Molecular Characterization and Identification of Potential Inhibitors for 'E' Protein of Dengue Virus.

Dengue is an arthropod-borne acute febrile illness caused by Dengue Virus (DENV), a member of Flaviviridae. Severity of the infection ranges from mild self-limiting illness to severe life-threatening hemorrhagic fever (DHF) and dengue shock syndrome (DSS). To date, there is no specific antiviral therapy established to treat the infection. The current study reports the epidemiology of DENV infections and potential inhibitors of DENV 'E' protein. Among the various serotypes, DENV-2 serotype was observed more frequently, followed by DENV-4, DENV-1, and DENV-3. New variants of existing genotypes were observed in DENV-1, 2, and 4 serotypes. Predominantly, the severe form of dengue was attributable to DENV-2 infections, and the incidence was more common in males and pediatric populations. Both the incidence and the disease severity were more common among the residents of non-urban environments. Due to the predominantly self-limiting nature of primary dengue infection and folk medicine practices of non-urban populations, we observed a greater number of secondary dengue cases than primary dengue cases. Hemorrhagic manifestations were more in secondary dengue in particularly in the pediatric group. Through different computational methods, ligands RGBLD1, RGBLD2, RGBLD3, and RGBLD4 are proposed as potential inhibitors in silico against DENV-1, -2, -3, and -4 serotypes.

Study of Correlation of Serum Calcium Level with Disease Severity in Dengue Patients.

Dengue fever is the world's fastest growing vector borne viral disease. Dengue infection has high morbidity and mortality unless managed promptly and appropriately. Calcium regulates many physiological processes such as neuromuscular transmission, heart contractility, hormonal release, blood coagulation and is essential for cell function. Low calcium level is present in almost 80% of dengue cases and is more associated with severe cases. Hypocalcemia enhances the binding of the dengue virus to monocyte macrophages and cells of T cell and B cell lineages in dengue infection. However, there is scarcity of literature on calcium homeostasis in dengue infection, and current guidelines do not address the necessity to monitor or correct blood calcium levels in dengue patients. In present study, we evaluated serum calcium level in dengue patients and correlated it with disease severity. MATERIAL: The present observational cross-sectional study conducted in the Department of Medicine and Biochemistry, VMMC and Safdarjung Hospital, New Delhi, included 60 patients of dengue infection, satisfying the inclusion and exclusion criteria over a period of 18 months. Inclusion criteria were patients with age above 12 years, any gender, and diagnosed as having dengue infection, either by NS1Ag or by IgM ELISA for dengue antibodies, were clinically classified as Dengue Fever (DF), Dengue Haemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) as per National Guidelines for Clinical Management of Dengue Fever developed by NVBDCP. Exclusion criteria were patients with diseases like hypertension, diabetes, cardiac disease, liver disease, malabsorption syndrome, renal dysfunction and patients taking drugs causing hypocalcemia and oral calcium and vitamin D supplements. In present study, serum calcium level used was corrected for hypoalbuminemia. OBSERVATION: The mean age was 27 years with a male and female ratio of approximately 3:2. The present study shows that the mean serum calcium level (mg/dL) of patients in Dengue Fever, Dengue Haemorrhagic Fever and Dengue Shock Syndrome was 8.85, 8.27 and 7.95 respectively(p<0.0001). Serum calcium level was lower in DSS and DHF patients than DF patients. Negative correlation between severity of dengue infection and serum calcium level was found with correlation coefficient of -0.892. CONCLUSION: The present study revealed significant negative correlation between Serum calcium level and severity of dengue infection. Therefore, it can be considered to use serum calcium level as a potential biomarker in order to identify severe dengue patients and this investigation will help in early identification, diagnosis and management of dengue infection but further studies are required to support this.

Heme oxygenase-1 inhibits DENV-induced endothelial hyperpermeability and serves as a potential target against dengue hemorrhagic fever.

