Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (518 page)

   Laboratory Findings

Direct detection
: The identification of stage 1 rhabditiform larvae in stool has formed a primary method for diagnosis, but sensitivity is limited in patients with asymptomatic, uncomplicated infection. A single stool O&P examination shows a sensitivity of 30–60%. Sensitivity is improved by multiple O&P examinations. Sensitivity may also be improved by examination of duodenal fluid collected by endoscopy or other method (sensitivity: 60–80%). In the hyperinfection syndrome, adult and larval forms may be detected in a variety of affected organs.

Serology
: May be useful, but the performance of different assays, based on different antigen preparations, has not been standardized.

Core laboratory
: Eosinophilia is seen in approximately 70% of infected patients.

TOXOPLASMOSIS

   Definition

Toxoplasmosis is used to describe diseases caused by the intracellular protozoan parasite
Toxoplasma gondii
. Infection is most commonly transmitted by ingestion of oocytes (sporozoites) in cat feces or by ingestion of cysts (bradyzoites) in raw or undercooked meat of infected animals (e.g., lamb, pork, goat). Acute infection most commonly occurs in the muscle, liver, spleen, lymph nodes, and CNS. Infected monocytes die, resulting in an inflammatory reaction in the affected organ. Bradyzoite-filled cysts are formed, but organ function usually returns to normal in immunocompetent hosts. Indications for serologic screening of asymptomatic patients include pregnancy, new diagnosis of HIV-1 infection, transplant donors and recipients, and patients who will be treated with immunosuppressive drugs.

WHO SHOULD BE SUSPECTED?

   Most infections are asymptomatic.

   Acute infection may be manifested by adenopathy and fever. Occasionally patients develop malaise, headache, myalgias, and hepatosplenomegaly. Atypical lymphocytosis may be seen on blood differential, suggesting mononucleosis syndrome, which may last for weeks or months. Toxoplasmosis may cause up to 15% of cases of unexplained lymphadenopathy.

   Congenital infection may occur when the mother acquires acute infection during pregnancy (which is usually clinically unapparent). The risk of transmission is 15–25% for maternal infections in the first trimester, 30–45% in the second, about 65% in third trimester, and near 100% at term. Severe congenital disease is more likely with fetal infection in the first trimester, with high mortality; 90% have CNS sequelae. Most infected infants (85%) eventually develop sequelae, even if asymptomatic at birth, some years later. Neurologic sequelae include seizures, psychomotor retardation, hydrocephalus, microcephalus, ocular abnormalities (e.g., retinal necrosis and granulomatous inflammation of the choroid, optic atrophy), deafness, and other abnormalities. Intracerebral calcifications are common. Infants may show fever, jaundice, vomiting and diarrhea, hepatosplenomegaly, pneumonitis, and other symptoms.

   Laboratory Findings

Histology
: Organisms may be identified by histologic examination of infected tissues. Detection is improved by the use of specific immunohistologic staining. Direct detection is low yield for specimens other than tissue. Organisms may be seen in Giemsa-stained BAL or CSF specimens.

Serology

   See: Toxoplasma Serology Screen (
Toxoplasma gondii
IgG and IgM) in Chapter
17
, Infectious Disease Assays.

   Serology is the diagnostic method of choice for most patients. Results of serologic tests must be interpreted based on patient age, clinical status, and other factors, including performance characteristics of the test method.

   Diagnosis of acute or congenital infection is more difficult.

   Acute infection may be documented by detection of specific IgM or a fourfold rise in antibody titer between acute and convalescent titers. IgM reactivity usually appears within 2 weeks of primary infection. IgG usually develops within 4 weeks. Peak titers usually occur between 4 and 8 weeks after primary infection. A fourfold increase in the IgG titer supports a diagnosis of acute infection. IgG levels usually reach a titer of 1:1,000 or greater. Specific IgM appears in the first week of infection and peaks within 1 month. Reactivity usually disappears in 3–5 months (as early as 1 month) but may persist for up to 2 years in IgM capture assays.