Spatiotemporal distribution and socioeconomic disparities of dengue, chikungunya and Zika in two Latin American cities from 2007 to 2017.

OBJECTIVE: To assess the presence, pattern and magnitude of socioeconomic inequalities on dengue, chikungunya and Zika in Latin America, accounting for their spatiotemporal distribution. METHODS: Using longitudinal surveillance data (reported arboviruses) from Fortaleza, Brazil and Medellin, Colombia (2007-2017), we fit Bayesian hierarchical models with structured random effects to estimate: (i) spatiotemporally adjusted incidence rates; (ii) Relative Concentration Index and Absolute Concentration Index of inequality; (iii) temporal trends in RCIs; and (iv) socioeconomic-specific estimates of disease distribution. The spatial analysis was conducted at the neighbourhood level (urban settings). The socioeconomic measures were the median monthly household income (MMHI) for Brazil and the Socio-Economic Strata index (SES) in Colombia. RESULTS: There were 281 426 notified arboviral cases in Fortaleza and 40 887 in Medellin. We observed greater concentration of dengue among residents of low socioeconomic neighbourhoods in both cities: Relative Concentration Index = -0.12 (95% CI = -0.13, -0.10) in Fortaleza and Relative Concentration Index = -0.04 (95% CI = -0.05, -0.03) in Medellin. The magnitude of inequalities varied over time across sites and was larger during outbreaks. We identified a non-monotonic association between disease rates and socioeconomic measures, especially for chikungunya, that changed over time. The Relative Concentration Index and Absolute Concentration Index showed few if any inequalities for Zika. The socioeconomic-specific model showed increased disease rates at MMHI below US$400 in Brazil and at SES-index below level four, in Colombia. CONCLUSIONS: We provide robust quantitative estimates of socioeconomic inequalities in arboviruses for two Latin American cities. Our findings could inform policymaking by identifying spatial hotspots for arboviruses and targeting strategies to decrease disparities at the local level.

Genome-wide Ancestry and Demographic History of African-Descendant Maroon Communities from French Guiana and Suriname.

The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa.

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

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

Ischemic Stroke During Dengue Infection: A Report of 2 Cases.

BACKGROUND Involvement of the central nervous system during infection with dengue virus (DENV) is recognized. However, ischemic stroke is rarely reported. Herein are described 2 cases of patients with ischemic stroke in which DENV infection was demonstrated. CASE REPORT The first patient was a 51-year-old woman that presented altered consciousness, monoparesis, facial palsy, dysarthria, Babinski sign, and syncope 7 days from the onset of fever. She had a history of carotid artery atherothrombosis and previous stroke. Magnetic resonance imaging (MRI) showed an acute infarction of the right middle cerebral artery. DENV was confirmed by the presence of NS1 and IgM in serum. The patient was treated with intravenous fluids and recovered well, with only right facial paresis still present at discharge. The second patient was a 50-year-old man who presented with headache, altered consciousness, and mutism after a febrile episode 1 week prior. This patient had a previous history of stroke, glioblastoma resection, epilepsy, hypothyroidism, and diabetes. MRI demonstrated a subacute ischemic event. The diagnosis of dengue was confirmed by serum NS1 and IgM and by RT-PCR in serum and cerebrospinal fluid. DENV-1 serotype was observed in serum and cerebrospinal fluid. The patient was treated with intravenous fluids and was discharged in good condition. In both patients, thrombocytopenia and leukopenia was demonstrated, and hemoconcentration was demonstrated in the second patient. CONCLUSIONS In tropical and subtropical countries, DENV infection can represent a potential cause of ischemic stroke in patients with a history of comorbidities, including stroke.

Decomposition of socioeconomic inequalities in arboviral diseases in Brazil and Colombia (2007-2017).

