RESUMO
Zika, a viral disease transmitted to humans by Aedes mosquitoes, emerged in the Americas in 2015, causing large-scale epidemics. Colombia alone reported over 72,000 Zika cases between 2015 and 2016. Using national surveillance data from 1121 municipalities over 70 weeks, we identified sociodemographic and environmental factors associated with Zika's emergence, re-emergence, persistence, and transmission intensity in Colombia. We fitted a zero-state Markov-switching model under the Bayesian framework, assuming Zika switched between periods of presence and absence according to spatially and temporally varying probabilities of emergence/re-emergence (from absence to presence) and persistence (from presence to presence). These probabilities were assumed to follow a series of mixed multiple logistic regressions. When Zika was present, assuming that the cases follow a negative binomial distribution, we estimated the transmission intensity rate. Our results indicate that Zika emerged/re-emerged sooner and that transmission was intensified in municipalities that were more densely populated, at lower altitudes and/or with less vegetation cover. Warmer temperatures and less weekly-accumulated rain were also associated with Zika emergence. Zika cases persisted for longer in more densely populated areas with more cases reported in the previous week. Overall, population density, elevation, and temperature were identified as the main contributors to the first Zika epidemic in Colombia. We also estimated the probability of Zika presence by municipality and week, and the results suggest that the disease circulated undetected by the surveillance system on many occasions. Our results offer insights into priority areas for public health interventions against emerging and re-emerging Aedes-borne diseases.
Assuntos
Aedes , Cadeias de Markov , Infecção por Zika virus , Zika virus , Infecção por Zika virus/transmissão , Infecção por Zika virus/epidemiologia , Colômbia/epidemiologia , Humanos , Animais , Aedes/virologia , Teorema de Bayes , Mosquitos Vetores/virologia , Surtos de DoençasRESUMO
BACKGROUND: Colombia has one of the highest burdens of arboviruses in South America. The country was in a state of hyperendemicity between 2014 and 2016, with co-circulation of several Aedes-borne viruses, including a syndemic of dengue, chikungunya, and Zika in 2015. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the cases of dengue, chikungunya, and Zika notified in Colombia from January 2014 to December 2018 by municipality and week. The trajectory and velocity of spread was studied using trend surface analysis, and spatio-temporal high-risk clusters for each disease in separate and for the three diseases simultaneously (multivariate) were identified using Kulldorff's scan statistics. During the study period, there were 366,628, 77,345 and 74,793 cases of dengue, chikungunya, and Zika, respectively, in Colombia. The spread patterns for chikungunya and Zika were similar, although Zika's spread was accelerated. Both chikungunya and Zika mainly spread from the regions on the Atlantic coast and the south-west to the rest of the country. We identified 21, 16, and 13 spatio-temporal clusters of dengue, chikungunya and Zika, respectively, and, from the multivariate analysis, 20 spatio-temporal clusters, among which 7 were simultaneous for the three diseases. For all disease-specific analyses and the multivariate analysis, the most-likely cluster was identified in the south-western region of Colombia, including the Valle del Cauca department. CONCLUSIONS/SIGNIFICANCE: The results further our understanding of emerging Aedes-borne diseases in Colombia by providing useful evidence on their potential site of entry and spread trajectory within the country, and identifying spatio-temporal disease-specific and multivariate high-risk clusters of dengue, chikungunya, and Zika, information that can be used to target interventions.
Assuntos
Aedes , Febre de Chikungunya , Dengue , Infecção por Zika virus , Zika virus , Animais , Febre de Chikungunya/epidemiologia , Colômbia/epidemiologia , Dengue/epidemiologia , Humanos , Infecção por Zika virus/epidemiologiaRESUMO
The pathogenesis of the severity of chikungunya infection is not yet fully understood. OBJECTIVE: To assess the role of the cytokines/chemokines and system of complement in the evolution of chikungunya infection. METHODS: In both acute and chronic phases, we measured the serum levels of 12 cytokines/chemokines and two complement mediators: mannose-binding lectin (MBL) and C3a, in 83 patients with chikungunya infection and ten healthy controls. RESULTS: During the acute phase, 75.9% of the patients developed musculoskeletal disorders, and in 37.7% of them, these disorders persisted until the chronic phase. In general, patients had higher levels of cytokines than healthy controls, with significant differences for IFN-γ, IL-6, IL-8, IL-10, and MIP-1. Most cytokines exhibited a downward trend during the chronic phase. However, only IL-10, and MIP-1 levels were significantly lower in the chronic phase. Additionally, these levels never decreased to concentrations found in healthy controls. Moreover, MBL levels were significantly higher in the acute phase compared with the chronic phase. C3a levels were significantly higher in patients with musculoskeletal disorder compared with patients without it, in both acute-phase 118.2 (66.5-252.9), and chronic phase 68.5 (64.4-71.3), P < 0.001. Interestingly, C3a levels were significantly higher when patients had a severe disease version. Besides, in the acute phase, C3a levels were higher in patients that suffer arthritis as opposed to when they suffer arthralgia, 194.3 (69.5-282.2), and 70.9 (62.4-198.8), P = 0.013, respectively. CONCLUSIONS: Our results showed an immunological response that persisted until the chronic phase and the role of the complement system in the severity of the disease.
