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Toxoplasmosis and pregnancy

Toxoplasmosis and pregnancy
Authors:
Eskild Petersen, MD, DMSc, DTM&H
Laurent Mandelbrot, MD
Section Editors:
Lynn L Simpson, MD
Peter F Weller, MD, MACP
Deputy Editors:
Vanessa A Barss, MD, FACOG
Jennifer Mitty, MD, MPH
Literature review current through: Apr 2022. | This topic last updated: Mar 25, 2022.

INTRODUCTION — Toxoplasma gondii is a ubiquitous protozoan parasite that infects humans in various settings. The parasite is usually acquired during childhood and adolescence [1]. When toxoplasmic infection is acquired for the first time during pregnancy, the parasites can be transmitted from the mother to the fetus, resulting in congenital toxoplasmosis. The frequency of congenital toxoplasmosis increases with increasing gestational age at maternal infection, but the frequency of severe sequelae in offspring is greater when infection occurs early in pregnancy [2,3].

Congenitally infected infants who are symptomatic at birth may have clinical findings localized to the central nervous system or eye or have generalized manifestations of the disease. Those with mild or subclinical disease at birth may have no manifestations on routine physical examination but remain at risk for long-term sequelae from chorioretinitis. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

This topic will focus on issues related to T. gondii infection during pregnancy. Other aspects of this infection in adults are reviewed separately:

(See "Diagnostic testing for toxoplasmosis infection".)

(See "Toxoplasmosis: Ocular disease".)

(See "Toxoplasmosis: Acute systemic disease".)

(See "Toxoplasmosis in patients with HIV".)

MATERNAL INFECTION

Acquisition of infection

ParasiteT. gondii is an obligate intracellular parasite that exists in three forms [4]:

Sporozoite (in sporulated oocysts), which is shed only in the feces of definitive hosts

Tachyzoite (a rapidly dividing form observed in the acute phase of infection), and

Bradyzoite (a slow-growing form observed within tissue cysts)

Host and cycle – Members of the family Felidae (eg, domestic cats, mountain lion, bobcat, tiger) are the definitive hosts and therefore the only animals in which T. gondii can complete its reproductive cycle. During primary infection in the host (eg, cat), the host can shed millions of oocysts daily from its alimentary canal for a period of one to three weeks. These oocysts become infective (sporulated) one to five days later and may remain infectious for over a year, especially in warm, humid environments. The host typically develops immunity after a primary infection; therefore, recurrent infection with passage of oocysts is unlikely.

Sources of transmission

Raw, undercooked, or cured meat or meat products – In resource-abundant, temperate-climate countries, the main source of maternal infection is thought to be ingestion of bradyzoites contained in raw, undercooked, or cured meat or meat products. Food animals (pigs, chickens, lambs, goats) become infected by the same routes as humans, resulting in meat containing bradyzoites [5].

Contaminated soil or water – Maternal ingestion of sporozoites from consumption of contaminated soil or water or soil-contaminated fruit or vegetables is also a major source of infection, and may be the main source of infection in some countries [4,6-12].

Unpasteurized milk, contaminated seafood – Other potential sources of maternal infection include drinking unpasteurized goat's milk and consuming raw oysters, clams, or mussels (ie, filter feeders) harvested from contaminated water [13-16].

Transplant, transfusion – An infected organ transplant or blood transfusion is a rare source of infection. (See "Toxoplasmosis: Acute systemic disease", section on 'Transmission'.)

In a study from the United States, household members of a patient with acute toxoplasmosis were at higher risk of acquiring the infection, which suggests a common environmental or food source [17].

Seroprevalence among females of childbearing age — In industrial, temperate-climate countries, 10 to 50 percent of adults aged 15 to 45 years have serologic evidence of past T. gondii infection, which represents a decline in seroprevalence over recent decades [1,18]. In the United States, the age-adjusted seroprevalence among females of childbearing age (15 to 44 years) was 7.5 percent in 2011 to 2014 compared with 11 percent in 1999 to 2004 and 15 percent in 1988 to 1994 [19]. Robust recent data are not available.

Prevalence varies widely across Europe: Norway (7 percent), United Kingdom (10 percent), Italy (19 percent), Spain (32 percent), Austria (33 percent), Slovenia (34 percent), and France (31 percent) [20,21]. High seroprevalence rates (up to 80 percent) are found in some areas of the tropics, particularly in communities exposed to contaminated soil, undercooked meat, or unfiltered water [4,6,7,22-25]. A 2022 study in over 1000 pregnant individuals in Benin reported toxoplasmosis seroprevalence, seroconversion, and congenital infection rates of 52.6, 3.4, and 0.2 percent [25].

Incidence of acute primary infection in pregnancy — Incidence data are limited and often not contemporary. The incidence of acute maternal infection during pregnancy ranged from 0.5 to 8.0 per 1000 susceptible pregnancies in a study conducted in six European countries in the 1990s [26]. Although France has historically reported rates at the upper end of this range, the rate in France has significantly decreased in the past decade: the incidence of T. gondii infection diagnosed by seroconversion in French females is 2.0 to 2.5 per 1000 seronegative females [21]. In the United States, one review estimated the incidence of acute primary infection was 0.2 per 1000 pregnant individuals [27]. Data for 1986 to 1992 from the New England Regional Newborn Screening Program suggest congenital infection is present in 1 in 10,000 live births [28].

Clinical manifestations — Acute maternal infection is usually asymptomatic (≥80 percent of cases). When symptoms of infection occur, they are typically nonspecific and mild: fever, chills, sweats, headaches, myalgias, pharyngitis, hepatosplenomegaly, and/or a diffuse nonpruritic maculopapular rash. The febrile episodes usually last two to three days. (See "Toxoplasmosis: Acute systemic disease", section on 'Clinical manifestations'.)

Lymphadenopathy is the most common symptom. In a prospective European study, lymphadenopathy was noted in 7 percent of infected pregnant individuals [29]. It is typically bilateral, symmetrical, nontender, and cervical, but generalized lymphadenopathy occurs in a minority of patients. The lymph nodes are usually smaller than 3 cm and nonfluctuant. Unlike the fever, which lasts a few days, lymphadenopathy can persist for weeks.

Ocular disease (chorioretinitis [posterior uveitis]) may occur with acute disease but is more common with reactivation. It presents with visual loss or floaters. (See "Toxoplasmosis: Ocular disease".)

Clinical manifestations are affected by T. gondii genotype. There are three main T. gondii genotypes (types 1, 2, and 3), whose prevalence varies in different geographic areas. In Europe and North America, the large majority of patients are infected with less virulent genotypes (eg, types 2 and 3). Most immunocompetent patients are able to limit the spread of the parasite and the associated tissue damage, ensuring that the parasite remains in its dormant form in neural and muscle tissue (latent infection) for the life of the host, whereas immunosuppressed patients are at risk for reactivation of the parasite in these tissues [30]. By comparison, in South and Central America, more virulent genotypes (eg, types 4, 5, 8, 9, and 10) are prevalent and associated with a higher rate and increased severity of maternal disease after infection [30]. Severity of congenital infection may also be affected by the T. gondii genotype [31].

