[Epidemiology of dengue in Central America and the Dominican Republic]. / Epidemiología del dengue en Centroamérica y República Dominicana.

BACKGROUND: Central America experiences a high burden of dengue reporting about 8% of all cases in the continent. This work reports the epidemiology of dengue in the sub region in a 10 years period. AIM: To describe the epidemiology of dengue in Central America and the Dominican Republic. METHODS: Study period from 2005 to 2014. The data on dengue cases and deaths of the countries of Central America and the Dominican Republic, reported by the Ministries of Health, were compiled and analyzed and corroborated with the data published in the online bulletins and the interactive database of the Pan American Health Organization (PAHO). Population statistics were obtained from the National Statistics and Census Institutes of each country. RESULTS: During the study period, 1,118,464 cases of dengue were notified. There were 32,431 serious cases reported, 888 people died. The lethality per case of dengue was on average 0.08%. The four dengue serotypes circulated during the decade analyzed. DISCUSSION: Clinical and epidemiological information indicates high incidence rates, which have fluctuated in recent years, with significant co-circulation of several serotypes at the same time. CONCLUSIONS: Notorious surveillance data collection differences were identified between countries, determining a heterologous epidemiological pattern.

Evaluation of immunological markers in serum, filter-paper blood spots, and saliva for dengue diagnosis and epidemiological studies.

BACKGROUND: Numerous immunological approaches exist to diagnose dengue or detect dengue virus (DENV) infections. OBJECTIVES: To determine the best immunological markers and specimen types for dengue diagnosis and for measuring incidence of DENV infection in community-based studies. STUDY DESIGN: In one study, acute- and convalescent-phase samples were collected from hospitalized suspected pediatric dengue cases in Managua, Nicaragua, from September 2003 to February 2004. A second study examined specimens collected in a community setting in Managua before and after the 2003-2004 dengue season to measure incidence of DENV infection. In both studies, detection of anti-DENV IgM, IgA, and IgG in serum, filter-paper blood spots, and saliva was compared to a gold standard performed on serum samples. RESULTS: For dengue diagnosis, the highest sensitivity and specificity was obtained by measuring IgM or IgA in serum or filter-paper blood spots; intermediate and poor results were obtained in saliva for IgM and IgA, respectively. Detection of IgG alone in serum, filter-paper blood spots, or saliva functioned best for measuring DENV infection. CONCLUSIONS: Detection of IgM and IgA in serum and filter-paper blood spots yielded optimal results for diagnosis of dengue cases, whereas IgG was the best marker for measuring incidence of DENV infection.

Ultrasound measurement of gallbladder wall thickening as a diagnostic test and prognostic indicator for severe dengue in pediatric patients.

Gallbladder wall thickening measured by ultrasound was significantly associated with severe dengue, as well as with hallmark features of thrombocytopenia and elevated hematocrit/hemoconcentration, in children with suspected dengue in Nicaragua. We demonstrate that gallbladder wall thickening serves as a clinically relevant diagnostic test and prognostic indicator of severe dengue in pediatric populations.

Serotype-specific differences in clinical manifestations of dengue.

Dengue, the most prevalent arthropod-borne viral disease of humans, is caused by four serotypes of dengue virus (DENV 1-4). Although all four DENV serotypes cause a range of illness, defining precisely which clinical characteristics are associated with the distinct serotypes has been elusive. A cross-sectional study was conducted on 984 and 313 hospitalized children with confirmed DENV infections during two time periods, respectively, in the same hospitals in Nicaragua: a 3-year period (1999-2001) when DENV-2 accounted for 96% of the viruses identified, and the 2003 dengue season when DENV-1 predominated (87% of identified serotypes). When the two periods were compared, more shock (OR 1.91, 95% CI 1.35-2.71) and internal hemorrhage (OR 2.05, CI 1.16-3.78) were observed in the period when DENV-2 predominated, whereas increased vascular permeability was associated to a greater degree with the DENV-1 period (OR 2.36, CI 1.80-3.09). Compared with the DENV-2 period, the DENV-1 season was associated with more hospitalized primary dengue cases (OR 3.86, CI 2.72-5.48) and more primary DENV infections with severe manifestations (OR 2.93, CI 2.00-4.28). These findings provide new data to characterize the pathogenic potential of distinct DENV serotypes in human populations.

