AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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Background

Toxoplasma gondii is an obligate intracellular parasite that produces a wide range of clinical syndromes in humans, land and sea mammals, and various bird species. T gondii has been recovered from locations throughout the world, except Antarctica. Nicolle and Manceaux first described the organism in 1908 after they observed the parasites in the blood, spleen, and liver of a North African rodent, Ctenodactylus gondii. The parasite was named Toxoplasma (arclike form) gondii (after the rodent) in 1909. In 1923, Janku reported parasitic cysts in the retina of an infant who had hydrocephalus, seizures, and unilateral microphthalmia. Wolf, Cowan, and Paige (1937-1939) determined that these findings represented the syndrome of severe congenital T gondii infection.

T gondii infects a large proportion of the world's population but uncommonly causes clinically significant disease. However, certain individuals are at high risk for severe or life-threatening disease due to this parasite. Individuals at risk include fetuses, newborns, and immunologically impaired patients. Congenital toxoplasmosis is usually a subclinical infection. Among immunodeficient individuals, toxoplasmosis most often occurs in those with defects of T-cell–mediated immunity, such as those with hematologic malignancies, bone marrow and solid organ transplants, or AIDS.

In most immunocompetent individuals, primary or chronic (latent) infection with T gondii is asymptomatic. A small percentage of these eventually develop chorioretinitis, lymphadenitis, or, rarely, myocarditis and polymyositis.

The organism of toxoplasmosis has 2 distinct life cycles. The sexual cycle occurs only among cats, the definitive host. The asexual cycle involves other mammals (including humans) and various strains of birds. It consists of 2 forms, known as tachyzoites (the rapidly dividing form observed in the acute phase of infection) and bradyzoites (the slowly growing form observed in tissue cysts). The sexual cycle begins in the gastrointestinal tract of the cat. Macrogametocytes and microgametocytes develop from ingested bradyzoites and fuse to form zygotes. The zygotes then become encapsulated within a rigid wall and are shed as oocysts. The zygote sporulates and divides to form sporozoites within the oocyst. Sporozoites become infectious 24 hours or more after the cat sheds the oocyst. During a primary infection, the cat can excrete millions of oocysts daily for 1-3 weeks. The oocysts are very hardy and may remain infectious for more than one year in warm, humid environments.

T gondii oocysts, tachyzoites, and bradyzoites can cause infection in humans. Infection can occur by ingestion of oocysts following the handling of contaminated soil or cat litter or the consumption of contaminated water or food sources (eg, unwashed garden vegetables). Transmission of tachyzoites to the fetus can occur via the placenta following primary maternal infection. Rarely, infection by tachyzoites occurs from ingestion of unpasteurized milk or by direct entry into the bloodstream through a blood transfusion or laboratory accident. Transmission can occur by ingestion of tissue cysts (bradyzoites) present in undercooked meat (in many areas of the world, approximately 5-35% of pork, 9-60% of lamb, and 0-9% of beef contain T gondii) or through transplantation of an organ containing tissue cysts.

Pathophysiology

Oocysts are ingested in material contaminated by feces from acutely infected cats. Oocysts also may be transported to food by flies and cockroaches. When the organism is ingested, bradyzoites are released from cysts or sporozoites are released from oocysts, and the organisms enter gastrointestinal cells. They multiply, rupture cells, and infect contiguous cells. They are transported via the lymphatics and disseminated hematogenously throughout the tissues.

The ability of T gondii to actively penetrate host cells results in formation of a vacuole that is derived from the plasma membrane, which is entirely distinct from a normal phagocytic or endocytic compartment. Following apical attachment, the parasite rapidly enters the host cell in a process that is significantly faster than phagocytosis. The vacuole is formed primarily by invagination of the host cell plasma membrane, which is pulled over the parasite through the concerted action of the actin-myosin cytoskeleton of the parasite. During invasion, the host cell is essentially passive and no change is detected in membrane ruffling, the actin cytoskeleton, or phosphorylation of host cell proteins.

Tachyzoites proliferate, producing necrotic foci surrounded by a cellular reaction. With the development of a normal immune response, tachyzoites disappear from tissues. In immunodeficient individuals and in some apparently immunologically healthy patients, the acute infection progresses and may cause potentially lethal consequences such as pneumonitis, myocarditis, or necrotizing encephalitis.

