Pathology of

Parasitic Infections

Julie A Ribes, MD, PhD

Director of Clinical Microbiology

UK HealthCare

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Objectives

• Identify structures in tissues/fluids that should make

you think of parasites

• Describe inflammatory changes that may result from

parasitic infections

• Delineate parasite-tissue tropisms

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Measure about 110-150 uM in length

A Urine was submitted to cytology (PAP stain) from

a 36-year-old emigrant from the Republic of Congo

for evaluation of recent onset of dysuria, hematuria

and increased urinary frequency

130 uM

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~140 uM

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~120 uM in length

www.cdc.gov

Range 112-170 uM

Range of egg size seen

~120- 150 uM

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Schistosomiasis:

Stages Found in

Human Tissues and

Fluids

1. Adult worms

2. Eggs

3. Egg contents

(miracidia)

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Eggs in Bladder Tissue

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Schistosome Adult Worms in Vessels

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Schistosome Tropism

Species Adult Location Egg Location

Schistosoma mansoni Veins of colon and lower

ileum

Portal veins of liver

Shed in stool

Seen in colonic mucosa and

liver

Schistosoma haemotobium Veins of the bladder and

lower rectum

Shed in urine and infrequently

seen in stool

Seen in bladder wall

Schistosoma intercalatum Veins of rectum Shed only in stool, not urine

Seen in rectal mucosa

Schistosoma japonicum

Schistosoma mekongi

Veins of the small

intestine

Shed in stool

Seen in intestinal mucosa

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Schistosoma mansoni in liver

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Schistosma masoni in Colon Wall

1310x 50x

Schistosomiasis Summary

• Eosinophils in blood, fluids, tissues should make you think of parasitic infection with helminths

• Eggs in urine/stool with knobs and spines should make you think of a schistosomal infection

• Male and female worms in vessels should make you think of schistosomes

• Tissue tropism will suggest the specific schistosome causing the infection

• Ciliates in urine should make you think of Schistosoma haematobium

• Eggs are often distorted and fractured so ID of diagnostic knobs and spines may be difficult – egg size and tropism may be helpful

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The patient is a 64-year-old Vietnamese man who had lived in the United States for

decades – specifically in KY. He was diagnosed with a non-Hodgkin’s lymphoma for

which he had undergone transplantation. He was immunosuppressed to support the

transplant (Cellcept and Prednisone). Following a prednisone taper, the patient was

admitted for evaluation of diarrhea and weakness. An endoscopic biopsy of his

duodenum was taken when ulcerative lesions were detected as part of this work up.

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50 um

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30 um Hookworm egg

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50 um

Strongyloidiasis:

Stages Found in

Human Tissues and

Fluids

1. Adult worms

2. Eggs

3. Larvae

a. Filariform

b. Rabditiform

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www.cdc.gov

Larvae of Strongyloides and Hook worm

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www.cdc.gov

Larvae of Strongyloides and Hook worm

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Colon Full of Eosinophils

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Filariform Larvae Invading Colon Wall

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Strongyloides stercoralis Hyper infection

Syndrome

• Strong association with steroids

• Filariform larvae may be found in any tissue

• Sepsis or fungemia often noted

• Meningitis with GNR, Enterococci, or non-

cryptococcal yeasts should raise suspicion

• Often fatal

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Filariform Larvae Transiting

Through Lung

Wright’s Giemsa GMS

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Pap

Strongyloidiasis Summary

• Eosinophils in blood, fluids, tissues should make you think of parasitic infection with helminths – for Strongyloides, eosinophilia is variable

• Inflammation is variable – patients are often profoundly immunocompromised

• Female worms in small intestinal crypts should make you think of Strongyloides

• Eggs resembling those of Hook worm retained within the intestinal crypts should make you think of Strongyloides

• Embryonated eggs in the intestinal crypts should make you think Strongyloides

• History of recent steroid use should make you think of Strongyloides hyper infection symdrome

• Filariform larvae look like “speckled bands” on H&E may be seen in colon and other tissues in hyper infection syndrome

• Filariform larvae may be seen in BAL and sputum

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A 60-year-old female with Hodgkin’s Disease presented for increased

lethargy and phantosmia during a period of chemotherapy-induced

neutropenia. Head MRI demonstrated lesions in the occipital and

parietal lobes. Once admitted, she demonstrated a rapid decline in

neurological status. A brain biopsy was obtained.

