Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

Effectiveness of diaphragmatic ultrasound as a predictor of successful weaning from mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Several measurements have been used to predict the success of weaning from mechanical ventilation; however, their efficacy varies in different studies. In recent years, diaphragmatic ultrasound has been used for this purpose. We conducted a systematic review and meta-analysis to evaluate the effectiveness of diaphragmatic ultrasound in predicting the success of weaning from mechanical ventilation. METHODS: Two investigators independently searched PUBMED, TRIP, EMBASE, COCHRANE, SCIENCE DIRECT, and LILACS for articles published between January 2016 and July 2022. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool; additionally, the certainty of the evidence is evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Sensitivity and specificity analysis was performed for diaphragmatic excursion and diaphragmatic thickening fraction; positive and negative likelihood ratios and diagnostic odds ratios (DOR) with their confidence intervals (95% CI) were calculated by random effects analysis, summary receiver operating characteristic curve was estimated. Sources of heterogeneity were explored by subgroup analysis and bivariate meta-regression. RESULTS: Twenty-six studies were included, of which 19 were included in the meta-analysis (1204 patients). For diaphragmatic excursion, sensitivity was 0.80 (95% CI 0.77-0.83), specificity 0.80 (95% CI 0.75-0.84), area under the summary receiver operating characteristic curve 0.87 and DOR 17.1 (95% CI 10.2-28.6). For the thickening fraction, sensitivity was 0.85 (95% CI 0.82-0.87), specificity 0.75 (95% CI 0.69-0.80), area under the summary receiver operating characteristic curve 0.87 and DOR 17.2 (95% CI 9.16-32.3). There was heterogeneity among the included studies. When performing a subgroup analysis and excluding studies with atypical cutoff values, sensitivity and specificity increased for diaphragmatic thickening fraction; sensitivity increased and specificity decreased for diaphragmatic excursion; when comparing studies using pressure support (PS) versus T-tube, there was no significant difference in sensitivity and specificity; bivariate meta-regression analysis shows that patient position at the time of testing was a factor of heterogeneity in the included studies. CONCLUSIONS: Measurement of diaphragmatic excursion and diaphragmatic thickening fraction predict the probability of successful weaning from mechanical ventilation with satisfactory diagnostic accuracy; however, significant heterogeneity was evident in the different included studies. Studies of high methodological quality in specific subgroups of patients in intensive care units are needed to evaluate the role of diaphragmatic ultrasound as a predictor of weaning from mechanical ventilation.

Co-circulation of dengue, chikungunya, and Zika viruses in Colombia from 2008 to 2018.

OBJECTIVE: This study aimed to identify the co-circulation patterns of three viruses (dengue, Zika, and -chikungunya) in Colombia from 2008 to 2018 by using notification reports provided to the national surveillance system. METHODS: This cross-sectional study was conducted through a review of data for 2008 through 2018 from Colombia's Public Health Surveillance System (SIVIGILA). RESULTS: In 2015, when chikungunya was first detected, it had a higher incidence (1 359.0 cases per 100 000 persons) than did the two other diseases. In 2016, when the circulation of Zika virus was first found, the incidence was 296.4 cases per 100 000 persons; that incidence declined dramatically in the next two years. Between 2015 and 2018, there was a substantial decrease in the frequency of dengue circulation, with it going from 334.1 cases per 100 000 persons in 2015 to 90.7 cases per 100 000 in 2017 and 173.1 cases per 100 000 in 2018. CONCLUSIONS: The decrease in the number of dengue cases after co-circulation of the three viruses could indicate possible cross-protection. This finding should be further analyzed.

Neutralizing Antibodies from Convalescent Chikungunya Virus Patients Can Cross-Neutralize Mayaro and Una Viruses.