Cysts form as early as 7 days after infection and remain for the lifespan of the host. They produce little or no inflammatory response but cause recrudescent disease in immunocompromised patients or chorioretinitis in congenitally infected older children.

When a mother acquires the infection during gestation, the organism may be disseminated hematogenously to the placenta. When this occurs, infection may be transmitted to the fetus transplacentally or during vaginal delivery. If the mother acquires the infection in the first trimester and the infection is not treated, approximately 17% of fetuses are infected, and disease in the infant is usually severe. If the mother acquires infection in the third trimester and the infection is not treated, approximately 65% of fetuses are infected, and involvement is mild or inapparent at birth. These different rates of transmission are most likely related to placental blood flow, the virulence and amount of T gondii acquired, and the immunologic ability of the mother to restrict parasitemia.

Almost all congenitally infected individuals have signs or symptoms of infection (eg, chorioretinitis) by adolescence if they are not treated in the newborn period. Some infants with more severe congenital infection appear to have Toxoplasma antigen-specific anergy of their lymphocytes, which may be important in the pathogenesis of their disease.

Monoclonal gammopathy of the immunoglobulin G (IgG) class has been described in congenitally infected infants, and immunoglobulin M (IgM) levels may be elevated in newborns with congenital toxoplasmosis. Glomerulonephritis with deposits of IgM, fibrinogen, and Toxoplasma antigen has been reported in congenitally infected individuals. Circulating immune complexes have been detected in sera from an infant with congenital toxoplasmosis and in older individuals with systemic, febrile, and lymphadenopathic forms of toxoplasmosis, but these complexes did not persist after signs and symptoms resolved. Diminished total serum levels of immunoglobulin A may occur in congenitally infected babies, but no predilection toward associated infections has been noted. The predilection toward predominant involvement of the CNS and eye in this congenital infection has not been fully explained.

Profound and prolonged alterations in T-lymphocyte subpopulations occur during acute acquired T gondii infection. These have been correlated with disease syndromes but not with disease outcome. Some patients with prolonged fever and malaise have lymphocytosis, increased suppressor T-cell levels, and a decreased helper-to-suppressor T-cell ratio. These patients may have fewer helper cells even when they are asymptomatic. In some patients with lymphadenopathy, helper cell numbers are diminished for more than 6 months after the onset of infection. Asymptomatic patients also may have abnormal ratios of T-cell subpopulations. Some patients with disseminated disease have a very marked reduction in T cells and a marked depression in the ratio of helper to suppressor T lymphocytes. Depletion of inducer T lymphocytes in AIDS patients may contribute to the severe manifestations of toxoplasmosis observed in these patients.

Frequency

United States

Serologic surveys indicate that 3-70% of healthy adults in the United States have been infected with T gondii. Cultural habits of a population may affect the acquisition of T gondii infection from ingested tissue cysts in undercooked meat. In general, the incidence of the infection varies with the population group and geographic locale studied. The prevalence of T gondii antibodies in US military recruits decreased by one third from 1965-1989; the crude seropositivity rate among recruits from 49 states was 9.5% in 1989 compared with 14.4% in 1965. T gondii infection affects more than 3500 newborns in the United States each year. T gondii seropositivity rates among HIV-infected patients vary from 10-45%.

Toxoplasmic encephalitis (TE) has been reported in 1-5% of AIDS patients. TE has been reported to be the index AIDS diagnosis in 44-58% of HIV-infected patients who have TE. Within the United States, significant differences are recognized in the incidence of TE, both in different geographic regions and among various ethnic groups. Toxoplasmosis in AIDS patients is reported to occur 3 times more frequently in Florida than in other areas of the United States; in AIDS patients of Haitian origin who live in Florida, 12-40% develop TE.

Around 225,000 cases of toxoplasmosis are reported each year, which result in 5000 hospitalizations and 750 deaths, making T gondii the third most common cause of lethal food-borne disease in the United States.

International

In many populations, such as those in El Salvador and France, the seropositivity prevalence rate is as high as 75% by the fourth decade of life. As many as 90% of adults in Paris are seropositive. Approximately 50% of the adult population in Germany is infected. Women of childbearing age in much of Western Europe, Africa, and South and Central America have seroprevalence rates of greater than 50%. In HIV-infected individuals, the seropositivity rate is approximately 50-78% in certain areas of Western Europe and Africa.

