Risk Factors for Mortality Among Children Younger Than Age 5 Years With Severe Diarrhea in Low- and Middle-income Countries: Findings From the World Health Organization-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks.

BACKGROUND: Diarrhea is the second leading cause of death in children younger than 5 years of age globally. The burden of diarrheal mortality is concentrated in low-resource settings. Little is known about the risk factors for childhood death from diarrheal disease in low- and middle-income countries. METHODS: Data from the World Health Organization (WHO)-coordinated Global Rotavirus and Pediatric Diarrhea Surveillance Networks, which are composed of active, sentinel, hospital-based surveillance sites, were analyzed to assess mortality in children <5 years of age who were hospitalized with diarrhea between 2008 and 2018. Case fatality risks were calculated, and multivariable logistic regression was performed to identify risk factors for mortality. RESULTS: This analysis comprises 234 781 cases, including 1219 deaths, across 57 countries. The overall case fatality risk was found to be 0.5%. Risk factors for death in the multivariable analysis included younger age (for <6 months compared with older ages, odds ratio [OR] = 3.54; 95% confidence interval [CI], 2.81-4.50), female sex (OR = 1.18; 95% CI, 1.06-1.81), presenting with persistent diarrhea (OR = 1.91; 95% CI, 1.01-3.25), no vomiting (OR = 1.13; 95% CI, .98-1.30), severe dehydration (OR = 3.79; 95% CI, 3.01-4.83), and being negative for rotavirus on an enzyme-linked immunosorbent assay test (OR = 2.29; 95% CI, 1.92-2.74). Cases from the African Region had the highest odds of death compared with other WHO regions (OR = 130.62 comparing the African Region with the European Region; 95% CI, 55.72-422.73), whereas cases from the European Region had the lowest odds of death. CONCLUSIONS: Our findings support known risk factors for childhood diarrheal mortality and highlight the need for interventions to address dehydration and rotavirus-negative diarrheal infections.

Update on Immunodeficiency-Associated Vaccine-Derived Polioviruses - Worldwide, July 2018-December 2019.

Since establishment of the Global Polio Eradication Initiative* in 1988, polio cases have declined >99.9% worldwide; extensive use of live, attenuated oral poliovirus vaccine (OPV) in routine childhood immunization programs and mass campaigns has led to eradication of two of the three wild poliovirus (WPV) serotypes (types 2 and 3) (1). Despite its safety record, OPV can lead to rare emergence of vaccine-derived polioviruses (VDPVs) when there is prolonged circulation or replication of the vaccine virus. In areas with inadequate OPV coverage, circulating VDPVs (cVDPVs) that have reverted to neurovirulence can cause outbreaks of paralytic polio (2). Immunodeficiency-associated VDPVs (iVDPVs) are isolated from persons with primary immunodeficiency (PID). Infection with iVDPV can progress to paralysis or death of patients with PID, and excretion risks seeding cVDPV outbreaks; both risks might be reduced through antiviral treatment, which is currently under development. This report updates previous reports and includes details of iVDPV cases detected during July 2018-December 2019 (3). During this time, 16 new iVDPV cases were reported from five countries (Argentina, Egypt, Iran, Philippines, and Tunisia). Alongside acute flaccid paralysis (AFP) surveillance (4), surveillance for poliovirus infections among patients with PID has identified an increased number of persons excreting iVDPVs (5). Expansion of PID surveillance will facilitate early detection and follow-up of iVDPV excretion among patients with PID to mitigate the risk for iVDPV spread. This will be critical to help identify all poliovirus excretors and thus achieve and maintain eradication of all polioviruses.

Adherencia y potenciales eventos adversos prevenidos durante la administración de medicamentos endovenosos empleando bombas de infusión inteligentes en cuatro unidades de cuidados intensivos en Colombia / Adherence and potential adverse events prevented during the administration of intravenous medications using Smart infusion pump in four intensive care units in Colombia

Resumen Introducción: Las bombas de infusión inteligentes, constituyen una herramienta útil para la administración segura de medicamentos endovenosos dado que permiten prevenir potenciales eventos adversos. Objetivo: Evaluar la adherencia y los potenciales eventos adversos prevenidos, durante la administración de medicamentos endovenosos empleando bombas de infusión inteligentes. Metodología: Estudio observacional, realizado en cuatro unidades de cuidados intensivos usando datos del software Hospira MedNetTM. Un análisis descriptivo fue llevado a cabo junto con un análisis bivariado empleando una prueba U de Mann-Whitney, una prueba de Kruskal-Wallis y un test de Bonferroni para evaluar la adherencia y los potenciales eventos adversos prevenidos por año y servicio. Resultados: La adherencia fue del 74,0%, se presentaron 78.299 alertas de seguridad y se previnieron 4,54% (n=16.288) potenciales eventos adversos. Se encontraron diferencias entre el primer y segundo año en la adherencia [Mediana: 69,15 (Q1:64,2-Q3:75,5) Vs Mediana: 84,2(Q1:72,15-Q3:89,05), p<0.001], adherencia a la seguridad [Mediana: 87,1% (Q1:83,05-Q3:91,2) Vs Mediana: 94,05 (Q1:89,95-Q3:96,2), p<0.001] y las ediciones de alertas de limite relativo [Mediana:17,0 (Q1:8,5-Q3:24,5) Vs Mediana: 12,0 (Q1:7,0-Q3:17,5), p=0.013]. La solución salina, la norepinefrina, el lactato de ringer, la piperacilina-tazobactam, la nitroglicerina y la heparina presentaron el mayor número de alertas de seguridad. Conclusión: Se encontró una buena adherencia (uso de la farmacoteca) y adherencia a la seguridad (indicador de uso de la bomba), con una reducción de los potenciales eventos adversos; así el uso de bombas inteligentes podría contribuir en la prevención de potenciales errores durante la administración de medicamentos endovenosos en la unidad de cuidados intensivos.

