eMedicine Specialties > Infectious Diseases > Parasitic Infections

Toxoplasmosis: Differential Diagnoses & Workup

Author: Murat Hökelek, MD, PhD, Technical Consultant of Parasitology Laboratory, Associate Professor, Department of Clinical Microbiology, Ondokuz Mayis University Medical School, Turkey
Contributor Information and Disclosures

Updated: Jan 27, 2009

Differential Diagnoses

Brain Abscess
Metastatic Cancer, Unknown Primary Site
Catscratch Disease
Mycosis Fungoides
Cytomegalovirus
Pneumocystis Carinii Pneumonia
Herpes Simplex
Sarcoidosis
Histoplasmosis
Sepsis, Bacterial
Infectious Mononucleosis
Syphilis
Leprosy
Tuberculosis
Listeria Monocytogenes
Tularemia
Lymphoma, Lymphoblastic

Other Problems to Be Considered

Congenital toxoplasmosis -Rubella, encephalopathies, erythroblastosis fetalis
Toxoplasma encephalitis - Vasculitis, progressive multifocal leukoencephalopathy, tumor

Workup

Laboratory Studies

  • The diagnosis of toxoplasmosis is confirmed with the demonstration of T gondii organisms in blood, body fluids, or tissue.
  • Isolation of T gondii from amniotic fluid is diagnostic of congenital infection by mouse inoculation.
  • Lymphocyte transformation to T gondii antigens is an indicator of previous toxoplasmosis in adults.
  • Detection of T gondii antigen in blood or body fluids via enzyme-linked immunosorbent assay (ELISA) technique indicates acute infection.
  • The Sabin-Feldman dye test is a sensitive and specific neutralization test for toxoplasmosis. It is used to measure primarily IgG antibody and is the standard reference test for toxoplasmosis. However, it requires live T gondii organisms; therefore, it is not available in most laboratories. High titers suggest acute toxoplasmosis.3
  • The indirect fluorescent antibody test is used to measure the same antibodies as the dye test. Titers parallel dye test titers.
  • The IgM fluorescent antibody test is used to detect IgM antibodies within the first week of infection, but titers fall within a few months.
  • The indirect hemagglutination test is easy to perform. However, it usually does not detect antibodies during the acute phase of toxoplasmosis. Titers tend to be higher and remain elevated longer.
  • The results from a double-sandwich IgM ELISA are more sensitive and specific than the results from other IgM tests.
  • The results of the IgG avidity test may help differentiate those with acute infection from those with chronic infections better than alternative assays, such as assays that measure IgM antibodies. As is true for IgM antibody tests, the avidity test is most useful when performed early in gestation because a long-term pattern occurring late in pregnancy does not exclude the possibility that the acute infection may have occurred during the first months of gestation.4
  • Polymerase chain reaction on body fluids, including CSF, amniotic fluid, BAL fluid, and blood, may be useful in the diagnosis.

Imaging Studies

  • Head CT scanning in cerebral toxoplasmosis (general)
    • In most immunodeficient patients with toxoplasmic encephalitis, CT scans show multiple bilateral cerebral lesions.
    • Although multiple lesions are more common in persons with toxoplasmosis, they may be solitary; a single lesion should not exclude toxoplasmic encephalitis as a diagnostic possibility.
    • MRI has superior sensitivity (particularly if gadolinium is used for contrast) to CT scanning, and MRIs often demonstrate a single or multiple lesion(s) or more extensive disease not apparent on CT scans.
    • Various positron emission tomography scanning, radionuclide scanning, and magnetic resonance techniques have been used to evaluate patients with AIDS who have focal CNS lesions and to specifically differentiate between toxoplasmosis and primary CNS lymphoma.
    • Ultrasonographic diagnosis of congenital toxoplasmosis in a fetus is available at 20-24 weeks' gestation.
  • Head CT scanning in cerebral toxoplasmosis (in patients with AIDS)
    • CT scans in patients with AIDS who have toxoplasmic encephalitis reveal multiple ring-enhancing lesions in 70-80% of cases.
    • In patients with AIDS who have detectable Toxoplasma IgG and multiple ring-enhancing lesions on CT scans or MRIs, the predictive value for toxoplasmic encephalitis is approximately 80%.
    • Lesions tend to occur at the corticomedullary junction (frequently involving the basal ganglia) and are characteristically hypodense.
    • The number of lesions is frequently underestimated when assessed using CT scan images, although delayed imaging after a double dose of intravenous contrast material may improve the sensitivity of this modality.
    • An enlarging hypodense lesion that does not enhance is a poor prognostic sign.
    • Toxoplasmic encephalitis lesions on MRIs appear as high-signal abnormalities on T2-weighted studies and have a rim of enhancement surrounding the edema on T1-weighted contrast-enhanced images.
    • MRI has superior sensitivity (particularly if gadolinium is used for contrast) to CT scanning, and MRIs often demonstrate a lesion or lesions or more extensive disease not shown on CT scans. Hence, MRI should be used as the initial procedure when feasible (and especially if a single lesion is demonstrated on CT scan images). Nevertheless, even characteristic lesions on CT scans or MRIs are not pathognomonic of toxoplasmic encephalitis.
    • The major differential diagnosis of focal CNS lesions in patients with AIDS is CNS lymphoma, which manifests as multiple enhancing lesions in 40% of cases.
    • The probability of toxoplasmic encephalitis falls and the probability of lymphoma rises in the presence of single lesions on MRIs. Therefore, a brain biopsy may be required to obtain a definitive diagnosis in patients with a solitary lesion (especially if confirmed with MRI).
    • CT scanning abnormalities improve after 2-3 weeks of treatment in approximately 90% of patients with AIDS who have toxoplasmic encephalitis.
    • Complete resolution takes 6 weeks to 6 months; peripheral lesions resolve more rapidly than deeper ones.
    • Smaller lesions usually resolve completely within 3-5 weeks as shown on MRI, but lesions with a mass effect tend to resolve more slowly and leave a small residual lesion.
    • A radiologic response to therapy lags behind the clinical response, with better correlation by the end of acute therapy.

