Opportunistic Infections in Immunocompromised Patients
Moderator: Dr. Paul Hofman
Section 2 -
Diagnosis of Select Parasitic Infections in the Immunocompromised Host
Ronald C. Neafie
Chief, Parasitic Disease Pathology Branch
Department of Environmental and Infectious Disease Sciences
Armed Forces Institute of Pathology
An elderly man with Hodgkin Disease for several years had been treated with chemotherapy. Terminally,
he developed clinical evidence of central nervous system disease that was thought to be progressive
multifocal leukoencephalopathy (PML). His condition gradually deteriorated, and he died. Autopsy was
limited to examination of the brain. Grossly, there were 2 foci suggestive of areas of softening and
The tachyzoites of Toxoplasma gondii are free in tissue or in groups. In
fresh preparations and smears, they are crescentric-shaped with a maximum size of 7 mm by 1-3 mm and have
a prominent nucleus near the middle of the parasite. In tissue sections, they are round or oval and 2-3
m m in diameter, have a prominent spherical nucleus, and divide by binary fission. Bradyzoites occur in
cysts, which have a maximum diameter of 100 mm and a thin cyst wall. Individual bradyzoites are
morphologically nearly identical to tachyzoites.
The differential diagnosis of toxoplasmosis includes histoplasmosis, leishmaniasis, Chagas disease,
cytomegalovirus (CMV) infection, sarcocystosis, and microsporidiosis. Histoplasma
capsulatum is GMS-positive, shows budding, and contains vacuoles. Amastigotes have kinetoplasts.
The intracytoplasmic inclusions of CMV lack nuclei. The cysts of Sarcocystis are larger and have septa. Microsporidia are elongate, birefringent,
and variably staining.
A 34 year-old man from Colorado with AIDS presented with a 4 month history of fever, night
sweats, intractable cough and weight loss. He was treated with trimethoprim-sulfamethoxazole prophylaxis
for pneumocystosis. Previous biopsies of bone marrow, tongue ulcer and maxillary sinus contents were
unrewarding. Open lung biopsy was performed, and small ovoid unidentified structures were observed.
The spores of Encephalitozoon cuniculi are ovoid to elongate and 2-3 mm
by 1.0-1.5 mm. They stain poorly with hematoxylin-eosin. Frequently there is a thin band across the
spore. Some spores are birefringent, acid-fast, and gram positive.
A 38 year-old man from Maine had a history of AIDS for 1 year when he developed viral hepatitis and
pneumocystosis. He was admitted to hospital with weakness, anorexia, bloody stools, vomiting, and
extreme weight loss. His course was steadily downhill, and the patient expired about 2 months after
Cryptosporidium parvum oocysts lie within a p arasitophorous vacuole that
is within the microvillous border just below the plasma membrane. It is intracellular but
extracytoplasmic. Oocysts are spherical and 2-6 m m in diameter. Oocysts in stool specimens are
acid-fast when stained with modified Kinyoun, but are not acid-fast in tissue sections.
The differential diagnosis of cryptosporidiosis includes Cyclospora sp.
and Isospora belli. In tissue, variable morphologic forms of Cyclospora sp. or Isospora belli are within vacuoles
of enterocytes. In stool specimens, oocysts of Cyclospora sp. are 8-10 m m
in diameter, and oocysts of Isospora belli are 20-33 mm in length. Both are
acid-fast with modified Kinyoun stain.
A 38 year-old HIV-positive man from El Salvador residing in Virginia was admitted to hospital
semicomatose. A laboratory technician saw moving organisms during routine cell count of his
cerebrospinal fluid. The patient developed AIDS and died shortly thereafter.
Diagnosis: Chagas Disease
Amastigotes of Trypanosoma cruzi are found in myofibers and
brain. They are spherical, and 1-5 mm in diameter, and have cytoplasm with a round nucleus and a
rod-shaped kinetoplast. The trypomastigote form is found in peripheral blood. It is elongate
(frequently C-shaped) and 16-22 m m long and has cytoplasm with an oval nucleus and a round terminal
kinetoplast, an undulating membrane and a free flagellum.
