Chapter 354. Toxoplasmosis

It is estimated that 500 million people worldwide are infected with Toxoplasma gondii.1 Seroprevalence studies have uniformly indicated increasing rates with age (eFig. 354.1). Between 1999 and 2004, the age-adjusted T. gondii seroprevalence rate declined from 14.1% to 9% among U.S.-born persons ages 12 to 49 years.2 The rates varied among regions, probably due to differing climates, culinary practices, and immigration patterns from areas of the world that have higher endemic rates of Toxoplasma infections. Data from Europe generally indicates a slightly higher prevalence rate compared to the United States, with rates in Central Europe ranging from 24% in Greece to 41% in France and Poland.3-5 In the United States, seroprevalence rates in women of childbearing age are approximately 15%, whereas rates in similar populations from western Europe, Africa, and Central and South America are greater than 50%.1,6 The general population of blood donors from Turkey was found to have a 20% seroprevalence rate, while the seroprevalence restricted to women was found to be relatively high at 52.1%.7,8 In the last two decades, most European countries have noted a decrease in seroprevalence of Toxoplasma, possibly due to less infection in farm animals, more filtration of drinking water, and concerns about consuming undercooked meat.

Seroprevalence rates in India, Sudan, Uganda, and Malaysia range from 20% to 55% in recent studies.9-12 In New Zealand, 33% of women who had antenatal blood work were found to have antibodies to T gondii, indicating past infection.13 Seroprevalence in Brazil was estimated to be between 40% to 80%.14 Globally, infection rates primarily reflect soil temperatures—infection is much more common in warmer or temperate climates and is much less common in colder climates, such as in the northern hemispheres. Specific populations at risk included butchers and individuals of lower socioeconomic status.15,16 A study of children in a low-socioeconomic community in Brazil found a seroprevalence rate of 32.4%.17

T. gondii is a parasite for which the members of the feline species (ie, cats, kittens, cougars) are the definitive hosts.18 Felines ingest the cyst form that is present in soil, which germinates in the cat’s small intestine and produces oocysts. The oocysts are then excreted in the feces for a period of 7 to 20 days into the surrounding environment. The oocyst can sporulate and become infective in the proper environmental conditions (such as warm soil). The oocyst does not sporulate below 4°C, which explains why colder climates would be inhospitable to sporulation. It is the sporulated oocyst that is infective when ingested by other mammals, including humans and other felines. Oocysts can remain viable in warm, moist soil or in salt and fresh water, which can be an ongoing source of infection for other mammals. The tachyzoite, which is the active proliferative form, develops from ingested sporulated oocysts. Within tissues and under the influence of the immune system, tachyzoites transform into bradyzoites, which exist within cysts as the latent form of infection. Although they can be present in any tissue, they are most numerous in the heart, brain, and skeletal muscle.

Host susceptibility to infection as well as variation in strain virulence may have an impact on the development of human infection.19 Humans either ingest infective sporulated oocysts or animal products containing tissue cysts. T. gondii invades and multiplies in the epithelial cells of the intestinal wall, releasing tachyzoites. The tachyzoite penetrates lymphatics and the bloodstream and disseminates to organs, where it invades cells, causing cell death, tissue necrosis, and an intense inflammatory response. In pregnant women, dissemination to the placenta and fetal tissues can occur with the same consequences to the fetus. Replication takes place rapidly until the host cell is disrupted, releasing more tachyzoites into contiguous tissues. The immune response to infection transforms the tachyzoites into bradyzoites, which multiply slowly and reside in tissue cysts, mainly in the brain and in skeletal and heart muscle, where the parasite survives in a latent form. In immunocompetent individuals, this chronic form generally has no adverse consequences. However, if subsequent immunosuppression occurs, especially impairment of cell-mediated immunity, bradyzoites can be released from cysts and can transform back into tachyzoites, causing recrudescence of infection.20

