Los arbovirus constituyen una de las principales causas de emergencia en salud por la morbilidad y mortalidad que producen y el estres sanitario que conllevan. Cuba no ha estado excenta de riesgo, y el enfrentamiento del dengue inicialmente y de otros arbovirus despues, ha sido, y es, una prioridad de las maximas autoridades del pais. La vigilancia de laboratorio de dengue se establecio desde inicios de la decada del 70 aunque sus objetivos y estrategias han cambiado segun la situacion epidemiologica nacional y regional y la tecnologia de diagnostico disponible. Se destacan cuatro etapas en su desarrollo. En este trabajo se resumen las estrategias desarrolladas para la vigilancia de laboratorio de dengue y de otros arbovirus en el periodo de 1970 a 2017. Se describe ademas el papel desempenado por el Instituto de Medicina Tropical, Pedro Kouri (IPK) como Laboratorio Nacional de Referencia.

Introduccion: Se considera una prioridad para el diseno de una vacuna eficaz y segura contra el dengue, distinguir entre una respuesta inmune protectora y una patogenica frente a la infeccion natural. Las citoquinas se han asociado a la patogenesis del cuadro grave, sin embargo, muchos de los resultados de estudios realizados en diferentes partes del mundo son contradictorios o no reproducibles. El objetivo del presente trabajo es seleccionar los modelos mas utiles para el estudio de las citoquinas en la patogenesis del dengue. Material y metodos: Se determinaron los niveles de citoquinas proinflamatorias y antiinflamatorias en muestras de sueros de pacientes de dengue y se midio la expresion genica de esos mediadores en tejidos de fallecidos por dengue. Ademas se cuantifico el ARNm de las citoquinas en celulas sanguineas cultivadas in vitro con virus dengue y se evaluo la asociacion de variantes alelicas de los genes de las citoquinas estudiadas con las formas clinicas de la infeccion por dengue. Resultados: Los estudios in vivo sugirieron una aparente asociacion de las citoquinas antiinflamatorias con la gravedad del cuadro clinico, mientras los experimentos in vitro y el estudio del polimorfismo de genes evidenciaron el papel de los mediadores proinflamatorios en la patogenia del dengue grave y la infeccion secundaria heterotipica. Conclusiones: Son necesarios distintos modelos con enfoques complementarios para discernir el papel de los mediadores de respuesta inmune en la patogenesis de la enfermedad por dengue. Estudios con modelos unicos pueden llevar a conclusiones erradas.

Dengue virus infection has emerged as one of the most important arthropod-borne viral diseases. Some dengue infected individuals develop the severe, life-threatening form of the disease, dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). Host genetic factors may be relevant and may predispose some individuals to the severe illness. Human leukocyte antigen (HLA), FcγR, tumor necrosis factor (TNF)–α, and dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), among others genes have been associated with the pathogenesis of dengue. Little is known, however, about the predictive value of cytokine genotypes for the clinical outcome of dengue infection. In this study, the TNF-α, interleukin (IL)–6, interferon (IFN)–γ, IL-10 and transforming growth factor (TGF)–β1 gene single nucleotide polymorphisms (SNP) were studied by polymerase chain reaction–sequence-specific primer in a group of individuals with the antecedent of DHF during a secondary infection in the sequence dengue 1/dengue 2. A control group was also included. TNF-α (−308) A allele and IL-10 (−1082/−819/−592) ACC/ATA haplotype were significantly associated with DHF. TNF-α (−308) GG and TGF-β1 (c25) GG genotypes were associated with protection. Our results suggest that genetic predisposition to a high TNF-α production and a low IL-10 production seems to increase the susceptibility to DHF during a secondary dengue 2 infection, whereas TGF-β1 high producers might be protected for developing DHF.

OBJECTIVE: to asses result of the actions aimed at control and eradication of a dengue outbreak in santiago de cuba in september 2001. METHODS: a descriptive retrospective crosssectional study was performed in order to describe the dengue outbreak and the actions aimed at control and eradication. RESULTS: this outbreak gave rise to 38 serologically confirmed cases as well as other 16 cases in other health areas. The implementation of rapid and effective actions as part of the anti-vector fight, the organized detection and management of cases as well as the community and central state bodies involvement made it possible to eradicate this outbreak in 45 days. CONCLUSIONS: the experiences accumulated in the anti-vector fight and the early use of residual action pesticide treatments were key elements for the control of this dengue