Clinical differential — Differential diagnosis of the clinical features of toxoplasmosis includes acute Epstein-Barr virus infection, cytomegalovirus infection, HIV infection, syphilis, Zika virus infection, sarcoidosis, and lymphoma. (See "Toxoplasmosis: Acute systemic disease", section on 'Differential diagnosis of acute systemic infection'.)

Pregnancy outcome — Among pregnant individuals with documented seroconversion, the risk for congenital infection depends on several factors, which are discussed below. (See 'Fetal infection' below.)

The overall risk for miscarriage is approximately 0.5 percent among pregnant individuals who seroconvert [21]. In pregnancies with proven fetal infection, the risk of fetal demise is estimated to be 1.3 to 1.6 percent.

INDICATIONS FOR MATERNAL DIAGNOSTIC TESTING — Diagnostic testing using serology for toxoplasmosis should be performed if there is clinical suspicion of acute toxoplasmosis during pregnancy, such as [27]:

Maternal symptoms (eg, fever and adenopathy, particularly cervical) conferring a high clinical suspicion of acute infection. (See "Toxoplasmosis: Acute systemic disease".)

Fetal sonographic abnormalities that suggest congenital toxoplasmosis (eg, intracranial hyperechogenic foci or calcifications and/or cerebral ventricular dilation). (See 'Ultrasound findings in congenital toxoplasmosis' below.)

The diagnosis of toxoplasmosis in symptomatic pregnant individuals, including choice of test(s), interpretation, and follow-up serologic studies, is reviewed in detail separately. (See "Diagnostic testing for toxoplasmosis infection", section on 'Approach to diagnosis' and "Diagnostic testing for toxoplasmosis infection", section on 'Considerations in pregnant women'.)

SCREENING

Should all pregnant individuals be screened? — The balance of risks and benefits of prenatal screening/treatment must be estimated by individual countries/continents/regions because the balance shifts depending on disease prevalence and prevalence of more virulent strains of T. gondii (eg, Western Europe has mostly less virulent strains, and South America has more virulent strains [27]).

To be effective, screening needs to be performed frequently in order to detect and, in turn, treat asymptomatic maternal infection early (ideally within three weeks of infection [32,33]) when treatment might prevent fetal infection and damage (see 'Efficacy' below). However, frequent rescreening increases costs and is bothersome to patients: In a study from France, seronegative pregnant patients missed 19 percent of the expected monthly tests [34].

National societies in the United States, Canada, the United Kingdom, and some parts of Europe recommend against routine universal screening for toxoplasmosis in pregnancy [26,35,36] because the prevalence of the disease and incidence of maternal infection are very low and screening is costly. Other parts of Europe have taken a different approach; screening is performed at monthly, bimonthly, or every three-month intervals throughout pregnancy as part of routine prenatal care [29,37]. In 2020, an expert group of the French College of Obstetricians and Gynecologists reviewed the evidence and recommended continuing the monthly screening program [21].

It is important to note that the nonscreening policy in the United States, Canada, and several European countries cannot be extrapolated to South America, where there are more virulent genotypes, which alters the balance between the risks of prenatal screening and the benefits of prenatal treatment. Prenatal screening has been encouraged in some parts of South America, such as Brazil, where virulent T. gondii is prevalent and many individuals have risk factors for acquiring the infection because of low sanitation, feeding habits, contact with cats, contact with contaminated soil, and consumption of unboiled, untreated water [38,39]. The Brazilian Ministry of Health recommends quarterly prenatal screening as a strategy to control congenital toxoplasmosis; however, regional, economic, and social diversities have made it difficult to implement universally [40].

Interpretation of screening results — The diagnosis of toxoplasmosis in asymptomatic pregnant individuals who screen positive is complicated because determining whether infection occurred prior to conception or during pregnancy is critical and false-positive tests are common.

A toxoplasmosis pregnancy panel from a nonreference laboratory (eg, commercial, clinic, or hospital laboratory) can be used for initial screening, and:

If the immunoglobulin M (IgM) is positive or equivocal (regardless of the IgG), the diagnosis should be confirmed by an experienced reference laboratory (in the United States: Dr. Jack S. Remington Laboratory for Specialty Diagnostics, 650-853-4828).

If screening is performed early in pregnancy, particularly in the first trimester, negative IgM and positive IgG antibodies indicate prior immunity; confirmatory testing is not recommended [41].

If screening is performed later in pregnancy, particularly after approximately 20 weeks, and the IgM is negative and the IgG is positive, the timing of infection is less clear, and confirmatory testing by an experienced reference laboratory is recommended [27].

As a brief synopsis, IgM antibodies appear as early as two weeks after infection and may persist for years, while IgG antibodies peak six to eight weeks after infection and then decline over the next two years but remain positive [42]. The diagnosis of recent toxoplasmosis can be made with greatest confidence when both IgM and IgG seroconversion are documented on serial testing. However, paired screening serologies showing this type of response are uncommon. Instead, screening serologic assays often demonstrate both positive IgM and IgG antibodies at the first prenatal visit. For patients who are initially screened at the end of the first trimester and have positive IgM and IgG, the probability that infection occurred after conception is 1 to 3 percent, depending on the test used [42]. To establish whether the positive IgM and IgG antibodies reflect recent or chronic infection or a false-positive result, confirmatory testing must be obtained with avidity testing. High IgG avidity is a hallmark of chronic infection (>4 months old), but low avidity is not diagnostic of recent infection as low IgG avidity can persist for years in some individuals [43-45].

A rising IgG titer is another factor to consider in establishing a diagnosis of probable recent versus chronic infection. A twofold or greater increase in IgG titer over two sequential samples obtained three weeks apart and tested simultaneously in the same laboratory with the same technique can also suggest recent infection. (See "Diagnostic testing for toxoplasmosis infection".)

FETAL INFECTION

Pathogenesis of fetal infection — Fetal infection results from transplacental transmission of tachyzoites following primary maternal infection [4]. Transmission may occur during the parasitemic phase in the days after maternal infection and before the development of a maternal serologic response, or secondarily, following infection of the placenta [46]. Tachyzoites invade host cells, especially in the brain and muscle. In immunocompetent animal models, tissue cysts in neural and muscle tissue can be formed within a week of infection [47,48]. It is not known how long this process takes in the relatively immunologically immature fetus. Once fetal infection has occurred, production and placental transfer of maternal IgG does not mitigate fetal sequelae [49].

Consequences of fetal infection — In France, approximately 90 percent of live born children with congenital toxoplasmosis are asymptomatic at birth; two-thirds of symptomatic newborns have moderate disease (intracranial calcifications, peripheral retinochoroiditis), and one-third have severe disease (disseminated form, hydrocephalus, or macular retinochoroiditis) [21]. The three most common symptoms are retinochoroiditis (15.5 to 26.0 percent), intracranial calcifications (9 to 13 percent), and hydrocephalus (1.0 to 2.4 percent). Clinical features, treatment, and outcome of congenital infection are discussed in detail separately. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

Risk factors for maternal-to-fetal transmission — Risk factors for maternal-to-fetal transmission include [27,31]:

Maternal infection at an advanced gestational age.

High parasite load.

Maternal parasite source (risk of fetal infection is higher when the source is sporozoites in oocysts [cat feces] than bradyzoites in tissue cysts [meat] (figure 1)).

