IFNγ Response to Mycobacterium tuberculosis, Risk of Infection and Disease in Household Contacts of Tuberculosis Patients in Colombia

OBJECTIVES: Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNgamma produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNgamma levels in HHCs correlate with tuberculosis development. METHODS: A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. RESULTS: Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNgamma responders to CFP-10 (HR 1.82 95% CI 0.79-4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNgamma producers was observed (trend Log rank p = 0.007). DISCUSSION: CFP-10-induced IFNgamma production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprophylaxis to child contacts regardless of BCG vaccination

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects

Background The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer’s disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies.Q2Q2Antecedentes La población colombiana, así como la de otras regiones latinoamericanas, surgió de una mezcla tricontinental reciente entre los nativos americanos, los invasores españoles y los africanos esclavizados, todos los cuales pasaron por un cuello de botella poblacional debido a enfermedades infecciosas generalizadas que dejaron a pequeños aislados. asentamientos locales. Como resultado, la población actual refleja múltiples efectos fundadores derivados de diversas ascendencias. Métodos Caracterizamos el papel de la mezcla y los efectos fundadores en el origen del paisaje mutacional que condujo a trastornos neurodegenerativos en estas circunstancias históricas. Genomas de 900 individuos colombianos con enfermedad de Alzheimer (EA) [n = 376], continuo degeneración lobar frontotemporal-enfermedad de la motoneurona (FTLD-MND) [n = 197], demencia de inicio temprano no especificada (EOD) [n = 73 ], y participantes sanos [n = 254] fueron analizados. Examinamos sus proporciones de ascendencia global y local y examinamos esta cohorte en busca de variantes nocivas en los genes que causan enfermedades y confieren riesgos. Resultados Identificamos 21 variantes patogénicas en genes relacionados con AD-FTLD, y PSEN1 albergaba la mayoría (11 variantes patogénicas). Se identificaron variantes de las tres ascendencias continentales. Las variantes heterocigotas y homocigotas de TREM2 fueron las más comunes entre los genes de riesgo de EA (102 portadores), un punto de interés porque el riesgo de enfermedad conferido por estas variantes difería según la ascendencia. Varias variantes genéticas que tienen una asociación conocida con MND en poblaciones europeas tenían fenotipos FTLD en un haplotipo nativo americano. De acuerdo con los efectos del fundador, la identidad por descendencia entre portadores de la misma variante fue frecuente. Conclusiones La demografía colombiana con múltiples mini-cuellos de botella probablemente mejoró la detección de eventos fundadores y dejó una frecuencia proporcionalmente más alta de variantes raras derivadas de las poblaciones ancestrales. Estos hallazgos demuestran el papel de la ascendencia definida genómicamente en la expresión fenotípica de la enfermedad, un rango fenotípico de diferentes mutaciones raras en el mismo gen, y enfatizan aún más la importancia de la inclusión en los estudios genéticos.https://orcid.org/0000-0001-6529-7077https://scholar.google.com/citations?hl=es&user=kaGongoAAAAJ&view_op=list_works&sortby=pubdatehttps://scienti.minciencias.gov.co/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000055000&lang=esRevista Internacional - Indexad

A neurodegenerative disease landscape of rare mutations in Colombia due to founder effects.

Background: The Colombian population, as well as those in other Latin American regions, arose from a recent tri-continental admixture among Native Americans, Spanish invaders, and enslaved Africans, all of whom passed through a population bottleneck due to widespread infectious diseases that left small isolated local settlements. As a result, the current population reflects multiple founder effects derived from diverse ancestries. Methods: We characterized the role of admixture and founder effects on the origination of the mutational landscape that led to neurodegenerative disorders under these historical circumstances. Genomes from 900 Colombian individuals with Alzheimer's disease (AD) [n = 376], frontotemporal lobar degeneration-motor neuron disease continuum (FTLD-MND) [n = 197], early-onset dementia not otherwise specified (EOD) [n = 73], and healthy participants [n = 254] were analyzed. We examined their global and local ancestry proportions and screened this cohort for deleterious variants in disease-causing and risk-conferring genes. Results: We identified 21 pathogenic variants in AD-FTLD related genes, and PSEN1 harbored the majority (11 pathogenic variants). Variants were identified from all three continental ancestries. TREM2 heterozygous and homozygous variants were the most common among AD risk genes (102 carriers), a point of interest because the disease risk conferred by these variants differed according to ancestry. Several gene variants that have a known association with MND in European populations had FTLD phenotypes on a Native American haplotype. Consistent with founder effects, identity by descent among carriers of the same variant was frequent. Conclusions: Colombian demography with multiple mini-bottlenecks probably enhanced the detection of founder events and left a proportionally higher frequency of rare variants derived from the ancestral populations. These findings demonstrate the role of genomically defined ancestry in phenotypic disease expression, a phenotypic range of different rare mutations in the same gene, and further emphasize the importance of inclusiveness in genetic studies

Personas adultas mayores frente a la inclusión digital en América Latina: un estudio en red - Volumen 1

