Pediatric Toxoplasmosis 

Updated: Sep 20, 2019
Author: Itzhak Brook, MD, MSc; Chief Editor: Russell W Steele, MD 



Pediatric toxoplasmosis can be acute or chronic and congenital or postnatally acquired. Toxoplasmosis refers to a symptomatic infection by Toxoplasma gondii, a widely distributed protozoan that usually causes an asymptomatic infection in the healthy host.[1]

Apart from toxoplasmosis in immunocompromised individuals, congenital toxoplasmosis is the most serious manifestation of infection, resulting from the vertical transmission of T gondii transplacentally from a parasitemic mother to her offspring. The severity of disease depends on the gestational age at transmission. Ophthalmologic and neurologic disabilities are the most important consequences of infection and can be present even when the congenital infection is asymptomatic.

The fetus, newborn, and young infant with congenital toxoplasmosis are at risk of infection-associated complications, particularly retinal disease that can occur into adulthood. Hosts who are immunocompromised, especially those with defects in cellular immunity such as AIDS, are also at increased risk for severe disease.

Congenital toxoplasmosis is a preventable disease. Prepregnancy screening accompanied by serial titers and appropriate counseling in women with initial negative titers may minimize cases.[2]


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 meat or other foods containing cysts or oocysts present in cat feces can cause infection. Thus, individuals who live in poor sanitary conditions and those who eat raw or poorly cooked meat are at an increased risk of acquiring Toxoplasma infection. Infection can also be transmitted by blood transfusion or organ transplantation.[3]

Hosts who are immunocompromised, especially those with defects in cellular immunity such as AIDS, are also at increased risk for severe disease.

Life cycle of T gondii

T gondii is a ubiquitous obligate intracellular protozoan that infects animals and humans. It has an intestinal and an extraintestinal cycle in cats but only an extraintestinal cycle in other hosts, including herbivores, omnivores, and carnivores. T gondii exists in 3 forms: bradyzoites, tachyzoites, and sporozoites.

Bradyzoites are slowly multiplying organisms contained in tissue cysts, usually localized to muscle (skeletal and cardiac) and brain. They live in their host cells for months to years. Once ingested, gastric enzymes degrade the cyst wall, liberating viable bradyzoites.

Tachyzoites are rapidly dividing organisms found in tissues during the acute phase of infection. The tachyzoites are the forms responsible for tissue destruction. Multiplication continues until either cyst formation or host cell destruction occurs. After cell death, the free tachyzoites invade other cells and resume rapid multiplication.

Sporozoites (oocysts) result from the parasite's sexual cycle, which takes place in the epithelial cells of the cat intestine. When eliminated by the cat, these cysts must first undergo sporulation to become infectious, a process that takes 2-3 days in temperate climates and longer in cold climates. Therefore, the risk of infection is minimized if cat litter boxes are cleaned daily. Cats shed 1-100 million oocysts after the first infection, but, because of immunity, reinfection is rarely followed by reshedding of oocysts. Passive antibody transference to newborn kittens does not prevent shedding of oocysts.

Horizontal transmission

Human horizontal infection occurs from ingesting food contaminated with oocysts or poorly cooked food containing tissue cysts (bradyzoites). Although experimental attempts to transmit tachyzoites by arthropods were negative, cockroaches and flies are believed to be able to transport oocysts to water and food. Because parasitemia can persist up to a year in healthy persons, blood transfusion is a potential source of infection.

Once the individual is infected, the organism persists as tissue cysts for life. The degree of organ involvement varies considerably among patients but mostly depends on the immune status of the host. Fetuses and immunocompromised patients are most severely affected.