Dengue virus (DENV) is a cause of vascular endothelial dysfunction and vascular leakage, which are characterized as hallmarks of dengue hemorrhagic fever or dengue shock syndrome, which become a severe global health emergency with substantial morbidity and mortality. Currently, there are still no promising therapeutics to alleviate the dengue-associated vascular hemorrhage in a clinical setting. In the present study, we first observed that heme oxygenase-1 (HO-1) expression level was highly suppressed in severe DENV-infected patients. In contrast, the overexpression of HO-1 could attenuate DENV-induced pathogenesis, including plasma leakage and thrombocytopenia, in an AG129 mouse model. Our data indicate that overexpression of HO-1 or its metabolite biliverdin can maintain endothelial integrity upon DENV infection in vitro and in vivo. We further characterized the positive regulatory effect of HO-1 on the endothelial adhesion factor vascular endothelial-cadherin to decrease DENV-induced endothelial hyperpermeability. Subsequently, we confirmed that two medicinal plant-derived compounds, andrographolide, and celastrol, widely used as a nutritional or medicinal supplement are useful to attenuate DENV-induced plasma leakage through induction of the HO-1 expression in DENV-infected AG129 mice. In conclusion, our findings reveal that induction of the HO-1 signal pathway is a promising option for the treatment of DENV-induced vascular pathologies.

Dengue Shock Syndrome: Its Similarity with Anaphylaxis and with the Homeopathic Medicine Apis mellifica (European Honeybee).

Dengue, with four viral serotypes, causes epidemics in tropical and sub-tropical regions. Allopathic antiviral therapies and a vaccine of general use are lacking. The homeopathic medicine Apis mellifica, advised in anaphylaxis from honeybee sting, is proposed to address the life-threatening dengue shock syndrome, which develops from dengue hemorrhagic fever and has features of anaphylaxis. In both dengue and anaphylaxis, immunoglobulin E activates, and released vasoactive mediators (importantly histamine, tryptase and platelet-activating factor) cause, a vascular permeability enabling shock. In dengue, another mechanism, namely antibody-dependent enhancement, due to secondary infection with a heterologous dengue serotype, is associated with release of vasoactive mediators. The homeopathic medicine Apis mellifica indicates plasma leak, shock, and the serous effusion that is noted in dengue patients, and is a suggested prophylactic and therapeutic medicine for dengue shock syndrome.

Síndrome hemofagocítico secundario a infección por virus del dengue / Hemophagocytic syndrome secondary to dengue virus infection

Introducción: El síndrome hemofagocítico se presenta como un cuadro clínico grave, provocado por una respuesta inadecuada del sistema inmunológico a un desencadenante infeccioso, neoplásico, reumatológico o metabólico, que origina una reacción inflamatoria no controlada; presenta una incidencia baja pero la letalidad sin el manejo adecuado es muy elevada. Objetivo: Destacar la importancia de diagnóstico oportuno del síndrome hemofagocítico en pacientes con dengue que presentan evolución tórpida. Presentación del caso: Paciente de 7 años de edad, con dengue grave dado por shock, hepatomegalia con elevación de transaminasas, con mala evolución clínica, quien cumple criterios de Síndrome hemofagocítico. Recibió manejo con inmunomoduladores con evolución satisfactoria. Conclusiones: Es importante considerar el Síndrome hemofagocítico como causa ante enfermedades con evolución tórpida a pesar de tener un manejo médico correcto(AU)

Introduction: Hemophagocytic syndrome is a severe clinical picture with an uncontrolled inflammatory reaction caused by an inadequate immune system response to an infectious, neoplastic, rheumatological, or metabolic trigger. The syndrome has low incidence but high fatality when the management is not adequate. Objective: To highlight the importance of a prompt diagnosis of hemophagocytic syndrome in patients with dengue who present a torpid evolution. Case presentation: Seven-year-old patient with severe dengue caused by shock, hepatomegaly with elevated transaminase levels and poor clinical evolution who meets hemophagocytic syndrome criteria. The patient had satisfactory progression after receiving immunomodulatory treatment. Conclusions: Hemophagocytic syndrome must be considered as a cause of pathologies in dengue patients with torpid evolution, even when correct medical management is made(AU)

Multi-Tissue Transcriptomic-Informed In Silico Investigation of Drugs for the Treatment of Dengue Fever Disease.