In North America and Europe, it is estimated that food-borne sources of toxoplasmosis are responsible for about 50% of infections.21,22 Food (pork, lamb, and their by-products such as salami, dried cured pork, or raw sausage) that has originated from animals infected with Toxoplasma are the principal sources.23If food is eaten raw or undercooked, T. gondii cysts may remain viable and may infect the human host. Although freezing and cooking may kill tissue cysts, curing meat is not effective in killing them.24 In some circumstances, surface water contaminated with T. gondii enters the municipal water supply.27,28 In addition, contact with cats has been seen as a risk factor. Studies have shown that between 36% and 70% of infected persons recall contact with a cat.21,23,25,26 Oocysts formed in the epithelial cell of the small intestine of the cat will rupture from this cell and are excreted in the feces for a period of 7 to 20 days. Subsequently, infected feline excrement permeates the soil and water, which contaminates foodstuffs such as vegetables and meat or the drinking water. The contact with soil or water is inadvertent and common and is therefore is not expressed as a specific risk factor. Risk factors may also vary depending on climate conditions, as the parasite will be less likely to survive in colder climates where soil freezes for long periods of time. Many individuals do not recall any known risk factor such as cat or undercooked meat exposure. Other sources of transmission are blood or granulocyte transfusions, organ transplants, laboratory accidents, or transplacental infection from an infected mother.

The relatively benign nature of Toxoplasma gondii infection in healthy children belies its devastating effects when the disease is either acquired congenitally or reactivates in immunocompromised states. In immunocompetent hosts, most (90%) acute infections are subclinical or asymptomatic. If clinical symptoms do occur, the most common manifestation of primary acquired toxoplasmosis is enlarged lymph nodes, particularly in the cervical area. In some cases, this is accompanied by systemic, nonspecific symptoms such as malaise or low-grade fever. The differential diagnosis includes other systemic infections, including Epstein-Barr virus, cytomegalovirus, rubella virus, cat-scratch disease, tuberculosis, or malignancy. Other less common clinical presentations include myositis and myocarditis.30Documented cases of severe acute toxoplasmosis have been seen in adults presenting with fever, interstitial pneumonia, myocarditis, and lymphadenopathy.31 Pregnant women who are well are also usually asymptomatic. Reactivation of Toxoplasma infection in pregnancy is rare but has been reported in those with HIV or systemic lupus.

Primary acquired Toxoplasma infection can also result in ocular lesions. Toxoplasma retinochoroiditis is one of the most common identifiable causes of posterior uveitis in the world. Although classic forms of retinitis are described, many atypical forms are now recognized as primary manifestations of acute infections in both immunocompetent and immunosuppressed individuals.32,33 Debate as to whether ocular toxoplasmosis could be related only to congenital infection was present until the 1970s. It is now generally accepted that chorioretinitis can be a manifestation of recently acquired Toxoplasma infection.34 During an outbreak recognized by ophthalmologists in Victoria, British Columbia, 21% of patients with acute infections presented with primary ocular toxoplasmosis.35 Recurrences of ocular toxoplasmosis, either from congenital or postnatal acquisition of disease, can occur over a period of years and is usually identified in the second through fourth decades of life.32,34,36 Usually, those who are immunocompetent have fewer lesions, whereas immunocompromised patients are more apt to have multifocal lesions. Healed foci of ocular toxoplasmosis may resemble other acute or healed retinal inflammatory lesions or rarely congenital anomalies. Since the differential can be broad, serology and laboratory testing are necessary to support the diagnosis of toxoplasmosis.

In immunocompromised patients, T. gondii infections can be of significant clinical consequence and are often fatal if not treated early. In these settings, infection is usually due to reactivation of a past infection. Patients at highest risk are those with a hematologic malignancy and those undergoing cytotoxic or immunosuppressive therapy. The incidence of Toxoplasma infection has dramatically decreased in those with HIV because of the widespread use of highly active antiretroviral therapy.

However, there are increasing reports of toxoplasmosis in those who have had organ transplants. Under the influence immunosuppressive therapy, T. gondii, present in the donor organ, can reactivate in the transplanted host. The highest risk of reactivation occurs when the donor is seropositive and the recipient seronegative. The most common clinical presentations include encephalitis, pneumonia, retinochoroiditis, or myocarditis, but disseminated disease can also occur. Encephalitis may be subacute and may present with either nonspecific symptoms such as lethargy and changes in behavior or with focal neurological signs such as speech or visual difficulties, seizures, or other focal deficits. These will occasionally be accompanied by systemic signs such as fever or malaise.37–39 In heart transplant recipients, signs of rejection may mimic reactivation of toxoplasmosis in the transplanted organ. It has been suggested that seropositivity alone can be associated with increased mortality.40,41 Prophylaxis and early recognition in this special population are essential to ensure survival.

