Repurposing the orphan drug nitisinone to control the transmission of African trypanosomiasis.

Tsetse transmit African trypanosomiasis, which is a disease fatal to both humans and animals. A vaccine to protect against this disease does not exist so transmission control relies on eliminating tsetse populations. Although neurotoxic insecticides are the gold standard for insect control, they negatively impact the environment and reduce populations of insect pollinator species. Here we present a promising, environment-friendly alternative to current insecticides that targets the insect tyrosine metabolism pathway. A bloodmeal contains high levels of tyrosine, which is toxic to haematophagous insects if it is not degraded and eliminated. RNA interference (RNAi) of either the first two enzymes in the tyrosine degradation pathway (tyrosine aminotransferase (TAT) and 4-hydroxyphenylpyruvate dioxygenase (HPPD)) was lethal to tsetse. Furthermore, nitisinone (NTBC), an FDA-approved tyrosine catabolism inhibitor, killed tsetse regardless if the drug was orally or topically applied. However, oral administration of NTBC to bumblebees did not affect their survival. Using a novel mathematical model, we show that NTBC could reduce the transmission of African trypanosomiasis in sub-Saharan Africa, thus accelerating current disease elimination programmes.

Varicela en la Casa Garrahan, 2008-2013: Evaluación de las medidas de profilaxis posexposición / Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis measures

Introducción. La Casa Garrahan (CG) aloja a niños con patologías complejas de todo el país, atendidos en los hospitales pediátricos de la Ciudad Autónoma de Buenos Aires. La varicela es una enfermedad muy contagiosa, cuya tasa de ataque alcanza el 90% en susceptibles. En comunidades cerradas, es fundamental implementar medidas de prevención ante brotes. Objetivos. Describir las características de los niños expuestos a casos de varicela en la CG, las medidas de profilaxis implementadas y su efectividad. Métodos. Estudio de cohorte prospectivo. Se evaluaron los niños expuestos a varicela en la CG entre 2008 y 2013, sus características demográficas, clínicas y vacunación y/o varicela previa, medidas de profilaxis y tasa de ataque secundaria. Resultados. N: 107. El 53% (n: 57) eran niñas. La mediana de edad fue 84 meses (RIC: 24144). El 95% (n: 102) teman enfermedad de base [oncohematológica: 39% (n: 42); neurológica: 18% (n: 19); cardiopatías congénitas: 9% (n: 10); y posoperatorios: 65 (n: 6)]. Tenían algún grado de inmunosupresión el 50% (n: 54). El 29% (n: 31) referían haber tenido varicela; el 27% (n: 29) referían no haber padecido la enfermedad; y el 41% (n: 44) no recordaban el antecedente. Solo 3% (n: 3) estaban vacunados. Sobre la base del estado inmunológico, edad y antecedentes de varicela previa, se indicó aciclovir como profilaxis en 61% (n: 65); vacuna, en 10% (n: 10); y gammaglobulina, en 1 paciente. No se observaron efectos adversos relacionados con las profilaxis. No se observó ningún caso secundario a los 30 días. Conclusiones. Las medidas implementadas resultaron efectivas en la prevención de casos secundarios. En niños sanos e inmunocomprometidos, la profilaxis con aciclovir fue efectiva y bien tolerada.

Introduction. Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. Objectives. To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. Methods. Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. Results. N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days. Conclusions. Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.

Varicela en la Casa Garrahan, 2008-2013: Evaluación de las medidas de profilaxis posexposición / Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis measures

Introducción. La Casa Garrahan (CG) aloja a niños con patologías complejas de todo el país, atendidos en los hospitales pediátricos de la Ciudad Autónoma de Buenos Aires. La varicela es una enfermedad muy contagiosa, cuya tasa de ataque alcanza el 90% en susceptibles. En comunidades cerradas, es fundamental implementar medidas de prevención ante brotes. Objetivos. Describir las características de los niños expuestos a casos de varicela en la CG, las medidas de profilaxis implementadas y su efectividad. Métodos. Estudio de cohorte prospectivo. Se evaluaron los niños expuestos a varicela en la CG entre 2008 y 2013, sus características demográficas, clínicas y vacunación y/o varicela previa, medidas de profilaxis y tasa de ataque secundaria. Resultados. N: 107. El 53% (n: 57) eran niñas. La mediana de edad fue 84 meses (RIC: 24144). El 95% (n: 102) teman enfermedad de base [oncohematológica: 39% (n: 42); neurológica: 18% (n: 19); cardiopatías congénitas: 9% (n: 10); y posoperatorios: 65 (n: 6)]. Tenían algún grado de inmunosupresión el 50% (n: 54). El 29% (n: 31) referían haber tenido varicela; el 27% (n: 29) referían no haber padecido la enfermedad; y el 41% (n: 44) no recordaban el antecedente. Solo 3% (n: 3) estaban vacunados. Sobre la base del estado inmunológico, edad y antecedentes de varicela previa, se indicó aciclovir como profilaxis en 61% (n: 65); vacuna, en 10% (n: 10); y gammaglobulina, en 1 paciente. No se observaron efectos adversos relacionados con las profilaxis. No se observó ningún caso secundario a los 30 días. Conclusiones. Las medidas implementadas resultaron efectivas en la prevención de casos secundarios. En niños sanos e inmunocomprometidos, la profilaxis con aciclovir fue efectiva y bien tolerada.(AU)

