Virus del dengue de serotipo 1 (DENV-1) de Colombia: su contribución a la presentación del dengue en el departamento de Santander / Dengue virus serotype 1 (DENV-1) from Colombia: its contribution to dengue occurrence in Santander

Introducción. Los cuatro serotipos del virus del dengue circularon en el departamento de Santander entre 1998 y 2008. No existe información sobre el papel del serotipo 1 (DENV-1) en la epidemiología de la enfermedad. Objetivo. Analizar la relación entre el cambio de predominancia del (DENV-1) con su diversificación genética, predominancia de los otros serotipos y presentación del dengue grave. Materiales y métodos. La diversificación genética se estudió por análisis filogenético usando la secuencia del gen E de 12 cepas del virus. Para el análisis se utilizaron datos sobre predominancia de los serotipos obtenidos en estudios previos y datos oficiales de incidencia del dengue. Resultados. Los virus seleccionados se agruparon en el genotipo V junto a (DENV-1) de países de Latinoamérica y se evidenció segregación en cuatro linajes. Los cambios en la predominancia del virus coincidieron con el reemplazo de linaje y esto, a su vez, con incremento en la prevalencia de DENV-2 y DENV-3, e incremento del dengue grave. Conclusión. La diversificación genética podría contribuir a cambios de predominancia de (DENV-1), y la relación del virus con el DENV-2 y DENV-3 en situaciones que favorecen la presentación de casos graves. Se necesitan más estudios para precisar el papel de los serotipos en la epidemiología del dengue.

Introduction: Between 1998 and 2008 all dengue virus serotypes circulated in the Departamento de Santander, an endemic region in northeastern Colombia. No information is available as to the role of serotype 1 (DENV-1) with respect to epidemiology of dengue. Objective: To analyze the relationship between changes in DENV-1 predominance with respect to genetic diversity, prevalence of others serotypes and occurrence of severe dengue. Methods: Virus genetic diversity was studied by phylogenetic analysis comparing E gene sequences from 12 viral strains. Data about serotypes predominance obtained in previous studies and official data about dengue incidence were used for analysis. Results: Selected viruses grouped into genotype V together DENV-1 from Latin America countries, and segregation in four lineages was evidenced. Changes in virus predominance coincided with replacement of lineage, increase in prevalence of DENV-2 and DENV-3 and increase of severe dengue. Conclusion: Genetic divergence could have contributed to changes in DENV-1 predominance. The relationship of the virus with DENV-2 and DENV-3 could create scenarios that promote occurrence of severe cases. More studies are required to ascertain the precise role of serotypes in the epidemiology of dengue.

Correlation of disease spectrum among four Dengue serotypes: a five years hospital based study from India

The recognition of DF (DHF Dengue Hemorrhagic Fever) is very complicated due to occurrence of a wide spectrum of clinical signs and symptoms during acute phase of illness. Moreover, presence of four serotypes further complicates the prognosis. To investigate the predictors of disease severity and elucidate the prognostic markers among four dengue serotypes, this study was conducted on 320 inpatients having acute febrile illness clinically suspected as DI, over a period of five years. Dengue serotypes were confirmed by multiplex reverse transcriptase (RT)-PCR. Eighty patients were positive for DI with presence of Den-1, Den-2, Den-3, and Den-4 in 8, 35, 27 and 10 patients, respectively. The severe clinical manifestations, abdominal pain and hepatomegaly, were comparatively higher in Den-2 patients. Liver aminotransferases levels were also higher in Den-2 patients (app. 5 fold). This study clearly indicates the hyperendemicity of all dengue serotypes. Nucleotide sequencing of Envelope region revealed that the presently emerged Den-3 belongs to type III, having high homology with genotype responsible for number of outbreaks in 1980s. The re-emergence of this deadly type can be suspected to cause more outbreaks in future and is a matter of great concern.