Abstract Introduction: Smart infusion pumps have become a useful tool for the safe administration of intravenous medications, since they allow the prevention of potential adverse events. Objetive: To assess adherence and potential adverse events prevented during intravenous medication administration using smart infusion pumps. Methods: Observational study, conducted in four intensive care units using data from Hospira MedNetTM software. A descriptive analysis was carried out together with a bivariate analysis using a Mann-Whitney U test, a KruskalWallis test and a Bonferroni test to assess adherence and potential adverse events prevented by year and service. Results: Adherence was 74.0%, 78,299 safety alerts were presented and 4.54% (n = 16,288) potential adverse events were prevented. Differences were found between the first and second year in adherence [Median: 69.15 (Q1: 64.2-Q3:75.5) versus Median: 84.2 (Q1: 72.15-Q3: 89.05), p<0.001]. Likewise safety adherence [Median: 87.1% (Q1: 83.05-Q3: 91.2) versus Median: 94.05 (Q1: 89.95-Q3: 96.2), p<0.001] and the relative limit alert editions [Median: 17.0 (Q1: 8.5-Q3: 24.5) versus Median: 12.0 (Q1: 7.0-Q3: 17.5), p=0.013]. The saline solution, norepinephrine, ringer's lactate, piperacillin-tazobactam, nitroglycerin and heparin presented the highest number of safety alerts. Conclusions: Adequate adherence (use of the drug library) and safety adherence (indicator of pump use) were found, with a reduction in potential adverse events; thus, the use of smart pumps could contribute to the prevention of potential errors during the administration of intravenous medications in the intensive care unit.

Whole-gene analysis of inter-genogroup reassortant rotaviruses from the Dominican Republic: Emergence of equine-like G3 strains and evidence of their reassortment with locally-circulating strains.

Inter-genogroup reassortant group A rotavirus (RVA) strains possessing a G3 VP7 gene of putative equine origin (EQL-G3) have been detected in humans since 2013. Here we report detection of EQL-G3P[8] RVA strains from the Dominican Republic collected in 2014-16. Whole-gene analysis of RVA in stool specimens revealed 16 EQL-G3P[8] strains, 3 of which appear to have acquired an N1 NSP1 gene from locally-circulating G9P[8] strains and a novel G2P[8] reassortant possessing 7 EQL-G3-associated genes and 3 genes from a locally-circulating G2P[4] strain. Phylogenetic/genetic analyses of VP7 gene sequences revealed nine G3 lineages (I-IX) with newly-assigned lineage IX encompassing all reported human EQL-G3 strains along with the ancestral equine strain. VP1 and NSP2 gene phylogenies suggest that EQL-G3P[8] strains were introduced into the Dominican Republic from Thailand. The emergence of EQL-G3P[8] strains in the Dominican Republic and their reassortment with locally-circulating RVA could have implications for current vaccination strategies.

Etiology of Severe Acute Watery Diarrhea in Children in the Global Rotavirus Surveillance Network Using Quantitative Polymerase Chain Reaction.

Background: The etiology of acute watery diarrhea remains poorly characterized, particularly after rotavirus vaccine introduction. Methods: We performed quantitative polymerase chain reaction for multiple enteropathogens on 878 acute watery diarrheal stools sampled from 14643 episodes captured by surveillance of children <5 years of age during 2013-2014 from 16 countries. We used previously developed models of the association between pathogen quantity and diarrhea to calculate pathogen-specific weighted attributable fractions (AFs). Results: Rotavirus remained the leading etiology (overall weighted AF, 40.3% [95% confidence interval {CI}, 37.6%-44.3%]), though the AF was substantially lower in the Americas (AF, 12.2 [95% CI, 8.9-15.6]), based on samples from a country with universal rotavirus vaccination. Norovirus GII (AF, 6.2 [95% CI, 2.8-9.2]), Cryptosporidium (AF, 5.8 [95% CI, 4.0-7.6]), Shigella (AF, 4.7 [95% CI, 2.8-6.9]), heat-stable enterotoxin-producing Escherichia coli (ST-ETEC) (AF, 4.2 [95% CI, 2.0-6.1]), and adenovirus 40/41 (AF, 4.2 [95% CI, 2.9-5.5]) were also important. In the Africa Region, the rotavirus AF declined from 54.8% (95% CI, 48.3%-61.5%) in rotavirus vaccine age-ineligible children to 20.0% (95% CI, 12.4%-30.4%) in age-eligible children. Conclusions: Rotavirus remained the leading etiology of acute watery diarrhea despite a clear impact of rotavirus vaccine introduction. Norovirus GII, Cryptosporidium, Shigella, ST-ETEC, and adenovirus 40/41 were also important. Prospective surveillance can help identify priorities for further reducing the burden of diarrhea.