RESUMO
The spatial distribution of surveillance-reported dengue cases and severity are usually analyzed separately, assuming independence between the spatial distribution of non-severe and severe cases. Given the availability of data for the individual geo-location of surveillance-notified dengue cases, we conducted a spatial analysis to model non-severe and severe dengue simultaneously, using a hierarchical Bayesian model. We fit a joint model to the spatial pattern formed by dengue cases as well as to the severity status of the cases. Results showed that age and socioeconomic status were associated with dengue presence, and there was evidence of clustering for overall cases but not for severity. Our findings inform decision making to address the preparedness or implementation of dengue control strategies at the local level.
Assuntos
Dengue , Dengue Grave , Teorema de Bayes , Colômbia/epidemiologia , Dengue/epidemiologia , Dengue/prevenção & controle , HumanosRESUMO
BACKGROUND: Chikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities. METHODOLOGY/PRINCIPAL FINDINGS: To assess the scope and degree of arboviruses reporting in Colombia between 2014-2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses' reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21-70%) followed by Zika (6-45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias. CONCLUSIONS: These findings reflect challenges on arboviruses' reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.
Assuntos
Arbovírus/patogenicidade , Febre de Chikungunya/epidemiologia , Dengue/epidemiologia , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Arbovírus/classificação , Febre de Chikungunya/mortalidade , Criança , Pré-Escolar , Cidades/epidemiologia , Colômbia/epidemiologia , Dengue/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Análise de Regressão , Adulto Jovem , Infecção por Zika virus/mortalidadeRESUMO
BACKGROUND: Etiologic studies provide evidence that IL-4R and IL-6R receptors may play important roles in the regulatory mechanisms of the development of clinical dengue, especially in children which is a segment of the population with high severe dengue risk. Moreover, the allele frequencies and genetic associations may be influenced by the populational genetic background. Therefore, we performed a case-control study to evaluate possible associations between SNPs in IL4R and IL6R genes and clinical dengue in children from two Colombian populations. METHODS: We genotyped the rs1805016 (IL4R) and rs8192284 (IL6R) by PCR-RFLP method, in 298 symptomatic children and 648 asymptomatic controls. Three individual genetic ancestral proportions (APs) (European, Amerindian, African) were inferred by genotyping 29 AIMs (Ancestry informative markers). The variables gender, APs, and the population of origin were used like confusion variables. RESULTS: We found IL4R-rs1805016 GG genotype and G-allele carriers and IL6R-rs8192284 AA genotype associated with clinical dengue in the pooled and Huila samples. Nevertheless, we found no association of these polymorphisms in the sample of Antioquia. CONCLUSIONS: For the first time, we report SNPs in IL4R and IL6R genes associated with clinical dengue, which contributes to understanding the genetic susceptibility to dengue disease. Moreover, these results may be influenced by genetic background and must be evaluated through functional analysis.