Epidemiología del dengue en Centroamérica y República Dominicana / Epidemiology of dengue in Central America and the Dominican Republic

Resumen Introducción: Centroamérica experimenta una alta carga de la enfermedad por dengue aportando cerca de 8% de todos los casos del continente. Este trabajo reporta la epidemiología del dengue en la subregión en un período de 10 años. Objetivos: Documentar la epidemiología del dengue en Centro América y República Dominicana. Material y Métodos: Período de estudio: años 2005-2014. Se recopilaron y analizaron los datos de casos y muertes por dengue de los países de Centro América y República Dominicana, reportados por los Ministerios de Salud y se corroboró con los datos publicados en los boletines en línea y la base de datos interactiva de la Organización Panamericana de la Salud (OPS). Se obtuvieron estadísticas poblacionales de los Institutos Nacionales de Estadística y Censo de cada país. Resultados: Durante el período de estudio fueron notificados 1.118.464 casos de dengue. Reportados 32.431 casos graves, 888 personas fallecidas. La letalidad por caso de dengue fue en promedio 0,08%. Los cuatro serotipos de dengue circularon durante el decenio estudiado. Discusión: La información clínica y epidemiológica, indica tasas de incidencia alta, que han fluctuado en los últimos años, con co-circulación significativa de varios serotipos a la vez. Conclusiones: Se identificaron diferencias notorias en la recolección de datos de la vigilancia entre países. Se determinó un patrón epidemiológico heterogéneo.

Background: Central America experiences a high burden of dengue reporting about 8% of all cases in the continent. This work reports the epidemiology of dengue in the sub region in a 10 years period. Aim: To describe the epidemiology of dengue in Central America and the Dominican Republic. Methods: Study period from 2005 to 2014. The data on dengue cases and deaths of the countries of Central America and the Dominican Republic, reported by the Ministries of Health, were compiled and analyzed and corroborated with the data published in the online bulletins and the interactive database of the Pan American Health Organization (PAHO). Population statistics were obtained from the National Statistics and Census Institutes of each country. Results: During the study period, 1,118,464 cases of dengue were notified. There were 32,431 serious cases reported, 888 people died. The lethality per case of dengue was on average 0.08%. The four dengue serotypes circulated during the decade analyzed. Discussion: Clinical and epidemiological information indicates high incidence rates, which have fluctuated in recent years, with significant co-circulation of several serotypes at the same time. Conclusions: Notorious surveillance data collection differences were identified between countries, determining a heterologous epidemiological pattern.

Gene expression patterns of dengue virus-infected children from nicaragua reveal a distinct signature of increased metabolism.

BACKGROUND: Infection with dengue viruses (DENV) leads to a spectrum of disease outcomes. The pathophysiology of severe versus non-severe manifestations of DENV infection may be driven by host responses, which could be reflected in the transcriptional profiles of peripheral blood immune cells. METHODOLOGY/PRINCIPAL FINDINGS: We conducted genome-wide microarray analysis of whole blood RNA from 34 DENV-infected children in Nicaragua collected on days 3-6 of illness, with different disease manifestations. Gene expression analysis identified genes that are differentially regulated between clinical subgroups. The most striking transcriptional differences were observed between dengue patients with and without shock, especially in the expression of mitochondrial ribosomal proteins associated with protein biosynthesis. In the dengue hemorrhagic fever patients, one subset of differentially expressed genes encode neutrophil-derived anti-microbial peptides associated with innate immunity. By performing a meta-analysis of our dataset in conjunction with previously published datasets, we confirmed that DENV infection in vivo is associated with large changes to protein and nucleic acid metabolism. Additionally, whereas in vitro infection leads to an increased interferon signature, this was not consistently observed from in vivo patient samples, suggesting that the interferon response in vivo is relatively transient and was no longer observed by days 3-6 of illness. CONCLUSIONS/SIGNIFICANCE: These data highlight important differences between different manifestations of severity during DENV infection as well as identify some commonalities. Compilation of larger datasets in the future across multiple studies, as we have initiated in this report, may well lead to better prediction of disease manifestation via a systems biology approach.

Improvement in hospital indicators after changes in dengue case management in Nicaragua.