Introduction. Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in childrens hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. Objectives. To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. Methods. Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. Results. N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days. Conclusions. Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.(AU)

Varicella at "Casa Garrahan", 2008-2013: Assessment of postexposure prophylaxis measures.

INTRODUCTION: Casa Garrahan (CG) accommodates children with complex conditions referred nationwide; these children are seen in children's hospitals located in the Autonomous City of Buenos Aires. Varicella is a highly-contagious disease, with attack rates of up to 90% among susceptible individuals. In closed communities, the implementation of outbreak control measures is critical. OBJECTIVES: To describe the characteristics of children exposed to varicella at CG, the implemented prophylaxis measures and their effectiveness. METHODS: Prospective, cohort study. Children exposed to varicella at CG between2008 and 2013, their demographic and clinical characteristics, immunization and/or history of varicella, prophylaxis measures, and secondary attack rate were assessed. RESULTS: N: 107. Fifty-three percent (n: 57) were girls. Their median age was 84 months old [interquartile range (IQR): 24-144]. Ninety-five percent (n: 102) had an underlying disease [hemato-oncological disease: 39% (n: 42); neurological disease: 18% (n: 19); congenital heart disease: 9% (n: 10); and post-operative period: 65 (n: 6)]. Fifty percent had some degree of immunosuppression (n: 54). Twenty-nine percent (n: 31) referred to have had varicella; 27% (n: 29) indicated that they never had the infection; and 41% (n: 44) did not recall a history of varicella. Only 3% (n: 3) had been vaccinated. Based on their immune status, age and history of varicella, acyclovir was indicated as prophylaxis in 61% (n: 65); immunization in 10% (n: 10); and gamma globulin in 1 patient. No adverse effects were observed in relation to the different prophylaxis measures. No secondary cases were observed at 30 days. CONCLUSIONS: Implemented measures were effective to prevent secondary cases. Among healthy and immunocompromised children, prophylaxis with acyclovir was effective and well-tolerated.

Absceso cerebral por Haemophilus influenzae serotipo e en un paciente pediátrico con Síndrome de Apert / Brain abscess caused by Haemophilus influenzae type e in a pediatric patient suffering from Apert syndrome

Se presenta el caso de un absceso cerebral causado por Haemophilus infl uenzae tipo e, en un paciente de 12 años con síndrome de Apert. El síndrome de Apert se caracteriza por el cierre prematuro de las suturas craneales. En 2010, el paciente presentó traumatismo craneano en región frontal, fractura y fístula de líquido cefalorraquídeo. En febrero de 2013 consultó por fi ebre, vómitos y convulsión tónica clónica generalizada, con deterioro progresivo del sensorio. La tomografía axial computarizada mostró una lesión frontal derecha, edema perilesional, leve dilatación ventricular y pansinusitis. Se diagnosticó absceso cerebral con pioventriculitis y se realizó drenaje. Se obtuvo desarrollo de un cocobacilo gram negativo, que fue identifi cado como H. infl uenzae serotipo e. Se realizó tratamiento empírico con meropenem (120 mg/kg/día) y vancomicina (60 mg/kg/día). Luego del resultado del cultivo, se rotó a ceftriaxona (100 mg/kg/día) y metronidazol (500 mg/8 h). El paciente cumplió 8 semanas de tratamiento y se observó evolución favorable

We report a case of a brain abscess caused by Haemophilus infl uenzae type e in a 12 year-old patient suffering from Apert syndrome. Apert syndrome is characterized by the premature closure of cranial sutures. In 2010 the patient suffered head trauma in the frontal area with cranial fracture and a cerebrospinal fl uid fi stula. In February 2013 he was admitted to hospital with fever, vomiting and generalized tonic-clonic seizure with deteriorating mental status/progressive sensory impairment. The computerized axial tomographic scan showed a right frontal lesion, perilesional edema, mild ventricular dilatation and pansinusitis. A brain abscess was diagnosed and drained. The clinical sample was then cultured. A gram negative coccobacillus was isolated and identifi ed as Haemophilus infl uenzae serotype e. Empirical treatment was started with meropenem (120 mg/kg/day) and vancomycin (60 mg/kg/day), which was later switched to ceftriaxone (100 mg/kg/day) and metronidazole (500 mg/8 h) after culture results arrived. The patient was discharged in good clinical condition