Most alphaviruses are mosquito-borne and can cause severe disease in domesticated animals and humans. The most notable recent outbreak in the Americas was the 2014 chikungunya virus (CHIKV) outbreak affecting millions and producing disease highlighted by rash and arthralgia. Chikungunya virus is a member of the Semliki Forest (SF) serocomplex, and before its arrival in the Americas, two other member of the SF complex, Una (UNAV) and Mayaro (MAYV) viruses, were circulating in Central and South America. This study examined whether antibodies from convalescent CHIKV patients could cross-neutralize UNAV and MAYV. Considerable cross-neutralization of both viruses was observed, suggesting that exposure to CHIKV can produce antibodies that may mitigate infection with UNAV or MAYV. Understanding the impact of CHIKV exposure on population susceptibility to other emerging viruses may help predict outbreaks; moreover, identification of cross-reactive immune responses among alphaviruses may lead to the development of vaccines targeting multiple viruses.

The Burden of Gastric Cancer Disease from 2010 to 2019 in Tunja, Boyacá, Colombia

Introduction: Gastric cancer (GC) is the first cause of death by neoplasm in Colombia, with 6,451 deaths in 2020. This pathology and its chronic manifestations pose a public health challenge. The objective is to estimate the disease burden of GC in Tunja, Boyacá, from 2010 to 2019. Materials and methods: An exploratory ecological study was conducted using disability-adjusted life years (DALYs) as the unit of measurement. The National Administrative Department of Statistics (DANE) mortality databases and prevalence information from the Integrated Social Protection Information System (SISPRO) records were used. Deaths and GC cases were pooled and then adjusted to control for bias. Results: In 2010-2019, 34.2 DALYs were lost for every 1,000 people secondary to GC in Tunja, 30.5 were due to years lost due to premature death, and 3.72 were due to years lived with disability. DALYs due to premature death were found to exceed DALYs due to disability. Conclusion: The morbidity burden of GC from 2010 to 2019 for Tunja was similar to that of other cancers because of years of life lost due to premature death, so public health efforts should be made to increase early detection.

Introducción: el cáncer gástrico (CG) es la primera causa de muerte por neoplasia en Colombia, con 6451 muertes durante el 2020. Esta patología y sus manifestaciones crónicas plantean un desafío en la salud pública. El objetivo fue estimar la carga de enfermedad por CG en Tunja, Boyacá, durante los años 2010 a 2019. Metodología: se realizó un estudio ecológico exploratorio en el que se utilizó como unidad de medida los años de vida ajustados por discapacidad (AVAD). Se emplearon las bases de datos de mortalidad del Departamento Administrativo Nacional de Estadística (DANE) e información de la prevalencia desde los registros del Sistema Integrado de Información de la Protección Social (SISPRO). Las muertes y los casos de CG se agruparon y luego se ajustaron para controlar sesgos. Resultados: en el período 2010-2019 se perdieron 34,2 AVAD por cada 1000 personas secundarios a CG en Tunja, de los cuales 30,5 fueron debido a años perdidos por muerte prematura y 3,72 por años vividos con discapacidad. Se encontró que los AVAD por muerte prematura superan a los AVAD por discapacidad. Conclusión: la carga de morbilidad por CG en el período 2010 a 2019 para la ciudad de Tunja fue similar a la carga de otros cánceres y fue debido a años de vida perdidos por muerte prematura, motivo por el cual se deben realizar esfuerzos de salud pública para aumentar la detección temprana.

The Cytokine Profile in Acute Chikungunya Infection is Predictive of Chronic Arthritis 20 Months Post Infection.

The cytokine profile during acute chikungunya infection that predicts future chronic arthritis has not yet been investigated. We conducted a nested case-control study comparing serum cytokine concentrations during acute chikungunya infection in cases (n = 121) that reported the presence of chronic joint pain versus age- and gender-matched controls (n = 121) who reported recovery at 20 months post infection. We observed that a robust cytokine response during acute infection was correlated with a decreased incidence of chronic joint pain and that low TNFα, IL-13, IL-2, and IL-4 during acute infection was predictive of chronic joint pain. These data suggest that a robust cytokine response is necessary for viral clearance and cytokines that are related to immune tolerance during acute infection may be protective for chronic arthritis pathogenesis.

Frequency of Chronic Joint Pain Following Chikungunya Virus Infection: A Colombian Cohort Study.