BACKGROUND: We used surveillance data from Brazil and Colombia during 2007-2017 to assess the presence of socioeconomic inequalities on dengue, chikungunya and Zika at the neighborhood level in two Latin American cities. METHODS: To quantify the inequality, we estimated and decomposed the relative concentration index of inequality (RCI) accounting for the spatiotemporal distribution of the diseases. RESULTS: There were 281 426 arboviral cases notified in Fortaleza, Brazil, and 40 889 in Medellin, Colombia. The RCI indicated greater concentration of dengue cases among people living in low socioeconomic settings in both sites. The RCIs for chikungunya in Fortaleza covered the line of equality during their introduction in 2014, while the RCIs for Zika and chikungunya in Medellin indicated the presence of a small inequality. The RCI decomposition showed that year of notification and age were the main contributors to this inequality. In Medellin, the RCI decomposition showed that age and access to waste management accounted for 75.5%, 72.2% and 54.5% of the overall inequality towards the poor for dengue, chikungunya and Zika, respectively. CONCLUSIONS: Our study presents estimates of the socioeconomic inequality of arboviruses and its decomposition in two Latin American cities. We corroborate the concentration of arboviral diseases in low socioeconomic neighborhoods and identify that year of occurrence, age, presence of healthcare facilities and waste management are key determinants of the heterogenous distribution of endemic arboviruses across the socioeconomic spectrum.

Importance of clinical and laboratory characteristics in the diagnosis of dengue and chikungunya co-infection: Probable case report / Importancia de las características clínicas y de laboratorio en el diagnóstico de las infecciones concomitantes por dengue y chikungunya: reporte de un caso probable.

We report the case of a 38-year-old woman who initially consulted for an undifferentiated fever. Although her clinical condition evolved with signs and symptoms compatible with dengue with alarm signs and that the anti-dengue IgM detection in a single sample indicated it was a probable case that could have happened during the previous three months, the patient kept consulting due to little improvement. On the tenth day after the onset of symptoms, she presented with painful polyarticular symmetric edema, as well as hyperpigmented lesions in the nasolabial fold. Chikungunya diagnosis was confirmed by the presence of IgM antibodies. In endemic countries for dengue and chikungunya, the possibility of co-infection exists, but it may go unnoticed. On the other hand, the co-infection may worsen the clinical course of these diseases. Therefore, physicians should evaluate the clinical and laboratory characteristics of both infections to be able to diagnose the coinfection for adequate management and to minimize complications.

Se presenta el caso de una mujer de 38 años que consultó inicialmente por fiebre indiferenciada. A pesar de que el cuadro clínico evolucionó con manifestaciones clínicas de dengue con signos de alarma y de que la detección de IgM antidengue en una sola muestra indicaba que se trataba de un caso probable que había podido ocurrir durante los tres meses anteriores, la paciente consultó de forma reiterada, pues no presentaba una mejoría significativa. En el décimo día del inicio de los síntomas, se observó edema simétrico en múltiples articulaciones acompañado de dolor, así como lesiones hiperpigmentadas en el surco nasogeniano. Se confirmó el diagnóstico de chikungunya por la presencia de anticuerpos IgM. Aunque puede pasar desapercibida, en los países endémicos para dengue y chikungunya existe la posibilidad de la infección concomitante, la cual puede agravar la evolución clínica de cada una de estas enfermedades. Por ello, es necesario que el médico considere las características clínicas y de laboratorio de ambas enfermedades para diagnosticar su presencia simultánea, garantizar un manejo adecuado y minimizar las complicaciones.

Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gamma in infants with and without dengue.

This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls). The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, although IL-6 and IFN-gamma levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-alpha levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-alpha were higher in secondary infection than in primary infection, although IFN-gamma levels were higher in primary infection. These results suggest that IL-6, TNF-alpha and IFN-gamma are involved in dengue infection independently of the clinical form.

Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia.