TE is the AIDS-defining diagnosis in 16% of AIDS patients. In France, 37% of AIDS patients have evidence of TE at autopsy.

The prevalence rate in different provinces ranged from 0.3-11.8% in China.

Mortality/Morbidity

• Acute toxoplasmosis is asymptomatic in 80-90% of healthy hosts. In some apparently immunologically healthy patients, the acute infection progresses and may cause potentially lethal consequences.
• T gondii is recognized as a major cause of neurologic morbidity and mortality among patients with advanced HIV disease.
• Similar to other opportunistic pathogens, T gondii causes asymptomatic or mildly symptomatic infections in healthy hosts but rapidly progressive, fatal disease in immunosuppressed patients.

Race

• The highest incidence among AIDS patients in the United States occurs in emigrants from Haiti (11.2%).

Sex

• The incidence does not vary significantly between sexes.

Age

• The occurrence of T gondii antibodies increases with age.
• The seroconversion rate for women of childbearing age is 0.8% per year. Risk of transplacental transmission is greatest during the third trimester of pregnancy.
• With acute congenital toxoplasmosis, children often die in the first month of life. Subacute congenital disease may not be observed until some time after birth, when symptoms start to appear.

CLINICAL

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History

Only 10-20% of cases of T gondii infection in adults and children are symptomatic. Toxoplasmosis is a serious and often life-threatening disease in immunodeficient patients. Congenital infection may manifest as a mild or severe neonatal disease, with onset during the first month of life or with sequelae or relapse of a previously undiagnosed infection at any time during infancy or later in life. A wide variety of manifestations of congenital infection occur in the perinatal period.

