Risk Factors Associated with Dengue Transmission and Spatial Distribution of High Seroprevalence in Schoolchildren from the Urban Area of Medellin, Colombia.

Dengue fever is an increasing health problem in tropical and subtropical regions. During 2010 in Medellin, the younger population presented a particularly high dengue incidence rate. This study estimated dengue virus (DENV) transmission in schoolchildren (aged 5-19 years) in Medellin from 2010 to 2012. A longitudinal serological survey (IgG) and spatial analysis were conducted to determine the distribution of DENV seroprevalence. A total of 4,385 schoolchildren participated for at least one year. Dengue seroprevalence significantly increased during the studied period (53.8% to 64.6%; p < 0.001). A significantly higher seroconversion rate was observed in 2010-2011 (16.8%) compared to 2011-2012 (7.8%). Multivariate regression analysis showed that the main factor associated with the seroprevalence was the aging. Furthermore, in 2010, patients with high socioeconomic status presented a lower risk. Predominant multitypic and DENV4 monotypic antibody responses were demonstrated. Geostatistical analysis evidenced a temporal clustering distribution of DENV seroprevalence in 2010. Population density and Ae. aegypti House Index were significantly correlated with the observed pattern. This study revealed high DENV transmission in schoolchildren determined as "sentinel population." High DENV risk was found in districts with combined poorly socioeconomic conditions and densest human and mosquito populations. These findings may allow to target population for effective prevention and vaccination campaigns.

[Dengue infection: A common cause of febrile syndrome in patients from Quibdó, Chocó, Colombia]. / Infección por dengue: una causa frecuente de síndrome febril en pacientes de Quibdó, Chocó, Colombia.

INTRODUCTION: Quibdó, a municipality in Chocó, has poor public services and weather and social conditions that favor dengue transmission. However, there are few studies about this problem in this district. OBJECTIVE: To determine the frequency of dengue infection in patients with acute febrile syndrome and to compare clinical features among dengue infected patients with other febrile diseases. MATERIALS AND METHODS: A cross-sectional study was conducted from January, 2008, to March, 2010. The study population comprised patients with febrile syndrome of seven or fewer days of evolution, recruited from hospitals in the town. Dengue diagnosis was made in serum samples by detection of IgM antibodies, NS1 antigen, reverse transcription polymerase chain reaction, and virus isolation. Clinical and laboratory information from the patients was obtained. RESULTS: During the study period, 469 patients with acute febrile syndrome were recruited, of whom 98.3% were Afro-descendant. Dengue fever was found in 28.4% of the cases. Four dengue serotypes were identified with DENV-1 predominance. The ages ranged from zero to 76 years. From all patients, 70.7% of cases were classified as dengue without warning signs. Nausea, vomiting, abdominal pain, cough, nasal congestion and sore throat were significantly more frequent in patients with another febrile disease. CONCLUSIONS: Active surveillance of the acute febrile syndrome allowed for the detection of undiagnosed cases of dengue; the observed frequency of this infection suggests that the study area has a high risk of dengue infection.

Factores asociados a extravasación plasmática en pacientes con dengue de Antioquia y Chocó entre el 2000 y 2013. Colombia / Associated factors to plasma leakage in dengue patients from Antioquia and Chocó between 2000 and 2013. Colombia

Introducción: la extravasación del plasma es la manifestación más severa de la enfermedad producida por los virus del dengue y que con mayor frecuencia conduce al estado de choque. Se caracteriza por derrames serosos a nivel de diversas cavidades y aumento del hematocrito. Se realizó el presente estudio con el objetivo de determinar los factores sociodemográficos, clínicos y de laboratorio que más se asocian a la presencia de extravasación plasmática en los pacientes con dengue. Materiales y métodos: estudio observacional analítico transversal, analizado bajo la metodología de casos y controles, a partir de registros clínicos de pacientes con dengue. Se utilizaron prueba Chi cuadrado de Pearson, prueba exacta de Fisher, prueba no paramétrica U de Mann-Whitney y un modelo de regresión logística multivariado de factores asociados. Fueron calculados los Odds Ratio con su intervalo de confianza al 95 %. Se consideró un nivel de significancia de 5 %. Resultados: fueron analizados un total de 350 registros, de los cuales 128 presentaron signos de extravasación plasmática (36,6 %). Después de ajustar por factores de confusión se observó que las variables que más se asocian a presencia de extravasación plasmática en los pacientes con dengue fueron el dolor abdominal, la leucopenia y las melenas. Conclusión: estos hallazgos clínicos y de laboratorio deben ser priorizados en su vigilancia en la atención al paciente con dengue, para identificar los casos con mayor probabilidad de extravasación plasmática para su manejo oportuno y adecuado.