Global Measles and Rubella Laboratory Network Support for Elimination Goals, 2010-2015.

In 2012, the World Health Assembly endorsed the Global Vaccine Action Plan (GVAP)* with the objective to eliminate measles and rubella in five World Health Organization (WHO) regions by 2020. In September 2013, countries in all six WHO regions had established measles elimination goals, and additional goals for elimination of rubella and congenital rubella syndrome were established in three regions (1). Capacity for surveillance, including laboratory confirmation, is fundamental to monitoring and verifying elimination. The 2012-2020 Global Measles and Rubella Strategic Plan of the Measles and Rubella Initiative(†) calls for effective case-based surveillance with laboratory testing for case confirmation (2). In 2000, the WHO Global Measles and Rubella Laboratory Network (GMRLN) was established to provide high quality laboratory support for surveillance (3). The GMRLN is the largest globally coordinated laboratory network, with 703 laboratories supporting surveillance in 191 countries. During 2010-2015, 742,187 serum specimens were tested, and 27,832 viral sequences were reported globally. Expansion of the capacity of the GMRLN will support measles and rubella elimination efforts as well as surveillance for other vaccine-preventable diseases (VPDs), including rotavirus, and for emerging pathogens of public health concern.

Maternal mortality due to pandemic influenza A H1N1 2009 virus in Colombia.

AIMS: The 2009 H1N1 pandemic illustrated the higher morbidity and mortality from viral infections in peripartum women. We describe clinical features of women who recently died of H1N1 in Colombia. METHODS: This is a case series study that was gathered through a retrospective record review of all maternal H1N1 deaths in the country. The national mortality database of confirmed mortality from H1N1 in pregnancy and up to 42 days after delivery was reviewed during the H1N1 season in 2009. Women with H1N1 infections were confirmed by the laboratory of virology. Demographic, clinical, and laboratory data were reviewed. Statistical analyses were performed and median values of non-parametric data were reported with inter-quartile range (IQR). RESULTS: A total of 23 H1N1 maternal deaths were identified. Eighty-three percent occurred in the third trimester. None of the mothers who died had received influenza vaccination. The median time from symptom onset to the initiation of antiviral treatment was 8.8 days (IQR 5.8-9.8). Five fatalities did not receive any anti-viral therapy. Median PaO2/FiO2 on day 1 was 80 (IQR, 60-98.5). All patients required inotropic support and mechanical ventilation with barotrauma-related complications of mechanical ventilation occurring in 35% of patients. CONCLUSION: In Colombia, none of the women suffering H1N1-related maternal deaths had received vaccination against the disease and most had delayed or had no anti-viral therapy. Given the lack of evidence-based clinical predictors to identify women who are prone to die from H1N1 in pregnancy, following international guidelines for vaccination and initiation of antiviral therapy in suspected cases would likely improve outcomes in developing countries.

Seroprevalence of measles and rubella antibodies in pregnant women Haiti, 2012.

BACKGROUND: Haiti had set a national goal to eliminate measles and rubella, as well as congenital rubella syndrome (CRS) by 2010. A 2007-2008 nationwide measles and rubella vaccination campaign targeting 1-19 years, however, reached only 79% of the target population. To assess whether population immunity was adequate to support elimination, we conducted a national serosurvey. METHODS: We systematically selected 740 serum specimens collected from pregnant women in a 2012 national antenatal HIV sentinel serosurvey across four age strata: 15-19, 20-24, 25-29 and 30-39 years. Sera were tested for measles and rubella specific immunoglobulin G antibodies (IgG) using commercial immunoassays. We classified sera as seropositive, seronegative or indeterminate per manufacturer's instructions, and analyzed seroprevalence according to age strata, and rural or urban residence. We assessed immunity by estimating antibody concentrations in international units per milliliter (IU/mL) for seropositive and indeterminate sera. Measles IgG concentrations >0.12 IU/mL and rubella IgG concentrations >10 IU/mL were considered clinically protective. RESULTS: Of 740 sera, 696 (94.1%) were seropositive and 20 (2.7%) were indeterminate for measles IgG; overall 716 (96.8%) sera had IgG concentrations >0.12 IU/mL. For rubella IgG, 691 (93.4%) sera were seropositive and 1 (0.1%) was indeterminate; a total of 687 (92.8%) had IgG concentrations >10 IU/mL. Measles seropositivity varied across age strata (p=0.003); seropositivity increased from 88.6% among 15-19 year olds to 98.4% among 30-39 year olds (Cochran-Armitage trend tes t ≤ 0.0001). Rubella seropositivity did not differ across age strata. There were no statistically significant differences in measles or rubella seropositivity by urban versus rural residence. CONCLUSION: Despite previous low vaccination coverage for measles, results from this serosurvey indicate high levels of measles and rubella seropositivity in pregnant women, and contribute to the evidence for measles, rubella and CRS elimination from Haiti by the target date.