• Acute toxoplasmosis in immunocompetent hosts
• • Approximately 80-90% of patients are asymptomatic.
  • Patients have cervical lymphadenopathy with discrete, usually nontender, nodes that are smaller than 3 cm in diameter.
  • Fever, malaise, night sweats, and myalgias are reported.
  • Patients have a sore throat.
  • Retroperitoneal and mesenteric lymphadenopathy with abdominal pain may occur.
  • Chorioretinitis is reported.
• Acute toxoplasmosis in hosts who do not have AIDS but are immunodeficient
• • Disease may be newly acquired or may be a reactivation.
  • CNS disease occurs in 50% of patients,
  • Patients may have encephalitis, meningoencephalitis, or mass lesions.
  • Hemiparesis, seizures, and mental status changes are reported.
  • Patients report visual changes.
  • They may have signs and symptoms similar to those observed in immunocompetent hosts.
  • Myocarditis and pneumonitis are reported.
• Clinical manifestations of toxoplasmosis in AIDS patients
• • Brain involvement (ie, TE) is the most common manifestation, with or without focal CNS lesions.
  • • Clinical findings are altered mental state, seizures, weakness, cranial nerve disturbances, sensory abnormalities, cerebellar signs, meningismus, movement disorders, and neuropsychiatric manifestations.
    • The characteristic presentation is usually a subacute onset with focal neurologic abnormalities in 58-89% of patients. However, in 15-25% of cases, the clinical presentation may be more abrupt, with seizures or cerebral hemorrhage.
    • Most commonly, hemiparesis, speech abnormality, or both are the major initial manifestation.
    • Brain stem involvement often produces cranial nerve lesions, and many patients exhibit cerebral dysfunction with disorientation, altered mental state, lethargy, and coma.
    • Less commonly, parkinsonism, focal dystonia, rubral tremor, hemichorea-hemiballismus, panhypopituitarism, diabetes insipidus, or the syndrome of inappropriate antidiuretic hormone secretion may dominate the clinical picture.
    • In some patients, neuropsychiatric symptoms such as paranoid psychosis, dementia, anxiety, and agitation may be the major manifestations.
    • The diffuse TE form may manifest acutely and can be rapidly fatal; generalized cerebral dysfunction without focal signs is the most common manifestation, and CT scan findings are within normal limits or reveal cerebral atrophy.
    • Spinal cord involvement manifests as motor or sensory disturbances of single or multiple limbs, bladder or bowel dysfunctions, or both and local pain. Patients may present with a clinical syndrome resembling a spinal cord tumor.
    • Cervical myelopathy, thoracic myelopathy, and conus medullaris syndrome have been reported.
  • Pulmonary disease (pneumonitis) due to toxoplasmosis is being increasingly recognized in AIDS patients who are not receiving appropriate anti-HIV drugs or primary prophylaxis for toxoplasmosis.
  • • The diagnosis may be confirmed by demonstrating the parasite in bronchoalveolar lavage (BAL) fluid.
    • Pulmonary toxoplasmosis mainly occurs in patients with advanced AIDS (mean CD4 count of 40 cells/µL ±75 standard deviation) and primarily manifests as a prolonged febrile illness with cough and dyspnea.
    • Illness may be clinically indistinguishable from Pneumocystis carinii pneumonia (PCP), and the mortality rate, even when treated appropriately, may be as high as 35%.
    • Extrapulmonary disease may be present in approximately 50% of persons with toxoplasmic pneumonitis.
  • Eye disease, ie, toxoplasmic chorioretinitis, is observed relatively infrequently in AIDS patients; it commonly manifests with ocular pain and loss of visual acuity.
  • • Funduscopic examination usually demonstrates necrotizing lesions that may be multifocal or bilateral.
    • Overlying vitreal inflammation is often present and may be extensive.
    • The optic nerve may be involved in as many as 10% of cases.
  • Other uncommon manifestations of toxoplasmosis in AIDS patients include the following:
  • • Panhypopituitarism and diabetes insipidus are reported.
    • Multiple organs may be involved, and findings manifest as acute respiratory failure and hemodynamic abnormalities similar to septic shock.
    • These patients may develop the syndrome of inappropriate antidiuretic hormone secretion, and they may develop orchitis.
    • Gastrointestinal involvement may result in abdominal pain, ascites (due to involvement of the stomach, peritoneum, or pancreas), or diarrhea.
    • Acute hepatic failure due to T gondii has been reported, as has musculoskeletal involvement.
• Congenital toxoplasmosis
• • This is most severe when maternal infection occurs early in pregnancy.
  • Approximately 67% of patients have no signs or symptoms of infection.
  • Chorioretinitis occurs in 15% of patients.
  • Intracranial calcifications develop in 10%.
  • Cerebrospinal fluid (CSF) pleocytosis and elevated protein values are present in 20% of patients.
  • Patients have anemia, thrombocytopenia, and jaundice at birth.
  • Microcephaly is reported.
  • Affected survivors may have mental retardation, seizures, visual defects, spasticity, or other severe neurologic sequelae.
• Ocular toxoplasmosis
• • Patients develop chorioretinitis (focal necrotizing retinitis).
  • They have a yellowish, white, elevated cotton patch with indistinct margins.
  • The lesions may occur in small clusters.
  • Congenital disease is usually bilateral.
  • Acquired disease is usually unilateral.
  • Symptoms include blurred vision, scotoma, pain, and photophobia.

Physical

• The most common form of symptomatic acute toxoplasmosis in immunocompetent individuals is lymphadenopathy.
• The typical presentation is painless, firm lymphadenopathy confined to one chain of nodes, most commonly cervical.
• The other physical manifestations are low-grade fever, hepatosplenomegaly, and rash.
• Ophthalmologic examination reveals multiple yellowish white, cottonlike patches with indistinct margins located in small clusters in the posterior pole.
• A flare-up of congenitally acquired chorioretinitis is often associated with scarred lesions juxtaposed to the fresh lesion.
• Because of multifocal involvement of the CNS, clinical findings vary widely; they include alterations in mental status, seizures, motor weakness, cranial nerve disorders, sensory abnormalities, cerebellar signs, meningismus, movement disorders, and neuropsychiatric manifestations in immunocompromised patients.

Causes

• The etiologic agent for each of the clinical syndromes is T gondii.
• • Congenital disease is passed transplacentally from the newly infected mother to the fetus during pregnancy.
  • Other syndromes may result from newly acquired infection or reactivation of latent infection.
  • Ingestion of meats or foods containing tissue cysts or oocysts present in cat feces can cause infection.
  • Infection can be transmitted by blood transfusion or organ transplantation.
• Risk factors for T gondii infection include the following:
• • Immunocompromised hosts, especially those with defects in cellular immunity such as AIDS, are at increased risk of infection.
  • Slaughterhouse workers may have an increased risk for infection.

