Options for clinical trials of pre and post-natal treatments for congenital toxoplasmosis

Clinical trials comparing different drug regimens and strategies for the treatment of congenital toxoplasmosis and its clinical manifestations in the liveborn child in different clinical settings should aim at formally evaluating the net benefit of existing treatments and at developing new therapeutic options. Currently, there is no ideal drug for congenital toxoplasmosis; future research should focus on the screening of new active drugs and on their pre-clinical and early clinical development, with a focus on pharmacokinetic/dynamic studies and teratogenicity. For the prenatal treatment of congenital toxoplasmosis, a trial comparing spiramycine to pyrimethamine-sulphadiazine and placebo would allow a formal estimation of the effect of both drugs in infected pregnant women. In newborn children, the net benefit of pyrimethamine-sulphadiazine should also be formally assessed. These trials will be implemented in settings where prenatal screening for Toxoplasma gondii is currently implemented. Trials should be carefully designed to allow for translation to other settings and modelling tools like cost-effectiveness analysis should be used to provide clinicians and founders with the best available evidence to establish recommendations.

Genetic improvement and population structure of the Nelore breed in Northern Brazil

The objective of this work was to evaluate the population structure and the genetic and phenotypic progress of Nelore cattle in Northern Brazil. Pedigree information concerning animals born between 1942 and 2006 were analyzed. Population structure was performed using the Endog program. Out of the 140,628 animals studied, 67.7, 14.52 and 3.18% had complete pedigree record of the first, second and third parental generation, respectively. Inbreeding and average relatedness coefficients were low: 0.2 and 0.13%, respectively. However, these parameters may have been underestimated, since information on pedigree was incomplete. The effective number of founders was 370 and the genetic contribution of 10, 50 and 448 most influent ancestors explained 13.2, 28 and 50% of the genetic variability in the population, respectively. The genetic variability for growth traits and population structure demonstrates high probability of increasing productivity through selective breeding. Moreover, management strategies to reduce the currently observed age at first calving and generation intervals are important for Nelore cattle genetic improvement.

Two pedigrees with restless legs syndrome in Brazil

Numerous studies have suggested a substantial genetic contribution in the etiology of the primary form of restless legs syndrome (RLS) and periodic leg movements (PLM). We describe the symptoms, the sleep profiles and physiological parameters of two families in which several members present RLS/PLM. The proband of family 1 is a 70-year-old woman and the proband of family 2 is a 57-year-old woman; both have exhibited the symptoms since the age of 20 years. All patients in both families were diagnosed with RLS according to the criteria of the International RLS Study Group. Polysomnographic recordings were performed to quantify and to describe PLM during sleep. Sleep parameters showed decreased sleep efficiency, increased sleep latency in the arousal index and the presence of PLM in all subjects. One of the families showed an exact profile of dominant inheritance with anticipation of age at onset. In the other family, the founders were blood relatives and there was no affected member in the third generation suggesting a recessive mode of inheritance. RLS/PLM is a prevalent sleep disorder affecting about 5 to 15% of the population and one that substantially impairs healthy sleep patterns. Efforts to understand the underlying pathophysiology will contribute to improve the sleep and life quality of these patients.