Tumor nasal de músculo liso de comportamiento maligno incierto: informe de un caso / Nasal smooth muscle tumor of uncertain malignant potential: A case report

Los tumores de músculo liso que no pueden ser clasificados según su histología como leiomiomas o leiomiosarcomas se denominan tumores de músculo liso de comportamiento maligno incierto. La localización nasal de estos tumores es muy infrecuente y la extensión adecuada de la cirugía para tratar estas neoplasias no está bien definida. Se describe el caso clínico de una adolescente de 16 años, que consultó por padecer un tumor de aspecto vascular en la cavidad nasal derecha y que fue tratada con éxito mediante cirugía intranasal. El diagnóstico histológico fue tumor de músculo liso de comportamiento maligno incierto. Por la rareza de estas neoplasias, su infrecuente localización nasal y la falta de evidencia que soporte cuál debe ser la extensión de la cirugía, es relevante la descripción y discusión del caso clínico.

Smooth muscle tumors that cannot be histologically classified as leiomyomas or leiomyosarcomas are defined as smooth muscle tumors of uncertain malignant potential. The location of these tumors in the nose is very rare, and the appropriate surgical extent to manage these neoplasms has not been adequately defined. Here we describe the case of a 16-year-old female adolescent who consulted due to a vascular-like tumor in the right nasal cavity who was successfully treated with intranasal surgery. The histological diagnosis was smooth muscle tumor of uncertain malignant potential. Given that these neoplasms are rare, the uncommon location in the nose, and the lack of evidence indicating the extent of surgery, it is relevant to describe and discuss this clinical case.

Nasal smooth muscle tumor of uncertain malignant potential: A case report. / Tumor nasal de músculo liso de comportamiento maligno incierto: informe de un caso.

Smooth muscle tumors that cannot be histologically classified as leiomyomas or leiomyosarcomas are defined as smooth muscle tumors of uncertain malignant potential. The location of these tumors in the nose is very rare, and the appropriate surgical extent to manage these neoplasms has not been adequately defined. Here we describe the case of a 16-year-old female adolescent who consulted due to a vascular-like tumor in the right nasal cavity who was successfully treated with intranasal surgery. The histological diagnosis was smooth muscle tumor of uncertain malignant potential. Given that these neoplasms are rare, the uncommon location in the nose, and the lack of evidence indicating the extent of surgery, it is relevant to describe and discuss this clinical case.

Los tumores de músculo liso que no pueden ser clasificados según su histología como leiomiomas o leiomiosarcomas se denominan tumores de músculo liso de comportamiento maligno incierto. La localización nasal de estos tumores es muy infrecuente y la extensión adecuada de la cirugía para tratar estas neoplasias no está bien definida. Se describe el caso clínico de una adolescente de 16 años, que consultó por padecer un tumor de aspecto vascular en la cavidad nasal derecha y que fue tratada con éxito mediante cirugía intranasal. El diagnóstico histológico fue tumor de músculo liso de comportamiento maligno incierto. Por la rareza de estas neoplasias, su infrecuente localización nasal y la falta de evidencia que soporte cuál debe ser la extensión de la cirugía, es relevante la descripción y discusión del caso clínico.

The Gut Microbiome of an Indigenous Agropastoralist Population in a Remote Area of Colombia with High Rates of Gastrointestinal Infections and Dysbiosis.

