is contagious in households. The familiar Scotch-tape test demonstrates diagnostic eggs. The worm may cause appendicitis, and pelvic inflammatory disease by migrating up the vagina and uterine cavity to the oviducts.

HHookworm infectionsookworm infections(Ancylostomiasis)(Ancylostomiasis)

Infection with Infection with Ancylostoma Ancylostoma duodenaleduodenale or or Necator americanusNecator americanus causing abdominal pain and iron-causing abdominal pain and iron-deficiency anemia.deficiency anemia.

Threadworm InfectionThreadworm Infectionss

Tapeworm infectionsCestodes

 

Intestinal tapeworm infections

Taenia saginata ...beef tapeworm Taenia solium ... pork tapeworm Hymenolepis nana... dwarf tapeworm Diphyllobothrium latum... fish tapeworm

BEEF TAPEWORM INFECTION(Taeniasis Saginata)

Infection of the intestinal tract with the cestode Taenia saginata, which is usually asymptomatic.Humans are infected by eating the cysts in raw or undercooked beef. The infection is usually asymptomatic.

PORK TAPEWORM INFECTION(Taenia Solium Infection; Cysticercosis)

Infection of the intestinal tract, often asymptomatic, with the adult cestode Taenia solium; infection with larval stages may lead to neurocysticercosis with seizures.Humans as definitive host; the infection is actually acquired (by both humans and pigs) from eating food contamined with eggs from feces. – In some of the poor nations, pigs are actually

used for human waste disposal, which keeps the epidemic going.

Humans become infected by eating Humans become infected by eating pork containing cysticerci. pork containing cysticerci. If a human ingests the egg of a pig tapeworm, it will hatch into a larva which will invade the tissues, preferring the subcutaneous tissue, subcutaneous tissue, muscle, viscera, andmuscle, viscera, and brain. Cysticercosis is the most common cause of epilepsy in many developing countries, especially in Latin America, South Africa, and India.

FISH TAPEWORM INFECTION(Diphyllobothriasis)

Infection of the intestinal tract with Diphyllobothrium latum, which is often asymptomatic but may cause vitamin B12 deficiency and megaloblastic anemia.

Infective larvae develop in the flesh of freshwater fish.

The worms mature in the human small intestine.

EchinococcosisEchinococcosis

HYDATID DISEASE(Echinococcus granulosus Infection; Echinococcosis)

Infection with larvae of Echinococcus granulosus, which may cause cysts in the liver and other organs.These tapeworms live in the intestines of dogs, which are usually symptomatic. The infections are transmitted between wolves and caribou, Eskimo sled dogs and moles, Scottish sheepdogs and sheep, etc.The disease is common in sheep-raising areas of the Mediterranean, Middle East, Australia, New Zealand, South Africa, and South America. Foci also exist in regions of Canada, Alaska, and California.

Echinococcus granulosus, causing unilocular hydatid cyst with scolices, is the most prevalent species. When a person ingests the eggs, they hatch, and the larvae go to the liver and anyplace else, where they can grow into large (>10 cm) cysts.The oncospheres penetrate the intestinal wall, migrate via the circulation, and lodge in the liver, lungs, and, less frequently, in the brain, bone, and other organs.

The larva develops slowly (usually over many years) into a large unilocular, fluid-filled cyst-the hydatid cyst. Brood capsules sprout from these cysts; within these capsules are numerous small infective scolices. Large cysts may contain several liters of highly antigenic hydatid fluid as well as millions of scolices. Daughter cysts sometimes form within or outside primary cysts.

The cyst compresses organs and can cause severe morbidity. If the cyst ruptures, anaphylaxis and sudden death is likely to result.

ALVEOLAR HYDATID DISEASE(Multilocular Echinococcosis)

The adult worms are found in foxes, and the hydatid larvae in small wild rodents. Infected dogs are the main link to occasional human infection. – The life cycle of the organism is similar to E.

granulosus.

Echinococcus multilocularis species cause multilocular (or alveolar) hydatid cysts with unrestricted budding and without scolices.

The larvae form irregular alveolar cysts The larvae form irregular alveolar cysts that usually contain no scolices. that usually contain no scolices.

The germinative tissue and brood capsules The germinative tissue and brood capsules spread rapidly and produce spongy tumors spread rapidly and produce spongy tumors that are difficult or impossible to treat that are difficult or impossible to treat surgically. surgically.

The cysts are found mainly in the liver but The cysts are found mainly in the liver but can metastasize to the lungs, lymph can metastasize to the lungs, lymph nodes, and other tissues.nodes, and other tissues.