Dengue is a major problem worldwide, and improving case management is a significant priority. In consultation with colleagues in Thailand, changes in management of hospitalized dengue cases were introduced in Nicaragua, including oral rather than intravenous (IV) fluids upon admission, continuous monitoring of clinical and laboratory signs, and use of IV fluids principally during the critical phase and colloids in management of shock. Two periods were compared, before (2003) and after (2005) their implementation, to assess impact. In 2003, 182 hospitalized laboratory-confirmed dengue cases 0-14 years of age who presented < or = 5 days post-symptom onset were included in the study; 46 were enrolled in 2005. Outcomes included significant reductions in days of IV fluid administration ( P = 0.0001), number of patients receiving IV fluids ( P < 0.0001), and duration of hospitalization ( P < 0.0001), and a non-significant reduction in the number of admissions to the intensive care unit from 8 in 2003 to 0 in 2005 ( P = 0.36). This study demonstrates concrete gains in dengue patient care and case management.

Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever.

In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14(+), CD32(+), CD86(+), CD11c(+)). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis.

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America.

OBJECTIVES: In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPw-HB/Hib) vaccine containing 5 microg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. METHODS: We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. RESULTS: Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. CONCLUSIONS: Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

A new DTPw-HB/Hib combination vaccine for primary and booster vaccination of infants in Latin America / Nueva vacuna combinada DTPw-HB/Hib para la vacunación primaria y de refuerzo de menores de un año en América Latina

Objectives. In 1998 the World Health Organization (WHO) recommended the inclusion of Haemophilus influenza type B (Hib) conjugate vaccines in infant immunization programs, whenever in accordance with national priorities. GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib (DTPwHB/Hib) vaccine containing 5 µg of polyribosylribitol phosphate (PRP), and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB (Tritanrix) and Hib (Hiberix) vaccines given as simultaneous concomitant injections. Methods. We performed a randomized, double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine given as a single injection, compared with the reference regimen. Results. Both vaccination regimens elicited excellent immune responses, with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of ≥ 0.15 µg/mL one month after primary vaccination. The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components. Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups, and a marked increase of all antibody concentrations was observed after the booster dose. Both vaccine regimens were similar in terms of their overall reactogenicity profiles. Conclusions. Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis.

OBJETIVOS: En 1998, la Organización Mundial de la Salud (OMS) recomendó que se incluyeran vacunas conjugadas contra Haemophilus influenzae tipo B (Hib) en los programas de vacunación de niños menores de un año, siempre que ello estuviera en consonancia con las prioridades nacionales. La compañía GlaxoSmithKline Biologicals ha creado una nueva vacuna pentavalente que es una combinación de la vacuna contra la difteria (D), el tétanos (T) y la tos ferina (P) (con antígeno tosferínico a base de células completas) y las vacunas contra la hepatitis B (HB) y contra Haemophilus influenzae tipo B (Hib) (DTPw-HB/Hib), con un total de 5 µg de fosfato de polirribosilrribitol (FPR). Hemos evaluado la inmunogenia y reactogenia observadas al aplicarse las dosis primaria y de refuerzo de esta nueva vacuna a niños sanos y las hemos comparado con las observadas al aplicar un régimen de referencia a base de las vacunas autorizadas DTPw-HB (Tritanrix) y antiHib (Hiberix) en forma de inyecciones simultáneas. MÉTODOS: Llevamos a cabo un estudio aleatorizado y con doble enmascaramiento de septiembre de 1998 a agosto de 1999 para establecer la inmunogenia y reactogenia observadas al administrarles a niños sanos la nueva vacuna combinada pentavalente (DTPw-HB/Hib) en una sola inyección, y compararlas con las observadas con el régimen de referencia. RESULTADOS: Se obtuvieron excelentes respuestas inmunitarias con ambos regímenes. Todos los niños vacunados en ambos grupos alcanzaron concentraciones séricas protectoras de anticuerpos antiFPR > 0,15 µg un mes después de recibir la dosis primaria. La vacuna combinada DTPw-HB/Hib no dio resultados inferiores a los obtenidos con las vacunas autorizadas en términos de los porcentajes de seroprotección, seropositividad y respuesta frente a todos los componentes antigénicos de la vacuna. La persistencia de anticuerpos contra todos los antígenos contenidos en ella hasta el momento en que se administró la dosis de refuerzo fue parecida en ambos grupos, y se observó un marcado aumento de las concentraciones de todos los anticuerpos después del refuerzo. La reactogenia general observada con ambos regímenes de vacunación fue parecida. CONCLUSIONES: Nuestros resultados indican que la nueva vacuna combinada pentavalente DTPw-HB/Hib ofrece una manera eficiente y confiable de poner en práctica las recomendaciones de la OMS para el control de la hepatitis B y de las infecciones por Hib en el mundo entero.