Dengue virus infection has emerged as one of the most important arthropod-borne diseases. In some dengue-infected individual, the disease progresses to its severe, life-threatening form, dengue hemorrhagic fever (DHF). Host genetic factors may be relevant and predispose some individuals to the severe dengue disease. The unique history of dengue outbreaks in Cuba is extremely advantageous for genetic studies of dengue disease resistance or susceptibility. Consequently, samples collected from 120 healthy individuals that developed dengue fever (DF) and DHF during the 1997 dengue 2 outbreak in the Santiago de Cuba municipality were HLA genotyped using polymerase chain reaction-sequence-specific primers. Polymorphism at the human leukocyte antigen (HLA) class I loci was significantly associated with DHF disease susceptibility, but polymorphism in the HLA-DRB1 was associated with protection. Amino acid peptides present in the poly-protein of the dengue 2 Jamaica strain, which are able to bind to the HLA class I and class II allotypes associated with susceptibility to or protection against the dengue clinical disease, respectively, were predicted using the BIMAS and SYFPEITHI predictive algorithms of peptide/MHC interaction.

Se diagnosticaron 3 012 casos, confirmados serologicamente, en una epidemia producida por el serotipo 2 del virus dengue en el municipio de Santiago de Cuba de la Republica de Cuba; 205 se clasificaron como casos de fiebre hemorragica de dengue (FHD) y 12 fallecieron. Se estimaron las afectaciones economicas incurridas durante la epidemia de dengue en este municipio y para ello se analizaron los costos por hospitalizacion y control clinico-terapeutico de los pacientes, lucha antivectorial y vigilancia de laboratorio. Se estimo un costo total de 10 251 539 USD, de los que 76 % se empleo en la lucha antivectorial y 18 % en costos hospitalarios. Se discutio el costo-beneficio de los programas de prevencion y control comparandolos con los costos necesarios para el control de la epidemia.

OBJECTIVE:Dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) is a growing global health problem. It is not known how age affects the outcome of secondary dengue infections. In an island setting, a large DHF/DSS outbreak in Cuba occurred in 1981. Involved were individuals, 3-40 year old, whose only lifetime dengue exposure was to DEN-1 in 1977 and DEN-2 in 1981. In this report we calculate age-specific DHF/DSS hospitalization and death rates based on secondary DEN 2 infections. METHODS:Published and unpublished hospital and seroepidemiologic data from the 1981 DHF/DSS outbreak were used for the analysis. RESULTS:Children, aged 3 and 4 years, with secondary DEN-2 infections were found to have a high death rate (25.4/10 000 secondary DEN-2 infections). The death rate fell with increasing age, being 15.9-fold lower in the 10-14-year age group. The death rate for children aged 3-14 years was 14.5-fold higher than in young adults aged 15-39 years. The death rate rose somewhat in adults aged 50 years and older. DHF/DSS hospitalization rates showed the same trend as death rates. CONCLUSIONS:Age is an important variable in the outcome of secondary DEN-2 infections. DHF/DSS case fatality and hospitalization rates are highest in young infants and the elderly. The risk that a child will die during a secondary DEN-2 infection is nearly 15-fold higher than the risk in adults.

Objective. To understand the possible effect that length of time has on disease severity with sequential dengue infections. Methods. Death and hospitalization rates for dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) per 10 000 secondary dengue-2 infections were compared in the same age group for two dengue-2 (DEN-2) epidemics in Cuba. The first DEN-2 epidemic affected all of Cuba in 1981; the second one, in 1997, impacted only the city of Santiago de Cuba. The sensitizing infection for DHF/DSS for each of the DEN-2 epidemics was dengue-1 (DEN-1) serotype virus, which was transmitted in 1977-1979, that is, 4 years and 20 years before the two DEN-2 epidemics. Using published seroepidemiological data from the cities of Havana and Santiago de Cuba, we estimated the rates at which persons aged 15-39 years old and those 40 years and older were hospitalized or died of DHF/DSS in Havana and in all of Cuba in 1981 and in just Santiago de Cuba in 1997. Results. Among adults 15-39 years old the death rate per 10 000 secondary DEN-2 infections was 38.5 times as high in Santiago de Cuba in 1997 as in Havana in 1981. As a further indication of the increased severity coming with a longer period between the initial DEN-1 infection and the secondary DEN-2 infection, the case fatality rate for that same age group was 4.7 times as high in Santiago in 1997 as it was in Havana in 1981. Conclusion. We found a marked increase in severity with the longer of the two intervals (20 years) between an initial DEN-1 infection and a secondary DEN-2 infection. Such a difference may be due to subtle shifts in causative dengue strains or to changes with the passage of time in the circulating population of human dengue antibodies. These observations have important implications for dengue control, pathogenic mechanisms, and vaccine development.

A dengue epidemic that Cuba reported in 1997 registered more than 500,000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344,203 clinical cases were reported, 10,312 of which were severe cases of hemorrhagic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3,012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called "fever alert" is not useful for early detection of an epidemic. Measures taken by the country's public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.