Congenital infections can occur when a mother acquires primary infection in the immediate preconception period or during gestation; rarely, the mother will experience a reactivation of Toxoplasma infection during gestation.42 The clinical manifestations in the offspring vary depending on the gestational age at the time of the acute maternal infection. Although the risk of transmission averages 29% (95% CI 25–33), the risk increases from 6% in the first trimester to 72% at 36 weeks gestation (Fig. 354-1).

Systematic screening studies have demonstrated that, of infants who have proven infection, up to 50% will have clinical signs that can only be detected with careful clinical examination; this suggests that subclinical disease is much more common than overt “classical” clinical manifestations.44,45The risk of developing clinical signs of infection is strongly related to the time of gestation when the infection took place. Infections in the first trimester of pregnancy are more likely to be associated with clinical signs compared to those that occur in the last trimester.43 It is also suspected that severity is related to parasite burden, as a high parasite amniotic fluid concentration is believed to be independently associated with the most severe signs of infection.46

The classic triad of hydrocephalus, intracranial calcifications, and retinochoroiditis is relatively uncommon, since it represents early congenital disease and specific neurological involvement. Neonates who are symptomatic at birth may present with neurological signs such as seizures, hydrocephalus, or microcephaly. Severe periaqueductal and periventricular vasculitis and necrosis (as evidenced by high levels of protein in the cerebrospinal fluid) cause the hydrocephalus typically seen with Toxoplasma cerebritis. Intracranial calcifications are usually seen on imaging studies of the brain47 (Fig. 354-2). Others may have retinochoroiditis or scars that can be seen only with fundoscopic examination. The differential diagnosis of neurological manifestations include other hereditary and infectious syndromes.48-51

Other signs of congenital Toxoplasma infection are the result of Toxoplasma cysts within different organs. These may include jaundice, fever, splenomegaly, hepatomegaly, lymphadenopathy, pneumonitis, and seizures. These clinical signs are not specific for Toxoplasma infection, but the constellation of signs and symptoms should prompt appropriate laboratory investigations for the diagnosis of toxoplasmosis. The differential diagnosis includes other acquired pathogens such as cytomegalovirus, rubella, herpes simplex and syphilis, and other causes of neonatal sepsis.

The apparent benign nature of the newly infected neonate may conceal the future impact of a potentially insidious and progressive infection. Since this is an ongoing infection in the infant, many of the signs or symptoms of infection, particularly the neurological sequelae, manifest themselves as the child grows and develops. In severely affected infants, microcephaly, deafness, visual loss, spasticity, mental retardation, and seizures may develop. Months to years later, there may be only ocular manifestations of the scars that are sequelae of retinochoroiditis. The consequences of damage caused by ocular inflammation may include optic atrophy, nystagmus, strabismus, and premature cataracts.52-58

Interpretation of tests for the diagnosis of T. gondii infection is highly dependant on the clinical stage of suspected infection and on the host.59 Clinical serological diagnostic tests are used routinely, while nucleic acid amplification tests are reserved for detecting the parasite in tissues or fluid.

Several caveats to diagnostic testing for toxoplasmosis are worth emphasizing. In all cases, more than one type of serology will be required. In most cases, paired sera taken 4 to 6 weeks apart are helpful for determining the timing of infection. Other supporting tests include histological studies of tissues and demonstration of the parasite or nucleic acid in tissues. Isolation of the organism is indicative of active infection.

Toxoplasma-specific IgG antibodies usually appear within weeks of infection, peak at 1 to 2 months, and decline but remain positive for life. In the absence of exogenous immunoglobulin, the presence of IgG to T. gondii indicates past infection or transplacental transfer of immunoglobulin from a mother to the newborn. Avidity tests based upon the binding of serum antibodies to fixed antigens that increase over time are more sensitive and specific for differentiating recent from past infection, particularly with only a single serum sample. High avidity is indicative of remote infection, while low avidity is observed with more recent infection.