Vertical transmission

Vertical transmission is the cause of congenital toxoplasmosis. The infection can occur in utero or during a vaginal delivery. Transmission by breastfeeding has not been demonstrated. In general, only primary infection during pregnancy results in congenital toxoplasmosis. Thus, it is exceedingly rare for a woman to deliver a second child with congenital toxoplasmosis unless she is immunocompromised, usually from acquired immunodeficiency syndrome (AIDS).[4]

Infections that occur within 6 months prior to conception may result in transplacental transmission. Intrauterine exposure can result in an uninfected infant or infection that ranges from being asymptomatic to causing stillbirth. Approximately 30% of exposed fetuses acquire the infection, but most of the infants are asymptomatic.

The severity of infection in the fetus depends on the gestational age at the time of transmission. In general, earlier infection is more severe but less frequent. As a consequence, 85% of live infants with congenital infection appear normal at birth. Very early infections (ie, occurring in the first trimester) may result in fetal death in utero or in a newborn with severe central nervous system (CNS) involvement, such as cerebral calcifications and hydrocephalus.


Occurrence in the United States

It is estimated that about 1 billion individuals worldwide are infected with T gondii. The highest rates of toxoplasmosis are in Europe, Central America, Brazil, and Central Africa.

The frequency of congenital toxoplasmosis depends on the incidence of primary infection in women of childbearing age. The earlier a woman acquires a primary infection, the less likely she is to transmit the parasite to her offspring. Prevalence increases with age. In New York, antibody prevalence was 16% in women aged 15-19 years, 27% in women aged 20-24 years, 33% in women aged 25-29 years, 40% in women aged 30-34 years, and 50% in women older than 35 years.

In addition, positive antibody titers were reported in 30% in women of childbearing age in Birmingham (1983), 12% in Chicago (1987), 14% in Massachusetts (1998), 3.3% in Denver (1986), 30% in Los Angeles (1993), 12% in Texas (1993), and 13% in New Hampshire (1998). Rates in women of childbearing age in Palo Alto, California, dropped from 27% in 1964 to 10% in 1987.

The prevalence of congenital toxoplasmosis ranges from 1 case per 1000 live births to 1 case per 10,000 live births, and this prevalence be indirectly estimated from the incidence rate of primary infection during pregnancy by multiplying the number of mothers who acquire infection during pregnancy by the transmission rate of the parasite to the fetus. On the basis of data from the National Health and Nutrition Examination Survey from 1989-1994, the incidence of primary infection for seronegative pregnant women was 0.27%. This indicates that, with 4 million births per year and an overall transmission rate of 33%, approximately 3500 infected children are born in the United States every year.[5] The rate likely varies by region.

Direct estimates of congenital infection may be derived by measuring anti-Toxoplasma immunoglobulin M (IgM) in newborn sera. However, this may underestimate the true incidence, because infants with toxoplasmosis may not have demonstrable IgM in up to 20% of cases. In Alabama, the incidence was 0.1 per 1000 births. Health care workers in Massachusetts began screening sera of newborns in 1986. From 1986-1998, a total of 99 cases were detected (incidence of 1 in 10,000 births) in Massachusetts, but at least 6 cases were missed by the screening.

International occurrence

Worldwide, the reported incidence of congenital toxoplasmosis is decreasing. The prevalence of positive antibody titers among pregnant women is often higher outside the United States. Rates of positive antibody titers internationally include the following:

  • Central African Republic - 81%

  • Tanzania - 48%

  • Zambia - 23%

  • Argentina - 53-58%

  • Austria - 36%

  • Belgium - 46%

  • Chile - 59%

  • Colombia - 60%

  • Ethiopia - More than 75%

  • France - 52%

  • Guatemala - 46%

The estimated incidence of congenital toxoplasmosis is 6 per 1000 births in France, 2 per 1000 births in Poland, 7-10 per 1000 births in Colombia, and 3 per 1000 births in Slovenia.

Age-related demographics

Incidence of T gondii antibodies increases with increasing age. The seroconversion rate in women of childbearing age is 0.8% per year. The risk of transplacental transmission is greatest during the third trimester of pregnancy.


