Reply to Wallon and Peyron

To The Editor—We appreciate and concur with Wallon and Peyrons insightful comments and cogent points [1]. Although parasite and host genetics and epigenetics influence infection, hydrocephalus, and/or pattern of hydrocephalus [2–10], they are probably not primarily responsible for current differences in increased frequency of hydrocephalus in congenital toxoplasmosis in the United States than in France. In France, in earlier decades before in utero treatment, hydrocephalus was not so rare in congenital toxoplasmosis [11–13]. Because patients contact the National Collaborative Chicago-Based Congenital Toxoplasmosis Study (NCCCTS) and physicians reach out to the NCCCTS for their patients, rather than patients being recruited by a systematic screening program for all pregnant women and infants, as occurs in France, the NCCCTS cohort has a high incidence of patients with symptomatic, obvious, severe illness, including hydrocephalus, which brings patients to medical attention [11, 14, 15].

Although treatment often improves outcomes markedly, even when initiated postnatally [5, 11, 16–18], without gestational screening, early detection, and early treatment, some preventable findings present at birth may already be irreversible, resulting in substantial long-term ophthalmologic and neurologic sequelae. Major differences between France and the United States almost certainly reflect differences in the timing of diagnosis and rapidity in initiation of treatment. A robust, universal, effective, prenatal screening program in France with prompt diagnosis and treatment during gestation has made a real difference in quality of life for many there [11, 19–21]. Furthermore, when we found an association with parasite genetics with prematurity and severity in our NCCCTS [5], we studied whether that association occurred for certain prespecified outcomes later in life among the small number of infants whose infection was diagnosed and treated during gestation or among children treated in the first year of life. Associations with strain types were no longer present for either the in utero or postnatally treated group [5]. This strongly suggests that active infection due to II and NE-II parasites can be treated with currently available medicines, leading to more favorable outcomes.

Improved outcomes in France developed in progressive steps [11, 19–22]. A landmark article in Clinical Infectious Diseases [20] reported that the frequency of infection dropped precipitously in France in 1992, after implementation of monthly serologic screening during gestation for early diagnosis, using polymerase chain reaction analysis of amniotic fluid. This facilitated rapid initiation of gestational treatment with pyrimethamine and sulfadiazine for the pregnant woman to treat her fetus. Congenital toxoplasmosis is no longer a severe disease in France, unlike what we still see in the United States. Toxoplasmosis is a treatable, and preventable, microorganism-caused disease, and like other such illnesses it responds best to prompt, early diagnosis leading to robust treatment, as now occurs during gestation in France.

Treating a pregnant woman with pyrimethamine-sulfadiazine to treat her infected fetus also has considerable benefit in the United States for the fortunate few for whom this is made available, as in France [23–28]. Readily available, reliable screening tests, an effective, clearly outlined, cost-benefit algorithm and guidelines [11, 22, 25–27], a reference laboratory for confirmatory testing, and effective medicines already exist in the United States. This approach to prevent congenital toxoplasmosis [11, 25–27] can easily and should be used widely in the United States. Only the will of those caring for pregnant women to implement gestational screening and treatment is needed. We are optimistic that with recent, increased knowledge, the will and time have come.