Desarrollo de un método de transcripción inversa seguida de reacción en cadena de la polimerasa para la detección del virus de la fiebre amarilla / Development of a reverse transcription polymerase chain reaction method for yellow fever virus detection

Introduction. Yellow fever is considered a re-emerging disease and is endemic in tropical regions of Africa and South America. At present, there are no standardized or commercialized kits available for yellow fever virus detection. Therefore, diagnosis must be made by time-consuming routine techniques, and sometimes, the virus or its proteins are not detected. Furthermore, co-circulation with other flaviviruses, including dengue virus, increases the difficulty of diagnosis. Objective. To develop a specific reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR-based assay to improve the detection and diagnosis of yellow fever virus using both serum and fresh tissue samples. Materials and methods. RT-PCR primers were designed to amplify a short fragment of all yellow fever virus genotypes reported. A second set of primers was used in a nested PCR to increase sensitivity. Thirty-three clinical samples were tested with the standardized reaction. Results. The expected amplicon was obtained in 25 out of 33 samples analyzed using this approach, and 2 more samples tested positive after a subsequent nested PCR approach. Conclusion. This improved technique not only ensures the specific detection of a wide range of yellow fever virus genotypes but also may increase the sensitivity of detection by introducing a second round of amplification, allowing a rapid differential diagnosis between dengue and yellow fever infection, which is required for effective surveillance and opportune epidemiologic measures.

Introducción. La fiebre amarilla se considera una enfermedad reemergente y endémica en regiones tropicales de África y Suramérica. Actualmente, no existen estuches estandarizados o comerciales disponibles para la detección del virus de la fiebre amarilla y, por lo tanto, el diagnóstico debe hacerse mediante técnicas de rutina que consumen mucho tiempo y algunas veces no garantizan la detección del virus o de sus proteínas. Además, la cocirculación con otros flavivirus, incluyendo el del dengue, hacen el diagnóstico más complicado. Objetivo. Desarrollar un ensayo específico de amplificación basado en transcripción inversa seguida de reacción en cadena de la polimerasa, con el fin de mejorar la detección y el diagnóstico de la fiebre amarilla, tanto a partir de suero como de tejido fresco. Materiales y métodos. Se diseñaron iniciadores específicos para amplificar un fragmento conservado del virus de la fiebre amarilla. Un segundo par de iniciadores se usó en una reacción de amplificación anidada para incrementar la sensibilidad. Se probaron 33 muestras clínicas con la técnica estandarizada. Resultados. El amplímero esperado se obtuvo en 25 de las 33 muestras analizadas usando este método y 2 más resultaron positivas después de la reacción anidada. Conclusión. Esta técnica mejorada garantiza la detección de todos los genotipos virales de fiebre amarilla y puede incrementar la sensibilidad del ensayo introduciendo una segunda etapa de amplificación, lo cual permite el diagnóstico diferencial con infección por dengue y otros flavivirus, lo cual es de gran importancia para la vigilancia y la toma de medidas epidemiológicas oportunas.

Development of a reverse transcription polymerase chain reaction method for yellow fever virus detection.

INTRODUCTION: Yellow fever is considered a re-emerging disease and is endemic in tropical regions of Africa and South America. At present, there are no standardized or commercialized kits available for yellow fever virus detection. Therefore, diagnosis must be made by time-consuming routine techniques, and sometimes, the virus or its proteins are not detected. Furthermore, co-circulation with other flaviviruses, including dengue virus, increases the difficulty of diagnosis. OBJECTIVE: To develop a specific reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR-based assay to improve the detection and diagnosis of yellow fever virus using both serum and fresh tissue samples. MATERIALS AND METHODS: RT-PCR primers were designed to amplify a short fragment of all yellow fever virus genotypes reported. A second set of primers was used in a nested PCR to increase sensitivity. Thirty-three clinical samples were tested with the standardized reaction. RESULTS: The expected amplicon was obtained in 25 out of 33 samples analyzed using this approach, and 2 more samples tested positive after a subsequent nested PCR approach. CONCLUSION: This improved technique not only ensures the specific detection of a wide range of yellow fever virus genotypes but also may increase the sensitivity of detection by introducing a second round of amplification, allowing a rapid differential diagnosis between dengue and yellow fever infection, which is required for effective surveillance and opportune epidemiologic measures.

Phylogenetic reconstruction of dengue virus type 2 in Colombia.