Early molecular markers predictive of dengue hemorrhagic fever

The management of acute dengue patients during outbreaks is a challenging problem. Most of the dengue fever cases are benign, but some cases develop into a severe and possibly lethal vasculopathy, known as dengue hemorrhagic fever. Early symptoms of dengue and hemorrhagic fever are very similar. An early differential diagnosis is needed to predict which of these two clinical presentations is crucial to proper patient care and public health management. This study evaluates the predictive potential of specific mRNA expression markers of dengue hemorrhagic fever using quantitative real-time PCR assays. Six candidate "dengue hemorrhagic fever specific signature genes" were evaluated and all showed good correlation among their transcription levels at early days of infection and the later development of severe vasculopathy. The markers selected were able to indicate, at early stages of infection, the evolution of a dengue-infected patient to the severe form of the illness. Despite the fact that these results grant further validation studies, the panel of candidate prognostic markers obtained demonstrated the potential to be useful for clinical use in the form of a fast assay based in blood samples.

O manejo de pacientes infectados pelo dengue ainda é um problema desafiador. A maioria dos casos de dengue é benigna mas parte desses casos pode evoluir para o desenvolvimento de vasculopatia severa conhecida como dengue hemorrágica, que pode ser letal. Os sintomas iniciais da dengue e sua forma hemorrágica são bastante similares. O desenvolvimento de um teste diagnóstico que seja rápido e capaz de diferenciar as duas formas clínicas da dengue é crucial para o cuidado adequado de pacientes. O presente estudo avalia, através da PCR quantitativa em tempo real, o potencial preditivo dos níveis de expressão de RNAm candidatos a marcadores da dengue hemorrágica, previamente identificados por estudos genômicos funcionais. Um conjunto de seis marcadores moleculares para a dengue hemorrágica foi avaliado e apresentou correlação entre seus níveis de transcrição e o posterior desenvolvimento da vasculopatia severa. Os marcadores selecionados foram capazes de indicar, nos momentos iniciais dos sintomas, a evolução de um paciente infectado pelo dengue para a forma severa da doença. O painel de candidatos a marcadores de prognóstico obtido demonstrou um bom potencial para uso clínico na forma de um ensaios rápido baseado em amostras de sangue.

Dengue em criança: aspectos clínicos e epidemiológicos, Manaus, Estado do Amazonas, no período de 2006 e 2007 / Dengue in children: clinical and epidemiological characteristics, Manaus, State of Amazonas, 2006 and 2007

O objetivo deste trabalho é apresentar os aspectos clínicos e epidemiológicos das crianças acometidas por dengue, em Manaus, AM, no período de 2006 a 2007. Foram analisados 482 casos de dengue confirmados laboratorialmente, em 2006, sendo 46,9 por cento nos menores de 15 anos, e 1.538 casos, em 2007, sendo 57,7 por cento nos menores de 15 anos. Os dados foram obtidos do Sistema Nacional de Agravos de Notificação (SINAN) de Manaus. As variáveis analisadas foram: idade, gênero, bairro de residência, mês do inicio dos sintomas, sorotipo e forma clínica da doença. Verificou-se um aumento estatisticamente significativo da proporção de casos em menores de 15 anos, bem como das formas graves entre 2006 e 2007. Apesar de a forma hemorrágica ter sido quase três vezes mais freqüente em 2007, houve uma redução do coeficiente de letalidade. Os sorotipos identificados foram DEN-3 em 2006 e DEN-1, DEN-2 e DEN-3 em 2007. Em 2007, houve registro de casos em todos os meses do ano.

This study presents the clinical and epidemiological aspects of children affected with dengue, in Manaus, AM, in 2006 and 2007. There were 482 The aim of this study was to present the clinical and epidemiological characteristics of children affected by dengue, in Manaus, State of Amazonas, in 2006 and 2007. Analysis was conducted on 482 dengue cases with confirmation from laboratory tests, in 2006 (46.9 percent in children under 15 years of age), and 1,538 cases in 2007 (57.7 percent in children under 15 years of age). The data were obtained from the National System for Notifiable Diseases (Sistema Nacional de Agravos de Notificação; SINAN) in Manaus. The variables analyzed were: age, gender, district where subject lived, month when symptoms started, serotypes and clinical form of the disease. Statistically significant increases in the proportion of cases in children under 15 years of age and in the proportion of severe forms were found between 2006 and 2007. Although the hemorrhagic form was almost three times more frequent in 2007, the mortality rate was lower. The serotypes identified were DEN-3 in 2006 and DEN-1, DEN-2 and DEN-3 in 2007. In 2007, cases were recorded in every month of the year.