The differential diagnosis of Chagas disease includes other trypanosomiasis and
leishmaniasis. The trypomastigotes of Trypanosoma rangeli are larger than
those of T. cruzi (25-50 mm), have a small kinetoplast, are not C-shaped,
and divide in peripheral blood. The trypomastigotes of Trypanosoma
rhodesiense/gambiense are also larger (14-33 mm), have a small kinetoplast, are not C-shaped, and
divide in peripheral blood. The amastigotes of Leishmania sp. are smaller
(2-3 mm) and are usually in different anatomic sites and host cells.
A 42 year-old Lebanese man with AIDS had been residing in the U.S.A. for 2 years when he
developed multiple nodular masses of his arms and legs. Clinically, the nodules were suggestive of
Kaposi sarcoma. The patient also had a clinical history of CMV infection and presumptive toxoplasmosis
encephalitis. A skin biopsy was taken of the left upper arm.
Diagnosis: Granulomatous Amebic Encephalitis (GAE)
Acanthamoeba sp. trophozoites are round to oval and 15-45
mm in diameter. They have foamy cytoplasm and are uninucleate with a large dense central karyosome.
They divide by binary fission. The cysts are spherical and 16-30 mm in diameter. They also have foamy
cytoplasm and are uninucleate with a large dense central karyosome. They are double-walled with an outer
wrinkled ectocyst and an inner round endocyst.
The differential diagnosis of GAE includes infection by Naegleria
fowleri or Entamoeba histolytica. The trophozoites of N. fowleri are smaller (9-14 mm) and uninucleate. The trophozoites of E. histolytica are similar in size (15-25 mm) to those of Acanthamoeba sp., but have anucleus with a tiny
karyosome. Neither N. fowleri or E. form
cysts in tissue
A 56 year-old man living in Kentucky presented with chills, fever, and headache.
Splenectomy had been performed 8 years previously. He had recently killed a deer that had ticks, but had
no known tick bites. During his work-up, the contributor noticed numerous intracellular organisms within
Babesia sp. are malaria-like parasites found in
normal-sized erythrocytes. On Giemsa stained blood smears, they have blue cytoplasm and red chromatin
material. They may be spherical, oval, pyriform, and rod-shaped. They are 1-5 m m and are frequently in
pairs or rarely in tetrads.
The differential diagnosis of babesiosis includes malaria. Compared to Plasmodium sp. parasites, Babesia sp. are smaller,
more pleomorphic and occur within normal sized erythrocytes.
A 60 year-old man living in California was diagnosed with asthma and treated with
steroids. Duodenal biopsy revealed unidentified nematodes. The pathologist notified the pulmonologist
and suggested a possible relationship between the nematodes and his asthma. The pulmonologist responded
that the patient was improving on steroids. He then developed lower gastrointestinal tract bleeding, and
colectomy was performed. Nematodes were found in the colon, appendix and ileum.
The adult parasitic female is parthenogenic, 2-3 mm by 30-60 m m, and contains eggs in
uteri. The eggs are oval, 50-60 mm by 30-35 mm, thin-shelled, and embryonated. Rhabditiform larvae are
200-400 mm by 10-20 mm and have an esophagus with a bulb and no alae. Filariform larvae are 300-600 mm
by 10-20 mm and have an esophagus without a bulb, minute double lateral alae, and a notched tail.
The differential diagnosis of strongyloidiasis includes intestinal capillariasis,
angiostrongyliasis costaricensis, toxocariasis and ancylostomiasis (hookworm infection). The adult worms
of Capillaria philippinensis have astichosome
in a long anterior end, bacillary bands, and eggs with bipolar plugs. The larvae of C. philippinensis have a stichosome in a long anterior end and no alae. The
larvae of Angiostrongylus costaricensis have
single lateral alae and are 8-11 mm in diameter. The larvae of Toxocara canis
have single lateral alae and are 8-21 mm in diameter. The eggs of hookworms are indistinguishable
from those of S. stercoralis.
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