Toxoplasmosis is a worldwide infection caused by the protozoan Toxoplasma gondii (T. gondii), an obligatory intracellular parasite.1 In Central and South America, 50–80% of individuals are seropositive for IgG antibodies against T. gondii, indicating their previous exposure to this parasite.2 The prevalence of this infection acquired during pregnancy ranges from 10.3% to 75.2% in different countries.3–7 In Brazil, the seroprevalence of anti-T. gondii IgG antibodies ranges from 49.2% to 91.6%,8–10 and the incidence of congenital toxoplasmosis varies from 0.3 to 5.0 per 1000 births.11–13

The risk of fetal transmission depends on factors, such as the maternal immune response, the gestational age at infection, and the parasite virulence. The risk of congenital transmission varies from up to 2% at the periconceptional period, 10–25% in the first trimester of pregnancy, 30–45% in the second trimester, 60–65% in the third trimester, and up to 80% before childbirth.1 However, the severity of congenital disease is high when transmission occurs in the beginning of the pregnancy and decreases with gestational age.1,2,4,7,8

The diagnosis of toxoplasmosis acquired during pregnancy is based on laboratory tests because more than 90% of infected pregnant women are asymptomatic. When clinical manifestations are present, in general, they are nonspecific and include fever, headaches, myalgia, lymphadenopathy, and rash.14

The majority of children with congenital toxoplasmosis do not exhibit signs or symptoms at birth, presenting instead as subclinical infections; nevertheless, infected children are at risk of developing late sequelae, mainly ocular and neurological. For the symptomatic children, the severity of clinical manifestations is related to the trimester of pregnancy when transmission occurred, as follows: fetal death in the first trimester; retinochoroiditis, microcephaly, and mental retardation in the second trimester; and lymphadenopathy, hepatosplenomegaly, eye injuries, and brain calcifications in the third trimester.15 All of the children whose mothers presented acute toxoplasmosis during pregnancy, symptomatic or not, may have congenital toxoplasmosis. Children born with signals or symptoms of congenital disease are also at risk and should undergo serological investigation to detect specific anti-T. gondii antibodies.15

The purpose of this study was to describe the demographic, clinical, and laboratory characteristics of children with congenital toxoplasmosis that received treatment for congenital toxoplasmosis at one medical center in southern Brazil.

As clinical signs and symptoms in pregnancy are limiting factors for diagnosis, systematic serological screening tests during pregnancy are important yet controversial tools, particularly in regions where immunoreactivity before pregnancy is low and the risk for seroconversion during the pregnancy is high. However, early diagnosis of T. gondii infection and appropriate anti-parasitic treatment are measures that can reduce transmission and the severity of fetal consequences, which justifies the screening of all pregnant women with serological tests that detect anti-T. gondii IgG and IgM antibodies.15,18 A study from southern Brazil showed that 47.8% of pregnant women were seropositive for T. gondii, indicating previous exposure to the parasite, and 27.2% were not correctly diagnosed for T. gondii during pregnancy due to some factors, such as lack of prenatal care or because the serological tests were not performed.13 Despite the good prenatal care for pregnant women evaluated in the present study, serological investigation for toxoplasmosis was not performed in the majority of pregnant women.

The high frequency of prematurity and the low birth weight of infants observed in the present study are consistent with previous Brazilian studies that showed birth weight of infected children varying from 1290 to 3790g.13,19–24

Congenital toxoplasmosis may present different clinical forms, including subclinical infection, disease during the neonatal period, severe disease, mild disease in the first month of life, sequelae or reactivation of previously undiagnosed infection.15

In newborns and symptomatic infants, clinical presentation is divided into neurological and generalized forms. One neurological form, Sabin's tetrad, results from fetal infection at the beginning of the pregnancy and produces diffuse cerebral calcifications, chorioretinitis, convulsions, hydrocephaly or microcephaly. The generalized form results from infection during late pregnancy and is characterized by chorioretinitis, changes in CSF, hepatosplenomegaly, jaundice, lymphadenomegaly, thrombocytopenia, and anemia.15,18

Brazilian studies carried out between 1990 and 2010 showed that early clinical manifestations were present in 56–100% of the children evaluated. Chorioretinitis was present in 67–80%, and brain calcifications were observed in 11–100% of the cases, many of them without prenatal treatment.13,19–25 Other studies reported the presence of hydrocephaly in 6.3–21% of children and microcephaly in 5.3% of the evaluated children.24,26

Ocular injuries are not totally dependent on the gestational age of maternal infection; they may result in severe cases of chorioretinitis, even if the infection is acquired in the second half of the pregnancy. Furthermore, the risk of chorioretinitis – the most frequent sequela – persists for many years.27 Of the ocular manifestations among Brazilian children with congenital toxoplasmosis, 29–100% presented chorioretinitis during the evolution of the disease, with 12–84% presenting bilateral injuries. Frequent symptoms include microphthalmia (9–25% of cases), strabismus (12–60%), nystagmus (3–47%), cataract (1–14%), vitreitis (3–50%), and visual damage (50–100%).13,19–28 Therefore, the results of the present study are in line with other Brazilian studies; however, it showed higher frequency of symptomatic children at birth and with ocular manifestations than other studies carried out with children from Europe and North America.27 One possible explanation for this result may be the presence of more virulent strains of T. gondii in Brazil.29

The risk factors associated with the development of chorioretinitis include female gender, brain calcifications, and delay of maternal treatment after seroconversion.18,30 In the present study, ocular injuries was neither associated with child gender nor with the presence of brain calcifications.