High-virulence T. gondii strain.

Maternal immunocompromise.

Impact of gestational age — The frequency of fetal infection increases steeply with advancing gestational age at the time of maternal seroconversion. In a meta-analysis of all available cohorts, the estimated probability of transmission by gestational age at documented seroconversion was [33]:

At 13 weeks – 15 percent (95% CI 13-17)

At 26 weeks – 44 percent (95% CI 40-47)

At 36 weeks – 71 percent (95% CI 61-76)

Although these figures are based on patients who were mostly treated during pregnancy, the impact of gestational age is likely to be similar in untreated patients. (See 'Modification of the drug regimen after fetal diagnosis' below.)

The frequency of fetal infection increases with gestational age at seroconversion; however, the overall frequency of clinical manifestations in the infant decreases with older gestational age at seroconversion, with a marked reduction in intracranial lesions with older gestational age at seroconversion, and a less marked reduction in ocular lesions [33]. In the Systematic Review on Congenital Toxoplasmosis (SYROCOT), the odds of developing chorioretinitis and/or intracranial lesions before age 3 years decreased by 4 percent per additional week of gestation at seroconversion; the incidence of eye lesions before age 3 was approximately 20 percent, with a much slighter decrease in trend with advancing gestational age [27]. In another study, after seroconversion at 13, 26, and 36 weeks, the frequency of symptomatic disease before age 3 years was 61, 25, and 9 percent, respectively [3]. Most mothers were treated in these studies.

Females infected prior to conception virtually never transmit toxoplasmosis to the fetus, although rare exceptions have been reported when infection occurred within one or two months before conception [50-54]. (See 'Timing pregnancy after maternal infection' below.)

Risk of fetal infection from reactivation or reinfection — Congenital toxoplasmosis secondary to maternal reinfection with a different T. gondii strain is a very rare event [55]. In one review, this phenomenon was reported in approximately six individuals over the past three decades [56]. One well-documented case in the review demonstrated that prior immunity to T. gondii did not protect against reinfection with an atypical strain.

Theoretically, reactivation of latent toxoplasmosis during pregnancy leading to congenital infection could occur in pregnant individuals with HIV infection who are severely immunocompromised, but the risk appears to be absent or very low.

In the European Collaborative Study, a prospective study of 1058 children born to mothers with HIV, it was estimated that 71 children were born to mothers with latent Toxoplasma infection, and none had serologic evidence of congenital infection [57,58].

In a Brazilian study, of 2007 infants born to mothers with HIV who were followed and systematically tested for toxoplasmosis in the first year of life, 10 (0.5 percent) had congenital toxoplasmosis [59]. Most of the mothers in the study were asymptomatic.

In one case of maternal-to-fetal transmission, the mother with HIV was severely immunocompromised and symptomatic [60]. Additional information on the evaluation and management of mothers with HIV and toxoplasmosis is presented elsewhere. (See "Toxoplasmosis in patients with HIV", section on 'Special considerations during pregnancy'.)

Patients receiving immunosuppressive therapies for conditions such as inflammatory bowel or rheumatic disease could also be at risk for having a congenitally infected infant due to reactivation, but no clear data in this population are available.

Ultrasound findings in congenital toxoplasmosis — Fetal ultrasound can provide diagnostic and prognostic information but is not a useful screening tool.

The following sonographic findings have been described [61-63]:

Intracranial hyperechogenic foci (calcifications/densities)

Ventricular dilation/hydrocephalus

Echogenic bowel

Hepatosplenomegaly

Intrahepatic calcifications/densities

Growth restriction

Ascites

Pericardial and/or pleural effusions

Hydrops fetalis

Fetal demise

Placental densities and/or increased thickness

The most common sonographic findings in fetal toxoplasmosis are intracranial hyperechogenic foci or calcifications and cerebral ventricular dilation, which often occur together [2,61-64]. Intracranial calcification or ventricular dilation was found in 6 percent (14 of 218) of infected fetuses in a European prospective cohort study [2]. Ventricular dilation is generally bilateral and can progress rapidly over a period of a few days or weeks [61]. Other brain findings in infected fetuses include periventricular abscesses or, less frequently, periventricular echogenicity, cortical gyration anomalies, lenticulostriate vessels vasculitis, shortened corpus callosum, cerebellar anomalies, and subependymal cysts [63]. Fetal magnetic resonance imaging may add prognostic information to detailed expert ultrasound evaluation in some cases.

Extracerebral abnormalities, when present, are usually associated with cerebral abnormalities. The more severe abnormalities are associated with first- or second-trimester infections, but the abnormalities may not become apparent until several weeks or months after maternal infection and transmission to the fetus [2,61]. Thus, sequential expert ultrasound follow-up of infected fetuses is important. (See 'Ultrasound follow-up' below.)

Diagnostic significance in the absence of prenatal screening — In the absence of maternal serologic screening, one or more of the ultrasound findings described above may lead to suspicion of congenital toxoplasmosis. However, the sonographic signs are nonspecific, so prenatal ultrasound cannot reliably distinguish between congenital toxoplasmosis and other congenital infections (eg, cytomegalovirus, Zika virus) or various genetic diseases (eg, ventricular dilation can be related to trisomy 21, echogenic bowel can be related to cystic fibrosis).

Therefore, when toxoplasmosis is suspected because of multiple ultrasound findings rather than a prenatal screening protocol, maternal serology for toxoplasmosis and cytomegalovirus, at a minimum, should be performed as these are the two most common infectious causes for these findings (panels including cytomegalovirus and Toxoplasma are available). However, serology is not recommended for isolated fetal growth restriction or isolated polyhydramnios because of very low yield [65]. If maternal IgG and IgM are negative for toxoplasmosis, fetal toxoplasmosis infection is ruled out, and further evaluation can be directed toward other causes for the sonographic findings. If maternal IgG is positive for toxoplasmosis (even in the absence of IgM), we offer amniocentesis for amniotic fluid analysis for T. gondii polymerase chain reaction (PCR) as a component of the work-up of the sonographic findings, guided by the clinical scenario. (See 'Prenatal diagnosis' below.)

Prognostic significance in infected fetuses — In infected fetuses, the prognosis likely depends on the severity of the cerebral damage, and not all abnormal fetal findings lead to serious disabling sequelae, particularly in the presence of early therapy [2,66].

In our clinical experience, the sonographic signs clearly associated with poor prognosis are:

Ventricular dilation

Large brain abscesses

Brain necrosis

Gyration disorders

Microcephaly

Ventricular dilation is the most common while the other findings are uncommon. Ventricular dilation is usually caused by obstruction of the aqueduct of Sylvius or foramina of Monro (ie, obstructive hydrocephalus) but can be due to abnormal resorption of cerebrospinal fluid (ie, absorptive hydrocephalus) because of generalized periventricular or leptomeningeal inflammation [67].

Intracranial hyperechogenic nodular foci without other lesions are not associated with developmental delay [68], and extracerebral signs are not associated with poor developmental outcomes if there are no associated cerebral signs, which is relatively uncommon [63]. Cerebral calcifications, however, are a risk factor for the development of retinochoroiditis during childhood [69]. Expert ultrasound follow-up is important to detect development of cerebral signs and, when in doubt, should be repeated one to two weeks later.