Relapse often occurs in patients with immunocompromise if treatment is stopped. Treatment may prevent the development of untoward sequelae in symptomatic and asymptomatic infants with congenital toxoplasmosis.

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

Fetuses and immunocompromised individuals are at particularly high risk for severe sequelae and even death. Newborns with acute congenital toxoplasmosis often die in the first month of life. Infection acquired postnatally is usually much less severe.[6]

Patient Education

Explain toxoplasmosis prevention methods, such as protecting children's play areas from cat litter, to parents. Mothers who are infected with T gondii must be completely informed of potential consequences to their fetus.




Congenital toxoplasmosis is the consequence of transplacental hematogenous fetal infection by T gondii during primary infection in pregnant women. Primary infection in an otherwise healthy pregnant woman is asymptomatic in 60% of cases. Symptoms during pregnancy are frequently mild. The most common manifestations are fatigue, malaise, a low-grade fever, lymphadenopathy, and myalgias. Latent Toxoplasma infection with reactivation during pregnancy may lead to congenital infection only in immunocompromised women (most commonly, those with AIDS).

The classic triad of chorioretinitis, hydrocephalus, and intracranial calcifications cannot be used as a strict diagnostic criterion for congenital toxoplasmosis because a large number of cases would be missed. Congenital toxoplasmosis may occur in the following forms:

  • Neonatal disease

  • Disease occurring in the first months of life

  • Sequelae or relapse of previously undiagnosed infection

  • Subclinical infection

When clinically recognized in the neonate, congenital toxoplasmosis is very severe. Spontaneous abortions, prematurity, or still birth may result. Signs of generalized infection, such as the following, are usually present:

  • Intrauterine growth restriction

  • Fever

  • Chorioretinitis (usually bilateral)

  • Cerebral calcification

  • Abnormal cerebrospinal fluid (xanthochromia and pleocytosis)

  • Vomiting

  • Eosinophilia

  • Abnormal bleeding

  • Jaundice

  • Hepatomegaly

  • Splenomegaly

  • Lymphadenopathy

  • Rash

Neurologic signs are severe and always present. They include the following:

  • Microcephaly or macrocephaly

  • Bulging fontanelle

  • Nystagmus

  • Abnormal muscle tone

  • Seizures

  • Delay of developmental milestone acquisition

Most cases of chorioretinitis result from congenital infection, although patients are often asymptomatic until later in life.[7] Symptoms include blurred vision, scotoma, pain, photophobia, and epiphora. Impairment of central vision occurs when the macula is involved, but vision may improve as inflammation resolves. Relapses of chorioretinitis are frequent but are rarely accompanied by systemic signs or symptoms.

Late manifestations of untreated congenital toxoplasmosis can include chorioretinitis and neurologic abnormalities such as motor abnormalities, intellectual disability, and hearing loss. This can occur even when there are no clinical symptoms or findings at the time of birth.

Latent toxoplasmosis may reactivate in women with human immunodeficiency virus (HIV) and result in congenital transmission. Congenital toxoplasmosis in the infant with HIV appears to run a more rapid course than in infants without HIV.

Physical Examination

In subacute congenital toxoplasmosis, symptoms may not be observed in patients until some time after birth.

Lymphadenopathy is the most common form of symptomatic acute toxoplasmosis in immunocompetent individuals. Patients typically present with painless, firm lymphadenopathy that is confined to one chain of nodes (most commonly cervical nodes). The suboccipital, supraclavicular, axillary, and inguinal groups may also be involved.

Other physical manifestations include a low-grade fever, occasional hepatosplenomegaly, and a rash. Other findings include anemia, disseminated intravascular coagulation, hepatitis, cholestasis, hepatic calcifications, hepatomegaly, splenomegaly, jaundice, myocarditis, pneumonitis, premature birth, rashes (maculopapular, petechial, purpura, blueberry muffin rash), sepsislike illness, temperature instability, and thrombocytopenia.