Functional immunological evidence supports the impact that the host genetic variability has on the susceptibility to develop asymptomatic or symptomatic dengue infection. Children are more prone to develop severe dengue. Thus, we have evaluated possible associations between single-nucleotide polymorphisms (SNPs) located in immune genes and the development of symptomatic dengue in children from two Colombian populations with differences in genetic backgrounds and geographical features. We genotyped 15 SNPs (in 12 genes) in 298 symptomatic children and 648 healthy controls. Ancestry proportions (APs) were inferred by genotyping 29 ancestry informative markers. We observed four SNPs associated with susceptibility to develop dengue in NOD1, RIPK2, MICB, or PLCE1 genes. Conversely, we found one SNP in TNF gene and two haplotypes in the IKBKE gene associated with resistance to develop dengue. These associations were adjusted by gender, APs, and the population of origin because the association of polymorphisms may be different in admixed populations like Colombian. To our knowledge, this is the first reported association study with dengue in IKBKE, RIPK2, and NOD1 genes. We have also confirmed previously reported associations in MICB and PLCE1 genes with dengue. Overall, our results contribute to the understanding of the genetic susceptibility/resistance to develop symptomatic dengue. Nevertheless, these associations must be validated through functional analysis.

[Variants in the TNFA, IL6 and IFNG genes are associated with the dengue severity in a sample from Colombian population].

INTRODUCTION: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines. OBJECTIVE: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population. MATERIALS AND METHODS: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chi-square and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component. RESULTS: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components. CONCLUSIONS: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.

[The clinical behavior of dengue in patients hospitalized in the Antonio Roldán Betancur Hospital of Apartadó, Antioquia, 2000]. / Caracterización clínica de los casos de dengue hospitalizados en la E.S.E. Hospital "Antonio Roldán Betancur", Apartadó, Antioquia, Colombia, 2000.

INTRODUCTION: Dengue has exhibited an epidemic behaviour in Apartad6 since 1998. OBJECTIVE: To describe the clinical behavior of dengue in patients hospitalized with this diagnosis in the Antonio Roldán Betancur Hospital of Apartadó in the year 2000. MATERIALS AND METHODS: Descriptive retrospective study with variables obtained from clinical records of patients hospitalized with dengue in the Antonio Roldán Betancur Hospital of Apartadó. RESULTS: 45 patients with the diagnosis of dengue were hospitalized during the study period, all of them with IgM antibodies against dengue virus. Three (6.7%) patients were classified as classic dengue fever, 22 (48.9%) as dengue fever with haemorrhagic manifestations, and 20 patients (44.4%) were classified as dengue haemorrhagic fever. Patient age ranged from 4 months to 68 years, with a mean of 22.1 years. The great majority of patients (82.8%) came from urban areas. The most frequent clinical manifestations were fever (100%), myalgia (71.1%), joint pain (71.1%), headache (70%) and abdominal pain (67.5%). The most frequent haemorrhagic manifestations were petechiae (60%), hematuria (31.7%), ecchymoses on venipuncture sites (24.4%), gastric bleeding (22.2%) and abnormal vaginal bleeding (15.5%). Platelet count ranged from 11.000 to 186.000/mm3, with a mean of 48.688. Hematocrit ranged from 26% to 59% with a mean of 41.5%. Four of the 45 patients died. 40% of patients had other co-morbidities; coinfection with malaria was the most frequent amongst them (8 patients, 17.7%). CONCLUSION: Two remarkable findings of our descriptive retrospective study were the high mortality of dengue in our population (8.8%) 4/45, specially in children under 1 year of age (3/4) and the high incidence of simultaneous infection with malaria parasites.

[Nutritional status of indigenous children aged up to six years in the Embera-Katio Indian reserve in Tierralta, Cordoba, Colombia]. / Estado nutricional de niños y niñas indígenas de hasta seis años de edad en el resguardo Embera-Katío, Tierralta, Córdoba, Colombia.

INTRODUCTION: Knowledge of the nutritional state of the children is an valuable indicator of the general state of development in an entire population. OBJECTIVE: The prevalence of malnutrition was determined in Embera-Katio's indigenous children, aged 0-6 years, and associated factors associated with malnutrition were identified. MATERIALS AND METHODS: A cross-sectional study was undertaken in the Resguardo Embera-Katío, in Tierralta in the Province of Cordoba, located in northern Colombia. The weight, height and cephalic perimeter was assessed for each of 272 children under six years of age. Nutritional paramterers were surveyed in 194 homes; fecal samples of 172 children were examined for evidence of intestinal parasites. RESULTS: Prevalence of moderate and severe chronic malnutrition was found in 63.6% of the children's; 8.8% were categorized with slight and moderate acute malnutrition. Chronic malnutrition was associated with age increase (p=0.005) and was greater in males than in females (89.9% versus 80.4%; p=0.028). Chronic malnutrition was greater in children with acute respiratory infection, acute diarrheas, and in homes with three or more children below the age of five. In 74% of the children, the cephalic perimeter was below the fifth percentile. After weaning, the children were fed a basic diet of rice and corn (80.4%) and plantain (80.9%). Only 28.9% ate meat, 4.6% eggs, 4.1% milk and 1.5% fruits and vegetables. The prevalence of intestinal parasitism was 78.1%. CONCLUSIONS: The prevalence of chronic malnutrition in the Embera-Katio children was high, reflecting the adverse nutritional and economic conditions in which they live.