Toxoplasma-specific IgM antibodies usually appear within the first weeks after an acute infection and become negative within a few months. Therefore, its presence is usually indicative of acute infection. However, in a significant proportion of people, persistence of IgM beyond a few months does occur. This is problematic because it can give the false impression of a recently acquired infection.63 In addition, testing for IgM has revealed a relatively high proportion of false-positive results because of cross-reactions with other IgM antibodies, rheumatoid factor, or antinuclear antibodies, thereby impairing its reliability as a marker of recent infection.64,65 Thus, a negative IgM has a good negative predictive value for a recent infection, but a positive IgM is not always indicative of a recent infection, and further testing is warranted in cases where timing of infection is important. Toxoplasma-specific levels of IgG, IgM, IgA, and IgE antibodies combined with avidity tests improves sensitivity and specificity regarding the presence and timing of infection. These are generally available in reference laboratories.60,66 Test combinations—including Sabin-Feldman dye test for IgG, IgM ELISA, IgA ELISA, IgE ELISA, and avidity testing—are more sensitive and specific than single tests alone in determining the timing of infection; these should be sought in most situations, since determining the timing and establishing the diagnosis will impact treatment decisions.60,65

Isolation of or histological visualization of replicating parasites will confirm the presence of the infection but cannot be relied upon to date the timing of infections. However, amplification of Toxoplasma DNA using polymerase chain reaction (PCR) or the demonstration of tachyzoites in fluid or tissues such as amniotic fluid, placenta, brain fluid, or cerebrospinal fluid is indicative of active infection.67,68

Evaluation of Children for Toxoplasma Infection

Serological tests are generally used to document infection in immunocompetent persons. If only IgG antibodies to Toxoplasma are present, then past infection with T. gondii has occurred. The finding of T. gondii–specific antibodies for IgM, IgA, or IgE suggests a recent infection in a single specimen; however, IgM may remain positive in older children and adults for years.60,66Initial titers of IgG may be negative or low if the infection is very recent, but a fourfold rise in titers of IgG from serial blood samples taken 3 weeks apart indicates a recent infection. Presence of this serological profile with a compatible clinical scenario is usually sufficient to confirm the diagnosis. Lymph node biopsy specimens in immunocompetent individuals may show characteristic histopathologic findings.

Immunocompromised children who have Toxoplasma-specific IgG antibodies may have active recent infection or may be at risk for reactivation. In clinical situations where the diagnosis is not certain, tissue sampling for histopathology and identification of the organisms and/or its nucleic acid may be required. Particularly in this population, it is critical for diagnosis to be made early in order that therapy be instituted.

Evaluation of Pregnant Women for Toxoplasma Infection

Universal screening for infection in pregnancy is routinely practiced in France and Austria. In other parts of the world, prenatal screening is performed sporadically depending on local epidemiology. More often, evaluation takes place if there is a clinical suspicion or if there are epidemiological factors to suggest infection. Since women rarely transmit infection to the fetus unless acutely infected, diagnosis is aimed at determining if acute infection took place during pregnancy. If serological testing reveals no Toxoplasma-specific antibodies, then the woman has not been previously infected and is considered to be at risk for acquiring infection. Remote infection in pregnant women is characterized by the presence of Toxoplasma-specific IgG and the absence of Toxoplasma-specific IgM, IgA, or IgE. In this case, there is no risk of infecting the fetus unless the mother is immunocompromised.

If Toxoplasma-specific IgM with or without IgG antibodies is detected, establishing if infection has occurred during gestation is important so the mother and fetus can potentially be treated. A clinical examination of the mother, with special attention to the presence of lymphadenopathy, should be done. Since T. gondii–specific IgM alone may persist for years following primary infection, its presence is not specific for recent infection. Serology should be repeated in 2 to 3 weeks to determine IgG seroconversion or a rise in T. gondii–specific IgG. Rising titers of IgG (twofold dilutions of specimens tested in parallel) or seroconversion from negative to positive in serial serum specimens is indicative of acute infection.60 In order to assess time of acquisition of infection, avidity testing and differential agglutination (AC/AS) testing, in addition to T. gondii–specific IgA and IgE, should be requested. A high-avidity test result indicates acquisition of infection more than 12 to 16 weeks earlier.

Testing should be done in a reference laboratory. Consultation with clinicians expert in interpreting serology is recommended.62 In addition, fetal ultrasounds should be performed to assess growth retardation, hydrocephalus, ascites, or calcifications.