OBJECTIVE: To estimate the frequency of chronic joint pain after infection with chikungunya virus in a Latin American cohort. METHODS: A cross-sectional follow-up of a prospective cohort of 500 patients from the Atlántico Department, Colombia who were clinically diagnosed as having chikungunya virus during the 2014-2015 epidemic was conducted. Baseline symptoms and follow-up symptoms at 20 months were evaluated in serologically confirmed cases. RESULTS: Among the 500 patients enrolled, 485 had serologically confirmed chikungunya virus and reported joint pain status. Patients were predominantly adults (mean ± SD age 49 ± 16 years) and female, had an education level of high school or less, and were of Mestizo ethnicity. The most commonly affected joints were the small joints, including the wrists, ankles, and fingers. The initial virus symptoms lasted a median of 4 days (interquartile range [IQR] 3-8 days). Sixteen percent of the participants reported missing school or work (median 4 days [IQR 2-7 days]). After 20 months, one-fourth of the participants had persistent joint pain. A multivariable analysis indicated that significant predictors of persistent joint pain included college graduate status, initial symptoms of headache or knee pain, missed work, normal activities affected, ≥4 days of initial symptoms, and ≥4 weeks of initial joint pain. CONCLUSION: This is the first report to describe the frequency of chikungunya virus-related arthritis in the Americas after a 20-month follow-up. The high frequency of chronic disease highlights the need for the development of prevention and treatment methods.

Chikungunya Arthritis Mechanisms in the Americas: A Cross-Sectional Analysis of Chikungunya Arthritis Patients Twenty-Two Months After Infection Demonstrating No Detectable Viral Persistence in Synovial Fluid.

OBJECTIVE: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis. METHODS: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014-2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis. RESULTS: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21-23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly. CONCLUSION: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid.

Eficacia de la tafenoquina en la profilaxis y tratamiento de la malaria por Plasmodium vivax, revisión sistemática y metaanálisis / Efficacy of tafenoquine in the prophylaxis and treatment of malaria by Plasmodium vivax, systematic review and meta-analysis

Introducción. La tafenoquina fue aprobada en el 2018 por la Food and Drug Administration de Estados Unidos y, en el 2019, por la Therapeutic Goods Administration en Australia. Su administración en dosis única y su mecanismo de acción en las fases aguda y latente han sido objeto de estudio para cambiar el esquema de tratamiento de la malaria por Plasmodium vivax. Objetivo. Evaluar la evidencia científica disponible sobre la eficacia de la tafenoquina en la profilaxis y el tratamiento de la malaria por P. vivax, entre el 2009 y el 2019. Materiales y métodos. Se establecieron los descriptores MeSH y DeCS. Se utilizó la sintaxis ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] en las siguientes bases de datos: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs y Scopus. Los resultados obtenidos se sometieron a análisis crítico (matriz CASPE). El análisis cuantitativo se realizó utilizando la diferencia de riesgos en análisis de supervivencia (Kaplan-Meier) en los tres artículos finales. Resultados. Se sometieron tres estudios a metaanálisis (Llanos-Cuentas, 2014; Llanos- Cuentas, 2019, y Lacerda, 2019) para evaluar la eficacia del tratamiento con tafenoquina en comparación con primaquina. Se obtuvo una diferencia de riesgo global de 0,04 (IC95% 0-0,08; p=0,07). La tafenoquina no mostró inferioridad en la eficacia del tratamiento frente al esquema de primaquina. Conclusión. La tafenoquina es una alternativa que mejora el cumplimiento del tratamiento, lo que podría acercar a Colombia a las metas de la Estrategia Técnica Mundial contra la Malaria, 2016-2030.

Introduction: Tafenoquine was approved in 2018 by the Food and Drug Administration in the United States and in 2019 by the Therapeutic Goods Administration in Australia. Its administration in a single dose and its mechanism of action in the acute and latent phases of the disease have been studied to change the treatment regimen for Plasmodium vivax malaria. Objective: To evaluate the available scientific evidence of the efficacy of tafenoquine in prophylaxis and treatment between 2009 and 2019. Materials and methods: We established the MeSH and DeCS descriptors and we used the syntax ((Malaria Vivax) AND (tafenoquine) AND (prophylaxis)) OR [(Malaria Vivax) AND (tafenoquine) AND (relapse)] in the following databases: Pubmed, The Cochrane Central Register of Controlled Clinical Trials (CENTRAL), ISIS Web of Science, Lilacs, and Scopus. The results obtained were subjected to critical analysis (CASPE matrix). The quantitative analysis was performed with risk differences in survival analysis (Kaplan Meier) in the final three articles. Results: Three studies underwent meta-analysis (Llanos-Cuentas, 2014; Llanos-Cuentas, 2019, and Lacerda, 2019) to evaluate the efficacy of the treatment with tafenoquine compared to primaquine. A global risk difference of 0.04 was obtained (95% CI: 0.00-0.08; p=0.07). Tafenoquine did not show inferiority in the efficacy of treatment compared to the primaquine scheme. Conclusion: Tafenoquine is a therapeutic alternative to primaquine that improves adherence, which could bring Colombia closer to the goals of the World Technical Strategy against Malaria 2016-2030.