Ophthalmologic examination reveals multiple yellow-white, cottonlike patches with indistinct margins located in small clusters in the posterior pole. Other ophthalmological findings include amblyopia; cataract; chorioretinitis; chorioretinal edema; chorioretinal edema, scars, and neovascular membrane; posterior hyaloid membrane iris detachment; leukocoria; macular or peripheral retinal lesions; microphthalmia or microcornea; nystagmus; papilledema; optical nerve atrophy; retinal detachment; strabismus; visual impairment; and vitritis.

Characteristically, a focal necrotizing retinitis develops that may atrophy and generate black pigment or that may be associated with panuveitis. Papillitis is usually indicative of CNS disease. Flare-up of congenitally acquired chorioretinitis is often associated with scarred lesions in proximity to the fresh lesions.

Because of multifocal involvement of the CNS, clinical findings widely vary. They include alterations in mental status, seizures, motor weakness, cranial nerve disorders, sensory abnormalities, cerebellar signs, meningismus, movement disorders, and neuropsychiatric manifestations in patients with immunocompromise. Other neurological findings include brain masses and calcifications, cerebrospinal fluid changes (pleocytosis, lymphocytosis, eosinophilia, elevated protein, low glucose), developmental delay, obstructive hydrocephalus, hypotonia, microcephaly or macrocephaly, palsies, and sensory hearing loss.



Diagnostic Considerations

Conditions to consider in the differential diagnosis of toxoplasmosis include the following:

  • Sarcoidosis

  • Sepsis

  • Syphilis

  • Tuberculosis

  • Tularemia

Conditions to consider in the differential diagnosis of congenital toxoplasmosis include the following:

  • Encephalopathies

  • Erythroblastosis fetalis

  • Lymphocytic choriomeningitis virus infection

  • Rubella

  • Cytomegalovirus infection

  • Syphilis

  • Congenital hypertrophy of the retinal pigmented epithelium

  • Congenital retinal abnormalities

Conditions to consider in the differential diagnosis of Toxoplasma encephalitis include the following:

  • Vasculitis

  • Progressive multifocal leukoencephalopathy

  • Malignancy

  • Lymphocytic choriomeningitis virus infection

Differential Diagnoses



Approach Considerations

The laboratory evaluation of congenital toxoplasmosis includes serology, polymerase chain reaction (PCR), and other tests that can confirm and evaluate the extent of the infection, and can establish baseline values prior to initiating antimicrobial treatment. T gondii can be recovered from clinical specimens; however, this requires additional time and is available only in some reference laboratories.[8]

Demonstration of T gondii in blood, body fluids (ie, peripheral blood, cerebrospinal fluid, urine), or tissues is evidence of toxoplasmosis infection (see the image below). Recovery or histologic demonstration of T gondii or T gondii nucleic acids from clinical specimens, accompanied by clinical and/or serologic findings, can establish the diagnosis of congenital toxoplasmosis. However, these methods are used less frequently than serological evaluations and may require tissue specimens.

Isolation by mouse inoculation of Toxoplasma from amniotic fluid or placental or fetal tissue is diagnostic of congenital infection. Lymphocyte transformation in response to Toxoplasma antigens indicates previous infection in adults. Detection of Toxoplasma antigens in blood or body fluids by means of enzyme-linked immunoassay (ELISA) or PCR indicates acute infection. A skin test showing delayed hypersensitivity to Toxoplasma antigens may be a useful screening test.

Laboratory tests include complete blood cell (CBC) count with differential, liver function tests, lumbar puncture, serum creatinine, urinalysis, urine viral culture for cytomegalovirus, serum quantitative immunoglobulin testing, and testing for other congenital infections such as cytomegalovirus, rubella, syphilis, congenital lymphocytic choriomeningitis virus syndrome, and Zika.[9]

Toxoplasma gondii trophozoites in tissue culture. Toxoplasma gondii trophozoites in tissue culture.