Prognostic data are limited because of the small number of fetuses with abnormal cranial imaging reported in the literature, lack of long-term follow-up with adequate neurologic assessment, retrospective reports that are subject to ascertainment bias, descriptions of fetuses with multiple findings of variable severity such that the prognosis of any specific finding is difficult to predict, and differences in prenatal and postnatal treatment. Even patients who initially present with severe hydrocephalus and cortical mantle thinning have had favorable responses to early postnatal shunt placement, including cortical reexpansion and normal cognitive function [70].

In a European prospective study, the probability of serious neurologic sequelae or death for fetuses with abnormal intracranial ultrasound findings was estimated to be 43 percent (95% CI 6-90 percent) [2]. Serious neurologic sequelae included a diagnosis of cerebral palsy, microcephaly, bilateral blindness, hydrocephalus, or epilepsy requiring treatment, and death included both postnatal death before age 2 years and terminations of pregnancy because of congenital toxoplasmosis; stillbirths were excluded. The estimated probabilities were much higher when the infection occurred early in pregnancy or was untreated. However, only 14 of the 218 infected fetuses had an abnormal ultrasound, and only 5 of the 14 had serious neurologic sequelae or death.

Prenatal diagnosis

Benefits and risks of prenatal diagnosis — When primary maternal infection during pregnancy has been confirmed or is strongly suspected or there are abnormal ultrasound findings, testing for fetal infection via amniocentesis can be helpful in decision making:

If fetal infection is diagnosed, maternal drug therapy can be used to mitigate fetal injury. (See 'Efficacy' below.)

Evidence of fetal infection may prompt some patients to terminate the pregnancy. Within the prenatal screening program in France, termination is discouraged unless there is definitive evidence of fetal infection based on PCR performed in a reference laboratory and evidence of severe cerebral abnormalities on fetal ultrasound (see 'Prognostic significance in infected fetuses' above). Most infected infants have a good prognosis and, on average, do not differ in their development at three to four years of age compared with uninfected children [71-73]. In France, 5.5 percent of pregnancies with proven fetal infection were terminated in 2017, which is 0.4 percent (4 of 959) of the total number of cases of prenatal diagnosis [74]. (See "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

Exclusion of fetal infection can prevent unnecessary empiric postnatal treatment of infants without clinical signs of toxoplasmosis and at low risk of congenital infection [2,75]. (See "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

Amniocentesis is an invasive test that is associated with a small risk of procedure-related pregnancy loss. Clinicians need to ensure that patients are sufficiently informed to enable them to weigh the potential benefits of the information gained versus this risk when deciding whether to undergo prenatal diagnosis. (See "Diagnostic amniocentesis".)

Timing of amniocentesis — Amniocentesis to obtain PCR for T. gondii DNA in amniotic fluid is offered to patients ≥18 weeks of gestation with serologically confirmed or strongly suspected recent infection for prenatal diagnosis of fetal infection [76]. When possible, amniocentesis is delayed until two weeks after documentation of seroconversion (or four weeks after the estimated date of maternal primary infection) to improve diagnostic performance.

Diagnostic testing (PCR) and performance — PCR should be performed in a reference laboratory (in the United States: Dr. Jack S. Remington Laboratory for Specialty Diagnostics, 650-853-4828). Management after testing is discussed below. (See 'Modification of the drug regimen after fetal diagnosis' below.)

In France, where national quality control has been established, overall sensitivity is approximately 90 percent when the amniocentesis is performed at ≥18 weeks of gestation and at least four weeks after the estimated date of maternal infection; negative PCR reduces the likelihood of infection to a residual risk of 1 percent in the first two trimesters and 16 percent in the third trimester [76-78], underscoring the need for postnatal follow-up.

False negatives are usually due to placental-to-fetal transmission after the date of amniocentesis [79], which is the reason for delaying amniocentesis for two weeks after seroconversion/four weeks after onset of maternal symptoms. However, if the mother begins treatment (especially pyrimethamine-sulfadiazine) before undergoing amniocentesis, the PCR test may become negative due to low parasite load from maternal treatment. (See 'Approach to maternal treatment for reduction of congenital toxoplasmosis' below.)

APPROACH TO MATERNAL TREATMENT FOR REDUCTION OF CONGENITAL TOXOPLASMOSIS — Our general approach to treatment of pregnant patients in toxoplasmosis screening programs is shown in the algorithm (algorithm 1).

Rationale — Antimicrobial therapy directed against T. gondii is offered to symptomatic and asymptomatic pregnant patients diagnosed with recent T. gondii infection (acquired during pregnancy) to reduce the risk of congenital toxoplasmosis [6,33]. There are no direct maternal benefits from treatment. Candidates for antimicrobial therapy should be managed in conjunction with maternal-fetal medicine, infectious disease, and neonatology specialists to review available data and help the patient make an informed decision. Clinicians and patients need to be aware that strong evidence of the efficacy of prophylactic therapy is lacking. (See 'Efficacy' below.)

For immunocompromised pregnant patients with prior toxoplasmosis, there is insufficient evidence to support the routine use of antimicrobial therapy to prevent congenital infection since transmission during reactivation is unlikely and no studies have evaluated this strategy. However, some pregnant patients living with HIV may already be on trimethoprim-sulfamethoxazole (cotrimoxazole) for Pneumocystis pneumonia and toxoplasmosis prophylaxis. (See "Overview of prevention of opportunistic infections in patients with HIV".)

Timing and choice of initial drug regimen (before fetal diagnosis)

Initiate pharmacotherapy during the window of opportunity – The initial antimicrobial regimen used for treatment of pregnant patients diagnosed with recent toxoplasmosis is begun as soon as possible upon documentation of probable maternal infection. We start therapy before amniocentesis, even in patients near 18 weeks of gestation. The time for transition from the acute infective tachyzoite form of the parasite, which is responsible for tissue destruction in the fetal brain, to the dormant bradyzoite form contained in tissue cysts is clinically important because the cysts are not susceptible to antibiotics. This time (ideally <3 weeks from seroconversion) is considered the therapeutic "window of opportunity" when maternal administration of antibiotics may prevent or reduce fetal neurologic damage [32,33].

Choice of antibiotic – The choice of drug(s) is based on the gestational age at diagnosis. There are two antimicrobial regimens that are typically used to reduce the risk of congenital toxoplasmosis: spiramycin and pyrimethamine-sulfadiazine. Although no international guidelines are available, we agree with the general consensus to use [27,41]:

Spiramycin, when therapy is begun in the first trimester (<14 weeks)

Pyrimethamine-sulfadiazine, when therapy is begun thereafter (≥14 weeks)

Dosing, administration, side effects, and alternatives are reviewed below. (See 'Dosing, administration, and side effects' below.)

