Efficacy of artesunate plus chloroquine for uncomplicated malaria in children in Sao Tome and Principe: a double-blind, randomized, controlled trial

We conducted a double-blind, randomized, placebo-controlled trial in Sao Tome and Principe to investigate the safety, tolerability and efficacy of chloroquine (CQ) combined with artesunate (AS) over CQ monotherapy. Four hundred children, aged 6-59 months, with acute uncomplicated Plasmodium falciparum malaria were randomized to receive a standard dose of CQ (25 mg/kg bodyweight) over 3 d or CQ + AS (4 mg/kg bodyweight) daily for 3 d. Children were followed-up for 28 d. The combined treatment was well tolerated and there were no serious drug-related adverse events. By day 2 parasite clearance was significantly faster for children treated with CQ + AS compared with CQ alone (29/194 [14.9%] vs. 168/190 [88.4%] still parasitaemic, P< 0.0001). Day 14 parasitological failure rates were 153/191 (80.1%) for CQ alone compared with 32/193 (16.6%) in the CQ + AS group (odds ratio [OR] =20.2, 95% CI 11.7-35.4, P< 0.001). Corresponding clinical failure rates were 128/161 (67.0%) and 12/193 (6.2%) (OR = 30.6, 95% CI 15.3-62.7, P< 0.001). By day 28 the parasitological failure rates (new infections excluded) were 155/191 (81.1%) in the CQ group and 63/194 (32.4%) in the CQ + AS group (OR = 8.9, 95% CI 5.4-14.7, P< 0.001). Symptoms resolved faster in children who received AS. They were also less likely to be gametocytaemic after treatment. The combination treatment was well tolerated and considerably improved treatment efficacy. However, the current levels of CQ resistance preclude its use in Sao Tome where CQ should be abandoned as first-line drug. However, CQ + AS may be an option in areas where CQ resistance is lower

Glucocerebrosidase gene variants in parkinsonian patients with Machado Joseph/spinocerebellar ataxia 3

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Machado-Joseph disease/spinocerebellar ataxia type 3 (MJD/SCA3) may rarely presents a parkinsonian phenotype. Considering that mutations in the glucocerebrosidase (GBA) gene have been associated with Parkinson disease, we investigated whether these would be more prevalent in MJD/SCA3 patients with parkinsonian manifestations than in those without them. Methods: MJD/SCA3 patients with parkinsonian features were identified and compared to relatives and to a MJD/SCA3 control group with no such features. The GBA gene was sequenced and, in a subset of patients and in normal volunteers, GBA enzyme activity was measured. Results: We have identified nine index MJD/SCA3 patients with parkinsonian manifestations. Overall. GBA sequence variations were found in 3/9 MJD/SCA3 index cases with parkinsonian manifestations (33%) and in 0/40 MJD/SCA3 controls without parkinsonism (p = 0.03, Fisher exact test). The GBA sequence variations found were p.K(-27)R, p.E326K, and p.T369M. The latter two sequence variations were also found in two symptomatic relatives with no parkinsonian manifestations. A MJD/SCA3 relative belonging to the first positive pedigree and carrier of the p.K(-27)R mutation also presented parkinsonian manifestations. GBA activity in MJD/SCA3 patients was similar to those found in the normal control group. Conclusion: Sequence variations at the GBA gene may play a role as a minor, modifying gene of MJD/SCA3 phenotype. This hypothetical role was not related to changes in GBA activity in peripheral leukocytes. (C) 2011 Elsevier Ltd. All rights reserved.182185190Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)FAPERGSFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)INAGEMPFIPE-HCPAFCT [SFRH/BPD/63121/2009]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Sleep disorders in cerebellar ataxias

Cerebellar ataxias comprise a wide range of etiologies leading to central nervous system-related motor and non-motor symptoms. Recently, a large body of evidence has demonstrated a high frequency of non-motor manifestations in cerebellar ataxias, specially in autosomal dominant spinocerebellar ataxias (SCA). Among these non-motor dysfunctions, sleep disorders have been recognized, although still under or even misdiagnosed. In this review, we highlight the main sleep disorders related to cerebellar ataxias focusing on REM sleep behavior disorder (RBD), restless legs syndrome (RLS), periodic limb movement in sleep (PLMS), excessive daytime sleepiness (EDS), insomnia and sleep apnea