Avaliação de parâmetros clínico laboratoriais para diagnóstico pós-natal da toxoplasmose congênita em crianças participantes do Programa de Controle da Toxoplasmose Congênita (PCTC) em Minas Gerais

Abstract

Introduction: Most children with congenital toxoplasmosis (CT) are born without noticeable clinical manifestations in the usual examination, but, when investigated, they usually present visual or neurological impairment in the first months of life or until adolescence. CT is more severe in Brazil compared to Europe, a difference attributed to well-known factors such as the gestational age of fetal infection and the absence of diagnosis and treatment of the pregnant woman. Furthermore, additional factors not yet well established may contribute, such as the acquisition of infection through oocysts, greater diversity, and pathogenicity of the parasite, parasitic load, and immune profile of the host. Prenatal and neonatal screening helps, respectively, to identify the infection in the fetus and newborn, allowing early treatment and improving the child's prognosis. In Brazil, prenatal screening is a non-mandatory public health measure. In 2013, a prenatal and neonatal screening program (Congenital Toxoplasmosis Control Program - CTCP) was initiated in Minas Gerais to detect pregnant women at risk of acute toxoplasmosis and their newborns. Objectives: To describe the clinical and laboratory parameters used for the diagnosis of congenital toxoplasmosis in this population and to describe the clinical manifestations observed. Methods: This is an observational, retrospective study of a cohort of children and their mothers, with suspected congenital toxoplasmosis and participants in the CTCP-MG between 2013 and 2020. The children were tested for IgM on filter paper and confirmatory serology (IgM, IgA and IgG) on serum. Clinical investigation, ophthalmologic and auditory evaluation, and neuroimaging examination were performed in all children with a confirmed diagnosis. Standardized medical records were used to care for this population and only one team of health professionals was responsible for caring for the children in the period. The project was approved by the Ethics and Research Committee of UFMG. Results: In total, 347 children participated in the study, and CT was confirmed in 228 children and excluded in 119. Out of 347 children, 314 (90.5%) underwent neonatal screening, and 269/314 (85.7%) presented positive or indeterminate IgM results. CT was confirmed in 186 (69.1%) of them. A lower proportion of children (45/314; 14.3%) had non-reactive IgM in neonatal screening and the investigation continued due to suspected maternal acute toxoplasmosis, with CT confirmed in 17 (37,8%) cases. Among the 228 children with CT, 203 (89%) underwent neonatal screening, and 186 (91.6%) presented positive or indeterminate IgM results. The neonatal screening resulted in IgM false negative in 17/203 (8.4%) cases, and most (9/17; 52,9%) of their mothers received some antiparasitic treatment during prenatal care. Four children with CT were asymptomatic and presented non-reactive IgM and IgA tests but showed persistence of positive IgG results or rising indices. Paired mother and newborn serum samples collected simultaneously after birth, showed a higher proportion of neonates with IgG indices higher than that of their mother among those infected (p = 0.003). The use of specific treatment during pregnancy (45/227; 19.8%) was associated with a lower number of positive IgM results on filter paper (p = 0.002) and serum (p = 0.001). A higher proportion of reagent IgM results on filter paper (p = 0.001) and serum (p = 0.004) was associated with increased gestational age. The treatment was initiated due to the presence of IgM and/or IgA in 176/226 (77.9%) children. For others, the criteria used were the presence of retinochoroiditis in 45/226 (19.9%), the persistence of positive IgG results or rising indices in 4/226 (1.8%), and the presence of intracranial calcification associated with maternal seroconversion in the second trimester in one child. Among the 119 children with excluded CT, complete clearance of IgG received from the mother was observed in the first year of life (median= 235 days). In the assessment of the children's impairment, 21% (48/228) were asymptomatic in the clinical and ophthalmological evaluation; and 73.2% (167/228) had retinochoroiditis. Most lesions were described as macular (78,4%; 131/167) and bilateral (63,5%; 106/167). Neurological impairment was observed in 36.9% (75/203) children who underwent neuroimaging tests, with hydrocephalus in 29.3% (22/75). There was an association between the presence of hydrocephalus and the lower gestational age of maternal infection (p <0.001). One patient developed unilateral mild sensorineural hearing loss. Five children had ocular reactivation with a median age of 33 months (P25 21.5 / P75 62.5). One child was excluded from the study, as the follow up was interrupted before the diagnostic conclusion. Conclusion: screening with sensitive and specific serology identified most, but not all, infected children, reinforcing the need for ophthalmological assessment in screening programs. Although few, the false-negative results warn of the need to investigate suspicious children, even if the screening is negative. Congenital toxoplasmosis is severe in Brazilian children, but the factors responsible for this remain uncertain. The structuring of a prenatal and neonatal screening program, which allows the early diagnosis and treatment of maternal and fetal infection, could contribute to better knowledge and actions to reduce the severity of the infection in Brazilian children.