This document discusses various parasitic infections caused by protozoa and metazoa. It describes the life cycles and pathologies of malaria, caused by Plasmodium parasites transmitted by mosquitoes; leishmaniasis, caused by Leishmania parasites transmitted by sandflies; tapeworm infections such as cysticercosis caused by Taenia solium larvae; hydatid disease caused by Echinococcus granulosus; schistosomiasis caused by blood flukes of the genus Schistosoma transmitted by snails; and lymphatic filariasis caused by Wuchereria bancrofti transmitted by mosquitoes. For each parasite, it details the clinical manifestations, histopathology, and

1. Parasitic Infections
PROTOZOA :
 Protozoa are unicellular, eukaryotic organisms.
transmitted by insects or by fecal-oral route.
 in humans mainly occupy the blood or intestine.
Malaria :
 caused by intracellular parasite Plasmodium.
 Plasmodium falciparum , P. vivax, P. ovale, and P. malariae
are transmitted by female Anopheles mosquitoes.
Life Cycle and Pathogenesis:
 P. vivax, P. ovale, and P. malariae : cause low parasitemia, mild
anemia, and rarely splenic rupture and nephrotic syndrome.
 P. falciparum: causes high levels of parasitemia, severe
anemia, cerebral symptoms, renal failure, pulmonary edema,
and death.

2.  The infectious stage of malaria, the sporozoites, is found
in salivary glands of female mosquitoes.
 When mosquito takes a blood meal, sporozoites are
released into human's blood and within minutes attach
to and invade liver cells by binding to hepatocyte
receptors for serum proteins thrombospondin and
properdin.
 Within liver cells, malaria parasites multiply rapidly, so
merozoites (asexual haploid forms) are released when
each infected hepatocyte ruptures.
 Once released from liver, merozoites bind by a parasite
lectin-like molecule to sialic residues on glycophorin
molecules on surface of red blood cells.

3.  Within red blood cells, the parasites grow in
a membrane-bound digestive vacuole, hydrolyzing
hemoglobin through secreted enzymes.
 The trophozoite is first stage of parasite in red blood cell
and is defined by presence of a single chromatin mass.
 The next stage, the schizont, has multiple chromatin
masses, each of which develops into a merozoite.
 On lysis of red blood cell, the new merozoites infect
additional red blood cells.
 Although most malaria parasites within red blood cells
develop into merozoites, some parasites develop into
sexual forms called gametocytes that infect the mosquito
when it takes its blood meal.

4. Morphology:
 Initially congestion and enlargement of spleen, and there is
increased phagocytic activity of macrophages in spleen.
 In chronic malaria infection, the spleen becomes increasingly
fibrotic and brittle, with thick capsule and fibrous trabeculae.
 the liver becomes progressively enlarged and pigmented.
 Kupffer cells are heavily laden with malarial
pigment, parasites, and cellular debris.
 Pigmented phagocytic cells may be found in bone
marrow, lymph nodes, subcutaneous tissues, and lungs.
 In malignant cerebral malaria caused by P. falciparum, brain
vessels are plugged with parasitized red cells .
 About the vessels, there are ring hemorrhages that are
probably related to local hypoxia.

5. [MALARIAL PARASITES IN BLOOD]. Note the presence of two chromatin dots in each
trophozoite inside red blood cells. Note also the two trophozoites in another red blood cell.
The presence of two chromatin dots and two trophozoites is a feature of P. falciparum.

6. Leishmaniasis:
 Leishmaniasis is a chronic inflammatory disease of
skin, mucous membranes, or viscera.
 caused by obligate intracellular kinetoplastid protozoan
parasites transmitted through the bite of infected
sandflies
Pathogenesis:
 The life cycle of Leishmania involves two forms:
 the promastigote, which develops and lives
extracellularly in sandfly vector.
 the amastigote, which multiplies intracellularly in host
macrophages.
 Mammals, including rodents, dogs, and foxes, are
reservoirs of Leishmania.

7.  The promastigotes are phagocytosed by macrophages,
and acidity within phagolysosome induces them to
transform into round amastigotes that lack flagella but
contain a single DNA-containing specialized
mitochondrion called kinetoplast.
 Amastigotes proliferate within macrophages, and dying
macrophages release progeny amastigotes which can
infect additional macrophages
Morphology:
Leishmania species produce four different lesions in
humans: visceral, cutaneous, mucocutaneous, and
diffuse cutaneous.

8. visceral leishmaniasis:
 caused by L. donovani or L. chagasi.
 parasites invade macrophages throughout mononuclear
phagocyte system and cause hepatosplenomegaly,
lymphadenopathy, pancytopenia, fever, and weight loss.
 Phagocytic cells crowd the bone marrow and also may
be found in lungs, gastrointestinal tract, kidneys,
pancreas, and testes.
 there is hyperpigmentation of skin in extremities, that is
why the disease is called kala-azar or "black fever" .
 In kidneys, there may be an immune complex-mediated
mesangioproliferative glomerulonephritis.
 in advanced cases, there may be amyloid deposition.