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

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

Importancia de las características clínicas y de laboratorio en el diagnóstico de las infecciones concomitantes por dengue y chikungunya: reporte de un caso probable / Importance of clinical and laboratory characteristics in the diagnosis of dengue and chikungunya co-infection: Probable case report

Se presenta el caso de una mujer de 38 años que consultó inicialmente por fiebre indiferenciada. A pesar de que el cuadro clínico evolucionó con manifestaciones clínicas de dengue con signos de alarma y de que la detección de IgM antidengue en una sola muestra indicaba que se trataba de un caso probable que había podido ocurrir durante los tres meses anteriores, la paciente consultó de forma reiterada, pues no presentaba una mejoría significativa. En el décimo día del inicio de los síntomas, se observó edema simétrico en múltiples articulaciones acompañado de dolor, así como lesiones hiperpigmentadas en el surco nasogeniano. Se confirmó el diagnóstico de chikungunya por la presencia de anticuerpos IgM. Aunque puede pasar desapercibida, en los países endémicos para dengue y chikungunya existe la posibilidad de la infección concomitante, la cual puede agravar la evolución clínica de cada una de estas enfermedades. Por ello, es necesario que el médico considere las características clínicas y de laboratorio de ambas enfermedades para diagnosticar su presencia simultánea, garantizar un manejo adecuado y minimizar las complicaciones.

We report the case of a 38-year-old woman who initially consulted for an undifferentiated fever. Although her clinical condition evolved with signs and symptoms compatible with dengue with alarm signs and that the anti-dengue IgM detection in a single sample indicated it was a probable case that could have happened during the previous three months, the patient kept consulting due to little improvement. On the tenth day after the onset of symptoms, she presented with painful polyarticular symmetric edema, as well as hyperpigmented lesions in the nasolabial fold. Chikungunya diagnosis was confirmed by the presence of IgM antibodies. In endemic countries for dengue and chikungunya, the possibility of co-infection exists, but it may go unnoticed. On the other hand, the co-infection may worsen the clinical course of these diseases. Therefore, physicians should evaluate the clinical and laboratory characteristics of both infections to be able to diagnose the coinfection for adequate management and to minimize complications.

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

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

African genetic ancestry is associated with a protective effect on Dengue severity in colombian populations.

The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African ancestry, 95% confidence interval (0.934-0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947-0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952-0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies.

Hallazgos postmortem en infección por el virus del dengue / Posmorten findings in dengue virus infection

Resumen El dengue es una arbovirosis de países tropicales y subtropicales. La infección por este virus se clasifica en dengue con o sin signos de alarma y dengue grave. Una consecuencia de las formas graves de esta infección es la letalidad que puede oscilar entre 1 a 5 %. Se considera que la extravasación de plasma es el fenómeno más importante que determina su severidad. Con el fin de darle una mejor comprensión de los efectos de esta enfermedad, se hizo una revisión narrativa de los hallazgos postmortem de pacientes que han fallecido por dengue.

Abstract Dengue is an arbovirus of tropical and subtropical countries. The infection caused by this virus may be classified such dengue with or without signs of alarm and severe dengue. One consequence of the severe forms of this infection is the lethality which can range from 1 to 5 %. It is considered that plasma leakage is the most important phenomen that determines the severity. In order to have a better understanding about of the effects of the dengue virus, a narrative review was done of post-mortem findings of patients who have died of dengue virus infection.