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 and thus is not available in most laboratories. High titers suggest acute disease.

The indirect fluorescent antibody (IFA) test measures the same antibodies as the dye test. Titers parallel dye test titers. The IgM fluorescent antibody test can be used to detect IgM antibodies within the first week of infection, but titers fall within a few months. The double-sandwich IgM ELISA test is more sensitive and specific than other IgM detection tests.

The indirect hemagglutination test measures a different antibody than does the dye test. Titers tend to be higher and remain elevated longer.

The IgG avidity test may be able to discriminate acute from chronic infection better than alternative assays, such as assays that measure IgM antibodies, can. As is true for IgM antibody tests, the avidity test is most useful when performed early in gestation, because a chronic pattern occurring late in pregnancy does not rule out the possibility that the acute infection may have occurred during the first months of gestation. A 2-fold rise in serum IgG obtained at 3-week intervals is diagnostic.

IgA and IgE ELISA should be determined when the infant’s IgM titers are negative or equivocal. Determination of Toxoplasma-specific IgA or IgE is more sensitive (but not specific) than detection of IgM for congenital toxoplasmosis (approximately 90% vs 75-80%). Repeating the test at least 10 days after delivery can assist in making the diagnosis. IgM and IgA titers in an infant who is not infected (usually an infant with low positive IgM and IgA titers) decrease with time, whereas the levels  remain positive for weeks to months in an infant who was congenitally infected.[10]

Perform an amniocentesis at 20-24 weeks' gestation in suspected cases of congenital disease. Performing PCR assay testing on body fluids, including cerebrospinal fluid, amniotic fluid, bronchoalveolar lavage fluid, and blood, may be useful in establishing the diagnosis.[11]

Antibody levels in aqueous humor or cerebrospinal fluid obtained through a lumbar puncture may reflect local antibody production and infection at these sites.

Imaging Studies


Ultrasonography of the fetus to evaluate for evidence of congenital toxoplasmosis can be performed at 20-24 weeks' gestation. Abdominal ultrasound can assist in detecting intrahepatic calcifications as well as hepatosplenomegaly.

CT scanning

Computed tomography (CT) scanning of the brain is useful in cerebral toxoplasmosis. It can detect intracranial calcifications, ventriculomegaly, and hydrocephalus. In 70-80% of immunodeficient patients with Toxoplasma encephalitis, the CT scan reveals multiple bilateral, ring-enhancing cerebral lesions. Although multiple lesions are more common, finding a solitary lesion should not exclude Toxoplasma encephalitis. There is an approximately 80% likelihood that the disease is present in patients with AIDS who have detectable Toxoplasma IgG and multiple ring-enhancing lesions. Lesions are characteristically hypodense and tend to occur at the corticomedullary junction; they frequently involve the basal ganglia.

CT scanning frequently underestimates the number of lesions, although delayed imaging after a double dose of intravenous (IV) contrast material may improve the sensitivity of this imaging modality. An enlarging, hypodense lesion that does not enhance is a poor prognostic finding.

Improvement is seen in as many as 90% of patients with AIDS and Toxoplasma encephalitis after 2-3 weeks of treatment. Complete resolution lasts from 6 weeks to 6 months; peripheral lesions resolve more rapidly than do deeper ones. Radiographic response tends to lag behind clinical response.


Magnetic resonance imaging (MRI) is the preferred imaging modality to evaluate for lesions. The lack of exposure to radiation is another advantage. MRI has superior sensitivity, particularly if gadolinium is used for contrast. It can often depict lesions or more extensive disease not apparent on CT scans. Hence, MRI should be used as the initial imaging procedure when feasible and should always follow CT demonstration of a single lesion.

MRI depicts Toxoplasma encephalitis lesions as high-signal abnormalities on T2-weighted studies and reveals a rim of enhancement surrounding the edema on T1-weighted, contrast-enhanced images.