Transcriptomics, proteomics and pathogen-host interactomics data are being explored for the in silico-informed selection of drugs, prior to their functional evaluation. The effectiveness of this kind of strategy has been put to the test in the current COVID-19 pandemic, and it has been paying off, leading to a few drugs being rapidly repurposed as treatment against SARS-CoV-2 infection. Several neglected tropical diseases, for which treatment remains unavailable, would benefit from informed in silico investigations of drugs, as performed in this work for Dengue fever disease. We analyzed transcriptomic data in the key tissues of liver, spleen and blood profiles and verified that despite transcriptomic differences due to tissue specialization, the common mechanisms of action, "Adrenergic receptor antagonist", "ATPase inhibitor", "NF-kB pathway inhibitor" and "Serotonin receptor antagonist", were identified as druggable (e.g., oxprenolol, digoxin, auranofin and palonosetron, respectively) to oppose the effects of severe Dengue infection in these tissues. These are good candidates for future functional evaluation and clinical trials.

Spectrum of activity testing for therapeutics against all four dengue virus serotypes in AG129 mouse models: Proof-of-concept studies with the adenosine nucleoside inhibitor NITD-008.

Dengue is a mosquito-borne disease of global public health importance caused by four genetically and serologically related viruses (DENV-1 to DENV-4). Efforts to develop effective vaccines and therapeutics for dengue have been slowed by the paucity of preclinical models that mimic human disease. DENV-2 models in interferon receptor deficient AG129 mice were an important advance but only allowed testing against a single DENV serotype. We have developed complementary AG129 mouse models of severe disseminated dengue infection using strains of the other three DENV serotypes. Here we used the adenosine nucleoside inhibitor NITD-008 to show that these models provide the ability to perform comparative preclinical efficacy testing of candidate antivirals in vivo against the full-spectrum of DENV serotypes. Although NITD-008 was effective in modulating disease caused by all DENV serotypes, the variability in protection among DENV serotypes was greater than expected from differences in activity in in vitro testing studies emphasizing the need to undertake spectrum of activity testing to help in prioritization of candidate compounds for further development.

Potential of Nigella sativa seed aqueous extract in ameliorating quinine-induced thrombocytopenia in rats.

Dengue infection is rapidly spreading in most of the countries of south Asia. It is of utmost importance to explore the plants with "anti-thrombocytopenic activity" the dreadful response of dengue fever. The present study was conducted to investigate the potential of aqueous extract of Nigella sativa (black cumin) seeds in alleviating the severity of dengue disease by raising the platelet count (PLT). Serum samples of thirty patients with dengue hemorrhagic fever (DHF) were analysed for different biochemical parameters. When compared with control groups, the patients were found with very low PLT count (7.62 fold), reduced antioxidant levels; catalase (1.4 fold), ascorbic acid (1.1 fold), bilirubin (1.06 fold), and severe deficiency of micronutrient concentrations; cobalt (2.27 fold), iron (2.35 fold) and nickel (71.46 fold). Similar parameters were studied in albino rats to observe the changes in serum levels of biochemical markers, after administration of single dose of choloroquine phosphate (IM, 1.5 mL saline). The drug successfully induced thrombocytopenia along with significant decrease in levels of antioxidants and trace metals. Administration of N. sativa aqueous seed extract (15.25 mg/kg/bw) for 12 days resulted in an increase in PLT count (1.59 fold) as compared to control group. N. sativa post-treatment was found effective in elevating the serum levels of catalase, ascorbic acid, and bilirubin (1.06, 1.58 and 0.4 folds respectively). However, the N. sativa pre-treatment was useful in increasing the levels of micronutrients; iron, nickel and cobalt when compared to quinine-induced group. From the above findings it was suggested that N. sativa seed aqueous extract supplementation would be a promising solution for declined PLT count and associated consequences.

Expresión de genes de IFN g y TNF a en tejidos de fallecidos por dengue / Expression of IFN g and TNF a genes in tissues from dengue fatal cases

INTRODUCCIÓN: el dengue es considerada la enfermedad viral transmitida por artrópodos de mayor importancia en el humano a nivel global, con un estimado de 100 millones de infecciones anuales y más de 20 000 muertes. La patogénesis de la enfermedad grave por dengue no está totalmente esclarecida. Sin embargo, existen estudios que la asocian con infecciones secuenciales por diferentes serotipos virales, activación de células T de memoria e hiperproducción de citocinas. OBJETIVOS: determinar la expresión cualitativa de genes de las citoquinas IFNγ y TNFα en tejidos de bazo e hígado de casos fatales por dengue 3 o dengue 4 mediante la detección de ARNm y comprobar su papel en la patogénesis de la enfermedad. MÉTODOS: El estudio se realizó a través de un método de retro-transcripción y reacción en cadena de la polimerasa (RT-PCR) con el uso de cebadores específicos. RESULTADOS: la expresión de IFNγ predominó a la de TNFα, y fue más evidente en los tejidos de bazo que del hígado. CONCLUSIONES: los resultados obtenidos apoyan el papel patogénico del patrón de respuesta Th1 en el dengue grave y constituye el primer estudio realizado de este tipo en la infección por dengue.