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

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

Variantes en los genes TNFA , IL6 e IFNG asociadas con la gravedad del dengue en una muestra de población colombiana / Variants in the TNFA , IL6 and IFNG genes associated with dengue severity in a sample of Colombian population

Resumen Introducción. La composición genética del huésped determina, entre otros aspectos, el perfil clínico del dengue, lo cual se debería al efecto de variantes en los genes que codifican citocinas proinflamatorias. Objetivo. Evaluar la asociación entre las variantes de tres polimorfismos en los genes candidatos TNFA, IL6 e IFNG con la gravedad del dengue en una población colombiana. Materiales y métodos. Se evaluaron los polimorfismos rs1800750, rs2069843 y rs2069705 de los genes TNFA, IL6 e IFNG, respectivamente, en 226 pacientes con dengue. Los genotipos se tipificaron usando la reacción en cadena de la polimerasa (PCR) y los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Para determinar el riesgo de diferentes fenotipos del dengue, se compararon las frecuencias alélicas con la prueba de ji al cuadrado, y los genotipos y los haplotipos, con regresión logística. Por último, los análisis se ajustaron utilizando datos de autoidentificación o del componente genético ancestral. Resultados. El alelo A del rs2069843, ajustado por autoidentificación, se asoció con casos de dengue hemorrágico en afrocolombianos. En la muestra completa, dicho polimorfismo, ajustado por componente genético ancestral, fue reproducible. Además, hubo asociaciones significativas entre las combinaciones alélicas GGT y GAC de los rs1800750, rs2069843 y rs2069705 en pacientes con dengue hemorrágico, con ajuste por componente genético ancestral y sin él. Además, la combinación alélica AGC produjo 58,03 pg/ml más de interleucina 6 que la GGC, independientemente de los componentes genéticos europeo, amerindio y africano. Conclusión. Las variantes de los polimorfismos GGT y GAC de los rs1800750, rs2069843 y rs2069705 en los genes TNFA, IL6 e IFNG, respectivamente, se correlacionaron con la gravedad del dengue en esta muestra de población colombiana.

Abstract Introduction: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines. Objective: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population. Materials and methods: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chisquare and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component. Results: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components. Conclusions: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.

[Serum platelet-activating factor acetylhydrolase activity in dengue patients of African or mestizo descendency]. / Actividad sérica de la acetilhidrolasa del factor activador de plaquetas en pacientes afrodescendientes y mestizos con dengue, Colombia.

INTRODUCTION: Severe dengue infection is characterized by enhanced vascular permeability produced by cytokines and biochemical mediators. One of these mediators is the platelet-activating factor. Degradation of platelet-activating factor is accomplished by its specific acetylhydrolase. Down or up regulation of this enzyme has been linked to several diseases. However, the role of this enzyme in dengue infection is unknown, a well as whether differential activity occurs by ethnic group. OBJECTIVE: The activity of the platelet-activating factor-acetylhydrolase was compared in patients infected with dengue virus in two ethnic groups. MATERIAL AND METHODS: A descriptive, prospective and longitudinal study was made in two states of Colombia (Antioquia and Chocó). Serum samples were taken from 43 mestizo patients and 33 patients of African descent, each taken during five consecutive days of the acute dengue phase. A second serum sample was taken during the convalescent phase. RESULTS: The mestizo patients showed higher frequency of dengue hemorrhagic fever than the patients of African descent (23.3% vs. 12.1%, p=0.25). The serum activity of the platelet-activating factor acetylhydrolase was higher in African descendents than in mestizos (0.89, CI: 0.72-1.10 vs. 0.76 CI: 0-1.03, p<0.001). This relationship is maintained for occurence of dengue fever (0.89, CI: 0.73­1.10 vs. 0.73, CI: 0­1.05, p<0.001), but not significant for dengue hemorrhagic fever (0.88, CI: 0.69­1.12 vs. 0.83, CI: 0.71­1.08, p=0.89). CONCLUSION. An increased production of platelet-activating factor-acetylhydrolase occurs in the serum of dengue-infected African descendants. However, a study of the frequencies of polymorphisms for this enzyme will permit more conclusive support for these observations.

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

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

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