Es la prueba del lazo un buen predictor de complicaciones hemorrágicas en pacientes con dengue? / Is the test of the tie a good predictor of hemorragic complication in patients with dengue?

Introducción: El dengue es una enfermedad que puede cursar con complicaciones hemorragicas. La prueba del lazo es un método recomendado como criterio diagnóstico de Fiebre Hemorrágica Dengue. Objetivos: Describir las manifestaciones hemorrágicas más frecuentes, hallar la sensibilidad y especificidad de la prueba del lazo, en relación al recuento de plaquetas y a la presencia de manifestaciones hemorrágicas espontáneas. Metodología: diseño observacional descriptivo, retrospectivo, de corte transverso, con componentes analíticos. Población de estudio: se estudiaron 245 pacientes, 170 mujeres (69%) y 75 varones (31%), con cuadro clínico compatible con dengue, que consultaron entre diciembre 2006 abril 2007 en el Hospital Nacional. Muestreo: no probabilístico, de casos consecutivos. Resultados:Las manifestaciones hemorrágicas espontáneas más frecuentes fueron las petequias 18 casos (7,3 %) , gingivorrágias 14 casos (5,7%) y epistaxis 11 casos (4,5 %) La sensibilidad y especificidad de la prueba del lazo, en relación con el recuento de plaquetas , fue del 27,7% y 84,5%. La prueba del lazo, en relación a la presencia de manifestaciones hemorrágicas, presentó una sensibilidad del 30,7% y especificidad del 85,4%. Conclusiones: La prueba del lazo no fue un buen método predictor de aparición de manifestaciones hemorrágicas por su baja sensibilidad. Sin embargo, cunado está ausente, ungran porcentaje de los pacientes no presentaron manifestaciones hemorrágicas, lo que dió una alta espeficidad...

Aedes aegypti, Aedes albopictus, and dengue in Argentina: current knowledge and future directions

Since the reinfestation of South American countries by Ae. aegypti, dengue fever (DF) and dengue hemorrhagic fever (DHF) have become a major public health concern. The aim of this paper was to review the information related with Aedes vectors and dengue in Argentina since the reintroduction of Ae. aegypti in 1986. The geographic distribution of Ae. albopictus is restricted to the Northeast, and that of Ae. aegypti has expanded towards the South and the West in comparison with the records during the eradication campaign in the 1960s. Since 1998, 4,718 DF cases have been reported concentrated in the provinces of Salta, Formosa, Misiones, Jujuy and Corrientes. Despite the circulation of three dengue virus serotypes (DENV-1, -2 and -3) in the North of the country, DHF has not occurred until the present. The information published over the last two decades regarding mosquito abundance, temporal variations, habitat characteristics, competition, and chemical and biological control, was reviewed. Considering the available information, issues pending in Argentina are discussed. The presence of three DENV, the potential spread of Ae. albopictus, and the predicted climate change suggest that dengue situation will get worse in the region. Research efforts should be increased in the Northern provinces, where DHF is currently an actual risk.

Aminotransferasas séricas en pacientes con Dengue tipo 3 / Aminotransferases serum levels in patients with Dengue type 3

Background: Dengue infections may affect the liver, causing inflammation and compromising its function. Aim: To determine serum aminotransferases in patients with Dengue. Material and methods: One hundred eighty four patients with Dengue confirmed with anti-Dengue IgG and IgM antibodies measured by ELISA, aged 1 month to 79 years, were studied. As controls, 40 patients with acute hepatitis B virus infection aged 11 to 59 years and 40 healthy individuals, aged 14 to 55 years, were also studied. Alanine and aspartate aminotransferases (ALT and AST) were determined using a colorimetric method. Results: Sixty one percent of patients with Dengue had elevated aminotransferase levels. In patients with Dengue and hepatitis B, mean ALT levels were 21.3±8.4 and 29.7±18.8 U/I, respectively. Mean AST values were 37.3±19, 19.6± 16.4 and 4.3±1.7 U/I in patients with Dengue, hepatitis B and controls, respectively. During the year 2001, there was an increase in the number of cases with hemorrhagic fever caused by Dengue and 65 percent had elevation of aminotransferases. Conclusions: An increase in aminotransf erase levels is common in patients with Dengue.