Assuntos
Dengue/genética , Predisposição Genética para Doença , Subunidade alfa de Receptor de Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
Although dengue can progress to severe stages, the exact causes of this phenomenon are unknown; however, the possibility of monocyte participation is acknowledged. It has been suggested that monocyte subsets (classical, intermediate and non-classical) play differential roles in dengue immunopathology. Therefore, we determined the count of monocyte subsets and obtained the clinical information of patients with dengue. We noted a significant decrease in the count of non-classical monocytes in patients compared with controls. With this finding, we focused on studying the phenotype of non-classical monocytes in the present study. An increase in activation and differentiation markers, such as CD64, CD86, the percentage of tumor necrosis factor-α+ cells and exposure of phosphatidylserine, were recorded in the non-classical monocytes of patients compared with controls. Moreover, a significant decrease in the expression of CX3CR1 with a corresponding increase in the expressions of CCR2, CCR5, CD11b and CD54 was detected in the non-classical monocytes of patients in comparison with that of the controls. Significant increases in the frequency of microparticles from endothelium and in the concentrations of interleukin-6 (IL-6), IL-8 and IL-10 were noted in the plasma of patients. These findings demonstrate that in patients with dengue, non-classical monocytes are activated, exhibiting a phenotype associated with more differentiation, produces tumor necrosis factor-α and has a profile of less endothelial surveillance closer to the cellular migration. These changes were associated with hepatic compromise, endothelial alteration and high concentration of circulating cytokines. Hence, alterations of non-classical monocytes seem to be associated with the immunopathology of dengue infection.
Assuntos
Dengue/imunologia , Endotélio Vascular/imunologia , Fígado/imunologia , Monócitos/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Adolescente , Adulto , Idoso , Antígenos CD/imunologia , Citocinas/imunologia , Dengue/patologia , Endotélio Vascular/patologia , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Receptores de Quimiocinas/imunologia , Síndrome de Resposta Inflamatória Sistêmica/patologiaRESUMO
RESUMEN Objetivo Determinar la actividad en suero de CK y CK-MB en pacientes con dengue. Métodos Se realizó un estudio de corte en el Departamento de Antioquia. La población de estudio estuvo constituida por 54 pacientes con diagnóstico de dengue y por 10 controles sanos. A todos los participantes se les tomó muestra de suero para confirmar la infección por dengue y para hacer la medición de la actividad de CK y CK-MB. Resultados La mediana de la edad de los casos de dengue fue 18 años y la de los controles fue 28,5 años. La mitad de los pacientes con dengue (50,9 %) y ninguno del grupo control presentaron CK-MB elevada. Ningún paciente presentó miocarditis, sin embargo, se observó CK-MB elevada en 33,3 %, 44,4 % y 40 % de los casos con bradicardia, taquicardia e hipotensión respectivamente. En 29,6 % de los pacientes con dengue se detectó CK elevada, en contraste con 10 % en el grupo control. Se observó actividad de CK en pacientes con dengue con presencia de síntomas como vómito, hematemesis y dolor abdominal, 87,5 %, 60 % y 50 % respectivamente. Conclusiones En este estudio ningún paciente con dengue presentó cardiopatía o miositis, sin embargo, el hecho de encontrar mayor frecuencia de CK y CK-MB elevadas en los pacientes con dengue con respecto al grupo control, sugiere compromiso del músculo estriado y cardíaco en este grupo. Por esta razón sería pertinente el monitoreo de estas enzimas en pacientes con dengue como parte de la evolución de la enfermedad.(AU)
ABSTRACT Objective To determine the serum activity of CK and CK-MB in patients with dengue infection. Methods A cross section study was conducted in the State of Antioquia, Colombia. The study population consisted in 54 patients with diagnosis of dengue infection and 10 healthy controls. A blood sample was taken from all participants to confirm dengue infection and to measure the activity of CK and CK-MB. Results The median age of dengue cases was 18 years and the median age of healthy controls was 28.5 years. Half of dengue patients (50.9 %) had elevated levels of CK-MB, in contrast with the healthy controls in which none presented increase of this enzyme. No patient presented myocarditis; however, elevated CK-MB was observed in 33.3 %, 44.4 % and 40 % of cases with bradycardia, tachycardia and hypotension respectively. In 29.6 % of the dengue patients, high level of CK was detected, in contrast to 10 % in the control group. Activity of CK elevated was observed in dengue patients with symptoms such as vomiting, hematemesis and abdominal pain, 87.5 %, 60 % and 50 %, respectively. Conclusions In this study, no patient with dengue infection had heart disease or myositis; however, the finding of a higher frequency of elevated level CK and CK-MB in the dengue patients compared to the control group suggests the involvement of the striated muscle and of the cardiac muscle in this group. For this reason, the monitoring of these enzymes should be considered as part of the monitoring of patients with dengue.(AU)
Assuntos
Humanos , Creatina/sangue , Dengue/epidemiologia , Vírus da Dengue/isolamento & purificação , Epidemiologia Descritiva , Colômbia/epidemiologiaRESUMO
OBJECTIVE: To determine the serum activity of CK and CK-MB in patients with dengue infection. METHODS: A cross section study was conducted in the State of Antioquia, Colombia. The study population consisted in 54 patients with diagnosis of dengue infection and 10 healthy controls. A blood sample was taken from all participants to confirm dengue infection and to measure the activity of CK and CK-MB. RESULTS: The median age of dengue cases was 18 years and the median age of healthy controls was 28.5 years. Half of dengue patients (50.9 %) had elevated levels of CK-MB, in contrast with the healthy controls in which none presented increase of this enzyme. No patient presented myocarditis; however, elevated CK-MB was observed in 33.3 %, 44.4 % and 40 % of cases with bradycardia, tachycardia and hypotension respectively. In 29.6 % of the dengue patients, high level of CK was detected, in contrast to 10 % in the control group. Activity of CK elevated was observed in dengue patients with symptoms such as vomiting, hematemesis and abdominal pain, 87.5 %, 60 % and 50 %, respectively. CONCLUSIONS: In this study, no patient with dengue infection had heart disease or myositis; however, the finding of a higher frequency of elevated level CK and CK-MB in the dengue patients compared to the control group suggests the involvement of the striated muscle and of the cardiac muscle in this group. For this reason, the monitoring of these enzymes should be considered as part of the monitoring of patients with dengue.