Epidemiologia de cáncer de ovario colombia 2009- 2016 / Epidemiology of ovarian cancer colombia 2009- 2016

Resumen Introducción el cáncer es una de las enfermedades más temidas por la humanidad y el tumor maligno de ovario no es la excepción. Se caracteriza por su alta agresividad y por presentar síntomas inespecíficos, además de no contar, hasta el momento, con pruebas de tamizaje que permitan una detección precoz, convirtiéndose en uno de los cánceres femeninos con alta mortalidad ocupando el séptimo lugar a nivel mundial. Objetivo Medir la prevalencia, mortalidad y la letalidad asociadas al cáncer de ovario entre 2009 a 2016 en la población colombiana. Método se realizó un estudio descriptivo, transversal, ecológico. A partir de una base de datos en el RIPS de SISPRO y DANE se seleccionaron las mujeres con diagnóstico de tumor maligno de ovario. Resultados se hallaron 36.798 mujeres con diagnóstico de cáncer de ovario, la edad media fue de 63 años con una prevalencia de 31,66 por 100.000 mujeres, en los departamentos de Antioquia, Santander, y Bogotá. Se estimó una tasa de mortalidad de 3,9 por 100.000 mujeres, predominio en educación básica primaria, y régimen de seguridad social contributivo. La letalidad fue de 15,75%. Conclusiones En Colombia la prevalencia, mortalidad y letalidad entre 2009 a 2016 presentó una tendencia al incremento, predominio en casadas, bajo nivel educativo y menor acceso a los servicios de salud. En virtud de lo anteriormente expuesto, se abre la posibilidad de establecer prioridades sanitarias, diseño de futuras estrategias en prevención de la enfermedad en salud pública, detención precoz y con la consecuente disminución de la mortalidad.

Authors’ response to the letter to the editor entitled: Co-circulation of dengue, chikungunya, and Zika viruses and cross-protection

To the editor: Dengue, zika, and chikungunya outbreaks in Central and South America countries have presented significant challenges related to their prevention and control. From the virologic point of view, the possibility has been raised that the co-circulation of the three viruses could generate cross-protection between the three alphaviruses. In order to discuss this hypothesis it must be taken into account that Zika, dengue (DENV) and chikungunya viruses are closely related flaviviruses, with identical urban transmission and some immune interactions (1). Also, it is known that secondary DENV infections may be more severe than primary infections due to the antibody-dependent immune response (i.e., heterotypic sub-neutralizing antibodies that increase virus entry into poorly susceptible cells) (2,3). In addition, the recent introduction of Zika and chikungunya viruses in the Americas and the large-scale exposure of a uniformly unexposed population could affect subsequent transmission of dengue virus. This hypothesis has not been tested, largely because insufficient epidemiological data are available for the affected sites. However, in Salvador, Brazil, after the zika outbreak there was a significant decrease in the frequency of dengue cases (4). A similar situation was observed in Colombia, where the decrease in dengue cases following the zika and chikungunya outbreaks went from 334.1 cases per 100 000 people in 2015 to 90.7 cases per 100 000 in 2017 and 173,1 cases per 100 000 in 2018 (5). Although temporary associations do not prove causation, the strength and consistency of the observations suggest that infections with Zika virus and chikungunya virus could induce cross-protective immunity against dengue. Prospective studies are needed to fully assess the risk of dengue infection after exposure to Zika and chikungunya viruses and to determine whether the supposed cross-protection is long-lasting. Although observations support this hypothesis, the potential direct implications of this hypothesis for epidemiological surveillance, immunological research on pathogenesis and vaccine development require additional studies.