Introduction: Plasma leakage is the most severe complication caused by dengue virus infection and is also the mechanism that frequently leads to dengue shock syndrome. Plasma leakage is characterized by ascites, pleural and pericardial effusion and increased hematocrit level. The present study was conducted to identify socio-demographic, clinical and laboratory factors that more are associated to the presence of plasma leakage in dengue infected patients. Materials and methods: A cross sectional analytic study was performed on clinical records from dengue infected patients using the casecontrol methodology. Pearson's chi-square test or Fisher's exact test, Mann-Whitney's non-parametric U test and a multivariate logistic regression model of associated factors were used to evaluate the data. Odd Ratios with 95 % confidence intervals were calculated and significance level of 5 % was considered. Results: A total of 350 clinical records were analyzed, 128 cases (36.6 %) presented signs of plasma leakage. After adjustments by confounding factors, we observed that abdominal pain, leukopenia and melena were the variables that explain the presence of plasma leakage in dengue infected patients. Conclusion: During the follow-up of dengue infected patients priority should be given to the survey of these clinical and laboratory findings in order to identify the cases with higher probabilities of developing plasma leakage, allowing achieving more timely and appropriate management.

Frequency and clinical manifestations of dengue in urban medellin, Colombia.

A dengue fever surveillance study was conducted at three medical facilities located in the low-income district of San Javier in Medellin, Colombia. During March 2008 to 2009, 781 patients with fever regardless of chief complaint were recruited for acute dengue virus infection testing. Of the 781 tested, 73 (9.3%) were positive for dengue infection. Serotypes DENV-2 (77%) and -3 (23%) were detected by PCR. One patient met the diagnostic criteria for dengue hemorrhagic fever. Only 3 out of 73 (4.1%) febrile subjects testing positive for dengue infection were diagnosed with dengue fever by the treating physician. This study confirms dengue virus as an important cause of acute febrile illness in Medellin, Colombia, but it is difficult to diagnose without dengue diagnostic testing.

Frequency and clinical features of dengue infection in a schoolchildren cohort from medellin, Colombia.

To determine the incidence of dengue infection, we established active surveillance of febrile episodes in a cohort of schoolchildren from three schools in Medellin, Colombia. We followed a cohort of 2,379 schoolchildren in 2010 and followed 1,840 of these children the following year. During the follow-up time, 264 schoolchildren displayed 297 febrile episodes; of these, 23 episodes (7.7%) were caused by acute dengue infection. All four dengue serotypes were found, and all of the cases were mild. The most common symptoms in the dengue cases compared with those in other febrile illness were asthenia (96% versus 87%), anorexia (78% versus 57%), rhinorrhea (65.2% versus 58%), abdominal pain (56.5% versus 47.8%), arthralgia (43% versus 33%), and positive tourniquet test (13% versus 3%). This difference was not statistically significant. Pulse was elevated, and systolic arterial pressure was lower in dengue cases compared with other febrile illness (P < 0.05). Mosquito indexes were determined in 8 children's houses and in the schools. Aedes aegypti adults were found in both households and in schools, whereas Aedes aegypti larvae were found only in schools. These results showed an elevated dengue frequency in children, with symptoms similar to those of other febrile illness and transmission risk in households and schools.

Papel del dominio V1/V2 de la glucoproteína 120 del virus de la inmunodeficiencia humana de tipo 1 en la inducción de anticuerpos neutralizantes / Role of the HIV-1 V1/V2 domains in the induction of neutralizing antibodies

El desarrollo de una vacuna preventiva contra el virus de la inmunodeficiencia humana de tipo 1 (VIH-1) es una de las mayores esperanzas para el control de la pandemia en los próximos años. Sin embargo, es claro que una de las mayores dificultades de una vacuna contra el virus es su alta tasa de mutación, lo que le permite evadir la respuesta inmune del húesped. La producción de anticuerpos neutralizantes (AcN) contra la envoltura vírica parece tener un papel importante en el control de la infección y en la ejecución de una protección eficaz luego de la inmunización. Diversos trabajos han mostrado que el dominio V1/V2 de la glucoproteína 120 del VIH-1 se encuentra involucrado en el tropismo vírico durante la infección, en el enmascaramiento de epítopes neutralizantes conservados, en los cambios conformacionales tras la unión a los correceptores y en la inducción de AcN. Sin embargo, hay pocos estudios enfocados sobre este dominio. Por otra parte, por ser uno de los dominios altamente glucosilados, numerosos estudios han determinado la influencia de los hidratos de carbono sobre la producción de AcN. Por tanto, la presente revisión está enfocada en la importancia de los AcN dirigidos contra epítopes de las regiones variables (principalmente V1/V2), su importancia en la protección contra la infección por el VIH-1, el papel que desempeñan esas regiones en la evasión de la respuesta inmune y, finalmente, se discute la importancia de los AcN en la búsqueda de una vacuna eficaz contra el virus (AU)

