Scientific advances in therapeutic strategies against disease by ebola virus

La enfermedad por el virus del Ébola se conoce desde hace treinta años como mortal, contagiosa y de difícil diagnóstico y tratamiento. Numerosos estudios se han realizado para comprender la patogénesis del virus y con ello los posibles tratamientos que puedan generar control de la enfermedad. Sin embargo, no hay hasta la fecha un fármaco o vacuna con licencia para combatir el virus del Ébola. El tratamiento está basado solo en aliviar los síntomas y prevenir el contagio por medio de acciones que ayuden a minimizar el riesgo de infección. En esta revisión, se presentan las diferentes perspectivas del estado actual de la investigación sobre fármacos antivirales y vacunas en fases de desarrollo para la infección del virus del Ébola.Ebola virus disease has been known for thirty years as a lethal, contagious and difficult to diagnose and treat disease. Numerous studies have been conducted to understand the pathogenesis of the virus and thus the possible treatments that may promote disease control. However, to date there is no licensed vaccine or medicine to fight Ebola virus. The treatment is based only on relieving symptoms and preventing contagion through actions that help minimize the risk of infection. This review presents different perspectives of the current state of research on antiviral medicine and vaccines in development stages for Ebola virus infection

MUTATION IN THE GLYCOGEN PHOSPHORYLASE KINASE (PHKA2) GENE IN TWO PATIENTS FROM CARTAGENA DE INDIAS: REPORT OF THE FIRST CASES IN COLOMBIA

The glycogen storage disease (GSD) type IX is a rare disease of variable clinical severity that mainly affects the liver tissue. Individuals with hepatic phosphorylase b-kinase (PHK) deficiency due to mutation in the PHKA2 gene (GSD IXa) may present hepatomegaly with elevated serum transaminases, ketotic hypoglycemia, hyperlipidemia, and poor growth with considerable variation in clinical severity. To identify and describe the different clinical manifestations of two brothers with the same type of mutation in the PHKA2 gene (GSD IXa), which represent the first two cases described in Colombia. Two children were studied, from the city of Cartagena, who according to the symptoms, findings to the physical, clinical and biochemical examinations performed in the Biochemistry Laboratory of the University of Cartagena, had high suspicion that they had some glycogenosis In addition, genetic studies were carried out at the Center for the Diagnosis of Molecular Diseases (CEDEM) in Madrid-Spain, through massive sequencing analysis, bioinformatic analysis, bioinformatic analysis of mutations and confirmation by sequencing of Sanger. We present the cases of two siblings, who according to the symptomatology, clinical, biochemical and genetic tests carried out, get to diagnose and confirm that they suffer from GDS IXa with mutation c.919-2A> G in hemicigosis of the PHKA2 gene, the which represents a new variant of this gene. The development of the so-called next generation sequencing technologies (NGS), such as those used in this study, is currently the method of choice to confirm the diagnosis of GSD, avoiding the use of a test invasive as the liver biopsy

Nuevos enfoques prometedores en el tratamiento frente al virus chikungunya

El Virus Chikungunya es un patógeno transmitido por mosquitos que tiene un impacto importante en la salud de los seres humanos, causando enfermedad febril aguda, dolores en las articulaciones y en muchos casos artralgia persistente que dura semanas o años. El resurgimiento de este virus ha dado lugar a numerosos brotes en varios países del mundo, con amenaza de propagarse aún más en un futuro próximo. Actualmente no hay fármacos antivirales o vacunas registradas para la prevención y tratamiento de la infección por chikungunya. En esta revisión, se presentan las diferentes perspectivas del estado actual de la investigación sobre fármacos antivirales y vacunas en fases de desarrollo para la infección del virus chikungunya