INTRODUCTION: dengue is considered to be the most important arthropod-borne human disease worldwide, with an estimated 100 million new cases per year and more than 20 000 deaths. The pathogenesis of severe dengue is not fully understood. However, certain studies have associated it with sequential infections by different viral serotypes, memory T cell activation and cytokine hyperproduction. OBJECTIVES: determine the qualitative expression of genes of cytokines IFNγ and TNFα in spleen and liver tissues from dengue 3 and 4 fatal cases, detecting RNAm and verifying their role in the pathogenesis of the disease. METHODS: the study was conducted by retrotranscription and polymerase chain reaction (RT-PCR) using specific primers. RESULTS: expression of IFNγ predominated over that of TNFα, and was more evident in spleen than in liver tissues. CONCLUSIONS: results support the pathogenic role of the Th1 response pattern in severe dengue. This is the first study of its type about dengue infection.

Manifestações clínicas na dengue: diagnóstico laboratorial / Clinical manifestations in dengue: laboratory diagnosis

A dengue é uma doença infecciosa de evolução aguda, transmitida por vírus (RNA vírus). Infecta o homem através da picada do inseto fêmea Aedes aegypti. Seus sinais e sintomas são variáveis, com formas oligossintomáticas, formas clássicas (febris) e formas graves hemorrágicas, podendo até apresentar síndrome cardiovascular hipovolêmica. O diagnóstico envolve critérios clínico-laboratoriais. O diagnóstico sorológico tem fundamental importância na classificação de infecção primária ou secundária, já que a dengue hemorrágica surge com maior frequência nas infecções secundárias. O isolamento do vírus é geralmente realizado para fins de pesquisa ou epidemiológicos. As epidemias ocorrem principalmente no verão, durante ou após períodos chuvosos.

The dengue is an infectious disease of acute evolution transmitted by virus (RNA virus), infecting humans through the bite of the Aedes aegypti female insect. Presenting signs and symptoms variables with oligosymptomatic forms, classical forms (fever) and severe hemorrhagic form (DHF), this can lead to cardiovascular hypovolemic syndrome. The diagnoses of dengue disease involves clinical and laboratory criteria. Serological diagnosis has fundamental importance in the classification of primary or secondary infection, since DHF appears most often in secondary infections.Virus isolation is usually carried out for research or epidemiological studies. Epidemics occur mainly in the summer, during or after rainy periods.

Laboratory observations on the larvicidal efficacy of three plant species against mosquito vectors of malaria, dengue/dengue hemorrhagic fever (DF/DHF) and lymphatic filariasis in the semi-arid desert.