Co-circulation of dengue, chikungunya, and Zika viruses in Colombia from 2008 to 2018

[ABSTRACT]. Objective. This study aimed to identify the co-circulation patterns of three viruses (dengue, Zika, and chikungunya) in Colombia from 2008 to 2018 by using notification reports provided to the national surveillance system. Methods. This cross-sectional study was conducted through a review of data for 2008 through 2018 from Colombia’s Public Health Surveillance System (SIVIGILA). Results. In 2015, when chikungunya was first detected, it had a higher incidence (1 359.0 cases per 100 000 persons) than did the two other diseases. In 2016, when the circulation of Zika virus was first found, the incidence was 296.4 cases per 100 000 persons; that incidence declined dramatically in the next two years. Between 2015 and 2018, there was a substantial decrease in the frequency of dengue circulation, with it going from 334.1 cases per 100 000 persons in 2015 to 90.7 cases per 100 000 in 2017 and 173.1 cases per 100 000 in 2018. Conclusions. The decrease in the number of dengue cases after co-circulation of the three viruses could indicate possible cross-protection. This finding should be further analyzed.

[RESUMEN]. Objetivo: Establecer las características de la cocirculación de tres virus (dengue, Zika y chikunguña) en Colombia desde el 2008 hasta el 2018. Para ello, en este estudio se han utilizado los informes de notificación que se proporcionan al sistema nacional de vigilancia. Métodos: Este estudio transversal se llevó a cabo mediante el análisis de los datos correspondientes al período 2008-2018 del Sistema Nacional de Vigilancia en Salud Pública de Colombia (SIVIGILA). Resultados: En el 2015, cuando se detectó por primera vez el chikunguña, este virus tuvo una incidencia mayor (1 359,0 casos por 100 000 personas) que las otras dos enfermedades. En el 2016, cuando se detectó por primera vez la circulación del virus del Zika, la incidencia fue de 296,4 casos por 100 000 personas; el número de casos disminuyó enormemente en los siguientes dos años. Entre el 2015 y el 2018, se observó una reducción sustancial en la frecuencia de la circulación del dengue: se pasó de 334,1 casos por 100 000 personas en el 2015 a 90,7 casos por 100 000 en el 2017 y a 173,1 casos por 100 000 en el 2018. Conclusiones: La disminución en el número de casos del dengue que siguió a la cocirculación de los tres virus podría indicar una posible protección cruzada. Este resultado debe analizarse en otros estudios.

[RESUMO]. Objetivo. Identificar padrões de co-circulação de três vírus (dengue, Zika e chikungunya) na Colômbia de 2008 a 2018 mediante análise de casos notificados ao sistema nacional de vigilância. Métodos. Estudo transversal realizado através de análise de dados de 2008 a 2018 obtidos do Sistema de Vigilância em Saúde Pública da Colômbia (SIVIGILA). Resultados. Em 2015, quando o chikungunya foi detectado pela primeira vez, sua incidência foi superior à das duas outras doenças (1.359,0 casos por 100,000 habitantes). Em 2016, quando a circulação do vírus zika foi detectada pela primeira vez, a incidência foi de 296,4 casos por 100,000 pessoas, decaindo drasticamente nos dois anos seguintes. Entre 2015 e 2018, houve uma redução importante na frequência de circulação do vírus dengue, de 334,1 casos por 100,000 habitantes em 2015 a 90,7 casos por 100,000 em 2017 e 173,1 casos por 100,000 em 2018. Conclusões. A redução do número de casos de dengue após o estabelecimento da co-circulação dos três vírus pode indicar proteção cruzada. Este achado requer análise adicional.

Clinical characteristics of patients hospitalized with severe respiratory illness during influenza seasons in the cities of Bogota and Manizales, Colombia 2000-2006.