Smaller lesions usually completely resolve on MRI studies within 3-5 weeks, but lesions with a mass effect tend to resolve more slowly and leave a small, residual lesion.

Even characteristic lesions on CT or MRI are not pathognomonic of Toxoplasma encephalitis. The major differential diagnosis in patients with AIDS is CNS lymphoma, which appears with multiple enhancing lesions in 40% of cases.

When single lesions are depicted on MRI, the probability of Toxoplasma encephalitis falls and that of lymphoma rises. Brain biopsy findings are generally required to obtain a definitive diagnosis.

Other modalities

To evaluate patients with AIDS and focal CNS lesions, various positron emission tomography (PET) and radionuclide scans have been used, generally with minimal benefit over the above modalities.

Initial auditory brain steam responses and yearly audiological evaluation in the first 3 years of life are helpful.

Histologic Findings

The histopathology of toxoplasmosis varies with the immune status of the host. In the healthy host with acquired toxoplasmosis, the characteristic histopathology of the lymph node is diagnostic, despite the relative paucity of organisms present. Typical findings include reactive follicular hyperplasia, irregular clusters of histiocytes encroaching on the margins of germinal centers, and focal distention of sinuses with monocytoid cells. Necrosis, granuloma formation, microabscesses, and vasculitis do not occur. At autopsy of normal hosts, tissue cysts are noted as incidental findings in skeletal muscle and myocardium, invoking little inflammatory response.

In contrast, in patients who are immunodeficient and in children with severe congenital toxoplasmosis, tachyzoite proliferation is accompanied by tissue necrosis and an intense, usually monocytic, inflammatory response. In patients with AIDS, toxoplasmosis typically produces brain abscesses that have a characteristic appearance. A central avascular area is surrounded by a region of necrosis and inflammatory cells that may also contain free and intracellular tachyzoites. Outside of the region of inflammation are cysts.

Demonstration of tachyzoites in a tissue specimen is required for definitive diagnosis of active infection. The presence of multiple cysts near an inflammatory lesion makes the diagnosis highly likely. Stains used to detect tachyzoites or cysts include hematoxylin and eosin, periodic acid-Schiff, and Gomori-methenamine silver. Immunoperoxidase and fluorescein-conjugated antibody stains can also be used.

Wright-Giemsa staining of body fluid sediments of biopsy tissue touch preparations is a rapid and simple method for visualizing the organisms.



Approach Considerations

Outpatient care is sufficient for acquired toxoplasmosis in patients with ocular toxoplasmosis and hosts who are immunocompetent. Immunocompetent patients who are not pregnant and have no vital organ damage can be observed without therapy.

Initial inpatient care is appropriate for patients with CNS toxoplasmosis and immunocompromised hosts with acute disease.

Usually, no treatment is necessary for asymptomatic hosts, except in those younger than 5 years. Symptomatic patients should be treated until immunity is assured. Suppressive therapy must continue for patients who are HIV positive with active infection and a CD4+ count less than 200.

Limitation of activity in patients with toxoplasmosis depends on the severity of disease and the organ systems involved.


A study by Carellos et al that included 190 children identified with congenital toxoplasmosis who were treated with sulfadiazine, pyrimethamine, and folinic acid reported that 44% of the children had hematologic adverse events (neutropenia occurred in 31%); however, most were not severe cases and reversed after an increase in folinic acid dose (25.7%) or suspension of treatment (1.8%).[12]


The following consultations are indicated:

  • Infectious disease specialist
  • Ophthalmologist
  • Neurologist
  • Radiologist
  • Audiologist


Preventing the infection is particularly important for women who are pregnant and for patients who are seronegative and immunocompromised.[13]

Avoid consuming raw or undercooked meat, unpasteurized milk, and uncooked eggs. Wash hands after touching raw meat and after gardening or having other contact with soil. Wash fruits and vegetables. Avoid contact with cat feces. Disinfect litter for 5 minutes with nearly boiling water. In an attempt to prevent congenital toxoplasmosis, routine serologic screening of pregnant women has been performed in order to identify fetuses at risk of becoming infected. Treatment during pregnancy results in a 50% reduction in incidence of infection in infants.