DIFFERENTIALS

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Other Problems to be Considered

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

WORKUP

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Lab Studies

• Evidence of infection is the demonstration of the T gondii organism 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 by enzyme-linked immunosorbent assay (ELISA) technique indicates acute infection.
• The Sabin-Feldman dye test is a sensitive and specific neutralization test. It measures IgG antibody and is the standard reference test for toxoplasmosis. However, it requires live T gondii organisms; therefore, it is not available in most labs. High titers suggest acute disease.
• The indirect fluorescent antibody test measures the same antibodies as the dye test. Titers parallel dye test titers.
• The IgM fluorescent antibody test detects IgM antibodies within the first week of infection, but titers fall within a few months.
• The indirect hemagglutination test measures a different antibody than the dye test. 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 discriminate 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.
• Polymerase chain reaction on body fluids, including CSF, amniotic fluid, BAL fluid, and blood, may be useful in the diagnosis.

Imaging Studies

• Head CT scan in cerebral toxoplasmosis (general)
• • In most immunodeficient patients with TE, CT scans show multiple bilateral cerebral lesions.
  • Although multiple lesions are more common in persons with toxoplasmosis, they also may be solitary; a single lesion should not exclude TE as a diagnostic possibility.
  • MRI has superior sensitivity (particularly if gadolinium is used for contrast) to CT scan, and images often demonstrate a single or multiple lesion(s) or more extensive disease not apparent on CT scan images.
  • A variety of positron emission tomography scanning, radionuclide scanning, and magnetic resonance techniques have been used to evaluate AIDS patients who have focal CNS lesions and to specifically differentiate between toxoplasmosis and primary CNS lymphoma.
  • Ultrasound diagnosis of congenital toxoplasmosis in a fetus is available at 20-24 weeks' gestation.
• Head CT scan in cerebral toxoplasmosis (in AIDS)
• • CT scan images in AIDS patients who have TE reveal multiple ring-enhancing lesions in 70-80% of cases.
  • In AIDS patients who have detectable Toxoplasma IgG and multiple ring-enhancing lesions on image from CT scan or MRI, the predictive value for TE 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.
  • TE lesions on images from MRI studies 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 scan, and images often demonstrate a lesion or lesions or more extensive disease not shown on CT scan images.
  • 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 scan images or MRI studies are not pathognomonic of TE.
  • The major differential diagnosis of focal CNS lesions in AIDS patients is CNS lymphoma, which may manifest with multiple enhancing lesions in 40% of cases.
  • The probability of TE falls and the probability of lymphoma rises in the presence of single lesions on images from MRI studies. Therefore, a brain biopsy may be required to obtain a definitive diagnosis in the patient with a solitary lesion (especially if confirmed based on MRI findings).
  • Approximately 90% of AIDS patients who have TE have an improvement in abnormalities on CT scan images after 2-3 weeks of treatment.
  • Complete resolution takes 6 weeks to 6 months; peripheral lesions resolve more rapidly than deeper ones.
  • Smaller lesions usually resolve completely on images from MRI studies within 3-5 weeks, 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 between them observed by the end of acute therapy.

Other Tests

• Skin test results showing 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.

TREATMENT

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Medical Care

• Outpatient care is sufficient for acquired disease in hosts who are immunocompetent and in persons with ocular toxoplasmosis.
• Inpatient care is appropriate initially for persons with CNS toxoplasmosis and for acute disease in hosts who are immunocompromised.
• Usually, no treatment is necessary in asymptomatic hosts, except in children younger than 5 years.
• Symptomatic patients should be treated until immunity is assured.

Consultations

Consultations with infectious diseases and other specialists are recommended:

• Parasitologist
• Ophthalmologist
• Neurologist
• Radiologist
• Gynecologist
• Pediatrician

Diet

No special diet is required.

Activity

The level of activity depends on the severity of disease and the organ systems involved.