Available evidence supports the superiority of pyrimethamine-sulfadiazine over spiramycin for therapy [80]. The rationale for only beginning this treatment at ≥14 weeks is that any risk of teratogenesis would be low after the first trimester [81]. Patients who begin spiramycin before 14 weeks can continue this drug until polymerase chain reaction (PCR) results from amniocentesis at 18 weeks are available, or they may switch to pyrimethamine-sulfadiazine at 14 weeks and continue pyrimethamine-sulfadiazine until PCR results from amniocentesis at 18 weeks are available. Some clinicians suggest continuing spiramycin in this setting because no studies have evaluated whether there is any benefit from switching drug regimens at 14 weeks, while other clinicians suggest switching to pyrimethamine-sulfadiazine at 14 weeks because it has been shown to be more effective than spiramycin in second- and third-trimester pregnancies with recent seroconversion. (See 'Pyrimethamine-sulfadiazine versus spiramycin for reducing maternal-to-fetal transmission' below.)

Modification of the drug regimen after fetal diagnosis

Positive PCR — If amniotic fluid PCR for T. gondii is positive and the patient plans to continue the pregnancy, we treat with pyrimethamine-sulfadiazine until birth in accordance with several national guidelines [36,41,82]; shorter durations of treatment have not been studied. After birth, the child will be treated with the same regimen.

If the patient had been on spiramycin for prophylaxis, we advise that they switch to pyrimethamine-sulfadiazine because it appears to be more effective in treating congenital infection. (See 'Pyrimethamine-sulfadiazine versus spiramycin for reducing maternal-to-fetal transmission' below.)

Negative PCR

Patients with a normal fetal ultrasound examination undergoing fetal diagnosis because of seroconversion during routine prenatal screening.

If amniotic fluid PCR for T. gondii is negative and fetal ultrasound is normal, some authorities do not continue treatment whereas others continue treatment because of concerns about placental transmission occurring after the amniocentesis. The risk of this happening is rare when maternal infection occurs early in pregnancy but increases when the infection occurs in the late second to third trimesters [78].

There is no worldwide consensus regarding the best regimen for those who choose to continue treatment after a negative amniotic fluid PCR, and no data are available on which to base recommendations for the optimal duration of treatment. Many experts take into account the gestational age at the time of maternal infection, which is known when sequential serologic screening has been performed. As an example, in France, the following approach has been recommended by a multidisciplinary working group [41]:

-In cases of periconceptional or first-trimester seroconversion, spiramycin is preferred for continuing therapy after the negative amniotic fluid PCR because the likelihood of fetal infection is very low, it has been used safely for decades in pregnancy, and it has fewer tolerance issues than pyrimethamine-sulfadiazine.

-In cases of second- or third-trimester seroconversion, patients on pyrimethamine-sulfadiazine are switched to spiramycin when the amniotic fluid PCR is negative, but after a total of at least four weeks of pyrimethamine-sulfadiazine prophylaxis, and then spiramycin is continued until delivery.

Other approaches after a negative amniotic fluid PCR include:

-If seroconversion occurred after 33 weeks (arbitrary but traditional cutoff), some clinicians continue pyrimethamine-sulfadiazine until birth unless side effects are bothersome, given the high false-negative amniotic fluid PCR rate in the third trimester.

-Some clinicians use pyrimethamine-sulfadiazine in all patients who choose to continue therapy after a negative amniotic fluid PCR because it appeared to be more effective than spiramycin prophylaxis when administered in the TOXOGEST trial of patients who seroconverted during pregnancy [32]. (See 'Pyrimethamine-sulfadiazine versus spiramycin for reducing maternal-to-fetal transmission' below.)

Screened patients who seroconvert, have a normal ultrasound, and decline amniocentesis for PCR — Some patients who undergo routine screening may decline to undergo amniocentesis for PCR, particularly when the fetal ultrasound examination is normal. If a patient in a screening program declines amniocentesis, we suggest treatment with pyrimethamine-sulfadiazine from diagnosis of maternal infection ≥14 weeks until birth since fetal infection cannot be excluded and treatment may improve outcome. (See 'Efficacy' below.)

If the patient does not want prolonged treatment, we suggest treatment for at least 8 weeks and until results from a fetal ultrasound after 22 weeks are available and negative for anomalies, with the understanding that the risk is not eliminated because a normal ultrasound does not exclude the possibility of congenital toxoplasmosis. In the absence of prenatal diagnosis, particularly patients who declined amniocentesis, cord blood for antitoxoplasmosis IgM and IgA testing should be performed in a reference laboratory. Some centers attempt to diagnose congenital toxoplasmosis by collecting amniotic fluid for PCR at the time of cesarean birth or vaginally at the time of membrane rupture or during labor [83]. However, the sensitivity and specificity of these investigations are uncertain, and careful follow-up of the child is important. The interferon-gamma release assay, a T-cell-based test performed on peripheral blood, appears to be useful for diagnosis of congenital toxoplasmosis in infants [84].

Unscreened patients undergoing fetal diagnosis because of abnormal findings on fetal sonography — The timing of maternal seroconversion in such cases usually cannot be determined with certainty. When the amniocentesis is performed because of fetal ultrasound anomalies suspicious for congenital toxoplasmosis in a patient who is IgG positive, we consider a negative amniotic fluid PCR result from a reference laboratory reliable evidence to exclude congenital toxoplasmosis as the cause of the anomalies. In this situation, the clinician should evaluate for other diagnoses with similar fetal findings. Antiparasitic therapy is not indicated.

Dosing, administration, and side effects

Spiramycin — Spiramycin is licensed in Europe and Canada and is available in the United States for use in pregnant patients with toxoplasmosis. Information on how to obtain spiramycin can be found in the Lexicomp drug information monograph in UpToDate.

Dose – The dose of spiramycin is 1 g (3 million international units) orally three times daily, without food.

Contraindications – Long QT syndrome is a contraindication as polymorphic ventricular tachycardia can occur in patients with a long QT interval.

Side effects – Side effects include nausea, vomiting, diarrhea, skin reactions (pruritus, rash, urticaria) [85].

Monitoring – No laboratory monitoring is required.

Pyrimethamine-sulfadiazine — In the United States, access to pyrimethamine may be limited, and this agent must be obtained through a program administered by the manufacturer or from a compounding pharmacy. Information on how to obtain pyrimethamine can be found in the Lexicomp drug information monograph in UpToDate.

Dose – Various dosing regimens have been proposed.

In the United States, the Committee for Infectious Diseases of the American Academy of Pediatrics recommends [27]:

-Pyrimethamine 100 mg/day orally divided into two doses for two days followed by 50 mg orally daily plus

-Sulfadiazine 75 mg/kg per dose orally for one dose, followed by 100 mg/kg per day orally divided into two doses (maximum sulfadiazine 4 g/day) plus

-Folinic acid (leucovorin) 10 to 20 mg/day orally during and one week after pyrimethamine therapy (folic acid is not an appropriate substitute), administered to prevent pyrimethamine-induced hematologic toxicity.

In France, where prenatal screening has operated for 30 years, treatment regimens vary [4,21,29,71], but the most common regimen is:

-Pyrimethamine 50 mg once per day orally plus

-Sulfadiazine 3 g/day orally divided into two or three doses plus

-Folinic acid (leucovorin) 50 mg weekly orally (folic acid is not an appropriate substitute), administered as above to prevent pyrimethamine-induced hematologic toxicity.

Contraindications Sulfadiazine can precipitate serious hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD). Such patients should be managed jointly with a hematologist.