If acute infection is diagnosed or suspected in the mother, attempts to diagnose fetal infection are warranted.69 Currently, demonstration of Toxoplasma DNA from amniotic fluid is the preferred method for diagnosing fetal congenital infection. This technique has supplanted fetal blood sampling using cordocentesis because of decreased risk to the fetus and higher sensitivity.69,70 False negatives may occur if the infection is acquired very early (4–16 weeks gestation) or late (greater than 22 weeks) in gestation.71 Since transmission to the fetus must have occurred prior to the testing, infections in the mother that have not had sufficient time to transmit to the fetus will result in negative PCR testing of the fetal-placental unit. The sensitivity of prenatal diagnosis with PCR is estimated at 42.9% between 4 to 16 weeks gestation, 92.9% between 17 to 21 weeks gestation, and 61.7% at 22 weeks or more of gestation. The negative predictive value up to 21 weeks gestation is between 90% and 100% and then falls to 77% after 22 weeks gestation and to 14.3% after 31 weeks gestation. It is, however, highly specific with a positive predictive value of 100%.71 Therefore, a negative PCR in amniotic fluid cannot completely rule out congenital toxoplasmosis, especially after 22 weeks, but a positive result in a reference laboratory is highly specific for diagnosis. Serial ultrasounds of the fetus should be performed to detect hydrocephalus, microcephaly, or any other clinical indication of congenital infection and should be performed at monthly intervals on all infected pregnant women.69

Evaluation of the Newborn with Suspected or Confirmed Toxoplasma Infection

The clinical manifestations of congenital toxoplasmosis range from nonexistent to very subtle or overt and may be nonspecific. Proper diagnosis includes careful clinical evaluation and laboratory testing. Evaluation should include a history and physical examination with additional specific neurological and ophthalmological examinations. Baseline complete blood counts, liver function tests, total IgM, cerebrospinal fluid analysis (protein, glucose, cell count, T. gondii–specific IgM, IgA, and IgG, and PCR for T. gondii), computed tomography of the brain without contrast, and tests of hearing function should be obtained.42 Abnormal cerebrospinal fluid (high protein content and pleocytosis) and abnormalities of brain imaging suggest infection.6,47,72

Specific serological evaluation is also critical for diagnosis in the newborn period.42 In addition to IgG, the presence of Toxoplasma-specific IgA, IgM, and IgE should be sought in the sera of all newborns suspected of having Toxoplasma infection and should be performed in a reference laboratory. If the diagnosis of acute infection in the mother during gestation has not been established, serum specimens from the mother should be sent in parallel and tested for IgG, IgM, and IgA in a differential agglutination test (AC/HS) with an avidity assay. False positives can occur if there has been contamination in the first few days of life by maternal IgM and IgA, depending on the type of assay used.73

A positive T. gondii–specific IgM in a newborn indicates primary infection, as IgM does not cross the placenta. IgA-specific antibodies to T. gondii are also indicative of primary infection in infants infected congenitally and after postnatal primary infection. Similar to IgM, however, they can also persist for prolonged periods of time and cannot be relied upon for timing in many instances. The sensitivity of T gondii–specific IgA is higher than IgM for the occurrence of primary infection in a newborn.74 The level of IgG antibodies in the infant will fluctuate according to age, depending on the rate of loss of maternal antibody and the infant’s production of IgG antibody. Thus, a congenitally infected infant may initially have a high titer that decreases as they lose maternal IgG. The titer of IgG antibody may then increase as the child produces his or her own IgG. In infants whose mothers have been treated with pyrimethamine and sulfadiazine during pregnancy, serological titers may also vary depending on the timing and effectiveness of therapy.

Interpretation of such tests should be performed in conjunction with a reference laboratory experienced in interpreting Toxoplasma serology. Measuring antibody levels in cerebrospinal fluid (CSF) is not accurate if the mother’s IgG in the dye test is above 300 IU/L. However, the presence of T. gondii–specific IgM in the CSF is indicative of acute infection.

The placenta, peripheral blood clots, and CSF specimens should be conserved to determine the presence of Toxoplasma organisms. Isolation of T. gondii or detection of DNA in a reference laboratory from any of these sites is indicative of acute infection in the infant.75

Usually immunocompetent children who have primary infection do not require treatment. Rare cases of severe disease including pneumonia, sepsis syndromes or myocarditis should be treated with standard therapy as described in Table 354-1.6,79 Active retinochoroiditis should be treated as indicated in Table 354-1.6,80 Oral prednisone has been used when there is an active inflammatory process that threatens vision through involvement of the macula or optic nerve and active vitritis.33,80,81 Preventing reactivation in persons who have had relapse of ocular lesions should be considered in patients with frequent or recurrent retinochoroiditis.82

In immunocompromised hosts, reactivation of, or primary infection with, T. gondii is more likely to be life or sight-threatening and therefore requires therapy. Primary therapy followed by maintenance therapy to prevent relapse is recommended unless the immunodeficient state reverses. Primary therapy with pyrimethamine and sulfadiazine or clindamycin and leucovorin is recommended, followed by pyrimethamine and sulfadiazine at lower doses for maintenance. Difficulties with long-term therapy include development of hypersensitivity and toxicity of medication.