Comparative larvicidal efficacy of aqueous and organic solvent extracts from seeds, leaves and flowers of three desert plants viz. Calotropis procera (Aiton), Tephrosia purpurea (L.) Pers. and Prosopis juliflora (Sw.) DC. was evaluated against Anopheles stephensi (Liston), Aedes aegypti (Linnaeus) and Culex quinquefasciatus (Say). For this purpose larvae of all the three mosquito species were reared in the laboratory and studies carried out on late 3rd or early 4th instars using standard WHO technique. Based on concentration mortality data 24 and 48 hr LC50and LC90 values along with their 95% fiducial limits, regression equation, chi-square (chi2)/ heterogeneity of the response were determined by log probit regression analysis. Experiments were carried out with different solvent extracts of seeds of C. procera which revealed that methanol (24 hr LC50: 127.2, 194.8, 361.0) and acetone (229.9, 368.1,193.0 mg l(-1)) extracts were more effective with the three mosquito species, respectively. Petroleum ether extract was effective only on An. stephensi while aqueous extracts were not effective at all with any of the mosquito species (mortality < 10-30%). Tests carried out with methanol extracts of fresh leaves (24 hr LC50: 89.2, 171.2, 369.7) and flowers (24 hr LC50: 94.7,617.3, 1384.0 mg l-(-1)) of Calotropis showed that preparations from fresh parts were 2-3 times more effective as compared to the stored plant parts. Efficacy was less than 10-30% with both An. aegypti and Cx. quinquefasciatus while An. stephensi was still susceptible to extracts from both leaves and flowers even after two years of storage. The 24 hr LC50 values as observed for methanol extracts of seeds of T. purpurea and leaves of P. juliflora were 74.9, 63.2 and 47.0 and 96.2,128.1 and 118.8 mg l(-1) for the above three mosquito species, respectively. Experiments carried out up to 500 mg l-(1) with leaves (T. purpurea) and seeds (P. juliflora) extracts show only up to 10-30% mortality indicating that active larvicidal principle may be present only in the seeds of Tephrosia and leaves of Prosopis. In general, anophelines were found more susceptible than the culicines to the plant derived derivatives. More studies are being carried outon some other desert plants found in this arid region. The study would be of great importance while formulating vector control strategy based on alternative plant based insecticides in this semi-arid region.

Expresión clínica del dengue en usuarios del Instituto Mexicano del Seguro Social, Veracruz, México / Clinical expression of dengue in beneficiaries of the Instituto Mexicano del Seguro Social in Veracruz, Mexico

Objective: To describe and compare the clinical behavior of Dengue Fever (DF) and Hemorrhagic Dengue Fever (HDF) in beneficiaries of the Instituto Mexicano del Seguro Social (IMSS). Methods: Transversal study in beneficiaries from Veracruz, selected among those who sought attention at two medical attention units, with probable dengue diagnosis. Surveys were performed to know personal and epidemiological data, as well as a clinical follow up. Blood samples were taken for RT-PCR viral identification and antibodies against Dengue. In the same way, platelet, hemoglobin, and hematocrit tests were performed for their determination. The SPSS 12.0 software was used for the process and analysis of the information, and simple frequencies, proportions, and means were estimated. Results: 109 patients were studied, classified as 72 DF and 37 as HDF. 40 isolations were performed, and the circulation of the four types of dengue virus was identified, although most of the isolations corresponded to serotype 2 (Asian-American genotype). In one patient, a simultaneous infection of dengue viruses 1 and 2 was identified. A group of patients did not present hemorrhages, capillary fragility, or liquid permeation, but with important thrombocytopenia and hemoconcentration, all infected with den-1 and den-2. Conclusions: The presence of cases with atipical behavior of the diseases were identified. The characteristics and immunologic experience of the populations, as well as the simultaneous circulation of various dengue viruses and their changing structure could be related with the current clinical behavior of Dengue in Mexico. It is important to continue the research to confirm these asseverations.

Evolución clínica de pacientes hospitalizados por dengue en una institución de salud de Bucaramanga, Colombia / Clinical evolution of dengue in hospitalized patients

Introducción. El dengue hemorrágico abarca todas las áreas tropicales y subtropicales del planeta, y causa medio millón de hospitalizaciones al año en el mundo. Se ha descrito que esta enfermedad afecta a un grupo cada vez mayor de adolescentes y adultos jóvenes. Objetivo. Describir las características clínicas de la población, tanto adulta como pediátrica, hospitalizada por dengue durante un periodo endémico y determinar los factores de riesgo asociados a mal pronóstico. Materiales y métodos. Cohorte retrospectiva de pacientes hospitalizados por dengue en los años 2006 y 2007 en la Clínica Chicamocha. Resultados. Se evaluaron 328 pacientes, 165 mujeres y 163 hombres, con mediana de edad de 25 años. Se encontraron 116 casos de dengue hemorrágico, de los cuales, 113 eran de grado II. De los 212 pacientes con dengue clásico, 156 presentaron extravasación, sangrado o trombocitopenia. El 82,4 por ciento tuvieron serología positiva. Los pacientes con dengue hemorrágico eran más jóvenes (20,1 contra 25,7 años, p=0,0054). El número mínimo de plaquetas y el valor máximo del hematocrito se alcanzaron alrededor del sexto día de enfermedad. Los menores de 13 años presentaron con menor frecuencia los síntomas típicos de dengue, aunque con un mayor porcentaje de ascitis, derrame y sangrado; además, tuvieron mayor riesgo de desarrollar dificultad respiratoria (riesgo relativo (RR)=3,59, IC95 por ciento 1,3-9,9, p=0,014) e hipotensión (RR=10,77, IC95 porcentaje 5,56-20,86, p<0,001). Conclusiones. La edad continúa siendo el factor predominante en la gravedad intrahospitalaria del dengue. Independientemente de ésta, un grupo de signos, síntomas y hallazgos de laboratorio al ingreso permite predecir la aparición de complicaciones.