Side effectsPyrimethamine is a folic acid antagonist, which can cause dose-related bone marrow suppression with resultant anemia, leukopenia, and thrombocytopenia. It is teratogenic in some animals when given in large doses [4]. Sulfadiazine, another folic acid antagonist, works synergistically with pyrimethamine against T. gondii tachyzoites and can also cause bone marrow suppression and reversible acute renal failure.

Adverse drug effects are more common with pyrimethamine-sulfonamide combinations than with spiramycin. A European multicenter cohort study found adverse effects requiring treatment cessation in 3.4 percent (11 of 322) of pregnant patients prescribed pyrimethamine-sulfonamide compared with 1.7 percent (13 of 780) of pregnant patients prescribed spiramycin alone [29]. The main adverse effect is skin rash; because of the potential risk of toxidermia, the treatment should be stopped in case of rash.

Crystalluria can occur during treatment with sulfonamides [86], so patients should be instructed to drink at least 2 liters per 24 hours and consume foods that alkalinize the urine (eg, citrus fruits, some vegetables, nuts).

Monitoring – Complete blood counts and platelet counts should be performed weekly. If a significantly abnormal result is reported, the therapy should be stopped and/or the dose of leucovorin increased and the blood count repeated after a week.

If pyrimethamine or sulfadiazine is not available — If pyrimethamine or sulfadiazine cannot be obtained expeditiously, trimethoprim-sulfamethoxazole (also known as cotrimoxazole) may be used (160 mg trimethoprim and 800 mg sulfamethoxazole administered orally twice daily) [87]. The patient should be switched to a pyrimethamine-containing regimen when available; however, trimethoprim-sulfamethoxazole can be continued until delivery if that is the only option.

Other drugs — There is no information on the efficacy of other drugs for treating in utero toxoplasmosis infection. Alternative regimens (eg, pyrimethamine-clindamycin or pyrimethamine-azithromycin) used in other settings may be considered. (See "Toxoplasmosis: Acute systemic disease", section on 'Treatment of acute infection' and "Congenital toxoplasmosis: Treatment, outcome, and prevention", section on 'Treatment regimen'.)

Efficacy

Pyrimethamine-sulfadiazine versus spiramycin for reducing maternal-to-fetal transmission — Experimental evidence supports the superiority of pyrimethamine-sulfadiazine over spiramycin for preventing maternal-to-fetal transmission. No randomized trials of drug therapy versus no drug therapy have been performed. The retrospective observational studies in humans are insufficient to offer definitive proof of the effectiveness of preventive treatment because all have treatment biases, but suggest overall that prompt prophylactic therapy with pyrimethamine-sulfadiazine following maternal seroconversion reduces the risk of congenital toxoplasmosis [88].

In the only randomized trial, the French multicenter TOXOGEST trial compared the efficacy and safety of spiramycin versus pyrimethamine-sulfadiazine in preventing maternal-to-fetal transmission of T. gondii [32]. Patients were eligible if toxoplasmosis seroconversion was diagnosed by a positive serology with specific IgG following a prior negative test and gestational age was over 14 weeks. Treatment was started as soon as possible after the diagnosis of seroconversion.

Among 143 patients randomized, transmission rates (after exclusion of children with insufficient follow-up) trended lower in the pyrimethamine-sulfadiazine group (18.5 percent [12/65] versus 30 percent [18/60], odds ratio [OR] 0.53, 95% CI 0.23-1.22). A greater reduction in congenital toxoplasmosis was noted when pyrimethamine-sulfadiazine was started within three weeks of seroconversion (OR 0.03, 95% CI 0.00-1.63).

The results of this randomized trial suggest superiority of pyrimethamine-sulfadiazine over spiramycin. The trend toward higher efficacy of pyrimethamine-sulfadiazine than spiramycin supports the efficacy of prophylactic treatment, although it does not prove that treatment is more effective than no treatment. A limitation of these findings is that the trial was stopped early because recruitment was slow and additional funding could not be obtained. A larger trial may have been able to increase confidence that the differences in outcome between regimens were clinically and statistically significant. However, this trial is expected to be the last such trial in Europe due to the declining incidence of Toxoplasma infections in pregnancy.

The largest epidemiologic study was the Systematic Review on Congenital Toxoplasmosis (SYROCOT), a 2007 systematic review and individual patient data meta-analysis of 20 European cohort studies (1438 participants) in which universal screening for toxoplasmosis in pregnancy was performed [33]. The analysis assessed the effects of timing and type of prenatal treatment on mother-to-child transmission of infection and clinical manifestations before age 1 year. Prenatal regimens included spiramycin alone, spiramycin followed by pyrimethamine-sulfonamide, and pyrimethamine-sulfonamide alone. The major findings were:

Treatment started within three weeks of seroconversion reduced mother-to-child transmission compared with treatment started after eight or more weeks (OR 0.48, 95% CI 0.28-0.80).

Treatment initiated more than three but within eight weeks of seroconversion showed a trend toward reduced mother-to-child transmission.

The authors could not distinguish whether the reduction in transmission was a real benefit of treatment or a bias since patients were less likely to be treated after a long delay from seroconversion or shortly before delivery unless they had sonographic signs of fetal infection. Subsequent to this analysis, several observational studies in Europe have reported a reduction in mother-to-child transmission after national prenatal maternal screening, fetal diagnosis, and prenatal/postnatal treatment programs were initiated [37,89,90].

Two Brazilian retrospective studies also found that prophylactic therapy was associated with a lower rate of vertical transmission [38,91]. An additional study of 120 pregnancies from Italy observed that transmission after maternal primary infection was lower under cotrimoxazole-spiramycin or pyrimethamine-sulfonamide than under spiramycin; results were adjusted for the trimester of infection [87]. However, significant differences between screened/unscreened patients and treated/untreated patients could have accounted for some or all of the observed benefit.

Lastly, in pharmacokinetic studies, spiramycin levels in fetal blood samples are approximately one-half those found in maternal serum; thus, it may be effective for preventing placental infection after a recent maternal infection but may be insufficient for treating fetal infection after placental transmission has occurred [4,35,92]. Pyrimethamine-sulfadiazine is able to pass the blood-brain barrier whereas spiramycin does not reach the brain.

In a rhesus monkey model of congenital toxoplasmosis, early treatment with pyrimethamine-sulfadiazine was effective in reducing the number of parasites in the infected fetus; parasites were not detectable in the amniotic fluid 10 to 13 days after initiation of maternal treatment; however, spiramycin had to be administered for at least three weeks to achieve the same effect [93].

In murine studies, placental transfer of spiramycin was poor, but it did concentrate in the placenta and thus may have local effects [4,94,95].

