High burden of congenital toxoplasmosis in the United States: the strain hypothesis?

Rima McLeod, the leading author of an article published in this issue of Clinical Infectious Diseases [1], has accumulated a unique and remarkable database on congenital toxoplasmosis in the United States through the National Collaborative Chicago-based Congenital Toxoplasmosis Study (NCCCTS), which began in 1981 and continues to date. In a recent study [2], she and colleagues at the reference Palo Alto Medical Foundation Toxoplasma Serology Laboratory (PAMFTSL) revealed that severe clinical signs of congenital toxoplasmosis, including hydrocephalus, eye disease, or intracranial calcifications, occurred in 84% of 116 infants from birth to 180 days of age who had laboratory confirmation of congenital toxoplasmosis and in whom clinical information was available during a period of 15 years in the United States. The big question that needs to be answered is why these figures in the United States are in marked contrast with those reported in France, where roughly 90% of children with congenital toxoplasmosis are free of lesions at birth. There are obvious differences between France and the United States in the management of congenital toxoplasmosis that are likely to explain, at least partially, the different burden of the disease on both sides of the Atlantic. There is a national screening program at the prenatal and postnatal levels in France but not in the United States. The prenatal screening permits early detection of seroconversion in the mother and early diagnosis of infection in the fetus. In France, a prenatal treatment is offered during pregnancy with a double goal: to reduce the risk of mother-tochild transmission and, if fetal infection has occurred, to reduce the risk of intracranial and ocular damage in the child. Although the benefit of prenatal treatment is unclear and has yet to be evidenced in a large randomized controlled clinical trial, the lack of prompt diagnosis and treatment of the mother during gestation in the United States is a major factor that is likely to partly explain the worse outcome at birth in this country in comparison with the French data. The absence of prenatal and postnatal screening in the United States adds other biases in the comparison of data between both countries. In France, independent of clinical and imaging results, all cases of congenital toxoplasmosis are laboratory confirmed in a score of reference laboratories across the territory. On the contrary, samples are sent to 1 reference laboratory in the United States (PAMF-TSL) when there are clinical signs in favor of congenital infection. This referral bias is likely to induce an underdiagnosis of congenitally infected infants free of lesions and may explain the overrepresentation of severe cases in the United States. Finally, because of this lack of screening, the gestational age at which maternal infection is acquired is not known in the United States. Keeping in mind that infection acquired by the mother early in gestation is clearly associated with more severe outcome in the child, this kind of information is sorely lacking when data on clinical severity are compared. Even if the French prenatal screening and the biases discussed above are of major importance to explain the better outcome of congenital toxoplasmosis in France, additional factors are required to fully explain such a huge difference with the US data. Among these factors, attention has been focused on genetic variability among Toxoplasma gondii strains. The influence of strain in congenital toxoplasmosis has been clearly addressed in Brazil, where children with congenital toxoplasmosis have a 5 times higher risk than European children of developing Correspondence: Daniel Ajzenberg, PhD, PharmD, INSERM UMR 1094, Neuroépidémiologie Tropicale, Laboratoire de Parasitologie-Mycologie, Faculté de Médecine, Université de Limoges, Limoges 87025, France ([email protected]).