En 1977, Cuba informó de su primera epidemia de dengue, durante la cual se registraron más de 500 000 casos de fiebre del dengue causados por el serotipo 1 del virus. En 1981, se produjo una gran epidemia de dengue hemorrágico causada por el serotipo 2. Esa vez se notificaron 344 203 casos en total, 10 312 casos clínicos de dengue hemorrágico y 158 defunciones, de las cuales 101 correspondieron a niños. Por medio de una búsqueda activa con confirmación de laboratorio, en el municipio de Santiago de Cuba de la provincia del mismo nombre se detectó precozmente en enero de 1997 la reintroducción del dengue, específicamente del virus del tipo 2, genotipo Jamaica. En este trabajo se presentan los aspectos epidemiológicos de mayor interés referentes a esa epidemia. Se notificaron 3 012 casos confirmados por serología, 205 clasificados como fiebre hemorrágica del dengue/síndrome de choque del dengue, de los cuales 12 fallecieron (todos adultos). La infección secundaria por virus del dengue fue uno de los principales factores de riesgo en el desarrollo de dengue hemorrágico y 98% de los casos, así como 92% de los fallecidos, manifestaron una respuesta de tipo secundario. Por primera vez se observó la posibilidad de contraer dengue hemorrágico en personas con una infección secundaria de 16 a 20 años después de la primera infección. Pertenecer a la raza blanca fue otro factor de riesgo de importancia, tal como se había observado desde la epidemia de 1981. En la última epidemia se demostró que la llamada “alerta de fiebre” no es útil para la detección temprana de una epidemia. Las medidas tomadas por las autoridades sanitarias del país evitaron la extensión de la epidemia a otros municipios que estaban infestados por Aedes aegypti.A dengue epidemic that Cuba reported in 1997 registered more than 500 000 cases of dengue fever produced by viral serotype 1. In 1981, there was an epidemic of dengue hemorrhagic fever produced by serotype 2 of the virus. This time 344 203 clinical cases were reported, 10 312 of which were severe cases of hemorragic fever that led to 158 fatalities (101 of them among children). The reintroduction of dengue, and specifically of dengue viral serotype 2 (Jamaica genotype), was quickly detected in January 1997 through an active surveillance system with laboratory confirmation of cases in the municipality of Santiago de Cuba, in the province of the same name. The main epidemiological features of this outbreak are reported in this paper. A total of 3 012 cases were reported and serologically confirmed. These included 205 cases classified as dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), 12 of which were case fatalities (all among adults). Secondary infection with dengue virus was one of the most important risk factors for DHF/DSS. Ninety-eight percent of the DHF/DSS cases and 92% of the fatal cases had contracted a secondary infection. It was the first time dengue hemorrhagic fever was documented as a secondary infection 16 to 20 years after initial infection. Belonging to the white racial group was another important risk factor for DHF/DSS, as had been observed during the 1981 epidemic. During the most recent epidemic it was demonstrated that the so called “fever alert” is not useful for early detection of an epidemic. Measures taken by the country’s public health officials prevented spread of the epidemic to other municipalities plagued by Aedes aegypti.

A 1997 outbreak of dengue fever and dengue hemorrhagic fever in Santiago Cuba is described in detail. Epidemics of dengue in 1977 caused by serotype 1 and of hemorrhagic dengue in 1981 caused by serotype 2 led to implementation of control measures throughout Cuba. The province of Santiago eliminated the vector Aedes aegypti in 1987 and remained free until 1992. Deteriorating control measures allowed the vector slowly to extend its geographic distribution and density. An active program of epidemiological surveillance with laboratory confirmation led to the first or index case of the new outbreak in January 1997 caused by viral serotype 2 (Jamaican genotype). By the end of the outbreak a total of 17259 suspected cases were identified. Serological samples were obtained within 5-10 days of fever onset in 10024 cases. 3012 cases were confirmed at the reference laboratory including 205 cases of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) from which 12 patients died. The last case was reported in mid-November. 98% of the cases of DHF/DSS and 92% of the deaths were in patients who had contracted a secondary infection. This study for the first time documented DHF/DSS as a secondary infection 16-20 years after initial infection. As in the 1981 epidemic White racial background was a significant risk factor for DHF/DSS. Spread of the epidemic to other areas with A. aegypti vector populations was prevented by timely public health measures.

Objectives: After more than 15 years without dengue activity, a dengue II epidemic was reported in Cuba in 1997. Three thousand and twelve serologically confirmed cases were reported, with 205 dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) cases and 12 fatalities. This report presents the clinical, serologic, and virologic findings in the 12 fatal DHF/DSS cases.