Efficacy of maternal treatment for reducing serious clinical sequelae in offspring — Even if it is not possible to prevent maternal-to-fetal transmission, transplacental fetal therapy that reduces the risk of serious neurologic sequelae or postnatal death in children with congenital toxoplasmosis would be a benefit of maternal therapy. There is limited evidence that reduction of clinical sequelae in offspring is possible:

In a European observational study of a cohort of 293 infected fetuses of whom two-thirds received prenatal treatment, prenatal treatment was estimated to reduce the risk of serious neurologic sequelae or death by three-quarters (OR 0.24, 95% CI 0.07-0.71) [2]. After maternal seroconversion at 10 weeks of gestation, the estimated absolute risk of serious neurologic sequelae or death in treated and untreated pregnancies was 25.7 and 60.0 percent, respectively. Serious neurologic sequelae or death included microcephaly, insertion of intraventricular shunt, an abnormal or suspicious neurodevelopmental examination that resulted in referral to a specialist, seizures that required anticonvulsant treatment, severe bilateral visual impairment cerebral palsy, death before age 2 years, or termination of pregnancy.

To prevent one case of serious neurologic sequelae or death after maternal infection at 10 weeks of pregnancy, it would be necessary to treat three fetuses with confirmed infection. To prevent one case of serious neurologic sequelae or death after maternal infection at 30 weeks of pregnancy, 18 fetuses would need to be treated. However, these findings should be interpreted cautiously because of the small number of cases and uncertainty about the timing of maternal seroconversion.

In the randomized prophylaxis trial (TOXOGEST, described above), the incidence of cerebral ultrasound abnormalities was significantly lower in the group receiving pyrimethamine-sulfadiazine than in the group receiving spiramycin (0/73 versus 6/70, respectively), suggesting that very early active antiparasitic therapy reduces the risk of cerebral lesions [32]. However, the correlation between cerebral ultrasound abnormalities and clinical sequelae is difficult to predict.

Note, these findings only relate to the more benign strains of T. gondii that predominate in Europe and North America, not the more virulent strains that occur in Central and South America. (See 'Clinical manifestations' above.)

Efficacy of maternal treatment for reducing nonserious clinical sequelae in offspring — SYROCOT (individual patient data meta-analysis of 20 European cohort studies described above) found no reduction in retinochoroiditis in pregnancies in which maternal treatment was initiated after seroconversion [33]. A subsequent study of 281 children with congenital toxoplasmosis in whom 50 developed ocular disease also found that prenatal treatment had no significant effect on the age at first or subsequent lesions [96]. However, some observational studies have reported that early maternal treatment was associated with a reduction in retinochoroiditis detected during infancy. In one such study of 36 infants with retinochoroiditis, multivariate analysis suggested that a delay of >8 weeks between maternal seroconversion and the beginning of treatment, female sex, and cerebral calcifications were risk factors for retinochoroiditis during the first two years of life in infants treated for congenital toxoplasmosis [69].

PRENATAL CARE AND DELIVERY — Prenatal care is routine, exclusive of the diagnostic and treatment issues described above. Congenital toxoplasmosis does not affect the timing or route of birth.

Ultrasound follow-up — After fetal infection has been diagnosed by polymerase chain reaction (PCR), fetal ultrasound follow-up is recommended at least monthly. Sonographic abnormalities may appear or worsen several weeks after fetal infection; for example, mild ventricular dilation may progress to periventricular destruction, which has a poorer prognosis. If severe lesions develop, the patient may wish to consider termination of pregnancy depending on the laws where they live.

The appearance of fetal lesions suggestive of infection on ultrasound following a negative PCR is exceptional. Nevertheless, because of the residual risk of congenital toxoplasmosis after a primary infection despite a negative amniocentesis, ultrasound follow-up is suggested every four to six weeks [81,97]. This may require a large number of repeated ultrasounds for which the benefit has not been demonstrated.

Placental histology — Placental findings of toxoplasmosis (picture 1) include granulomatous villitis, cysts, plasma cell deciduitis, villous sclerosis, and chorionic vascular thromboses. Free trophozoites may be observed in villous stroma, amniotic epithelium, chorion, and Wharton's jelly. However, placental histology or parasitology is not recommended for postnatal diagnosis because sensitivity and specificity are insufficient to make a reliable diagnosis of congenital toxoplasmosis.

NEONATAL MANAGEMENT AND OUTCOME — Toxoplasma infection in the newborn is discussed in detail separately. (See "Congenital toxoplasmosis: Clinical features and diagnosis" and "Congenital toxoplasmosis: Treatment, outcome, and prevention".)

PREVENTION

Behaviors to avoid — Prevention of primary infection is based on avoidance of sources of infection. While access to reliable information on sources of infection is undoubtedly important, systematic reviews have found no high-quality evidence that such information changes maternal behavior during pregnancy [98,99]. Evidence from case-control studies of risk factors in Europe has identified the principal sources of infection, which should be avoided when possible. In addition, travel to countries where more virulent parasite genotypes predominate (Central and South America) or resource-limited countries where the prevalence of toxoplasmosis is high is a major risk factor [7,8]. If such travel is necessary, it is particularly important to adhere to the following behaviors to reduce the risk of infection:

Avoid drinking unfiltered water in any setting [6,7,100].

Avoid ingesting soil by observing strict hand hygiene after touching soil (eg, gardening). Fruit and vegetables should be washed before eating [8,10]. Hand washing is the single most important measure to reduce transmission of microorganisms from one site to another.

Raw or undercooked meat is an important source of infection. Cutting boards, knives, counters, and the sink should be washed after food preparation. Avoid mucous membrane contact when handling uncooked meat. Pregnant individuals should also avoid tasting meat while cooking [6-8,10].

Meat should be cooked to 152°F (66°C) or higher or frozen for 24 hours in a household freezer (at less than 10°F [-12°C]), both of which are lethal to tachyzoites and bradyzoites [101]. Freezing meat before consumption appears to be the most effective intervention in preventing toxoplasmosis transmitted by meat [102].

Meat farmed in strict indoor conditions is less likely to be contaminated than outdoor-reared meat [7]. There is weak evidence that meat that has been smoked or cured in brine is not safe. The risk of infection is likely to be increased when cured products involve meat from more than one animal and limited drying and curing, as in some local production methods [7,9,103].

Avoid eating raw shellfish since seawater can be contaminated by T. gondii oocysts that survive or bypass sewage treatment [14].

Owning a cat is only weakly associated with acute infection. This is probably because cats only excrete oocysts for three weeks of their life, and people are just as likely to be exposed to oocysts excreted outdoors by someone else's cat. Nevertheless, it seems sensible for pregnant individuals with cats to ask someone else to change the litter box daily so only fresh feces are present (fresh cat feces are not infectious) [7,8,10].

Timing pregnancy after maternal infection — There are limited data on which to base a recommendation for how long to delay pregnancy after an acute toxoplasmosis infection. Although a delay of six months has been suggested [35], parasitemia is very short lived [104], and it is likely that encystment occurs rapidly in patients with adequate immune function; thus, immunocompetent patients who become pregnant at least one to three months after an acute infection are extremely unlikely to transmit the infection to the fetus.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Toxoplasmosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Avoiding infections in pregnancy (The Basics)")

Beyond the Basics topics (see "Patient education: Avoiding infections in pregnancy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Acquisition and transmission – The main sources of maternal toxoplasmosis infection are ingestion of contaminated raw, undercooked, or cured meat or meat products; soil-contaminated fruit or vegetables; or raw seafood from contaminated water. (See 'Acquisition of infection' above.)