Aspectos clínicos e epidemiológicos do dengue hemorrágico no Ceará, no período de 1994 a 2006 / Clinical and epidemiological aspects of hemorrhagic dengue in Ceará in the period 1994 to 2006

Casos de dengue hemorrágico começaram a ser notificados no Estado do Ceará em 1994, com letalidade elevada. O objetivo desse trabalho foi analisar as características clinicas e epidemiológicas dos casos de dengue hemorrágico no Ceará, no período de 1994 a 2006, buscando fatores associados à ocorrência de casos graves e óbitos. Foram analisados 868 casos confirmados pela Secretaria da Saúde do Ceará, que apresentaram início dos sintomas entre 1º de Janeiro de 1994 a 31 de dezembro de 2006. As análises foram realizadas utilizando os programas Terra View, Epi-Info 6.0 e Stata. Houve um aumento significativo no percentual de casos de dengue hemorrágico em relação aos casos clássicos, passando de 0,05 por cento em 1994 para 0,67 por cento em 2006. A letalidade no período foi de 10,7 por cento, variando de 6,8 a 75,0 por cento. O número de municípios com casos hemorrágicos passou de 3 em 1994 para 36 em 2003. A maioria dos casos (64 por cento) foram confirmados na capital. Não houve diferença significativa entre os sexos. Foi observado um aumento de casos em menores de 12 anos (p<0,000), e uma diminuição nos maiores de 19 anos. As manifestações hemorrágicas mais freqüentes foram petéquias (40 por cento), gengivorragia (18,7 por cento) e sangramento gastrointestinal (17,3 por cento). A prova do laço foi realizada em 52,5 por cento dos pacientes e positiva em 36,5 por cento do total de casos. O sinal de alerta mais freqüente foi a dor abdominal (48,3 por cento). Os pacientes do interior apresentaram maior percentual de choque, com 20 por cento e na capital 11,9 por cento (p=0,007). A letalidade foi maior nos pacientes residentes do interior, com 16,1 por cento na capital e 9,6 (p=0,016). A média dos valores de hematócrito foi mais elevada nos pacientes que evoluíam para cura com 41,6 por cento e os valores médios de menor contagem de plaquetas foram menores nos que evoluíram para óbito com 41.400 por mm3 enquanto que nos que sobreviveram foi de 51.063 por mm3. Percebeu-se um agravamento da situação epidemiológica no Estado, com destaque para Fortaleza aumento da proporção de casos graves em relação aos casos de dengue clássico e um aumento dos casos nas faixas etárias mais jovens. Sugere-se a realização de estudos com o objetivo de determinar valor prognóstico dos fatores associados ao óbito encontrados.

Effect of pretreatment with chromium picolinate on haematological parameters during dengue virus infection in mice.

BACKGROUND & OBJECTIVE: Dengue virus (DV) has caused severe epidemics of dengue fever (DF) and dengue haemorrhagic fever (DHF) and is endemic all over India. We have earlier reported that exposure of mice to hexavalent chromium [Cr(VI)] compounds increased the severity of dengue virus infection. Trivalent chromium picolinate (CrP) is used worldwide as micronutrient and nutritional supplement. The present study was therefore, carried out to investigate the effects of CrP on various haematological parameters during DV infection of mice. METHODS: The Swiss Albino smice were inoculated with dengue virus (1000 LD50, intracerebrally) and fed with chromium picolinate (CrP) in drinking water (100 and 250 mg/l) for 24 wk. Peripheral blood leucocytes and other haematological parameters, and spleens were studied on days 4 and 8 after virus inoculations and the findings were compared with those given only CrP and the normal control age matched mice. RESULTS: CrP in drinking water for 24 wk had no significant effects on peripheral blood cells of mice. On the other hand, there was significant decrease in different haematological parameters following inoculation of normal mice with DV. In CrP fed mice the effects of DV infection were abolished on most of the haematological parameters. INTERPRETATION & CONCLUSION: The findings of present study showed that the adverse effects of DV infection, specially on platelets and leucocytes, were abrogated by pretreatment of mice with CrP. The therapeutic utility of CrP in viral infections including dengue needs to be studied in depth.