BACKGROUND: Dengue fever is perhaps the most important viral re-emergent disease especially in tropical and sub-tropical countries, affecting about 50 million people around the world yearly. In Colombia, dengue virus was first detected in 1971 and still remains as a major public health issue. Although four viral serotypes have been recurrently identified, dengue virus type 2 (DENV-2) has been involved in the most important outbreaks during the last 20 years, including 2010 when the fatality rate highly increased. As there are no major studies reviewing virus origin and genotype distribution in this country, the present study attempts to reconstruct the phylogenetic history of DENV-2 using a sequence analysis from a 224 bp PCR-amplified product corresponding to the carboxyl terminus of the envelope (E) gene from 48 Colombian isolates. RESULTS: As expected, the oldest isolates belonged to the American genotype (subtype V), but the strains collected since 1990 represent the American/Asian genotype (subtype IIIb) as previously reported in different American countries. Interestingly, the introduction of this genotype coincides with the first report of dengue hemorrhagic fever in Colombia at the end of 1989 and the increase of cases during the next years. CONCLUSION: After replacement of the American genotype, several lineages of American/Asian subtype have rapidly spread all over the country evolving in new clades. Nevertheless, the direct association of these new variants in the raise of lethality rate observed during the last outbreak has to be demonstrated.

[Standardization of a method for concentration and detection of enteric viruses from drinking water]. / Estandarización de un método de concentración y detección de virus entéricos en aguas de consumo.

INTRODUCTION: Enteric viruses have been implicated in acute diarrheal disease, food-borne disease, hepatitis A and meningitis outbreaks, in which water was the vehicle of transmission. OBJECTIVE: A concentration method was standardized for the detection of enteric viruses in drinking water. MATERIALS AND METHODS: Twenty liters of water were concentrated to 6 ml by filtration and tangential ultrafiltration. Viral solutions of 20 L each were prepared at 1, 10, 50 and 100 TCID50 of Sabin poliovirus type 1 as positive controls. Viral particles were recovered by tissue culture and detected by conventional polymerase chain reaction (PCR), according to the international standards recommended by the Enterovirus Laboratory at the Centers for Disease Control and Prevention, Atlanta, GA. RESULTS: All positive controls showed cytopathic effect on L20B and RD cells and were amplified by conventional PCR directly from samples. Negative controls did not show any amplification or viral cytopathic effect. CONCLUSIONS: Tangential ultrafiltration for concentrating viruses proved to be a fast, efficient recovery and reproducible. It has the advantage of allowing the detection (at the 1 TCID50 level) and identification of viruses by RT-PCR and the demonstration of viral infectivity by tissue culture.

Phylogenetic history demonstrates two different lineages of dengue type 1 virus in Colombia.

BACKGROUND: Dengue Fever is one of the most important viral re-emergent diseases affecting about 50 million people around the world especially in tropical and sub-tropical countries. In Colombia, the virus was first detected in the earliest 70's when the disease became a major public health concern. Since then, all four serotypes of the virus have been reported. Although most of the huge outbreaks reported in this country have involved dengue virus serotype 1 (DENV-1), there are not studies about its origin, genetic diversity and distribution. RESULTS: We used 224 bp corresponding to the carboxyl terminus of envelope (E) gene from 74 Colombian isolates in order to reconstruct phylogenetic relationships and to estimate time divergences. Analyzed DENV-1 Colombian isolates belonged to the formerly defined genotype V. Only one virus isolate was clasified in the genotype I, likely representing a sole introduction that did not spread. The oldest strains were closely related to those detected for the first time in America in 1977 from the Caribbean and were detected for two years until their disappearance about six years later. Around 1987, a split up generated 2 lineages that have been evolving separately, although not major amino acid changes in the analyzed region were found. CONCLUSION: DENV-1 has been circulating since 1978 in Colombia. Yet, the phylogenetic relationships between strains isolated along the covered period of time suggests that viral strains detected in some years, although belonging to the same genotype V, have different recent origins corresponding to multiple re-introduction events of viral strains that were circulating in neighbor countries. Viral strains used in the present study did not form a monophyletic group, which is evidence of a polyphyletic origin. We report the rapid spread patterns and high evolution rate of the different DENV-1 lineages.

Importancia de los análisis serológicos, moleculares y virológicosen la vigilancia de la fiebre amarilla en Colombia, 2006-2008 / Serological, molecular and virological analyses associated with yellow fever surveillance in Colombia

Introducción. La fiebre amarilla es una fiebre hemorrágica viral inmunoprevenible que continúa causando importante morbilidad y mortalidad en regiones tropicales y subtropicales. En Colombia hay aproximadamente cinco millones de personas en riesgo de adquirir la infección. Objetivo. Describir la importancia de los análisis serológicos, moleculares y virológicos en la vigilancia de la fiebre amarilla en Colombia, con base en los resultados obtenidos de muestras recibidas en el Laboratorio de Arbovirus del Grupo de Virología del Instituto Nacional de Salud, entre 2006 y 2008, y recalcar la relevancia de una oportuna y adecuada recolección de muestras para la confirmación de casos. Materiales y métodos. Se procesaron 2.096 muestras de suero y tejidos utilizando las pruebas ELISA para IgM contra fiebre amarilla, aislamiento viral-inmunofluorescencia indirecta y transcriptasa inversa-reacción en cadena de la polimerasa. Las muestras positivas se correlacionaron con los hallazgos clínicos y epidemiológicos para su interpretación y confirmación.Resultados. El 82% de los casos confirmados por histopatología en este período también se confirmaron en nuestro laboratorio por técnicas serológicas y moleculares; estos casos provenían de zonas selváticas y del piedemonte de la Cordillera Oriental.Conclusión. Se observa la necesidad de seguir manteniendo y fortaleciendo los procesos de vigilancia en las regiones de mayor circulación del virus, para la captación oportuna de casos. Se recalca la importancia del diagnóstico por medio de las técnicas descritas, las cuales se pueden realizar en muestras de pacientes vivos, contrario a las pruebas histopatológicas que requieren muestras de casos fatales.

