Positive benefit of postnatal treatment in congenital toxoplasmosis

We read the editorial of Gilbert and Desateux.¹ In their analysis, they take into account some newborn screening programmes for congenital toxoplasmosis in developing countries such as Brazil and Mexico, with reported rates of up to a maximum of 20 cases/10 000 live births; however, they did not mention our recent report that found a prevalence of 0.5% in a reference hospital in Colombia.² This study found one child who died 1 week after birth. As we had information only on the frequency of deaths in a reference hospital, we carried out a study in a representative sample of all newborns from Quindio and found nearly the same prevalence: 0.6% (see letter in Archives of Disease in Children in response to the paper by Schmidt et al³). Clearly, prevalence is higher in South America than in Europe, but in addition our cases are more symptomatic. In an analysis in 17 children congenitally infected and detected in prenatal and newborn screening programmes, 41% were symptomatic. Two children (11.7%) died before 6 months of age; in four of 13 (30%), there were retinochoroidal lesions with ophthalmological examination and in four of 11 (36%) there was neurological involvement with ultrasound examination.⁴ Although only eight children were followed until the first year of life (two died before 6 months of age, thus 7 were lost to follow‐up), it is obvious that we did not need this period to conclude that our children are more affected than those reported by the group in Lyon (France), where 12% of children had ocular lesion during their first year of follow‐up.⁵

We are concerned about the affirmation (and conclusions that can be derived thereof by paediatricians and parents of infected children) that there is no evidence that postnatal treatment is benefical. This may be true with respect to preventing recurrences of retinochoroidal lesions after the first year of life, but we cannot agree that postnatal treatment and treatments with pyrimethamine and sulfanomids are not beneficial. The recent report of the National Collaborative Chicago‐Based, Congenital Toxoplasmosis Study validates a 1‐year treatment of ischaemia with pyrimethamine–sulfadiazine by comparing the outcomes with historical controls.⁶ As stated in the editorial to this work, a double‐blind study, including an arm of untreated patients, was ethically contraindicated. We think that congenital toxoplasmosis is a clinical situation where, in the context of our historical and contemporary knowledge, we can reasonably accept that postnatal treatment is better than no treatment, yet there are no double‐blind controlled trials. Particularly in our country, it is easy to obtain a natural history of what happens in cases of no treatment, which are in the majority. Thus, we can agree that more efficacious drugs are needed for postnatal treatment, but to advance new proposals for sound trials that would obtain conclusive evidence, the following steps need to be carried out:

1. Double‐blind trials should be conducted against a treated arm with a standard pyrimethamine–sulfonamids scheme for 1 year.

2. In the setting of our new knowledge about the geographical restriction of genotypes of toxoplasma, these trials should be carried out in sites with a homogenous distribution of these genotypes.

3. A concerted work plan should be established between the groups of researchers in toxoplasmosis to decide which is the best new drug to be tested in this trial based on the in vitro and in vivo data.

Researchers in South America would like to carry out clinical trials, but we are sure that our institutional review boards would never accept an untreated arm. The results would be useful to Europe if we were able to identify new combinations of drugs that are more efficacious and with relevant effect even in mild clinical forms of the disease.