The innate immune response status correlates with a divergent clinical course in congenital Chagas disease of twins born in a non-endemic country.

The innate immune response from diamniotic and dichorionic twin brothers congenitally infected with Trypanosoma. cruzi (strain DTU-V) who displayed different clinical symptomatology was studied. While Brother I manifested severe cardiac and digestive disorders, the Brother II showed slight splenomegaly. The secretion level of IL-1ß, TNF-α, IL-12, IL-10, IFN-α and IL-6 cytokines produced after stimulation of peripheral blood cells with TLR-2, TLR-4 and TLR-9 ligands was determined pre- and post-benznidazole treatment. Cells from 10 uninfected infants born to mothers seropositive for Chagas disease were included as control. The obtained data show that the cells of Brother I secreted lower levels of the pro-inflammatory cytokines IL-1ß and TNF-α (upon TLR-2 and TLR-4 stimulation) relative to those secreted by cells from Brother II and uninfected controls. The cells from Brother II secreted high levels of the IL-1ß cytokine following TLR-2 stimulation relative to uninfected controls. The cells from both brothers secreted a higher level of IL-6, following TLR-4 stimulation, than that secreted by uninfected infant cells. After treatments, the cytokine secretion levels were similar in both children and comparable to those of uninfected donors. Treatment success in Brother I and treatment interruption in Brother II was detected by the use of serological biomarkers (KMP11, HSP70, PFR2, Tgp63) as well as follow-up done by PCR. Therefore, the Brother II required a second treatment. The data presented suggest that benznidazol treatment allows the innate immune system to reach a fully functional status similar to that of uninfected subjects.

Keeping CSF valve function with urokinase in children with intra-ventricular haemorrhage and CSF shunts.

BACKGROUND: Intra-ventricular haemorrhage (IVH) can occur spontaneously or during the surgical revision of ventricular cerebrospinal fluid (CSF) shunts. AIM: The aim of the study was to report the safety and efficacy of an original method for treatment of IVH that may occur at the time of valve revision aimed at maintaining the function of previously implanted CSF shunts. PATIENTS AND METHODS: We reviewed the medical records of six patients who experienced an IVH in the presence of a previously placed ventriculoperitoneal (VP) shunt. Five of the haemorrhages occurred during ventricular catheter replacement and the remaining one in a child given a VP shunt who sustained a spontaneous intra-cerebral haemorrhage. We inserted an external ventricular drainage without removing the original shunt. Urokinase was administered via the ventricular drain during several days until blood clearance in the CSF. Disappearance of the ventricular clots was checked by a cranial computerised tomography scan, while CSF shunt function was verified by the children's evolution and/or by a reservoir tap. RESULTS: Follow-up evaluation of the six patients demonstrated that the existing VP shunts were functioning appropriately and that the treatment was safe. CONCLUSIONS: Patients with IVH complicating ventricular catheter replacement and patients with spontaneous bleeding who harbour a VP shunt can be treated by intra-ventricular urokinase to avoid the removal of the initial shunt. The technique has proven to be safe and utilises the ventricular drain placed for the acute management of the IVH. Shunt replacement will always be possible in case of failure of the technique we are reporting.