Manifestaciones clínicas inusuales del dengue hemorrágico en niños / Abnormal clinical manifestations of dengue hemorrhagic fever in children

Introducción. Recientemente han venido aumentando los reportes de dengue hemorrágico con manifestaciones inusuales, principalmente neurológicas y hepáticas, que aumentan la morbimortalidad. Objetivo. Describir las manifestaciones inusuales del dengue hemorrágico en niños.Materiales y métodos. En el Departamento de Pediatría del Hospital Universitario de Santander en Bucaramanga, Colombia, de 913 pacientes con diagnóstico de dengue hemorrágico entre 1992 y 2004, se seleccionaron aquéllos que presentaron manifestaciones inusuales. Se clasificaron de acuerdo con los criterios de definición de caso, se agruparon según los órganos o sistemas principalmente comprometidos y se describieron los principales hallazgos clínicos, de laboratorio y relativos a la evolución. Resultados. Se encontraron 168 pacientes que presentaron manifestaciones inusuales, con predominio del sexo masculino, edad escolar y grados III y IV de dengue hemorrágico. Las manifestaciones más frecuentes fueron hepáticas, 53 (27 por ciento), y neurológicas, 49 (25 por ciento), además de renales, 14 (7 por ciento); cardíacas, 15 (8 por ciento); pulmonares, 18 (9 por ciento); colecistitis alitiásica, 18 (9 por ciento); síndrome hemofagocítico, 5 (2,5 por ciento); pancreatitis, 2 (1 por ciento), y 21 casos de abdomen agudo (11 por ciento). Fallecieron 10 pacientes. Conclusión. Se analizan los resultados y se comparan con otros de países endemoepidémicos de dengue; se discute el significado e importancia de las manifestaciones clínicas inusuales, su difícil diagnóstico, casi siempre en forma retrospectiva, y se destaca la frecuencia de las manifestaciones hepáticas y neurológicas que pueden aumentar la morbimortalidad, ante las cuales deben estar alertas los médicos que trabajan en zonas endémicas para reconocerlas.

A preliminary study on the mosquito repellent effect of tea tree (Melaleuca alternifolia) oil

BACKGROUND: Dengue Fever (DF) and Dengue Hemorrhagic Fever (DHF) are now considered as major health problems in the Philippines. N,N,-dietyl-3-toluamide (DEET) is recognized as the most effective against Aedes aegypti. However, the concern about its use have underscored the need to find a safer alternative repellent.OBJECTIVES: This study aims to determine and compare the repellent activity of tea tree (Melaleuca alternifolia) oil against Aedes aegypti with 7% DEET using a double-blind controlled experimental trialMETHODOLOGY: Twenty healthy subjects were allocated systematically by alternate assignment into three treatment groups (Control vs. Tea Tree oil, control vs. 7 percent DEET, Tea Tree oil vs DEET). All subjects were exposed to Aedes aegypti for 5 minutes every hour for 8 hours and the number of mosquitoes biting/landing were recorded and compared for each treatment groupRESULTS: Fifty percent tea tree oil has a repellent activity against Aedes aegypti and its efficacy is comparable to 7% DEET. Both treatments were equally effective in repelling mosquitoes for 7 hours. No cutaneous reactions to both repellents were notedCONCLUSION: The efficacy of tea tree oil is comparable to 7% DEET and is recommended as an alternative natural mosquito repellent.

Technology evaluation: ChimeriVax-DEN, Acambis/Aventis.

Acambis, in collaboration with Aventis Pasteur, is developing a chimeric vaccine based on a recombinant yellow fever vaccine for the potential prevention of dengue virus infection. The vaccine is undergoing phase I clinical trials.