In agreement with other studies conducted in the pre-treatment period among Brazilian and American children,18 the present study showed that 55.2% of infants exhibited neurological injuries in imaging exams, with calcification in 44.8% of cases.

Asymptomatic infants at birth may progress with no infection sequelae, but may also develop visual damage, delayed neuropsicomotor development, hydrocephaly, convulsions or deafness months or years after birth.15,18,20 Sequelae were identified in 68.9% of patients evaluated in this study, and the most frequent sequelae were visual impairment and neurological damage.

One of the benefits of treatment is the decrease in ocular and neurological sequelae in T. gondii-infected children.18,31 Early treatment prevents ocular damage in children, as shown in two longitudinal studies where a new lesion during the follow-up was detected in 72% of untreated children compared to 31% of treated children.32,33

Studies suggest that CT is more sensitive than USG for detecting brain calcifications.34 However, a study comparing brain CT and USG in 33 children with congenital toxoplasmosis found 94% agreement between these imaging exams.35

In the present study, CT was more sensitive for detecting brain calcifications, and USG was more sensitive for detecting hydrocephaly. However, specific treatment for toxoplasmosis provided during the period between USG and CT evaluations may have been responsible for missing hydrocephaly in CT that was shown with USG. The majority of USG evaluations were performed during the first month of life. The higher number of cases with brain calcifications observed by CT compared to those observed by USG may be explained by the natural evolution of the CNS lesions.

Congenital toxoplasmosis can be transmitted by pregnant women infected with HIV-1 who are those chronically infected with T. gondii;29,36 there are also reported cases of CMV and T. gondii co-infection.15,37 In the present study, the four infants co-infected with CMV showed clinical improvement when ganciclovir was added to the specific therapy for toxoplasmosis. This result demonstrates the importance of excluding other associated infections in patients with congenital toxoplasmosis.

Among the adverse effects of toxoplasmosis treatment, the most harmful is neutropenia caused by the myelotoxicity of sulfadiazine and pyrimethamine.15 In the present study, severe and moderate neutropenia were observed in a few cases, and the majority of them had been treated with other myelotoxic drugs associated with toxoplasmosis treatment, although all adverse effects were reversible with increased folinic acid doses and temporary interruption of the treatment. Reversible neutropenia was also observed in a cohort of patients, evaluated from 1981 to 2004 in North America, with daily doses of pyrimethamine for two or six months.31

In the present study, anti-T. gondii IgM seroprevalence was lower than observed in previous studies that confirmed T. gondii infection by the detection of IgM antibodies in 50–75% of newborns.15,22,38 The presence of anti-T. gondii IgG antibodies in a newborn serum sample is not evidence of infection because maternal IgG antibodies are passively transmitted. The half-life of this immunoglobulin is 23 days and maternal antibodies may persist in the newborn circulation for one year, and about three months are necessary for a 10-fold reduction in titer. Therefore, anti-T. gondii IgG antibodies must be assayed in serial samples from the child to confirm a congenital infection.15,26 However, in the present study due to wide variation (ranging from 1:16 to 1:128,000) serum anti-T. gondii IgG was of little help to diagnose congenital disease. Other serological methods are necessary to identify cases with false negative results for anti-T. gondii IgM.

Although the quality of prenatal care for suspected cases of toxoplasmosis in Londrina and northern Paraná in 2006 was not ascertained, a robust multi-professional team, with the support of governmental institutions, started discussions about this important public health problem, which resulted in the implementation of the Surveillance Program of Congenital Toxoplasmosis, first in the Basic Health Units of Londrina, north of Paraná, and afterwards in other locations in Paraná state.39,40 Its objective is to inform, standardize, and guide the management of medical professionals in caring for pregnant women with suspected or confirmed toxoplasmosis and children with congenital toxoplasmosis. To date, there has been excellent adherence to the proposed program in the primary health care units, decreasing the number of pregnant women and children unnecessarily referred to reference centers for diagnosis and treatment of toxoplasmosis by 63.9% and 42.6%, respectively, at the University of Londrina Hospital. Furthermore, the incorrect use of sulfadiazine was decreased by 67.4% after the program was implemented.39,40

Altogether, the results of the present study demonstrated that from 2000 to 2010, the majority of pregnant women whose children presented congenital toxoplasmosis and had received care at the reference center for Pediatric Infectious Diseases of the Outpatient Clinical Hospital of State University of Londrina, were given no treatment for toxoplasmosis during the pregnancy because no diagnostic tests for toxoplasmosis had been requested. The majority of children were symptomatic in the first month of life, and chorioretinitis was the most frequent ocular damage. A high frequency of sequelae was also observed in this cohort of patients. These data reinforce the importance of diagnosis and treatment of toxoplasmosis acquired during pregnancy to reduce the occurrence of congenital toxoplasmosis and its complications in the child. Continuous assessment, consolidation, and expansion of the Surveillance Program of Congenital Toxoplasmosis39,40 can contribute to the improvement of health care for pregnant women with suspected toxoplasmosis and for the reduction of congenital toxoplasmosis in the Brazilian population.

The authors declare no conflicts of interest.