Introduction. Yellow fever is an immunopreventable viral hemorrhagic fever that causes high morbidity and mortality in tropical and sub-tropical regions. In Colombia, approximately 5 million persons are at risk of becoming infected with yellow fever virus.Objective. The serological, molecular and virological analyses on the yellow fever surveillance samples were summarized in order to indicate the importance of appropriate and timely sampling in the process of case confirmation. Materials and methods. The survey was based on samples received at the Arbovirus Laboratory, Virology Group, Instituto Nacional de Salud, Bogotá, during years 2006 to 2008. A total of 2,096 serum and tissue samples were tested for IgM antibodies against yellow fever by capture enzyme-linked immunosorbent assay, viral isolation-indirect fluorescence antibody technique, and reverse transcriptase-polymerase chain reaction. Positive samples were correlated with the clinical and epidemiological findings for their interpretation and confirmation.Results. Of the 15 yellow fever cases confirmed in Colombia during 2006-2008 by histopathological techniques, 82% were confirmed at the Arbovirus Laboratory using serologic and molecular techniques. The positive cases were distributed in the rainforest region and in the foothills of the eastern chain of the Andes mountains. Conclusion. The case distribution and prognosis illustrated the necessity of maintaining and strengthening the surveillance processes in those regions where the yellow fever virus is circulating. The cases must be recruited and diagnosed sufficiently early in order to use the above techniques in samples from live patients, in contrast to the histopathological procedures that require samples from fatal cases.

Hospitalizaciones por tuberculosis en España: análisis de sus costes / Tuberculosis–related hospitalization in Spain: A cost analysis

Objetivo Evaluar los costes hospitalarios y globales de las altas por tuberculosis (TB) del Sistema Nacional de Salud (1999–2006).Métodos Se estudiaron los Grupos de Diagnósticos Relacionados (GDR) específicos de TB (GDR 705, 709, 711 y 798–801).Resultados Hubo disminución significativa del 25% en hospitalizaciones totales; del 8,7% de TB/infección por VIH y del 0,5% de letalidad (NS). Existió decremento de costes absolutos hospitalarios y globales (de 31,3 a 30,8 millones y de 40,6 a 40,0 millones de €) y relativos respecto a costes hospitalarios y globales (del 0,21 al 0,10% y del 0,15 al 0,07%, respectivamente).Conclusiones Aunque existe progresiva disminución en hospitalizaciones y mortalidad por TB, aún representan una considerable carga sanitaria (AU)

Objective To evaluate the number and cost of hospitalizations due to tuberculosis occurring in the Spanish National Health System (NHS) during 1999 to 2006.MethodsThe specific diagnosis-related groups (DRG) for tuberculosis (DRGs 705, 709, 711 and 798-802) were analyzed. Results We observed a striking decrease in hospitalizations (..) (AU)

Estandarización de un método de concentración y detección de virus entéricos en aguas de consumo / Standardization of a method for concentration and detection of enteric viruses from drinking water

Introducción. Los virus entéricos se han visto implicados en brotes de enfermedad diarreica aguda, enfermedades transmitidas por alimentos, hepatitis A y meningitis aséptica, en los que el vehículo de transmisión del agente ha sido el agua.Objetivo. Estandarizar un método de concentración para la detección de virus entéricos en aguas de consumo.Materiales y métodos. Se concentraron 20 litros de agua a un volumen de 6 ml mediante filtración y ultrafiltración tangencial. Como controles positivos se prepararon soluciones de 20 litros a concentraciones virales de 1, 10, 50 y 100 TCID50 (Tissue Culture Infectious Dose 50%) de Poliovirus Sabin de tipo 1. Las partículas virales fueron recuperadas por cultivo en células sensibles a la infección e identificadas por amplificación del genoma viral mediante reacción en cadena de la polimerasa, siguiendo los estándares internacionales de los Centers for Disease Control and Prevention (CDC) de Atlanta. Resultados. Todos los controles positivos causaron efecto citopático en células de rabdomiosarcoma y L20B y fueron detectados por RT- PCR (Real Time- PCR) convencional, directamente de las muestras. Los controles negativos no mostraron efecto citopático ni amplificación viral por RT-PCR.Conclusiones. La ultrafiltración tangencial mostró ser un método rápido y eficaz al recuperar virus desde una TCID50, además de ser reproducible y sencillo. Tiene la ventaja de permitir la detección de su capacidad de contagiosidad viral por el cultivo celular, y la identificación por RT-PCR.