MEDICATION

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Currently, recommended drugs against T gondii act primarily against the tachyzoite form; thus, they do not eradicate the encysted form (bradyzoite). Pyrimethamine is the most effective agent and is included in most drug regimens. Leucovorin (ie, folinic acid) should be administered concomitantly to avoid bone marrow suppression. Unless circumstances arise that preclude using more than one drug, a second drug (eg, sulfadiazine, clindamycin) should be added. Efficacy of azithromycin, clarithromycin, atovaquone, dapsone, and cotrimoxazole (eg, trimethoprim, sulfamethoxazole) is unclear; therefore, they should only be used as alternatives in combination with pyrimethamine. Most effective available therapeutic combination is pyrimethamine plus sulfadiazine or trisulfapyrimidines (eg, combination of sulfamerazine, sulfamethazine, and sulfapyrazine). These agents are active against tachyzoites and are synergistic when used in combination.

Careful attention to dosing regimen is necessary because differs depending on patient variables (eg, immune status, pregnancy). Pyrimethamine may be used with sulfonamides, quinine, and other antimalarials and with other antibiotics.

Drug Category: Sulfonamide antimicrobials

Exert bacteriostatic action through competitive antagonism with PABA. Microorganisms that require exogenous folic acid and do not synthesize folic acid (pteroylglutamic acid) are not susceptible to action of sulfonamides. Resistant strains are capable of using folic acid precursors or preformed folic acid. Exist as 3 forms in serum—free, conjugated (ie, acetylated and possibly others), and protein-bound. Free form is considered therapeutically active.

Drug Name	Dapsone (Avlosulfon)
Description	Bactericidal and bacteriostatic against mycobacteria. Mechanism of action is similar to that of sulfonamides, ie, competitive antagonists of PABA prevent formation of folic acid, inhibiting bacterial growth.
Adult Dose	Prophylaxis of TE in AIDS: 50 mg/d PO (plus pyrimethamine)
Pediatric Dose	>1 month: 1 mg/kg/d PO; not to exceed 100 mg
Contraindications	Documented hypersensitivity; known G-6-PD deficiency
Interactions	May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists (eg, pyrimethamine), monitor for agranulocytosis during second and third mo of therapy; probenecid increases toxicity; concurrent trimethoprim may increase toxicity of both drugs; due to increased in renal clearance, dapsone levels may significantly decrease when administered concurrently with rifampin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Perform weekly blood counts (first mo), then perform WBC counts monthly (6 mo), then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is observed; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M due to high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; may cause peripheral neuropathy (rare) or phototoxicity when exposed to UV light

Drug Category: Lincosamide antimicrobials

Treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibit bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Drug Category: Antiprotozoal agents

Protozoal infections occur throughout the world and are a major cause of morbidity and mortality in some regions. Immunocompromised patients are especially at risk. Primary immune deficiency is rare, whereas secondary deficiency is more common. Immunosuppressive therapy, cancer and its treatment, HIV infection, and splenectomy may increase vulnerability to infection. Infectious risk is proportional to neutropenia duration and severity. Protozoal infections are typically more severe in immunocompromised patients than in immunocompetent patients.

Drug Name	Atovaquone (Mepron)
Description	A hydroxynaphthoquinone that inhibits the mitochondrial electron transport chain by competing with ubiquinone at the ubiquinone-cytochrome-c-reductase region (complex III). Inhibition of electron transport by atovaquone results in inhibition of nucleic acid and ATP synthesis in parasites. Has shown activity against bradyzoites in animal models of toxoplasmosis.
Adult Dose	750 mg (5 mL) PO bid with food for 21 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease levels of TMP/SMZ; may increase zidovudine serum levels; coadministration with rifampin or rifabutin may decrease levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in elderly and in hepatic and renal impairment; adverse effects include rash, pruritus, headache, and nausea

Drug Category: Macrolide antimicrobials

Spiramycin is a macrolide antibiotic with an antibacterial spectrum similar to erythromycin and clindamycin. Bacteriostatic at serum concentrations, but may be bactericidal at achievable tissue concentrations. Mechanism of action is unclear, but acts on the 50S subunit of bacterial ribosomes and interferes with translocation. Absorption from the GI tract is irregular (20-50% of PO dose absorbed). Following PO administration, peak plasma levels achieved within 2-4 h. Spiramycin has a longer half-life than erythromycin and sustains higher tissue levels.