The development of a preventive vaccine against human immunodeficiency virus type-1 (HIV-1) provides hope for control of the pandemic over the coming years. Nevertheless, it is clear that one of the greatest difficulties in achieving this vaccine is the high mutation rate of the virus, which enables it to evade the host's immune response. The production of neutralizing antibodies (NAb) against the HIV-1 envelope proteins is believed to play an important role in controlling the infection and in providing effective protection following vaccination. Several studies have shown that the V1/V2 domain of the HIV-1 gp120 envelope protein is involved in viral tropism during infection, in masking conserved neutralizing epitopes, in the conformational changes occurring after coreceptor binding, and in NAb induction. Nonetheless, this domain has been poorly investigated. However, because the V1/V2 domain is highly glycosylated, numerous studies have determined the influence of carbohydrates on NAb production. The present review focuses on the importance of NAb directed against epitopes of the variable regions, mainly V1/V2, their importance in protecting against HIV-1 infection, and the role these regions play in evading the immune response. Lastly, we will discuss the importance of NAb in the search for an effective vaccine against HIV-1 (AU)

Neutralizing inter-clade cross-reactivity of HIV-1 V1/V2-specific secretory immunoglobulin A in Colombian and French cohorts.

Neutralizing activity of secretory immunoglobulin A (S-IgA) directed against the V1/V2 domain of HIV-1 was studied in parotid saliva of HIV-1- infected patients in Colombian and French cohorts. Purified V1/V2-specific S-IgA antibodies were found to neutralize clades A, B and C primary isolates in five out 76 and 82 patients from each cohort, respectively. These results suggest that neutralizing S-IgA antibodies targeting the V1/V2 domain may provide protection against HIV-1 infection in vivo and may be beneficial in mucosal vaccines.

[Role of the HIV-1 gp120 V1/V2 domains in the induction of neutralizing antibodies]. / Papel del dominio V1/V2 de la glucoproteína 120 del virus de la inmunodeficiencia humana de tipo 1 en la inducción de anticuerpos neutralizantes.

The development of a preventive vaccine against human immunodeficiency virus type-1 (HIV-1) provides hope for control of the pandemic over the coming years. Nevertheless, it is clear that one of the greatest difficulties in achieving this vaccine is the high mutation rate of the virus, which enables it to evade the host's immune response. The production of neutralizing antibodies (NAb) against the HIV-1 envelope proteins is believed to play an important role in controlling the infection and in providing effective protection following vaccination. Several studies have shown that the V1/V2 domain of the HIV-1 gp120 envelope protein is involved in viral tropism during infection, in masking conserved neutralizing epitopes, in the conformational changes occurring after coreceptor binding, and in NAb induction. Nonetheless, this domain has been poorly investigated. However, because the V1/V2 domain is highly glycosylated, numerous studies have determined the influence of carbohydrates on NAb production. The present review focuses on the importance of NAb directed against epitopes of the variable regions, mainly V1/V2, their importance in protecting against HIV-1 infection, and the role these regions play in evading the immune response. Lastly, we will discuss the importance of NAb in the search for an effective vaccine against HIV-1.

Las células dendríticas en la infección por el VIH-1 / Dendritic cells during the HIV-1 infection

Las células dendríticas son un componente de la inmunidad innata que cumple con la función crucial de activar los linfocitos T vírgenes. Son una de las células blanco de la infección por el VIH-1, aunque la replicación de este virus en las células dendríticas es muy inferior a la observada en los linfocitos T CD4+. Sin embargo, las células dendríticas almacenan viriones por largo tiempo, para transmitirlos después a otras células susceptibles, y se convierten en uno de los reservorios más importantes del VIH-1. Durante esta infección, las células dendríticas hacen parte inicialmente de la respuesta inmune contra el VIH-1, pero luego exhiben alteraciones cuantitativas y funcionales que potencian la inmunodeficiencia característica de esa infección. El papel que cumplen las células dendríticas en la inducción de la respuesta inmune innata y adaptativa indica que tienen un potencial terapéutico interesante en el desarrollo de vacunas e inmunoterapia para la infección por el VIH-1.

Dendritic cells are components of the innate immunity crucial for activating naïve T cells. They are one of the target cells for HIV-1 infection, but their ability to replicate HIV-1 is much more limited than that exhibited by CD4+ T cells. However, they have the capacity to store the virus for long periods of time which are able to infect susceptible cells later on. Therefore, dendritic cells are considered as one of the most important reservoirs for the HIV-1. At early stages of this infection, dendritic cells also contribute with the anti-HIV-1 immune response, but then they exhibit quantitative and functional alterations enhancing the severe immunodeficiency characteristic of this infection. The important role of dendritic cells in inducing innate and adaptive immune responses indicates that these cells have a promising therapeutic potential for the development of vaccines and immunotherapy for HIV-1 infection.