Serotipo, Patrón de Infección y Dengue Hemorrágico en Area Endémica Colombiana / Dengue hemorrhagic fever serotype and infection pattern in a Colombian endemic area

Objetivo: La relación entre serotipo del virus, patrón de infección y dengue hemorrágico es presentada. Métodos: Se estudiaron 1 545 pacientes febriles de municipios del Departamento de Santander, Colombia, entre 1998-2004. El dengue se confirmó por ELISA-IgM y el aislamiento viral se hizo en células C6/36. El patrón de infección se estableció investigando anticuerpos IgG en suero agudo. El título de anticuerpos neutralizantes se determinó usando la prueba de neutralización por reducción de placa (PRNT). Resultados: Predominancia del DEN-1 en 1998 y re-introducción del DEN-3 en 2001 coincidieron con epidemias. El dengue hemorrágico fue más frecuente en infecciones por virus DEN-2 que DEN-3 (24,5 por ciento vs 11,2 por ciento; p<0,05). El DEN-2 se asoció más con infección secundaria que el DEN-3 (56,8 por ciento vs 15,7 por ciento; p< 0,001). Disminución anual del DH correlacionó con disminución de la dominancia del DEN-2 (r = 0,95, p=0,01) y de la infección secundaria (r=0,9; p=0,03) e incremento de la dominancia del DEN-3 (r=-0,91; p=0,03). No se encontraron diferencias en el título de anticuerpos neutralizantes en los casos analizados. Los anticuerpos neutralizantes del DEN-1 fueron los de mayor título. Conclusión: Cambios en la abundancia relativa de serotipos del virus se asociaron con cambios en el patrón de infección y frecuencia del dengue hemorrágico. La vigilancia virológica permanente deberá ser prioridad para la prevención del dengue hemorrágico en áreas endémicas.

Objective: Describing the relationship between viral serotypes, infection pattern and dengue hemorrhagic fever. Methods: 1 545 febrile patients were studied from 1998-2004 in the Santander department of Colombia. Dengue infection was confirmed by IgM ELISA and the virus was isolated in C6/36 cells. Infection pattern was established by detecting IgG antibodies in acute serum. Neutralising antibody titres were investigated in dengue cases occurring during years when less (1998) and more (2001) dengue hemorrhagic cases were reported by using PRNT. Results: DEN-1 predominance in 1998 and the re-introduction of DEN-3 in 2001 coincided with an epidemic. DEN-2 infection caused more hemorrhagic cases than DEN-3 infection (24,5 percent cf 11,2 percent; p<0.05). DEN-2 was more associated with secondary infection than DEN-3 (56,8 percent cf 15,7 percent; p<0.001). An annual decrease of DHF was correlated with decreased DEN-2 dominance (r=0.95; p= 0.01), and secondary infection (r=0.9; p=0.03) and increased DEN-3 predominance (r=-0.91; p=0.03). There were no differences in neutralising antibody titres amongst analysed cases. DEN-1 neutralising antibodies presented the highest titres. Conclusions: Change in relative dengue virus serotype abundance was associated with changed infection pattern and DHF frequency. Continuing virological surveillance should become a priority for preventing dengue hemorrhagic fever in endemic areas.

Temporal distribution of dengue virus serotypes in Colombian endemic area and dengue incidence: re-introduction of dengue-3 associated to mild febrile illness and primary infection