Other Tests

  • Skin tests that show delayed skin hypersensitivity to T gondii antigens may be useful as a screening test.
  • Antibody levels in aqueous humor or CSF may reflect local antibody production and infection at these sites.
  • Perform amniocentesis at 20-24 weeks' gestation if congenital disease is suggested.

Histologic Findings

Histopathologic data of human toxoplasmosis has been obtained mostly from autopsy studies in infants and immunodeficient patients with serious infections. Such knowledge in immunocompetent patients is limited.

Pathological findings are usually obtained from lymph node biopsy specimens in these patients. Multiple brain abscesses are commonly found, often involving the cerebral cortex and deep gray nuclei, less often the brainstem and cerebellum, and rarely the spinal cord in the CNS.

In acute toxoplasmosis, lesions are composed of central necrotic foci with varying petechiae rounded by acute and chronic inflammation, vascular proliferation, and macrophage infiltration. Tachyzoites and bradyzoites in tissue cysts may be detected at the periphery of the necrotic foci. T gondii are commonly found on hematoxylin and eosin or Giemsa stains. However, parasites can be more easily described via immunohistochemical staining. The blood vessels in the area of necrotic lesions may demonstrate distinguished intimal proliferation or frank vasculitis with thrombosis and fibrinoid necrosis.

Chronic lesions are composed of small cystic fields containing a number of lipid- and hemosiderin-laden macrophages with surrounding gliosis. Parasites are difficult to find in older lesions.

More on Toxoplasmosis

Overview: Toxoplasmosis
Differential Diagnoses & Workup: Toxoplasmosis
Treatment & Medication: Toxoplasmosis
Follow-up: Toxoplasmosis
Multimedia: Toxoplasmosis
References
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Further Reading

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Keywords

toxoplasmosis, Toxoplasma gondii, T gondii, Toxoplasma infection, congenital toxoplasmosis, systemic toxoplasmosis, febrile toxoplasmosis, lymphadenopathic toxoplasmosis, pediatric toxoplasmosis, ocular toxoplasmosis, pulmonary toxoplasmosis, extrapulmonary toxoplasmosis, toxoplasmic pneumonitis, toxoplasmic chorioretinitis, Sabin-Feldman dye test, unilateral microphthalmia, tachyzoites, bradyzoites, pneumonitis, myocarditis, necrotizing encephalitis, brain abscess, toxoplasmic encephalitis, TE, diffuse toxoplasmic encephalitis, Toxoplasma encephalitis, cerebral toxoplasmosis, CNS toxoplasmosis

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Contributor Information and Disclosures

Author

Murat Hökelek, MD, PhD, Technical Consultant of Parasitology Laboratory, Associate Professor, Department of Clinical Microbiology, Ondokuz Mayis University Medical School, Turkey
Murat Hökelek, MD, PhD is a member of the following medical societies: Turkish Society for Parasitology
Disclosure: Nothing to disclose.

Medical Editor

Douglas A Drevets, MD, Assistant Professor, Department of Medicine, Section of Infectious Disease, Oklahoma University Health Sciences Center
Douglas A Drevets, MD is a member of the following medical societies: American Association of Immunologists, American Society for Microbiology, Central Society for Clinical Research, and Christian Medical & Dental Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

John L Brusch, MD, FACP, Assistant Professor of Medicine, Harvard Medical School; Consulting Staff, Department of Medicine and Infectious Disease Service, Cambridge Health Alliance
John L Brusch, MD, FACP is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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