When feasible, avoid transfusions of blood products from a donor who is seropositive to a patient who is seronegative and immunocompromised. In addition, transplant recipients who are seronegative should, if possible, receive organs from donors who are seronegative.[14]

Long-Term Monitoring

Follow-up visits should occur every 2 weeks until the patient is stable, then monthly during therapy. Obtain a complete blood count (CBC) weekly for the first month, then every 2 weeks. Perform renal and liver function tests monthly.



Medication Summary

The currently recommended drugs for T gondii infection act primarily against the tachyzoite form but do not eradicate the encysted form (bradyzoite). Effective treatment mandates the administration of combination of 2 agents effective against the pathogen. Leucovorin (folinic acid) should be administered concomitantly to avoid bone marrow suppression. Pyrimethamine is the most effective agent and is included in most drug regimens. Unless circumstances arise that preclude using more than one drug, a second drug, such as sulfadiazine, atovaquone, or clindamycin, should be added. Other effective agents include sulfamerazine and sulfamethazine, which are not available in the United States.[15]

The efficacy of azithromycin, clarithromycin, atovaquone, dapsone, and cotrimoxazole (ie, trimethoprim-sulfamethoxazole) is unclear; therefore, they should be used only as alternatives in combination with pyrimethamine. The most effective available therapeutic combination is pyrimethamine plus sulfadiazine or trisulfapyrimidine (ie, combination of sulfamerazine, sulfamethazine, and sulfapyrazine). These agents are active against tachyzoites and are synergistic when used in combination.

While spiramycin is not available in the United States, it is the drug of choice for maternal or fetal toxoplasmosis. It is used as an alternative therapy in other patient populations when pyrimethamine and sulfadiazine cannot be used.

A study that compared the effects of trimethoprim-sulfamethoxazole versus placebo in reducing the risk of recurrences of T gondii retinochoroiditis reported that trimethoprim/sulfamethoxazole therapy resulted in a 100% reduction in the recurrence of T gondii retinochoroiditis over 1 year of treatment.[16, 17, 18]

Children with renal insufficiency or glucose-6-phosphate-dehydrogenase (G6PD) deficiency and those receive anticonvulsants or antiretrovirals require special attention. Because sulfadiazine is excreted in the kidneys, its dose may require adjustment for those with renal insufficiency. Sulfadiazine should not be administered to children with G6PD deficiency because it can cause hemolysis. It should be substituted with another agent such as clindamycin. Because high-dose pyrimethamine can cause hemolytic anemia in individuals with G6PD deficiency, these patients should be under close observation. Dosing adjustments may be necessary when sulfadiazine is given to those receiving phenytoin as its half-life may be prolonged.

Additional therapy with corticosteroids (prednisone, 1 mg/kg/day) should be considered with markedly elevated CSF protein (>1 g/dL) and vision-threatening chorioretinitis. Corticosteroids are administered until the elevated CSF protein or active chorioretinitis resolves. The efficacy of corticosteroid therapy has not been observed in controlled studies. No adverse effects of corticosteroids have been noted in cohort studies.

Sulfonamide antimicrobials

Class Summary

These agents exert bacteriostatic action through competitive antagonism with para-aminobenzoic acid (PABA). Microorganisms that require exogenous folic acid and do not synthesize folic acid (pteroylglutamic acid) are not susceptible to the action of sulfonamides. Resistant strains are capable of using folic acid precursors or preformed folic acid. In serum, these agents exist in 3 forms: free, conjugated (ie, acetylated and possibly others), and protein bound. The free form is considered to be therapeutically active.