OBJETIVO: Determinar la actividad en suero de CK y CK-MB en pacientes con dengue. MÉTODOS: Se realizó un estudio de corte en el Departamento de Antioquia. La población de estudio estuvo constituida por 54 pacientes con diagnóstico de dengue y por 10 controles sanos. A todos los participantes se les tomó muestra de suero para confirmar la infección por dengue y para hacer la medición de la actividad de CK y CK-MB. RESULTADOS: La mediana de la edad de los casos de dengue fue 18 años y la de los controles fue 28,5 años. La mitad de los pacientes con dengue (50,9 %) y ninguno del grupo control presentaron CK-MB elevada. Ningún paciente presentó miocarditis, sin embargo, se observó CK-MB elevada en 33,3 %, 44,4 % y 40 % de los casos con bradicardia, taquicardia e hipotensión respectivamente. En 29,6 % de los pacientes con dengue se detectó CK elevada, en contraste con 10 % en el grupo control. Se observó actividad de CK en pacientes con dengue con presencia de síntomas como vómito, hematemesis y dolor abdominal, 87,5 %, 60 % y 50 % respectivamente. CONCLUSIONES: En este estudio ningún paciente con dengue presentó cardiopatía o miositis, sin embargo, el hecho de encontrar mayor frecuencia de CK y CK-MB elevadas en los pacientes con dengue con respecto al grupo control, sugiere compromiso del músculo estriado y cardíaco en este grupo. Por esta razón sería pertinente el monitoreo de estas enzimas en pacientes con dengue como parte de la evolución de la enfermedad.
Assuntos
Creatina Quinase Forma MB/sangue , Creatina Quinase/sangue , Dengue/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Colômbia , Dengue/sangue , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
During an active surveillance study in school children in Medellin, we assessed the performance of two diagnostic strategies for dengue virus. A total of 41 patients with suspected dengue acute infection were evaluated. Diagnostic strategies consisted of one combining Panbio(®) Dengue virus IgM and IgG Capture ELISAs (enzyme-linked immunosorbent assays) with reverse transcriptase polymerase chain reaction (RT-PCR) and another using a commercial rapid SD Bioline Dengue Duo (IgG/IgM + NS1 Ag) test. These two strategies were compared with the enzyme-linked immunospot microneutralization test (ELISPOT-MNT). The sensitivity and specificity were 53.9% and 80.0% for the combination of Panbio(®) ELISAs and RT-PCR tests, and 30.8% and 73.3% for the SD Bioline Duo test, respectively. ELISPOT-MNT detected 16.4% additional cases and revealed the presence of neutralizing antibodies in all the acute samples, evidencing that they were all secondary infections. In contrast, Panbio(®) and SD Dengue Duo rapid tests only classified 23.0% and 26.9% of the cases as secondary dengue infections, respectively. Cohen's kappa coefficient and McNemar's association tests demonstrated a significant disagreement between the two diagnostic strategies and ELISPOT-MNT. Overall, these results evidence the relatively poor performances of commercial assays for the diagnosis of acute and secondary dengue infections, compared with ELISPOT-MNT, and raise concern about the accuracy of these assays for the diagnostic of dengue in endemic areas.