El presente libro es la culminación de un proyecto denominado Personas adultas mayores frente a la inclusión digital en América Latina – un estudio en red, desarrollado mediante una red de investigadores latinoamericanos. La idea de dicho proyecto surgió cuando la profesora Maria Consuelo Oliveira Santos finalizó su posdoctorado en la Facultad de Ciencias de la Comunicación de la Universidad Autónoma deNuevo León (UANL), en la ciudad de Monterrey, estado de Nuevo León, México. En cierto modo, es la continuación de la investigación sobre las nuevas tecnologías y los adultos mayores en Monterrey, iniciada en dicha institución. Se constató que era una temática que suscitaba estudios más verticalizados y que sería oportuno poder establecer una red de investigadores y así obtener una visión más amplia sobre la inclusión digital, en la realidad latinoamericana. El propósito del estudio fue conocer, contrastar y comprender las relaciones de las personas adultas mayores con las nuevas tecnologías y la repercusión de dichas relaciones en sus vidas. Igualmente observar la importancia de las condiciones sociales, políticas y culturales que repercuten en el acceso o no a las nuevas tecnologías. La implicación de investigadores integrantes de diferentes instituciones académicas, pertenecientes a diversas áreas del conocimiento fue consecuencia de invitaciones formuladas directamente por diferentes medios de comunicación, explicándoles la idea del proyecto en red para estudiar dicha temática a partir de sus realidades.El presente libro es la culminación de un proyecto denominado Personas adultas mayores frente a la inclusión digital en América Latina – un estudio en red, desarrollado mediante una red de investigadores latinoamericanos. La idea de dicho proyecto surgió cuando la profesora Maria Consuelo Oliveira Santos finalizó su posdoctorado en la Facultad de Ciencias de la Comunicación de la Universidad Autónoma deNuevo León (UANL), en la ciudad de Monterrey, estado de Nuevo León, México. En cierto modo, es la continuación de la investigación sobre las nuevas tecnologías y los adultos mayores en Monterrey, iniciada en dicha institución. Se constató que era una temática que suscitaba estudios más verticalizados y que sería oportuno poder establecer una red de investigadores y así obtener una visión más amplia sobre la inclusión digital, en la realidad latinoamericana. El propósito del estudio fue conocer, contrastar y comprender las relaciones de las personas adultas mayores con las nuevas tecnologías y la repercusión de dichas relaciones en sus vidas. Igualmente observar la importancia de las condiciones sociales, políticas y culturales que repercuten en el acceso o no a las nuevas tecnologías. La implicación de investigadores integrantes de diferentes instituciones académicas, pertenecientes a diversas áreas del conocimiento fue consecuencia de invitaciones formuladas directamente por diferentes medios de comunicación, explicándoles la idea del proyecto en red para estudiar dicha temática a partir de sus realidades

Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent

Genomic Insights Into The Ixodes scapularis Tick Vector Of Lyme Disease

Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retrotransposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing B57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick–host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host ‘questing’, prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent

Second GHEP-ISFG exercise for DVI: “DNA-led” victims’ identification in a simulated air crash

The Spanish and Portuguese-Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) has organized a second collaborative exercise on a simulated case of Disaster Victim Identification (DVI), with the participation of eighteen laboratories. The exercise focused on the analysis of a simulated plane crash case of medium-size resulting in 66 victims with varying degrees of fragmentation of the bodies (with commingled remains). As an additional difficulty, this second exercise included 21 related victims belonging to 6 families among the 66 missings to be identified. A total number of 228 post-mortem samples were represented with aSTR and mtDNA profiles, with a proportion of partial aSTR profiles simulating charred remains. To perform the exercise, participants were provided with aSTR and mtDNA data of 51 reference pedigrees —some of which deficient—including 128 donors for identification purposes. The exercise consisted firstly in the comparison of the post-mortem genetic profiles in order to re-associate fragmented remains to the same individual and secondly in the identification of the re-associated remains by comparing aSTR and mtDNA profiles with reference pedigrees using pre-established thresholds to report a positive identification. Regarding the results of the post-mortem samples re-associations, only a small number of discrepancies among participants were detected, all of which were from just a few labs. However, in the identification process by kinship analysis with family references, there were more discrepancies in comparison to the correct results. The identification results of single victims yielded fewer problems than the identification of multiple related victims within the same family groups. Several reasons for the discrepant results were detected: a) the identity/non-identity hypotheses were sometimes wrongly expressed in the likelihood ratio calculations, b) some laboratories failed to use all family references to report the DNA match, c) In families with several related victims, some laboratories firstly identified some victims and then unnecessarily used their genetic information to identify the remaining victims within the family, d) some laboratories did not correctly use “prior odds” values for the Bayesian treatment of the episode for both post-mortem/post-mortem re-associations as well as the ante-mortem/post-mortem comparisons to evaluate the probability of identity. For some of the above reasons, certain laboratories failed to identify some victims. This simulated “DNA-led” identification exercise may help forensic genetic laboratories to gain experience and expertize for DVI or MPI in using genetic data and comparing their own results with the ones in this collaborative exercise.This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Peer reviewe

Malaria vector species in Colombia: a review

Here we present a comprehensive review of the literature on the vectorial importance of the major Anopheles malaria vectors in Colombia. We provide basic information on the geographical distribution, altitudinal range, immature habitats, adult behaviour, feeding preferences and anthropophily, endophily and infectivity rates. We additionally review information on the life cycle, longevity and population fluctuation of Colombian Anopheles species. Emphasis was placed on the primary vectors that have been epidemiologically incriminated in malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles nuneztovari. The role of a selection of local, regional or secondary vectors (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We highlight the importance of combining biological, morphological and molecular data for the correct taxonomical determination of a given species, particularly for members of the species complexes. We likewise emphasise the importance of studying the bionomics of primary and secondary vectors along with an examination of the local conditions affecting the transmission of malaria. The presence and spread of the major vectors and the emergence of secondary species capable of transmitting human Plasmodia are of great interest. When selecting control measures, the anopheline diversity in the region must be considered. Variation in macroclimate conditions over a species' geographical range must be well understood and targeted to plan effective control measures based on the population dynamics of the local Anopheles species