OBJECTIVE: Identifying clinical factors associated with respiratory tract diseases during human influenza circulation seasons in children aged less than two years old and adults aged over 65 years in two hospitals in the cities of Manizales and Bogota, Colombia. METHODS: A retrospective case study in patients hospitalized with acute respiratory illness was carried out during influenza circulation seasons from 2000 to 2006 in Bogota and Manizales. Complication frequency was studied, including death, and its relationship with baseline diseases. RESULTS: 535 children under two years of age and 288 adults over 65 years old were studied. 38.9 % of the children and 27 % of the adults had at least one complication. The presence of underlying disease in children was associated with complications such as hospital death (OR=16.5; 4.7-57.7 95%CI), being admitted to an intensive care unit (OR=6.3; 3.5-11.3 95%CI), respiratory distress needing FIO2> 40 % (OR=2.4; 1.6-3.7 95 %CI), mechanical ventilation (OR=2.4; 1.6-3.7 95 %CI) and multilobar pneumonia (OR=2.1; 1.3-3.4 95 %CI). This association remained after adjusting for confounding factors such as age and socioeconomic status, whilst such relationship was not observed in older adults. CONCLUSION: Children with underlying chronic diseases were more susceptible to clinical complications during influenza seasons. Those under 6 months of age were particularly prone to dying or being admitted to an ICU. These results suggested that vaccination policies need to be adjusted.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial.

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28-day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. SAFETY: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

[Cost effectiveness of influenza vaccination in children under 2 years old and elderly in Colombia]. / Costo efectividad de la vacunación contra influenza en menores de 2 años y mayores de 65 años en Colombia.

OBJECTIVE: Estimating the burden of disease associated with influenza virus season and modelling the epidemiological and economic impacts of introducing an inactivated vaccine to Colombia. METHODOLOGY: A complete economic evaluation was done in children aged less than 2 and adults aged over 65. The outcomes evaluated in the under 2-year olds included: the yearly number of cases of acute respiratory infection (ARI), medical visits, hospitalisations and deaths by ARI. The outcomes measured in adults were the number of yearly deaths and hospitalisations due to cardiocirculatory diseases (CCD). RESULTS: Influenza infection in children under 2 years old not having had vaccination may cause 4,300 cases, 2,700 medical visits, 900 hospitalisations and 230 deaths by ARI yearly. Amongst the elder group, influenza infection would be associated with 670 deaths by pneumonia and 1,870 deaths from CCD. The incremental cost effectiveness ratio (ICER) for flu vaccination among children under 2 ranged from USD$ 1,900 to USD$ 2,967 per averted death. ICER was cost saving in adults aged over 65. CONCLUSIONS: This study's results supported the Colombian Ministry of Health's initiative for introducing yearly flu vaccination amongst small children and older adults in Colombia.

Clinical characteristics of patients hospitalized with severe respiratory illness during influenza seasons in the cities of Bogota and Manizales, Colombia 2000-2006 / Características clínicas de pacientes hospitalizados con enfermedad respiratoria severa durante temporadas de influenza en las ciudades de Bogotá y Manizales, Colombia 2000-2006

Objective Identifying clinical factors associated with respiratory tract diseases during human influenza circulation seasons in children aged less than two years old and adults aged over 65 years in two hospitals in the cities of Manizales and Bogota, Colombia. Methods A retrospective case study in patients hospitalized with acute respiratory illness was carried out during influenza circulation seasons from 2000 to 2006 in Bogota and Manizales. Complication frequency was studied, including death, and its relationship with baseline diseases. Results 535 children under two years of age and 288 adults over 65 years old were studied. 38.9 % of the children and 27 % of the adults had at least one complication. The presence of underlying disease in children was associated with complications such as hospital death (OR=16.5; 4.7-57.7 95%CI), being admitted to an intensive care unit (OR=6.3; 3.5-11.3 95%CI), respiratory distress needing FIO2> 40 % (OR=2.4; 1.6-3.7 95 %CI), mechanical ventilation (OR=2.4; 1.6-3.7 95 %CI) and multilobar pneumonia (OR=2.1; 1.3-3.4 95 %CI). This association remained after adjusting for confounding factors such as age and socioeconomic status, whilst such relationship was not observed in older adults. Conclusion Children with underlying chronic diseases were more susceptible to clinical complications during influenza seasons. Those under 6 months of age were particularly prone to dying or being admitted to an ICU. These results suggested that vaccination policies need to be adjusted.