We have investigated the temporal distribution of dengue (DEN) virus serotypes in the department (state) of Santander, Colombia, in relation to dengue incidence, infection pattern, and severity of disease. Viral isolation was attended on a total of 1452 acute serum samples collected each week from 1998 to 2004. The infection pattern was evaluated in 596 laboratory-positive dengue cases using an IgG ELISA, and PRNT test. The dengue incidence was documented by the local health authority. Predominance of DEN-1 in 1998 and DEN-3 re-introduction and predominance in 2001-2003 coincided with outbreaks. Predominance of DEN-2 in 2000-2001 coincided with more dengue hemorrhagic fever (DHF). DEN-4 was isolated in 2000-2001 and 2004 but was not predominant. There was an annual increase of primary dengue infections (from 13.7 to 81.4 percent) that correlated with frequency of DEN-3 (r = 0.83; P = 0.038). From the total number of primary dengue infections DEN-3 (81.3 percent) was the most frequent serotype. DHF was more frequent in DEN-2 infected patients than in DEN-3 infected patients: 27.5 vs 10.9 percent (P < 0.05). DEN-3 viruses belonged to subtype C (restriction site-specific-polymerase chain reaction) like viruses isolated in Sri-Lanka and other countries in the Americas. Our findings show the importance of continuous virological surveillance to identify the risk factors of dengue epidemics and severity.

Complete genetic characterization of a Brazilian dengue virus type 3 strain isolated from a fatal outcome

We have determined the complete nucleotide and the deduced amino acid sequences of Brazilian dengue virus type 3 (DENV-3) from a dengue case with fatal outcome, which occurred during an epidemic in the state of Rio de Janeiro, Brazil, in 2002. This constitutes the first complete genetic characterization of a Brazilian DENV-3 strain since its introduction into the country in 2001. DENV-3 was responsible for the most severe dengue epidemic in the state, based on the highest number of reported cases and on the severity of clinical manifestations and deaths reported.

El dengue y el dengue hemorrágico: prioridades de investigación / Dengue and dengue hemorrhagic fever: research priorities

Dengue is one of the most important infectious diseases in tropical and subtropical countries. At present, the only strategy available to reduce the incidence of dengue is vector control. The World Health Organization and the Pan American Health Organization have called on all nations to take the needed steps to help diminish the burden of this disease and its medical and socioeconomic impact. It is hoped that it will be possible to reverse the increase in dengue and help control its spread through a coordinated, effective international response, along with epidemiological, clinical, and virological research that brings together the most advanced methods and techniques. This piece summarizes the most up-to-date information on dengue, analyzes current epidemiologic trends in the Region of the Americas, discusses the main global and Western Hemisphere initiatives to control the disease, and presents the main areas of research that should be developed in the immediate future.

Aspectos clínicos e epidemiológicos da epidemia de dengue no Recife, PE, em 2002 / Clinical and epidemiological aspects of the dengue epidemic in Recife, PE, 2002

Este estudo mostra os dados da epidemia de dengue e febre hemorrágica da dengue ocorrida na Cidade do Recife no ano de 2002 e as características clínicas, laboratoriais e de necropsia dos 14 casos de óbito por dengue. Foram notificados 35.597 casos, dos quais 208 foram febre hemorrágica da dengue e 14 evoluíram para óbito. O sorotipo Den-3 ocorreu em 76,3 por cento dos casos. A maioria dos óbitos ocorreu entre homens com mais de 20 anos, no 11º dia da doenca, assistidos nos hospitais privados. Os valores médios do hematócrito e das plaquetas foram 40,7 por cento e 56.313p/mm , respectivamente. A hepatite, com níveis elevados de transaminases, ocorreu na maioria dos pacientes, que geralmente encontravam-se anictéricos. Dos quatorze casos, 13 tiveram confirmacão laboratorial. Em oito casos o óbito decorreu de fenômenos hemorrágicos, entretanto, nos outros seis casos não foram identificados sangramentos significativos. O choque, decorrente do extravasamento vascular, associado ou não a sangramentos significativos, esteve presente em 12 (85,7 por cento) casos, sendo portanto a principal causa de óbito nos casos graves de dengue.

Pathologic study of a fatal case of dengue-3 virus infection in Rio de Janeiro, Brazil

Dengue hemorrhagic fever (DHF) is a severe febrile disease, characterized by abnormalities in hemostasis and increased vascular permeability, which in some cases results in hypovolemic shock syndrome and in dengue shock syndrome. The clinical features of DHF include plasma leakage, bleeding tendency and liver involvement. We studied the histopathological features of a fatal case of dengue-3 virus infection. The patient, a 63-year old male, presented with an acute onset of severe headache, myalgia and maculopapular rash. Tissue fragments (liver, spleen, lung, heart, kidney and lymph nodes) were collected for light microscopy studies and stained by standard methods. Histopathology revealed severe tissue damage, caused by intense hemorrhage, interstitial edema and inflammation. Some tissue sections were also processed with the immunoperoxidase reaction, which revealed the dengue viral antigen. Dengue-3 virus was isolated and identified with electron microscopy in a C6/36 cell culture inoculated with the patient's serum. Viral particles were detected in the infected cell culture.