9. A bone marrow aspirate shows intracellular and extracellular amastigotes (A), the form of
the leishmania organism that lacks an exteriorized flagellum. The kinetoplast is an
independently replicating organelle in the mitochondrion of the organism. AN denotes

10. Cutaneous leishmaniasis:
 caused by L. major, L. mexicana, and L. braziliensis.
 The lesion (often called tropical sore) begins as itching
papule surrounded by induration.
 changes into a shallow ulcer with irregular borders, and
usually heals by involution within 6 months without
treatment.
 On microscopic examination, the lesion is
granulomatous, usually with many giant cells and few
parasites.

11. .
Histology of cutaneous leishmaniasis (H&E stain): a) Diffuse chronic inflammatory cell
infiltrate in dermis with multiple non-caseating granulomata (×40); b) Tuberculoid-type
granuloma with central histiocytes and peripheral inflammatory cells (×100); c) Leishman-
Donovan bodies (arrows) within cytoplasm of epithelioid histiocytes (×600); d) Langhans
type giant cells (arrows) within a granuloma (×600).

12. Mucocutaneous leishmaniasis:
 caused by L. braziliensis.
 Moist, ulcerating or nonulcerating lesions, develop in
larynx and at mucocutaneous junctions of nasal septum,
anus, or vulva.
 On microscopic examination, there is mixed
inflammatory infiltrate with parasite-containing
histiocytes in association with lymphocytes and plasma
cells.
 Later, the tissue reaction becomes granulomatous, and
the number of parasites declines.
 Eventually, the lesions remit and scar, although
reactivation may occur after long intervals.

13. Diffuse cutaneous leishmaniasis :
 is a rare form of dermal infection.
 begins as a single skin nodule, which continues spreading
until the entire body is covered by bizarre nodular
lesions, which resemble keloids or large verrucae.
 The lesions do not ulcerate but contain vast aggregates of
foamy macrophages stuffed with leishmania.

14. METAZOA :
 are multicellular, eukaryotic organisms.
 are contracted by eating the parasite, often in
undercooked meat, and by direct invasion of host
through skin and through insect bites.
 They dwell in many sites of body, including intestine,
skin, lung, liver, muscle, blood vessels, and lymphatics
Tapeworms (Cestodes):
 Taenia solium and Echinococcus granulosus are cestode
parasites (tapeworms) that cause cysticercosis and
hydatid infections, respectively.
 Both diseases are caused by larvae that develop
following ingestion of tapeworm eggs.

15. T. solium:
 tapeworms consist of a head (scolex) that has suckers
and hooklets that attach to intestinal wall, and a neck
and many flat segments called proglottids that contain
male and female reproductive organs.
 T. solium can be transmitted to humans in two ways:
(1) Ingestion of undercooked pork containing larval cysts,
called cysticerci, leads to development of adult
tapeworms in intestine.
(2) When intermediate hosts (pigs or humans) ingest
eggs in food or water contaminated with humanfeces.
 the larvae hatch, penetrate the gut wall, disseminate
hematogenously, and encyst in many organs.

17.  Convulsions, increased intracranial pressure, and
neurologic disturbances are caused by T. solium cysts in
brain tissue.
 When cysticerci degenerate, an inflammatory response
develops.
Taenia saginata (the beef tapeworm), and
Diphyllobothrium latum ( the fish tapeworm ).
 are acquired by eating undercooked meat or fish.
 In humans, these parasites live only in gut, and they do
not form cysticerci
.

18. Hydatid disease:
 caused by ingestion of eggs of echinoccal species.
 Echinococcus granulosus, and Echinoccus multilocularis.
 Humans are accidental intermediate hosts, infected by
ingestion of food contaminated with eggs shed by dogs
or foxes.
 Eggs hatch in duodenum and the larvae invade liver,
lungs, or bones.
 Unilocular cysts caused by E. granulosus .
Multilocular cysts are caused by E. multilocularis.
Morphology:
 About two-thirds of human E. granulosus cysts are found
in liver, 5% to 15% in lung, and the rest in bones and
brain or other organs.

19.  In various organs, the larvae lodge within capillaries and
first incite an inflammatory reaction composed principally
of mononuclear leukocytes and eosinophils.
 Many such larvae are destroyed, but others encyst.
 The cysts begin at microscopic levels and progressively
increase in size, so that in 5 years or more, they may have
achieved dimensions of more than 10 cm in diameter.
 Enclosing opalescent fluid is an inner, nucleated,
germinative layer ; and an outer, opaque, nonnucleated
layer.
 The outer nonnucleated layer has delicate laminations
made up of many layers of gelatin.

20.  Outside this layer, there is a host inflammatory reaction
that produces a zone of fibroblasts, giant cells, and
mononuclear and eosinophilic cells.
 In time, a dense fibrous capsule forms.
 When these cysts have been present for about 6 months,
daughter cysts develop within them.
 These appear first as minute projections of germinative
layer that develop central vesicles and thus form tiny
brood capsules.
 Scolices of worm develop on inner aspects of these
brood capsules

21. Histopathology of hydatid cyst.

22. Schistosomiasis :
caused by Schistosoma mansoni , Schistosoma japonicum,
Schistosoma mekongi, and Schistosoma haematobium.
Pathogenesis:
 Infectious schistosome larvae (cercariae) swim through
fresh water and penetrate human skin with the aid of
powerful proteolytic enzymes that degrade the
keratinized layer.
 Schistosomes migrate into peripheral vasculature,
traverse to lung, and settle in portal or pelvic venous
system, where they develop into adult male and female
schistosomes.
 Females produce hundreds of eggs per day, around which
granulomas and fibrosis form.