Objetivo Identificar factores clínicos y sociodemográficos asociados a enfermedad respiratoria severa durante las temporadas de circulación de influenza Métodos Se realizó un estudio de casos retrospectivo en pacientes hospitalizados por enfermedad respiratoria aguda durante las temporadas de circulación del virus de la influenza del año 2000 al 2006 en tres hospitales de Bogota y Manizales. Se estudio la frecuencia de complicaciones, incluyendo la muerte, y su relación con la presencia de enfermedades de base. Resultados Se estudiaron 535 niños menores de dos años y 288 adultos mayores de 65 años. En los niños, la presencia de una enfermedad de base se relacionó con complicaciones como la muerte hospitalaria (OR=16,5 IC 95 % 4,7-57,7), , el ingreso a UCI (OR=6,3 IC 95 % 3,5-11,3 ), dificultad respiratoria que ameritaba uso de ventilación mecánica (OR= 2,4 IC 95 % 1,6-3,7),) y, la neumonía multilobar (OR=2,1 IC 95 %1,3-3,4),.Esta asociación se mantenia después de ajustar por factores de confusion como edad y estrato socioeconomico. En los adultos mayores no se observó esta relación. Conclusiones Durante las temporadas de influenza los niños con enfermedad crónica presentan una enfermedad más severa. Los niños menores de 6 meses, que no son objeto de vacunación, mostraron tener mayor frecuencia de complicaciones importantes como la muerte y el ingreso a UCI Es necesario por tal razón tener en cuenta este aspecto para el ajuste en las medidas de prevención y control tales como la vacunación.

Artesunate + amodiaquine versus artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in the Colombian Pacific region: a noninferiority trial / Artesunato + amodiaquina versus artemether-limefantrina para o tratamento da malaria não complicada por Plamodium falciparum no Pacifico Colombiano: um estudo de não inferioridade

INTRODUCTION: In Colombia, there are no published studies for the treatment of uncomplicated Plasmodium falciparum malaria comparing artemisinin combination therapies. Hence, it is intended to demonstrate the non-inferior efficacy/safety profiles of artesunate + amodiaquine versus artemether-lumefantrine treatments. METHODS: A randomized, controlled, open-label, noninferiority (Δ≤5%) clinical trial was performed in adults with uncomplicated P. falciparum malaria using the 28‑day World Health Organization validated design/definitions. Patients were randomized 1:1 to either oral artesunate + amodiaquine or artemether-lumefantrine. The primary efficacy endpoint: adequate clinical and parasitological response; secondary endpoints: - treatment failures defined per the World Health Organization. Safety: assessed through adverse events. RESULTS: A total of 105 patients was included in each group: zero censored observations. Mean (95%CI - Confidence interval) adequate clinical and parasitological response rates: 100% for artesunate + amodiaquine and 99% for artemether-lumefantrine; the noninferiority criteria was met (Δ=1.7%). There was one late parasitological therapeutic failure (1%; artemether-lumefantrine group), typified by polymerase chain reaction as the MAD20 MSP1 allele. The fever clearance time (artesunate + amodiaquine group) was significantly shorter (p=0.002). Respectively, abdominal pain for artesunate + amodiaquine and artemether-lumefantrine was 1.9% and 3.8% at baseline (p=0.68) and 1% and 13.3% after treatment (p<0.001). CONCLUSIONS: Uncomplicated P. falciparum malaria treatment with artesunate + amodiaquine is noninferior to the artemether-lumefantrine standard treatment. The efficacy/safety profiles grant further studies in this and similar populations.