This is a bacteriostatic agent that acts synergistically with pyrimethamine to treat T gondii.

Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Septra DS, Sulfatrim)

Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria

Trimethoprim: Inhibits dihydrofolate reductase, thereby blocking production of tetrahydrofolic acid from dihydrofolic acid

Sulfamethoxazole: Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid

Antiprotozoal and antimycobacterial agents

Class Summary

Protozoal infections occur throughout the world and are a major cause of morbidity and mortality in some regions. Patients who are immunocompromised 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.

Dapsone, a sulfone that has been widely used in the treatment of leprosy, has been administered in combination with pyrimethamine for prophylaxis against malaria.

Dapsone with trimethoprim is used as an alternative to trimethoprim-sulfamethoxazole for the treatment of mild to moderate Pneumocystis carinii pneumonia; dapsone alone can be used for prophylaxis. Dapsone and pyrimethamine have also been used in patients with HIV and low CD4+ T-cell counts to prevent T gondii encephalitis.


Mechanism of action similar to that of sulfonamides—competitive antagonists of PABA prevent formation of folic acid, inhibiting growth.

Pyrimethamine (Daraprim)

Pyrimethamine is a folic acid antagonist that selectively inhibits dihydrofolate reductase. It is highly selective against plasmodia and T gondii. Pyrimethamine has a synergistic effect when used conjointly with a sulfonamide to treat T gondii.

Atovaquone (Mepron)

Inhibits electron transport chain in mitochondria, which in turn inhibits synthesis of nucleic acid and ATP.

Lincosamide antimicrobials

Class Summary

These agents inhibit bacterial growth, possibly by blocking the dissociation of peptidyl transfer ribonucleic acid (tRNA) from ribosomes, causing RNA-dependent protein synthesis to arrest.

Clindamycin (Cleocin)

Clindamycin is used as an alternative to sulfonamides. It may be beneficial when used with pyrimethamine in short-term treatment of CNS toxoplasmosis in patients with AIDS.

Macrolide antimicrobials

Class Summary

Azithromycin, which belongs to the azalide subclass of macrolide antibiotics, is administered orally. Azithromycin is derived from erythromycin; however, it differs chemically from erythromycin in that a methyl-substituted nitrogen atom is incorporated into the lactone ring.

Azithromycin (Zithromax, Zmax)

Azithromycin acts by binding to the 50S ribosomal subunit of susceptible microorganisms, in that way interfering with microbial protein synthesis. Nucleic acid synthesis is not affected. Azithromycin concentrates in phagocytes and fibroblasts, as demonstrated by in vitro incubation techniques. In vivo studies suggest that concentration in phagocytes may contribute to drug distribution to inflamed tissues. The drug is used to treat mild to moderate microbial infections.

Clarithromycin (Biaxin, Biaxin XL)

Semisynthetic macrolide antibiotic that reversibly binds to P site of 50S ribosomal subunit of susceptible organisms and may inhibit RNA-dependent protein synthesis by stimulating dissociation of peptidyl t-RNA from ribosomes, thereby inhibiting bacterial growth.


Class Summary

Supplemental folinic acid is coadministered to prevent hematologic adverse effects caused by bone marrow suppression.


Leucovorin, also called folinic acid, is a derivative of folic acid used with folic acid antagonists, such as sulfonamides and pyrimethamine.


Class Summary

Glucocorticoids have anti-inflammatory properties and cause profound and varied metabolic effects, modifying the body’s immune response to diverse stimuli.

Prednisone (Prednisone Intensol, Rayos)

This agent elicits mild mineralocorticoid activity and moderate anti-inflammatory effects; controls or prevents inflammation by controlling rate of protein synthesis, suppressing migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at cellular level; in physiologic doses, corticosteroids are administered to replace deficient endogenous hormones; in larger (pharmacologic) doses, they decrease inflammation