Introduction. Enteric viruses have been implicated in acute diarrheal disease, food-borne disease, hepatitis A and meningitis outbreaks, in which water was the vehicle of transmission.Objective. A concentration method was standardized for the detection of enteric viruses in drinking water. Materials and methods. Twenty liters of water were concentrated to 6 ml by filtration and tangential ultrafiltration. Viral solutions of 20 L each were prepared at 1, 10, 50 and 100 TCID50 of Sabin poliovirus type 1 as positive controls. Viral particles were recovered by tissue culture and detected by conventional polymerase chain reaction (PCR), according to the international standards recommended by the Enterovirus Laboratory at the Centers for Disease Control and Prevention, Atlanta, GA. Results. All positive controls showed cytopathic effect on L20B and RD cells and were amplified by conventional PCR directly from samples. Negative controls did not show any amplification or viral cytopathic effect. Conclusions. Tangential ultrafiltration for concentrating viruses proved to be a fast, efficient recovery and reproducible. It has the advantage of allowing the detection (at the 1 TCID50 level) and identification of viruses by RT-PCR and the demonstration of viral infectivity by tissue culture.

[Serological, molecular and virological analyses associated with yellow fever surveillance in Colombia]. / Importancia de los análisis serológicos, moleculares y virológicos en la vigilancia de la fiebre amarilla en Colombia, 2006-2008.

INTRODUCTION: Yellow fever is an immunopreventable viral hemorrhagic fever that causes high morbidity and mortality in tropical and sub-tropical regions. In Colombia, approximately 5 million persons are at risk of becoming infected with yellow fever virus. OBJECTIVE: The serological, molecular and virological analyses on the yellow fever surveillance samples were summarized in order to indicate the importance of appropriate and timely sampling in the process of case confirmation. MATERIALS AND METHODS: The survey was based on samples received at the Arbovirus Laboratory, Virology Group, Instituto Nacional de Salud, Bogotá, during years 2006 to 2008. A total of 2,096 serum and tissue samples were tested for IgM antibodies against yellow fever by capture enzyme-linked immunosorbent assay, viral isolation-indirect fluorescence antibody technique, and reverse transcriptase-polymerase chain reaction. Positive samples were correlated with the clinical and epidemiological findings for their interpretation and confirmation. RESULTS: Of the 15 yellow fever cases confirmed in Colombia during 2006-2008 by histopathological techniques, 82% were confirmed at the Arbovirus Laboratory using serologic and molecular techniques. The positive cases were distributed in the rainforest region and in the foothills of the eastern chain of the Andes mountains. CONCLUSION: The case distribution and prognosis illustrated the necessity of maintaining and strengthening the surveillance processes in those regions where the yellow fever virus is circulating. The cases must be recruited and diagnosed sufficiently early in order to use the above techniques in samples from live patients, in contrast to the histopathological procedures that require samples from fatal cases.

[Tuberculosis-related hospitalization in Spain: a cost analysis]. / Hospitalizaciones por tuberculosis en España: análisis de sus costes.

OBJECTIVE: To evaluate the number and cost of hospitalizations due to tuberculosis occurring in the Spanish National Health System (NHS) during 1999 to 2006. METHODS: The specific diagnosis-related groups (DRG) for tuberculosis (DRGs 705, 709, 711 and 798-802) were analyzed. RESULTS: We observed a striking decrease in hospitalizations (-25%), concomitant tuberculosis-HIV infection (-8.7%), and tuberculosis-related deaths (-0.5%, NS). In addition, there was a drop in the absolute number of hospital admissions and overall cost (from 31.3 to 30.8 and from 40.6 to 40.1 million euro), and a significant decrease in the relative hospitalizations and cost with respect to the overall number and hospital budget (from 0.21% to 0.10% and from 0.15% to 0.07%). CONCLUSIONS: There is a marked decrease in tuberculosis-related hospitalizations and mortality, but the disease remains a considerable health burden.

Brote de rabia humana transmitida por gato en el municipio de Santander de Quilichao, Colombia, 2008 / An outbreak of human rabies transmitted by a cat in the town of Santander de Quilichao, Colombia, 2008

Objetivos En marzo de 2008 ocurrió en el municipio de Santander de Quilichao- Cauca, Colombia, un brote de rabia de origen silvestre con 2 víctimas humanas. El presente artículo apunta a describir las técnicas diagnósticas de laboratorio, las acciones de investigación de campo y control de foco empleadas, y su significado epidemiológico e implicaciones en salud pública. Métodos La rabia se diagnosticó por inmunofluorescencia directa, prueba biológica en ratón, histopatología e inmunohistoquímica, y se tipificó utilizando anticuerpos monoclonales. La investigación de campo se enfocó en la búsqueda de contactos humanos y animales, identificación de casos sospechosos y búsqueda institucional de accidentes rábicos. El control de foco consistió en aplicación de tratamiento post exposición a la población expuesta, vacunación canina y felina, recolección y eliminación de animales callejeros y educación a la comunidad. Resultados Dos casos de rabia en humanos fueron diagnosticados y uno en gato por nexo epidemiológico. La variante antigénica 3 fue aislada de los casos humanos. Se vacunaron en total 11 369 caninos, 3 325 felinos y 217 humanos. Conclusiones Se confirma la amenaza para los humanos que representa la rabia en el ecosistema silvestre. El brote tuvo origen en vampiro y el transmisor a los humanos fue un gato confirmando a esta especie doméstica como vínculo entre la rabia de origen silvestre y el ecosistema urbano, por ende su importancia en el enfoque de las acciones de prevención y control de la rabia. Se resalta la necesidad de implementar y mantener acciones para el control de la rabia silvestre que permitan minimizar su impacto en humanos.

