Berta Nelly Restrepo

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

This study compared the serum levels of IL-6, TNF-D and IFN-J, 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-J. No statistically significant differences were found between clinical forms, although IL-6 and IFN-J levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-D levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-D were higher in secondary infection than in primary infection, although IFN-J levels were higher in primary infection. These results suggest that IL-6, TNF-D and IFN-J are involved in dengue infection independently of the clinical form. Key-words: Dengue. IL-6. TNF-D . IFN-J. Children.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.

La leishmaniasis: conocimientos y prácticas en poblaciones de la costa del Pacífico de Colombia

En 1997 se realizo un estudio descriptivo con enfasis cualitativo con objeto de documentar los conocimientos y las practicas relacionados con la leishmaniasis cutanea, segun el sexo, en los habitantes de 14 anos en adelante de siete comunidades del departamento del Choco, Colombia. Los residentes de esa zona de la costa del Pacifico estaban en alto riesgo de contraer leishmaniasis, que se conoce localmente con los nombres de bejuco y yatevi, ya que las actividades de control llevadas a cabo por el Servicio Seccional de Salud del Choco no habian tenido el exito deseado. Se recogieron datos cualitativos involucrando directamente a cada comunidad en talleres de discusion y entrevistando a informantes calificados. Sobre esa base, se elaboro una encuesta de 10 preguntas cerradas, que los investigadores administraron a todas las personas mayores de 14 anos presentes en cada hogar elegido de forma aleatoria para ser visitado. Los resultados indican que 94% de la poblacion estudiada conocia la leishmaniasis como una enfermedad de la piel y este concepto era mas comun entre los hombres que entre las mujeres. En cuanto a la forma de transmision, 35% relacionaron la enfermedad con la picadura de un insecto, pero ignoraban el agente etiologico y consideraban que la producia un gusano que vive en el monte. En las comunidades estudiadas se empleaba una gran variedad de tratamientos para curar la enfermedad. Estos se basaban en el uso de plantas, sustancias quimicas, quemadura de las lesiones con metales calientes y, en menor proporcion, medicamentos. A pesar de que las mujeres tenian la responsabilidad de cuidar a los enfermos en el hogar, su falta de conocimientos sobre el tratamiento fue una variable de analisis estadisticamente significativa, pues no estaban familiarizadas con los tratamientos tradicionales de su comunidad. De las personas encuestadas, 45% no sabian como prevenir la enfermedad, especialmente las mujeres, segun pudo observarse en 102 de 155 respuestas. No se encontraron diferencias atribuibles al genero en los conocimientos y practicas acerca de la leishmaniasis, con excepcion de la falta de conocimiento de las mujeres acerca del tratamiento de la enfermedad. Esta investigacion resalta la importancia de estudiar los conocimientos y practicas de los habitantes locales antes de disenar y organizar programas educativos sobre el control de la leishmaniasis.

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.

Conocimiento y prácticas sobre teniasis-cisticercosis en una comunidad colombiana

Objetivo Determinar los conocimientos y practicas sobre teniasis-cisticercosis y la frecuencia de anticuerpos contra Taenia solium en habitantes de la localidad de Andagoya, Colombia. Metodos Se realizo un estudio cualitativo-cuantitativo. Las poblaciones de estudio fueron los criadores de cerdos y sus familias, poblacion local y cerdos. Resultados La poblacion tiene un conocimiento parcial del complejo teniasis-cisticercosis. Identifica la cisticercosis como una enfermedad solo del cerdo y no del humano, considera la teniasis como una enfermedad de transmision fecal y no ocasionada por el consumo de carne de cerdo con cisticercosis. La crianza de cerdos no se hace en confinamiento y aunque se conocen los habitos higienicos para el control de enfermedades parasitarias su cumplimiento no es adecuado. La presencia de anticuerpos contra T. solium en los criadores de cerdos y sus familiares fue del 8,7 % y en los cerdos del 20,9 %. Conclusion Se debe desarrollar un programa educativo sobre teniasis-cisticercosis que permita sensibilizar a la poblacion para el conocimiento y la aplicacion de medidas de control.

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.

Evaluation of Commercially Available Assays for Diagnosis of Acute Dengue in Schoolchildren During an Epidemic Period in Medellin, Colombia

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. Cohens kappa coefficient and McNemars 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.

Serum platelet-activating factor acetylhydrolase activity in dengue patients of African or mestizo descendency

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: 0.73–1.10 vs. 0.73, CI: 0–1.05, p<0.001), but not significant for dengue hemorrhagic fever (0.88, CI: 0.69–1.12 vs. 0.83, CI: 0.71–1.08, 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.

Association of IL4R-rs1805016 and IL6R-rs8192284 polymorphisms with clinical dengue in children from Colombian populations

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.

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.

Variantes en los genes TNFA, IL6 e IFNG asociadas con la gravedad del dengue en una muestra de población colombiana

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.