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Organism as Seen in Ocular

Infections

Trophs on Wright’s Giemsa Wet Mount of Cysts

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A 10 year-old child presented with headache and somnolence.

Three weeks PTA, the patient had participated in fresh-water

activities in 3 states during summer vacation. An LP was

obtained and showed a depressed glucose and elevated protein.

A Wright’s Giemsa stained cytocentrifuge slide of CSF is shown:

35Images provided by Dr. Kristi Adams

A 10 year-old child presented with headache and somnolence. Three weeks

PTA, the patient had participated in fresh-water activities in 3 states during

summer vacation. An LP was obtained and showed a depressed glucose and

elevated protein and many neutrophils. A second CSF was obtained 2 days

later and stained with Wright’s Giemsa. Specimen was sent to the CDC for

additional testing.

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Free-Living Amoebic

Infections:

Stages Found in

Human Tissues and

Fluids

1. Trophozoites

2. Possibly cysts

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Acanthamoeba

Free-Living Amoebic Tropisms and

Inflammatory Responses

Species Tissue Forms Seen Inflammatory Response

Acanthamoeba Keratitis mostly,

granulomatous

meningoencephalitis

Double-walled

Cysts & trophs

Chronic, granulomatous,

prominent necrosis,

rarely neutrophilic

Balamuthia Nodular meningo-

encephalitis

Triple-layered

Cysts & trophs

Chronic,

Prominent necrosis

Naegleria Primary amoebic

meningoencephalitis

Trophs only Neutrophilic infiltrate

with tissue necrosis

Entamoeba

histolytica

Colonic and skin

ulcers, liver, lung and

other organ abscesses,

rarely CNS

Trophs seen in

tissue, abscess

Cysts & trophs

seen in stool

Abscess formation,

necrosis extensive

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Free-Living Amoeba Summary

• Trophozoites in tissue/fluids may be very subtle

• Trophozoites in tissue/fluids may be decomposed

• Cysts in tissues/fluids may not be present based on the organism

• The inflammatory response varies from acute neutrophilic, to chronic, granulomatous, or necrotic based on organism

• CDC has special stains and PCRs to assist with dx.

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A 10-year-old male presents with a acute abdomen and

is taken to surgery for the removal of a probable

perforated appendix. The H&E images shows a

structure seen in the lumen.

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Enterobiasis:

Stages Found in Human

Tissues and Fluids

1. Adult worms

2. Eggs

1. Non-embryonated

2. Embryonated

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Stages of Enterobius seen in Stool

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Enterobiasis Summary

• See worms in the appendix, look for cuticular darts

(alae)or eggs in the uterus for identification

• See cuticular darts (alae) on the cross section of the

worm, think Enterobius vermicularis

• See eggs in the uterus with one flattened and one

convex side, think Enterobius vermicularis

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The patient is a 33-year-old recent emigrant from Thailand who

presented with chronic cough productive of non-bloody sputum

and weight loss. Three sputa were negative for AFB, but

demonstrated the following finding:

~60 x 120 uM

Auramine O stain for AFB44

Comparison with D. latum Egg

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58-75 x 40-50 uM

80-120 x 45-50

Paragonimiasis:

Stages Found in

Human Tissues and

Fluids

1. Adult worms

2. Eggs

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Paragonimus Fluke in Lungwhole fluke Cuticle Vitelline follicle

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Paragonimus Eggs

in Lung

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Paragonimiasis Summary

• 2 Adult flukes generally encyst in well-developed capsules in the lung parenchyma

• Lonely flukes may wander into other organs

• Adults are “medium sized” 4-6mm wide – 7.5-12 mm long

• Paragonimus flukes have pink spines, vitellaria, ovaries, testes and a uterus containing eggs, as well as suckers

• What you see depends on the cut through the fluke

• Eggs are seen in the uterus, capsule, surrounding tissue and in the bronchus – measure up and look for morphology

• Eggs are shed in sputum and, when swallowed, in stool

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A sushi-eating native from Japan presents for evaluation of anorexia,

diarrhea, jaundice and eosinophilia. The patient was diagnosed with a

probable colangiocarcinoma. On autopsy, the following were found in the

bile ducts:

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ovary

Uterus with eggs

Cuticle, no spines

Ventral suckers

Close up of the Uterus

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Egg Size =12-19 uM x 27-35 uM