Malaria Congénita por Plasmodium vivax: reporte de caso

Se describe el caso de malaria congénita por Plasmodium vivax de un neonato de 25 días de nacido, el cual consulta por fiebre e ictericia persistente. La sospecha inicial orientaba a un diagnóstico de sepsis neonatal. El neonato residente en Cartagena (Colombia), presentaba antecedente perinatal de ictericia y antecedente materno de malaria gestacional diagnosticada al cuarto mes. La madre refirió haber vivido los primeros siete meses de su embarazo en Tierralta, Córdoba (Colombia), la cual es una zona endémica de malaria. Posterior a los resultados del extendido de sangre periférica del neonato se demostró la presencia de Plasmodium vivax. El tratamiento antimalárico fue realizado con cloroquina, con eficaz mejoría clínica. Se destaca la importancia de tener a la malaria congénita como diagnóstico diferencial en infecciones neonatales, sepsis, fiebre inexplicable o en lactantes que presenten anemia hemolítica, ictericia y hepatoesplenomegalia en pacientes provenientes de zonas endémicas de malaria

Haemoglobin interference and increased sensitivity of fluorimetric assays for quantification of low-parasitaemia Plasmodium infected erythrocytes

<p>Abstract</p> <p>Background</p> <p>Improvements on malarial diagnostic methods are currently needed for the correct detection in low-density <it>Plasmodium falciparum </it>infections. Microfluorimetric DNA-based assays have been previously used for evaluation of anti-malarial drug efficacy on <it>Plasmodium </it>infected erythrocytes. Several factors affecting the sensitivity of these methods have been evaluated, and tested for the detection and quantification of the parasite in low parasitaemia conditions.</p> <p>Methods</p> <p>Parasitaemia was assessed by measuring SYBRGreen I^®(SGI) and PicoGreen^®(PG) fluorescence of <it>P. falciparum </it>Dd2 cultures on human red blood cells. Different modifications of standard methods were tested to improve the detection sensitivity. Calculation of IC₅₀for chloroquine was used to validate the method.</p> <p>Results</p> <p>Removal of haemoglobin from infected red-blood cells culture (IRBC) increased considerably the fluorescent signal obtained from both SGI and PG. Detergents used for cell lysis also showed to have an effect on the fluorescent signal. Upon depletion of haemoglobin and detergents the fluorescence emission of SGI and PG increased, respectively, 10- and 60-fold, extending notably the dynamic range of the assay. Under these conditions, a 20-fold higher PG vs. SGI fluorescent signal was observed. The estimated limits of detection and quantification for the PG haemoglobin/detergent-depleted method were 0.2% and 0.7% parasitaemia, respectively, which allow the detection of ~10 parasites per microliter. The method was validated on whole blood-infected samples, displaying similar results as those obtained using IRBC. Removal of white-blood cells prior to the assay allowed to increase the accuracy of the measurement, by reducing the relative uncertainty at the limit of detection from 0.5 to 0.1.</p> <p>Conclusion</p> <p>The use of PG microassays on detergent-free, haemoglobin-depleted samples appears as the best choice both for the detection of <it>Plasmodium </it>in low-density infections and anti-malarial drugs tests.</p

Parasitostatic effect of maslinic acid. II. Survival increase and immune protection in lethal Plasmodium yoelii-infected mice

<p>Abstract</p> <p>Background</p> <p>The anti-malarial activity of maslinic acid (MA), a natural triterpene which has been previously shown to exert a parasitostatic action on <it>Plasmodium falciparum </it>cultures, was analysed <it>in vivo </it>by using the <it>Plasmodium yoelii </it>17XL murine model.</p> <p>Methods</p> <p>ICR mice were infected with <it>P. yoelii </it>and treated with a single dose of MA by a intraperitoneal injection of MA (40 mg kg^-1day^-1) followed by identical dose administration for the following three days. Parasitaemia and accumulation of intraerythrocytic stages was monitored microscopically. To assess protective immunity, cured mice were challenged with the same dose of parasites 40 days after recovery from the primary infection and parasitaemia was further monitored for 30 days. Humoral response was tested by ELISA and visualization of specific anti-<it>P. yoelii </it>antibodies was performed by Western-blotting.</p> <p>Results</p> <p>ICR mice treated with MA increased the survival rate from 20% to 80%, showing an arrest of parasite maturation from day 3 to 7 after infection and leading to synchronization of the intraerythrocytic cycle and accumulation of schizonts by day 6, proving that MA also behaves as a parasitostatic agent <it>in vivo</it>. Mice which survived the primary infection displayed lower rates of parasitic growth, showing a decline of parasitaemia after day 15, and complete clearance at day 20. These mice remained immunoprotected, showing not malaria symptoms or detectable parasitaemia after rechallenge with the same lethal strain. The analysis of specific antibodies against <it>P. yoelii</it>, present in mice which survived the infection, showed a significant increase in the number and intensity of immunoreactive proteins, suggesting that the protected mice may trigger a strong humoral response.</p> <p>Conclusion</p> <p>The survival increase observed in MA-treated mice can be explained considering that the parasitostatic effect exerted by this compound during the first days of infection increases the chances to develop effective innate and/or acquired immune responses. MA may represent a new class of anti-malarial compounds which, as a consequence of its parasitostatic action, favours the development of more effective sterilizing immune responses.</p

Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages

<p>Abstract</p> <p>Background</p> <p>Natural products have played an important role as leads for the development of new drugs against malaria. Recent studies have shown that maslinic acid (MA), a natural triterpene obtained from olive pomace, which displays multiple biological and antimicrobial activities, also exerts inhibitory effects on the development of some Apicomplexan, including <it>Eimeria, Toxoplasma </it>and <it>Neospora</it>. To ascertain if MA displays anti-malarial activity, the main objective of this study was to asses the effect of MA on <it>Plasmodium falciparum</it>-infected erythrocytes <it>in vitro</it>.</p> <p>Methods</p> <p>Synchronized <it>P. falciparum</it>-infected erythrocyte cultures were incubated under different conditions with MA, and compared to chloroquine and atovaquone treated cultures. The effects on parasite growth were determined by monitoring the parasitaemia and the accumulation of the different infective stages visualized in thin blood smears.</p> <p>Results</p> <p>MA inhibits the growth of <it>P. falciparum </it>Dd2 and 3D7 strains in infected erythrocytes in, dose-dependent manner, leading to the accumulation of immature forms at IC₅₀concentrations, while higher doses produced non-viable parasite cells. MA-treated infected-erythrocyte cultures were compared to those treated with chloroquine or atovaquone, showing significant differences in the pattern of accumulation of parasitic stages. Transient MA treatment at different parasite stages showed that the compound targeted intra-erythrocytic processes from early-ring to schizont stage. These results indicate that MA has a parasitostatic effect, which does not inactivate permanently <it>P. falciparum</it>, as the removal of the compound allowed the infection to continue</p> <p>Conclusions</p> <p>MA displays anti-malarial activity at multiple intraerythrocytic stages of the parasite and, depending on the dose and incubation time, behaves as a plasmodial parasitostatic compound. This novel parasitostatic effect appears to be unrelated to previous mechanisms proposed for current anti-malarial drugs, and may be relevant to uncover new prospective plasmodial targets and opens novel possibilities of therapies associated to host immune response.</p

Histiocitosis congénita de células de Langerhans

Langerhans cell histiocytosis is a rare pathology with different clinical manifestations in the neonatal period ranging from isolated bone lesions to systemic compromise.We report a case of Langerhans cell histiocytosis including a literature review focused on the clinical manifestations, diagnosis, and treatment. A one-month-old patient was brought to medical consultation with lymphadenopathy and skin lesions, which were initially managed as an infectious pathology. The disease continued its progression without improvement with the treatment until the patient died due to respiratory failure.The lymph node and skin biopsies revealed infiltration of atypical cells with positive immunohistochemistry for S100, CD1, and CD68 confirming Langerhans cell histiocytosis.This disorder represents a great challenge and, therefore, it is important to alert and sensitize medical teams about it for timely diagnosis and management.La histiocitosis de células de Langerhans es una enfermedad poco frecuente, cuyas manifestaciones clínicas pueden aparecer en el periodo neonatal y varían desde lesiones óseas aisladas hasta un compromiso sistémico.Se describe un caso de histiocitosis de células de Langerhans y se revisa la literatura médica sobre las manifestaciones clínicas, el diagnóstico y el tratamiento. El paciente de un mes de nacido fue llevado a consulta por presentar adenopatías y lesiones en la piel que, inicialmente, fueron tratadas como reacción a una infección. La enfermedad continuó su progresión sin que hubiera mejoría con el tratamiento, hasta que el paciente falleció por falla respiratoria.La biopsia de ganglio linfático y la de piel revelaron infiltración de células atípicas, y la inmunohistoquímica resultó positiva para las proteínas S100, CD1 y CD68, con lo cual se confirmó el diagnóstico de histiocitosis de células de Langerhans.Esta alteración representa un gran desafío clínico, por lo que es importante alertar y sensibilizar al equipo médico para lograr un diagnóstico y un tratamiento más oportunos