INTRODUÇÃO: Na Colômbia não existem estudos publicados sobre o tratamento da malária não complicada por Plasmodium falciparum comparando as terapias combinadas com artemisinina. Destarte, quer se demonstrar a não inferioridade dos perfis de eficácia/segurança dos tratamentos com artesunato+amodiaquina versus artemeter-lumefantrina. MÉTODOS: Foi realizado um estudo clínico de não inferioridade (∆≤5%), aleatório, controlado, aberto, em adultos com malária não complicada por P. falciparum usando o desenho validado de 28 dias e os desenhos validados/definidos pela Organização Mundial da Saúde. Os pacientes foram aleatorizados (1:1) para ambos artesunato+amodiaquina ou artemeter-lumefantrina orais. Critérios primários de eficácia: resposta clínica e parasitológica adequada; Criterios de eficácia secundários: as falhas de tratamento definidos pela Organização Mundial da Saúde. A segurança: avaliada através de eventos adversos. RESULTADOS: Foram incursos 105 pacientes em cada grupo: zero observações censuradas. As taxas médias da resposta clínica e parasitológica adequada (95% IC - intervalo de confiança): 100% para artesunato+amodiaquina e 99% para artemeter-lumefantrina; atingiu-se o critério de não inferioridade (∆=1.7%). Houve uma falha terapêutica parasitológica tardia (1%; grupo artemeter-lumefantrina), caracterizada mediante reação em cadeia da polimerase como o alelo MAD20 MSP1. Tempo de remissão da febre (grupo artesunato+amodiaquina), foi significativamente mais curto (p=0.002). Dor abdominal, para artesunato+amodiaquina e artemeter-lumefantrina, respectivamente, 1.9% e 3.8% (p=0.68) na linha de base, 1% e 13.3% pós-tratamento (p<0.001). CONCLUSÕES: O tratamento com artesunato+amodiaquina da malária não complicada por P. falciparum é não inferior ao tratamento normal com artemeter-lumefantrina. Os perfis de eficácia/segurança justificam estudos adicionais nesta e outras populações semelhantes.

Costo efectividad de la vacunación contra influenza en menores de 2 años y mayores de 65 años en Colombia / Cost effectiveness of influenza vaccination in children under 2 years old and elderly in Colombia

Objetivo: Estimar la carga de enfermedad asociada a influenza y modelar el impacto epidemiológico y económico de la introducción de la vacuna para influenza en Colombia. Métodos: Se realizó un estudio de evaluación económica completa de la introducción de la vacuna de influenza en dos grupos poblacionales. Los desenlaces seleccionados en menores de dos años fueron la frecuencia de enfermedad respiratoria (ERA), consultas y hospitalizaciones por ERA. En mayores de 65 años se adicionaron las muertes y hospitalizaciones por enfermedad cardiosvascular y cerebrovascular. Resultados: En el escenario sin vacunación, el virus de influenza produciría anualmente 4 300 casos, 2 700 consultas, 900 hospitalizaciones y 230 muertes por ERA en menores de dos años. En mayores de 65 años, se presentarían anualmente 670 muertes por neumonía, 1 150 muertes por enfermedad cardiovascular y 720 muertes por enfermedad cerebrovascular relacionadas con influenza. El costo efectividad de la vacuna en menores de dos años oscila entre US $ 1 900 y US $ 2 967 por muerte evitada mientras que para mayores de 65 años la razón de costo efectividad seria costo ahorrativa. Conclusiones: Los resultados del presente estudio apoyarían la decisión del Ministerio de la Protección Social y algunas Secretarias de Salud de introducir la vacunación en Colombia para menores de dos años y mayores de 65 años.

Objective Estimating the burden of disease associated with influenza virus season and modelling the epidemiological and economic impacts of introducing an inactivated vaccine to Colombia. Methodology A complete economic evaluation was done in children aged less than 2 and adults aged over 65. The outcomes evaluated in the under 2-year olds included: the yearly number of cases of acute respiratory infection (ARI), medical visits, hospitalisations and deaths by ARI. The outcomes measured in adults were the number of yearly deaths and hospitalisations due to cardiocirculatory diseases (CCD). Results Influenza infection in children under 2 years old not having had vaccination may cause 4,300 cases, 2,700 medical visits, 900 hospitalisations and 230 deaths by ARI yearly. Amongst the elder group, influenza infection would be associated with 670 deaths by pneumonia and 1,870 deaths from CCD. The incremental cost effectiveness ratio (ICER) for flu vaccination among children under 2 ranged from USD$ 1,900 to USD$ 2,967 per averted death. ICER was cost saving in adults aged over 65. Conclusions This study's results supported the Colombian Ministry of Health's initiative for introducing yearly flu vaccination amongst small children and older adults in Colombia.

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.