Fetal infection usually results from transplacental transmission of tachyzoites following a recent primary maternal infection. Fetal infection rarely occurs from reinfection with a different toxoplasmosis strain and is unlikely during reactivation disease since parasitemia does not occur. (See 'Pathogenesis of fetal infection' above.)

Maternal clinical findings – Acute maternal infection is usually asymptomatic. When symptoms occur, they are typically nonspecific and mild: fever, chills, sweats, headaches, myalgias, pharyngitis, hepatosplenomegaly, and/or a diffuse nonpruritic maculopapular rash. A more specific symptom is bilateral, symmetrical, nontender cervical adenopathy, which occurs in approximately 20 to 30 percent of patients. Lymphadenopathy can persist for weeks. (See 'Clinical manifestations' above.)

Screening – In North America, the United Kingdom, and other areas of low virulence toxoplasmosis, we suggest not screening for toxoplasmosis in all pregnant individuals (Grade 2C). This approach is based on the relatively low prevalence of the disease in these areas, the limited availability of standardized serologic assays (except for a few reference laboratories), the lack of highly effective treatment, and the high cost of screening. However, screening may be appropriate in geographic areas where disease prevalence and/or virulence are higher and experience and resources are available for evaluating and managing affected pregnancies. (See 'Should all pregnant individuals be screened?' above.)

When serology is performed, the diagnosis of toxoplasmosis in asymptomatic pregnant individuals is relatively straightforward in case of seroconversion, but when the first test shows antitoxoplasmosis IgM, it is critical to determine whether infection occurred prior to conception or during pregnancy. Additional testing (eg, avidity and sequential testing) should be performed to help confirm the diagnosis and to clarify when the infection occurred. Estimating the timing is most complicated when the first available serology is after the first trimester. If a toxoplasmosis pregnancy panel from a nonreference laboratory (eg, commercial, clinic, or hospital laboratory) was used for initial screening, confirmatory testing should be performed by an experienced reference laboratory. (See 'Interpretation of screening results' above and "Diagnostic testing for toxoplasmosis infection".)

Congenital infection

Frequency – The frequency of fetal infection increases with advancing gestational age at the time of maternal infection (eg, the probability of maternal-to-fetal transmission at 13 and 36 weeks of gestation is 15 and 71 percent, respectively). By contrast, the risk of developing symptomatic congenital disease after seroconversion decreases with gestational age (eg, the probability of symptomatic disease from congenital infection at 13 and 36 weeks is 61 and 9 percent, respectively). (See 'Impact of gestational age' above and 'Risk of fetal infection from reactivation or reinfection' above.)

Sonographic findings – Fetal ultrasound findings in congenital toxoplasmosis are nonspecific. The most common sonographic findings are intracranial hyperechogenic foci or calcifications and cerebral ventricular dilation, which often occur together. Other brain findings in infected fetuses include periventricular abscesses or, less frequently, periventricular echogenicity, cortical gyration anomalies, lenticulostriate vessels vasculitis, shortened corpus callosum, cerebellar anomalies, and subependymal cysts. (See 'Ultrasound findings in congenital toxoplasmosis' above.)

Prognostic findings – The fetal sonographic signs clearly associated with poor prognosis are ventricular dilation and large brain abscesses and/or necrosis or gyration disorders or microcephaly, whereas intracranial hyperechogenic nodular foci without other lesions are not associated with developmental delay, and extracerebral signs are not associated with poor developmental outcomes if there are no associated cerebral signs, which is relatively uncommon. Cerebral calcifications, however, are a risk factor for the development of retinochoroiditis during childhood. (See 'Prognostic significance in infected fetuses' above.)

Management – Whether any treatment reduces the risk of mother-to-child transmission remains controversial. The best available data suggest that (1) maternal treatment started within three weeks of seroconversion reduces mother-to-child transmission compared with treatment started after eight or more weeks; (2) maternal treatment reduces the risk of serious neurologic sequelae or death in congenitally infected offspring; and (3) treatment with pyrimethamine-sulfadiazine is more effective than spiramycin. This evidence applies to European and North American settings.

For infection acquired in Central or South America, more virulent Toxoplasma parasite strains are associated with higher risks of serious neurologic sequelae. (See 'Efficacy' above.)

Our general approach to management of screened patients is shown in the algorithm (algorithm 1).

For pregnant patients <14 weeks of gestation with confirmed or possible recent toxoplasmosis, we suggest initiating treatment with spiramycin (Grade 2C). This may reduce mother-to-child transmission and avoids potential teratogenic effects of pyrimethamine-sulfadiazine in the first trimester. (See 'Timing and choice of initial drug regimen (before fetal diagnosis)' above and 'Prenatal diagnosis' above.)

For pregnant patients at ≥14 weeks of gestation with confirmed or possible recent toxoplasmosis, particularly in Central and South America, we suggest initiating treatment with pyrimethamine-sulfadiazine (Grade 2C). (See 'Timing and choice of initial drug regimen (before fetal diagnosis)' above and 'Prenatal diagnosis' above.)

Amniocentesis to obtain polymerase chain reaction (PCR) for Toxoplasma gondii DNA in amniotic fluid is recommended for patients at ≥18 weeks with serologically confirmed or strongly suspected recent infection for prenatal diagnosis of fetal infection. Amniocentesis is usually delayed until two weeks after documentation of seroconversion (or four weeks after the estimated date of maternal primary infection) to be reliable. (See 'Prenatal diagnosis' above.)

For patients who have a positive amniotic fluid PCR test who plan to continue the pregnancy, we treat with pyrimethamine-sulfadiazine until delivery. (See 'Positive PCR' above.)

For patients with a negative amniotic fluid PCR test after seroconversion during routine prenatal screening, there is no consensus as to whether to discontinue treatment or continue treatment because of the possibility that placental transmission may occur later in pregnancy after the amniocentesis. (See 'Negative PCR' above.)

For patients in a screening program who seroconvert and decline amniocentesis, we suggest treatment with pyrimethamine-sulfadiazine from diagnosis of maternal infection ≥14 weeks until delivery since fetal infection cannot be excluded and treatment may improve outcome (Grade 2C). If the patient does not want prolonged treatment, we suggest treatment for at least 8 weeks and until results from a fetal ultrasound after 22 weeks are available and negative for anomalies, with the understanding that the risk is not eliminated because a normal ultrasound does not exclude the possibility of congenital toxoplasmosis (Grade 2C). (See 'Screened patients who seroconvert, have a normal ultrasound, and decline amniocentesis for PCR' above.)

For patients who undergo amniocentesis because of fetal ultrasound anomalies suspicious for congenital toxoplasmosis and unclear timing of maternal infection (maternal IgG positive), we consider a negative amniotic fluid PCR result from a reference laboratory reliable evidence to exclude congenital toxoplasmosis as the cause of the anomalies. (See 'Unscreened patients undergoing fetal diagnosis because of abnormal findings on fetal sonography' above.)

Prevention – Females planning pregnancy or who are pregnant should adhere to strict hand hygiene after touching soil (eg, gardening) and avoid risky behaviors, such as consuming undercooked meat, raw shellfish, possibly contaminated fruits and vegetables, or unfiltered water. It is prudent to ask someone else to change the cat litter box daily (fresh cat feces are not infectious). (See 'Prevention' above.)

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