Caracterización clínica del dengue en un hospital infantil de Cartagena, Colombia

Objetivo: Caracterizar las manifestaciones clínicas del dengue en pacientes pediátricos en una institución de salud de tercer nivel de Cartagena (Colombia). Materiales y métodos: Estudio descriptivo por revisión de historias clínicas de pacientes hospitalizados por dengue en el Hospital Infantil Napoleón Franco Pareja de la ciudad de Cartagena, Colombia. Se evaluaron 136 niños con cuadros febriles agudos de etiología inaparente. Se utilizaron pruebas serológicas para confirmar la infección por el virus del dengue. Resultados: Se analizaron 98 casos de niños hospitalizados con diagnóstico de dengue. La edad osciló entre menores de 6 meses a 16 años, siendo el rango de edades con mayor frecuencia de la enfermedad de 10 a 16 años (33,7%). Los signos y síntomas más frecuentes fueron: exantema (49,0%), mialgia (35,7%), cefalea (33,7%), artralgia (33,7%), anorexia (24,5%), torniquete (19,4%), prurito (11,2%), escalofrío (8,2%), eritema facial (7,1%) y dolor retro ocular (6,1%). Conclusiones: La edad continúa siendo el factor predominante en la gravedad intrahospitalaria del dengue. Por lo tanto se necesitan con urgencia medidas preventivas en la población pediátrica

Hemorragia cerebrovascular asociada con infección por citomegalovirus en un lactante menor

Cytomegalovirus is the most frequent causative agent of perinatal infection and a major cause of acquired viral infections. This case report aims to show the broad clinical spectrum of the presentation of cytomegalovirus infection. The correct classification of congenital or acquired infection and its prompt treatment can prevent complications and sequelae in severe cases.We report the case of an infant with acquired cytomegalovirus infection, which presented an unusual feature of cerebral hemorrhage. The patient was treated with ganciclovir, with a favorable evolution of the clinical symptoms.Cytomegalovirus infection is common in children, both in its congenital and acquired forms. Acquired infection, as portrayed in this case, is mainly characterized by hematological compromise given by the marked thrombocytopenia, which may rarely result in cases of bleeding in the central nervous system.In this patient, no important clinical implications occurred. In addition, most of the acquired infections are self-limited and require no treatment.El citomegalovirus es el agente de infección perinatal más frecuente y una de las principales causas de infecciones virales adquiridas. En la presentación del siguiente caso se describe el amplio espectro clínico de la infección por citomegalovirus. La clasificación correcta de la infección como congénita o adquirida y el tratamiento oportuno pueden evitar complicaciones y secuelas en los casos graves.Se describe el caso de un lactante menor que presentaba una infección por citomegalovirus con la manifestación poco frecuente de hemorragia cerebral. Después del tratamiento con ganciclovir, los síntomas clínicos evolucionaron favorablemente. La infección por citomegalovirus es muy frecuente en la edad pediátrica, tanto en la forma congénita como en la adquirida. La forma adquirida, como la de este caso, se caracteriza principalmente por el compromiso hematológico, al producirse una importante trombocitopenia, lo que puede originar, aunque infrecuentemente, sangrado del sistema nervioso central; la mayoría de las infecciones adquiridas, sin embargo, son de resolución espontánea y no requieren tratamiento. En este paciente no se presentaron repercusiones clínicas de importancia