23.  Some schistosome eggs are passed from portal veins
through intestinal wall into colonic lumen, are shed with
feces, and release into freshwater miracidia that infect
snails to complete the life cycle.
Morphology:
 In mild S. mansoni or S. japonicum infections, white, pin
head-sized granulomas are scattered throughout gut and
liver.
 At the center of granuloma is schistosome egg, which
contains a miracidium; this degenerates over time and
calcifies.
 The granulomas are composed of
macrophages, lymphocytes, neutrophils, and eosinophils.

24. Histopathology of schistosomiasis haematobia, bladder Histopathology of bladder shows
eggs of Schistosoma haematobium surrounded by intense infiltrates of eosinophils.

25.  The surface of liver is bumpy, whereas cut surfaces reveal
granulomas ,and a widespread fibrous portal
enlargement without distortion of intervening
parenchyma.
 Because these fibrous triads resemble the stem of a pipe,
the lesion is named pipe-stem fibrosis.
 these portal triads , causing portal hypertension and
severe congestive splenomegaly, esophageal varices, and
ascites.
 In S. haematobium infection, bladder inflammatory
patches due to massive egg deposition and granulomas
appear early, and when they erode, they cause
hematuria.

26.  Later, the granulomas calcify and develop a "sandy" appearance,
which, if severe, may line the wall of bladder and cause a dense
concentric rim (calcified bladder) on radiographic films.
 The most frequent complication of S. haematobium infection is
inflammation and fibrosis of ureteral walls, leading to obstruction,
hydronephrosis, and chronic pyelonephritis.
 There is also an association between urinary schistosomiasis and
squamous cell carcinoma of bladder.
Lymphatic Filariasis :
transmitted by mosquitoes and caused by nematode Wuchereria
bancrofti.
filariasis causes a spectrum of diseases:
(1) asymptomatic microfilaremia.
(2) chronic lymphadenitis with swelling of dependent limb or
scrotum (elephantiasis).
(3) tropical pulmonary eosinophilia.

27. Pathogenesis:
 Infective larvae released by mosquitoes during blood
meal develop within lymphatic channels into adult males
and females, which mate and release microfilariae that
enter into bloodstream.
 When mosquitoes bite infected individuals, they can
take up the microfilariae and transmit the disease.
 adult filariae secrete factors that are capable of causing
lymphatic dilation, lymphedema, and elephantiasis.
 In contrast, microfilariae, even in massive numbers are
not directly toxic to host.

28.  adult filariae factors include:
(1) surface glycoproteins with antioxidant function.
(2) cysteine protease inhibitors, which impair MHC class II
antigen-processing pathway;
(3) serine protease inhibitors, which inhibit neutrophil
proteases
(4) homologues of TGF-β, which can bind to TGF-β receptors
and downregulate inflammatory responses.
 In chronic lymphatic filariasis damage to lymphatics is
caused directly by adult parasites and by a TH1-mediated
immune response, which stimulates formation of
granulomas around adult parasites.

29.  Finally, IgE-mediated hypersensitivity to microfilariae
result in tropical pulmonary eosinophilia.
 IgE and eosinophils may be stimulated by IL-4 and IL-5,
respectively secreted by filaria-specific TH2 helper T cells.
 Tropical pulmonary eosinophilia results in restrictive lung
disease.
Morphology:
 Chronic filariasis is characterized by persistent
lymphedema of scrotum, penis, vulva, leg, or arm .
 Frequently, there is hydrocele and lymph node
enlargement.
 In severe and long-lasting infections, chylous weeping of
enlarged scrotum may ensue, or a chronically swollen leg
may develop.

30.  Elephantoid skin shows dilation of dermal lymphatics with
widespread lymphocytic infiltrates and focal cholesterol
deposits.
 the epidermis is thickened and hyperkeratotic.
 Adult filarial worms—live, dead, or calcified—are present
in scrotal draining lymphatics or nodes, surrounded by
(1) mild or no inflammation, (2) intense eosinophilia with
hemorrhage and fibrin, or (3) granulomas.
 Lung involvement by microfilariae is marked by
• eosinophilia caused by TH2 responses and cytokine
production (tropical eosinophilia); or by
• dead microfilariae surrounded by stellate, hyaline,
eosinophilic precipitates embedded in small epithelioid
granulomas (Meyers-Kouvenaar bodies).

31. Lymphatic filariasis (LF) is caused by
filarial nematodes Wuchereria bancrofti,
Cross-sectional view of a filarial nematode in
spermatic cord, with surrounding intense eosinophilic inflammatory infiltrate .
U = uterine tubes. M = musculature. I = intestine. C = cuticle.

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