Objectives A sylvatic rabies outbreak during March 2008 caused two human deaths in the town of Santander de Quilichao in Cauca, Colombia. This article describes the diagnostic laboratory techniques used, the field investigation and focus control used, as well as this outbreak's epidemiological significance and implications for public health. Methods Rabies was diagnosed by direct immunofluorescence, biological tests involving inoculating mice, histopathology and immunohistochemistry and then typed by using monoclonal antibodies. Field investigation focused on searching for human and animal contacts, identifying suspicious cases and conducting an institutional search for rabid accidents. Focus control consisted of post-exposure treatment of the exposed population, vaccinating dogs and cats, collecting and eliminating stray animals and educating the community. Results Two human rabies cases were confirmed in the laboratory and another was inferred in a cat by epidemiological nexus. Antigenic variant 3 was isolated from the human cases. 11,369 dogs, 3,325 cats and 217 humans were vaccinated. Conclusions This study confirmed that rabies in the wild represents a threat for humans. The outbreak described here originated in vampire bats and was transmitted to humans by a cat, pointing out the nexus between wild rabies and the urban ecosystem which cats represent, thereby becoming a target for rabies' control and prevention activities. This study underlines the urgency of implementing and maintaining rabies control and prevention activities in the wild to minimise its impact on humans.

Mortalidad asociada con las temporadas de mayor circulación de los virus de la influenza en Bogotá, Colombia, 1997-2005 / Mortality associated with peak seasons of influenza virus circulation in Bogotá, Colombia, 1997-2005

OBJETIVO: Estimar el exceso de mortalidad potencialmente atribuible a los virus de la influenza A y B y al virus sincitial respiratorio humano (VSRH) en las temporadas de mayor circulación de los virus de la influenza en Bogotá, Colombia entre 1997 y 2005. MÉTODOS: Se relacionaron las tasas mensuales de mortalidad general, por neumonía en menores de 5 años y por neumonía y afecciones cardiovasculares en mayores de 60 años, en Bogotá, Colombia, con las temporadas de mayor circulación de los virus de la influenza en esa ciudad. Los datos de mortalidad se obtuvieron del Departamento Nacional de Estadísticas de Colombia; las temporadas de mayor circulación de los virus se definieron como los meses contiguos en los que el número de aislamientos era igual o superior a la mitad del total de los aislamientos del año. Se calcularon las razones de tasas de incidencia (RTI) y sus intervalos de confianza de 95 por ciento (IC95 por ciento). RESULTADOS: El virus de la influenza A mostró un patrón de circulación estacional, pero no el de la influenza B y el VSRH. La mayor circulación de los virus de la influenza se asoció con un incremento promedio anual de 5 por ciento en la mortalidad general durante el período estudiado (RTI = 1,05; IC95 por ciento: 1,046 a 1,064). En las temporadas de mayor circulación de los virus de la influenza, la mortalidad combinada por neumonía e influenza en todas las edades fue mayor en 11 por ciento que en el resto del período (RTI = 1,11; IC95 por ciento: 1,051 a 1,178). CONCLUSIONES: En las temporadas de mayor circulación de los virus de la influenza en Colombia puede aumentar la mortalidad, en particular por neumonía y afecciones cardiovasculares en mayores de 60 años. Deben emprenderse acciones de prevención específicas para prevenir la influenza, especialmente en estos dos grupos de edad.

OBJECTIVE: To estimate potential excess mortality attributable to influenza viruses A and B and human respiratory syncytial virus (HRSV) during peak seasons of influenza virus circulation in Colombia from 1997 to 2005. METHODS: A comparison of monthly, general mortality rates from pneumonia in children under 5 years of age and from pneumonia and cardiovascular disease in those more than 60 years of age in Bogota, Colombia, were compared to the city's peak seasons of influenza virus circulation. Mortality data were obtained from the National Bureau of Statistics of Colombia; peak seasons of virus circulation were defined as contiguous months in which the number of isolates was equal to or greater than half the total number of isolates for the year. Incidence rate ratios (IRR) and their 95 percent confidence intervals (95 percentCI) were determined. RESULTS: Influenza A demonstrated a pattern of seasonal circulation, but influenza B and HRSV did not. The increased circulation of influenza virus was associated with an average annual increase of 5 percent in overall mortality during the study period (IRR = 1.05; 95 percentCI: 1.046-1.064). During seasons of increased circulation of influenza viruses, the combined mortality from pneumonia and influenza for all ages was 11 percent higher than it was at other times (IRR = 1.11; 95 percentCI: 1.051-1.178). CONCLUSIONS: During peak seasons of influenza virus circulation in Colombia, there can be increased mortality, particularly from pneumonia and cardiovascular disease among those more than 60 years of age. Preventive actions specific to protecting against influenza should be taken, especially in these two age groups.