Spiramycin is a macrolide antimicrobial active in vivo against the tachyzoite form of T. gondii. Since it is concentrated in the placenta, it is used to decrease the risk of transmitting the infection transplacentally from mother to fetus. Pyrimethamine and sulfadiazine are synergistic against T. gondii. Both drugs in combination are used to treat infection. Pyrimethamine has a long half-life, about 60 hours, and inhibits dihydrofolate reductase. It can produce reversible bone marrow toxicity, resulting in anemia, neutropenia, and thrombocytopenia. To counter this effect, pyrimethamine is given with folinic acid in the form of leucovorin calcium and twice-weekly monitoring of blood counts is recommended. Teratogenic effects of pyrimethamine have been seen in animals in the first trimester; therefore, this drug should not be given until the second trimester. If there is hypersensitivity to pyrimethamine, second-line medication includes clindamycin, azithromycin/clarithromycin, or atovaquone; however, there are no studies that demonstrate efficacy in pregnant women.76–78

Treatment of the Pregnant Woman

If maternal infection was confirmed or suspected to be acquired at less than 18 weeks gestation, spiramycin treatment and fetal ultrasound, with amniotic fluid PCR at 18 weeks is indicated. If these are negative, spiramycin should be continued until delivery. If after 18 weeks, treatment with pyrimethamine, sulfadiazine and folinic acid should be administered pending results from fetal ultrasound. If the PCR is negative, a change to spiramycin can be considered. If either the PCR or ultrasound is positive, pyrimethamine, sulfadiazine and folinic acid should be administered until delivery (eFig. 354.2).

Sentinel treatment coupled with long-term follow-up studies have shown remarkable benefit for treating congenital toxoplasmosis in newborns and infants compared to historical controls.53,83In these studies, the treated group began therapy as soon as possible after birth and were treated for 1 year. Of these, children who had no, mild, or moderate systemic findings at birth had normal motor and cognitive function and hearing. Of those who had severe disease at presentation (retinochoroiditis, central nervous system calcifications, and hydrocephalus), all had normal hearing, 80% had normal motor function, and 73% had intelligent quotients above 70 points. Vision impairment occurred in about 85% of these children at birth. Toxicity included reversible neutropenia. Significant improvements in central nervous system imaging usually occurs with treatment. This may include disappearance or diminution of calcifications and improvements or normalization of CSF spaces. Other studies focusing on chorioretinitis have shown similar clinical improvement with prolonged treatment, but new retinal lesions have occurred, emphasizing the continued need for ophthalmological follow-up.52,84,85

Treatment regimens consist of pyrimethamine plus sulfadiazine and leucovorin (see Table 354-1). Corticosteroids can be given if cerebrospinal protein is greater than 1g/dl or if visual acuity is threatened; these can be continued until it is evident that active infection has resolved (usually weeks). The usual treatment length is 1 year. Selected countries using different regimens have treated infants for shorter or longer periods of time.42

Avoiding infection in pregnancy is particularly important to prevent fetal infection.22,86Primary prevention should focus on avoiding sources of tissue cysts (cat litter) or soil containing sporulated oocysts. Avoiding raw or undercooked food (especially meat or meat products) or cured meat or ingesting unfiltered water is paramount. Other food-preparation hygiene measures such as washing surfaces used to prepare meat is equally important. Since home freezer temperatures do not kill the parasite, thorough cooking of meat is essential to destroy any potential cysts.

Screening women prior to pregnancy is not routinely done, so preconception counseling is not widely practiced other than in France.77 In North America, routine screening of pregnant women and rescreening those who are negative is performed selectively, depending on obstetrician preferences. Guidelines for preventing infection in pregnancy have recently been published.69 Neonatal screening has also been used, and 40% of those infants detected had either central nervous system or eye signs at birth.45,87-89 Screening organ transplant recipients and donors permits prophylaxis of seronegative recipients who are, for example, receiving hearts from seropositive donors.38,40