Clonorchiasis:

Stages Found in

Human Tissues

and Fluids

1. Adult Fluke

2. Eggs

a. In utero

b. In bile

c. In stool

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Divided Testicles Vitellarian Follicles

Ovary Uterus

Oral sucker

Ventral sucker

Whole fluke measures 5.5-10 mm to 0.8-1.5 mm

Eggs measure 27-35 um by 12-19 um

Clonorchiasis Summary

• Adult flukes generally live in liver bile ductules, rarely in the bile or pancreatic ducts

• Adults are “small” 5.5-10 mm long by 0.8-1.5 mm wide

• Flukes have vitellaria, ovaries, testes and a uterus containing eggs, and suckers

• Clonorhis has no spines in the cuticle

• What you see depends on the cut through the fluke

• Eggs are seen in the uterus– measure up and look for morphology

• Eggs are shed in stool

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A hunter sacked a bear and then fed it to his extended family as a substitute for

hamburger meat. Two days after the picnic, family members began

complaining of abdominal pain and diarrhea that persisted for several days and

then passed. The next week after the meal, relatives developed fever, myalgia,

and periorbital edema. CBC demonstrated eosinophilia. Symptoms were most

severe in those who at the burgers cooked rare. Muscle biopsy taken at >6mos.

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Stitchosome =

anterior, multi-

celled end of

the larva

containing the

embedded

esophagus50x

Trichinellosis:

Stages Found in

Human Tissues

and Fluids

1. Adult worms

2. Larvae

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Tissues Involved with Infection

Adult worms

• Small bowel intestinal crypts

• Larvae are released starting at day 8 following infection

• Inflammation is lymphocytic and eosinophilic

• Adults live up to 16 weeks before being expelled

Larvae• Exit bowel by penetrating through the mucosa –

may look like microfilaria in bowel wall

• They migrate through many organs and tissues, but only encyst and mature in skeletal muscle

• Migration stimulates intense acute and eosinophilic inflammation

• Death seen during migration in a dose-dependent manner

• Encysted larvae persist until the host dies or is eaten

• Dead encysted larvae may calcify, young non-encysted larvae in non-skeletal muscle die and abscess

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Trichinellosis Summary

• Striated (skeletal) muscle with encapsulated larvae –think Trichinella species

• Small bowel with small worms in crypts, but no eggs, think Trichinella species – look for the stitchosome too!

• Eosinophilia should make you think of any migrating helminth

• Small abscesses in multiple tissues other than striated muscle should make you think of trichinellosis

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The patient was a homeless man who presented

to the ED with complaints of decreased vision

due to an exudate coming from his tear ducts.

The patient was a tampon-wearer who

presented for her routine pelvic. This

fellow was found in the specimen.

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Know Your Entomologists

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Translation, please?

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Lung Biopsy, R/O Parasite

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Myiasis: Stages

Found in Human

Tissues and

Fluids

1. Maggots (larvae)

2. Pupae

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Types of Myiasis

• Primary or Specific Myiasis

• Maggot requires living host tissue to complete its life cycle

• Secondary or Semispecific Myiasis

• Maggot lives in dead or decaying plant or animal matter (usually smells very bad): example wound, oral, or medicinal myiasis

• Accidental Myiasis

• Fly lays eggs in food and host ingests eggs and contracts gastric myiasis

• Factitious Myiasis

• Maggots in human or animal specimens not representing actual infection of the host (e.g. Maggots emerging from eggs laid in stool, maggots in food vomited or passed in stool)

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Myiasis Summary

• Entomologists are your friends as long as the maggot is intact

• Maggots have pigmented spines that can be seen coming from the larval cuticle- may be a clue to dx

• Not all “worms” seen in clinical specimens represent true parasitism

• Not all structures submitted as worms are indeed worms…..

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Take Home Messages From these Cases

• Microbiologists can contribute to anatomic diagnoses

• Develop a differential based on tissue/location

• Develop a differential based on stages of the parasite

seen

• Measure up (eggs and worms alike)

• Eosinophilia does not accompany all parasite infection

• Knowing parasite life cycles can be useful

References

• Thomas Orihel and Lawrence Ash. 1995. Parasites

in Human Tissues. ASCP Press.

• Lawrence Ash and Thomas Orihel. 2007. Atlas of

Human Parasitology. ASCP Press.

• www.CDC.gov

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