Servicios centinelas en la vigilancia epidemiologica del Dengue en Santa Cruz de la Sierra - Bolivia / Services sentries in the epidemic surveillance of the Fastidiousness in Santa Cruz of the Sierra - Bolivia

El Dengue en Santa Cruz-Bolivia esta adquiriendo cada vez mayor importancia, por diversos factores: a) reinfestacion del vector Aedes aegypti a niveles mas alla de los establecidos por la OMS. b) circulacion de serotipos Den-1 y Den-2 y riesgo de ingreso del Den 3 y c) deteccion de cuadros clinicos compatibles con Dengue Hemorragico. Para prevenir la aparicion de brotes epidemicos, se establecio en Santa Cruz de la Sierra un sistema de vigilancia, cuyos principales componentes eran el epidemiologico, el vectorial, y el laboratorial, los primeros a cargo de la Secretaria Dptal. de Salud y el ultimo a cargo de CENETROP; despues de evaluarse el mismo, se identifican problemas y surgen nuevas situaciones

Reacción en cadena de la polimerasa para la detección rápida y determinación del serotipo de virus del dengue en muestras clínicas / Polymerase chain reaction for rapid detection and serotyping of dengue viruses in clinical samples

El trabajo que aquí se presenta describe las ventajas de usar la reacción en cadena de la polimerasa con transcriptasa inversa (RCP-TI) para detectar e identificar con rapidez virus del dengue en muestras clínicas. Se sometieron directamente a RCP-TI 27 muestras obtenidas de pacientes con fiebre de dengue y fiebre hemorrágica de dengue durante epidemias en Colombia, Nicaragua y Panamá. El ADN de cadena doble obtenido con la RCP-TI se identificó mediante una segunda amplificación (RCP de anidación) utilizando cebadores específicos para cada tipo de virus, aislamiento vírico e inmunofluorescencia indirecta (IFI) y con electroinmunoensayo enzimático detector de anticuerpos IgM contra el virus del dengue. El genoma vírico amplificado se detectó e identificó en un máximo de 8 horas. Los parámetros calculados para hacer el diagnóstico por RCP-TI, usando el aislamiento vírico y la IFI como estándar de oro, fueron una sensibilidad de 100%; una especificidad de 78%; un valor predictivo positivo de 69% y un valor predictivo negativo de 100%. Cabe notar que dos de los especímenes que dieron resultados positivos a la prueba de RCP-TI anidada y negativos al aislamiento vírico mostraron anticuerpos específicos de tipo IgM. Los resultados de la RCP-TI en general mostraron una estrecha concordancia con los del aislamiento vírico, lo cual sugiere que la RCP es un procedimiento que facilita enormemente el diagnóstico rápido y temprano del dengue.

This study describes the benefits of using reverse transcriptase polymerase chain reaction (RT-PCR) for the rapid detection and typing of dengue virus in clinical samples. Twenty-seven serum specimens from patients with dengue fever and dengue hemorrhagic fever in Colombia, Nicaragua, and Panama were directly subjected to RT-PCR for the detection of dengue virus. The resulting double-stranded DNA product was typed by a second round of PCR amplification (nested PCR) with type specific primers, viral culture/indirect immunofluorescence (IIF), and enzyme-linked electroimmunoassay for IgM anti-dengue antibodies. The amplified virus genome was detected and typed within 8 hours. Nested RT-PCR, using viral culture and IIF as the gold standard, showed 100% sensitivity; 78% specificity; 69% positive predictive value, and 100% negative predictive value. It is noteworthy that two of the specimens whose results were positive with nested RT-PCR and negative with viral culture showed specific IgM antibodies. The results of the RT-PCR were in close agreement with those obtained through viral culture. This suggests PCR can greatly facilitate the rapid and early diagnosis of dengue infection.