Drug Name	Spiramycin (Rovamycine)
Description	DOC for maternal or fetal toxoplasmosis. Alternative therapy in other patient populations when unable to use pyrimethamine and sulfadiazine.
Adult Dose	3 g/d PO divided bid/qid for 3 wk; discontinue for 2 wk, then repeat 5-wk cycles throughout pregnancy
Pediatric Dose	50-100 mg/kg/d PO divided bid/qid for 3-4 wk
Contraindications	Documented hypersensitivity
Interactions	Decreases bioavailability of carbidopa, leading to decrease of levodopa levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Cross-resistance between microorganism resistant to erythromycin and carbomycin; acute colitis is experienced in 1% of patients; GI toxicity most common adverse effect; IV administration associated with peripheral paresthesias, irritation at injection site, dysesthesia, giddiness, pain, stiffness, burning sensation, and hot flashes; long-term use may result in superinfection; caution in cardiovascular disease because may prolong QT; may elevate LFTs

FOLLOW-UP

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Further Inpatient Care

• Standard precautions are recommended.

Further Outpatient Care

• Follow-up visits every 2 weeks until stable, then monthly during therapy
• CBC count weekly for first month, then every 2 weeks
• Renal and liver function tests monthly

Deterrence/Prevention

• Preventing the infection is particularly important for patients who are seronegative and immunocompromised and for women who are pregnant.
• • Avoid eating raw meat, unpasteurized milk, and uncooked eggs.
  • Wash hands after touching raw meat and after gardening or other contact with soil.
  • Wash fruits and vegetables.
  • Avoid contact with cat feces.
  • To attempt to prevent congenital toxoplasmosis, routine serologic screening of pregnant women has been performed in order to identify fetuses at risk of becoming infected.
• Avoiding transfusions of blood products from a donor who is seropositive to a patient who is seronegative and immunocompromised is prudent when feasible.
• If possible, recipients who are seronegative should receive transplanted organs from donors who are seronegative.

Complications

• Seizure disorder or focal neurologic deficits may occur in persons with CNS toxoplasmosis.
• Partial or complete blindness may occur in those with ocular toxoplasmosis.
• Multiple complications may occur in persons with congenital toxoplasmosis, including mental retardation, seizures, deafness, and blindness.

Prognosis

• Immunodeficient patients often relapse if treatment is stopped.
• Treatment may prevent the development of untoward sequelae in both symptomatic and asymptomatic infants with congenital toxoplasmosis.

Patient Education

• Infected mothers must be completely informed of potential consequences to the fetus.
• Explain prevention methods, eg, protecting children's play area from cat litter.
• For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Brain Infection.

MISCELLANEOUS

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• References

Medical/Legal Pitfalls

• Misdiagnosis is possible.

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Toxoplasmosis. Toxoplasma gondii tachyzoites (Giemsa stain).
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Media file 2:  Toxoplasmosis. Toxoplasma gondii tachyzoites in cell line.
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Media file 3:  Toxoplasma gondii in infected monolayers of HeLa cells (Giemsa stain).
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Media type:  Image

REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

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• Pickering LK, Peter G, Baker CJ. Drugs for Parasitic Infections. In: AAP 2000 Red Book: Report of the Committee on Infectious Diseases. 25th ed. Elk Grove Village, Ill: American Academy of Pediatrics;. 2000: 693-717.
• Pinon JM, Dumon H, Chemla C, et al. Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies. J Clin Microbiol. 2001;39:2267-71. [Medline].
• Remington JS, Thulliez P, Montoya JG. Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol. Mar 2004;42(3):941-5. [Medline]. [Full Text].
• Robert-Gangneux F. Contribution of new techniques for the diagnosis of congenital toxoplasmosis. Clin Lab. 2001;47:135-41. [Medline].
• Rothova A. Ocular manifestations of toxoplasmosis. Curr Opin Ophthalmol. Dec 2003;14(6):384-8. [Medline].
• Schwartzman JD. Toxoplasmosis. Curr Infect Dis Rep. 2001;3:85-89. [Medline].
• Switaj K, Master A, Skrzypczak M. Recent trends in molecular diagnostics for Toxoplasma gondii infections. Clin Microbiol Infect. Mar 2005;11(3):170-6. [Medline].
• Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000;30:1217-58. [Medline].
• Tierney,Jr LM, McPhee SJ, Papadakis MA, eds. Toxoplasmosis. In: Current Medical Diagnosis & Treatment. 40th ed. New York, NY: McGraw-Hill; 2001:. 1444-7.
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Article Last Updated: May 16, 2006