E. multilocularisE. multilocularis is present mainly in is present mainly in Central Europe, Alaska, Canada, Central Europe, Alaska, Canada, USA USA and and Siberia. Siberia.

Trematode (Fluke) Trematode (Fluke) InfectionsInfections

Schistosomiasis is by far the most important trematode infection. About 500 million people are at risk of infection, which is spreading as new dams are built in endemic areas.

Schistosomiasis Schistosomiasis ((BilharziasisBilharziasis, , blood flukes; travellers' blood flukes; travellers'

schistosomiasis)schistosomiasis) Infection with blood flukes of the genus Schistosoma, which may cause chronic disease of the intestine, liver, and GU tract.The life cycle of blood flukes is complex and requires particular snails. The infection is acquired from contact with contaminated water. Eggs are equipped with razor-sharp spines to cut their way into the intestine.

S. haematobium affects primarily the GU system and is widely distributed over the African continent; smaller foci are present in the Middle East and India. S. mansoni is widespread in Africa and is the only species in the Western Hemisphere (in Brazil, Surinam, Venezuela, and on some Caribbean islands). S. japonicum is present only in Asia, mainly in China and the Philippines.

Three worms which inhabit the veins of humans and cause problems when their eggs elicit a tissue reaction. Schistosomiasis is in the differential diagnosis of most things, and you should learn where it can be contracted and what it can do: – S. mansoni: Africa, Latin America, Puerto Rico

(hepatic fibrosis and cirrhosis),– S. hematobium Egypt & thereabouts (bladder

fibrosis and carcinoma),– S. japonicum China, Philippines (hepatic

fibrosis and cirrhosis).

Larvae penetrate the intestinal wall and migrate through liver, lungs, CNS, eyes, and almost all other tissues. Patients present with various confusing symptoms and signs. Lots of circulating eosinophils may suggest the diagnosis, which can be confirmed serologically. Cutaneous larva migrans is a similar process, localized to the skin.

TrichinosisTrichinosis

TrichiniasisInfection with Trichinella spiralis, which may cause mild GI symptoms followed by periorbital edema, muscle pains, fever, and eosinophilia.Infection by Trichinella spiralis follows ingestion of uncooked/smoked meat (wild pork, bear) with live cysts.

The larvae are released from cysts by digestion of the wall, and a mild GI upset is likely to follow. The worms breed in the gut, dying after they release larvae into the lacteal. In people, the worms encyst in individual striated muscle cells, beyond the reach of the immune system.They cause myalgia and sometimes cardiac failure. The organisms prefer well-oxygenated muscle (the heart, diaphragm and extraocular muscles).Muscle cells invaded by larvae cause symptoms that mimic polymyositis. Soreness may affect the muscles of respiration, speech, mastication, and swallowing. Severe dyspnea may occur in heavy infections.

FILARIAL NEMATODE INFECTIONSFILARIAL NEMATODE INFECTIONS

Threadlike adult filarial worms reside in tissues.

Gravid females produce live offspring (microfilariae) that circulate in blood or migrate through tissues.

When ingested by a suitable insect (mosquitoes or flies), microfilariae develop into infective larvae that are inoculated or deposited on the skin during the insect bite.

Only a few worm species regularly infect humans.

These problems are widespread in the tropics.

Lymphatic Filariasis Infections with 3 species of Infections with 3 species of FilarioideaFilarioidea, which , which may lead to acute adenolymphangitis and may lead to acute adenolymphangitis and chronic lymphedema, hydroceles, or chyluria.chronic lymphedema, hydroceles, or chyluria.Lymphatic filariasis is caused by Lymphatic filariasis is caused by Wuchereria Wuchereria bancrofti, Brugia malayi,bancrofti, Brugia malayi, or or B. timori,B. timori, which is which is spread by mosquitoes. spread by mosquitoes. Infective larvae escape from the proboscis as Infective larvae escape from the proboscis as the mosquito bites, enter the puncture the mosquito bites, enter the puncture wound, and migrate to the lymphatics, where wound, and migrate to the lymphatics, where they develop into adult worms within 6 to 12 they develop into adult worms within 6 to 12 mo. mo. Gravid females produce microfilariae that Gravid females produce microfilariae that circulate in blood.circulate in blood.

The larvae travel by way of the bloodstream. The mature worms (living or dead) harm the patients by plugging lymphatics, and producing granulomas and scarring which further obstruct the lymphatic channels.Heavy infestation results in chronic lymphedema (elephantiasis) of the genitals and less often of the extremities. The immune response varies greatly even within a community. Most people mount a good allergic response to these worms. A systemic illness with a high eosinophilic count is common.

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