An Indigenous agropastoralist population called the Wiwa from the Sierra Nevada de Santa Marta, in North-East Colombia, shows high rates of gastrointestinal infections. Chronic gut inflammatory processes and dysbiosis could be a reason, suggesting an influence or predisposing potential of the gut microbiome composition. The latter was analyzed by 16S rRNA gene amplicon next generation sequencing from stool samples. Results of the Wiwa population microbiomes were associated with available epidemiological and morphometric data and compared to control samples from a local urban population. Indeed, locational-, age-, and gender-specific differences in the Firmicutes/Bacteriodetes ratio, core microbiome, and overall genera-level microbiome composition were shown. Alpha- and ß-diversity separated the urban site from the Indigenous locations. Urban microbiomes were dominated by Bacteriodetes, whereas Indigenous samples revealed a four times higher abundance of Proteobacteria. Even differences among the two Indigenous villages were noted. PICRUSt analysis identified several enriched location-specific bacterial pathways. Moreover, on a general comparative scale and with a high predictive accuracy, we found Sutterella associated with the abundance of enterohemorrhagic Escherichia coli (EHEC), Faecalibacteria associated with enteropathogenic Escherichia coli (EPEC) and helminth species Hymenolepsis nana and Enterobius vermicularis. Parabacteroides, Prevotella, and Butyrivibrio are enriched in cases of salmonellosis, EPEC, and helminth infections. Presence of Dialister was associated with gastrointestinal symptoms, whereas Clostridia were exclusively found in children under the age of 5 years. Odoribacter and Parabacteroides were exclusively identified in the microbiomes of the urban population of Valledupar. In summary, dysbiotic alterations in the gut microbiome in the Indigenous population with frequent episodes of self-reported gastrointestinal infections were confirmed with epidemiological and pathogen-specific associations. Our data provide strong hints of microbiome alterations associated with the clinical conditions of the Indigenous population.

Integrated Drivers of Basal and Acute Immunity in Diverse Human Populations.

Prior studies have identified genetic, infectious, and biological associations with immune competence and disease severity; however, there have been few integrative analyses of these factors and study populations are often limited in demographic diversity. Utilizing samples from 1,705 individuals in 5 countries, we examined putative determinants of immunity, including: single nucleotide polymorphisms, ancestry informative markers, herpesvirus status, age, and sex. In healthy subjects, we found significant differences in cytokine levels, leukocyte phenotypes, and gene expression. Transcriptional responses also varied by cohort, and the most significant determinant was ancestry. In influenza infected subjects, we found two disease severity immunophenotypes, largely driven by age. Additionally, cytokine regression models show each determinant differentially contributes to acute immune variation, with unique and interactive, location-specific herpesvirus effects. These results provide novel insight into the scope of immune heterogeneity across diverse populations, the integrative effects of factors which drive it, and the consequences for illness outcomes.

Diagnosis and Prevalence of Chagas Disease in an Indigenous Population of Colombia.

Chagas disease (CD) is one of the leading neglected tropical diseases. In the Americas, CD is endemic in about 21 countries, but only less than 1% of the patients have access to medical treatment. Indigenous populations are particularly affected because they live in socio-economic and climate conditions that favor CD infections. In this study, diagnostic strategies and regional prevalence of the Chagas disease were assessed. In nine villages of the indigenous tribe Wiwa, 1134 persons were tested with a Chagas-antibody-specific rapid test (RT), two different Chagas-antibody-specific ELISAs and a Chagas-specific real-time polymerase chain reaction. The overall prevalence of CD in the villages was 35.4%, with a variation from 24.9% to 52.8% for the different communities. Rapid tests and ELISAs showed the same results in all cases. The proportion of replication-active infections, defined by positive PCR results, was 8.7%. In conclusion, the assessed indigenous population in Colombia was shown to be severely affected by CD. For a serological diagnosis, one rapid test was shown to be sufficient. Replacements of ELISAs by RT would decrease costs, increase feasibility and would relevantly help detect positive patients, especially if combined with the applied real-time PCR protocol. Real-time PCR can be considered for the detection of acute cases, outbreaks, chronic cases with re-infection/activation, as well as for therapy management and control.

Comparison of the Serion IgM ELISA and Microscopic Agglutination Test for diagnosis of Leptospira spp. infections in sera from different geographical origins and estimation of Leptospira seroprevalence in the Wiwa indigenous population from Colombia.

Leptospirosis is among the most important zoonotic diseases in (sub-)tropical countries. The research objective was to evaluate the accuracy of the Serion IgM ELISA EST125M against the Microscopic Agglutination Test (MAT = imperfect reference test); to assess its ability to diagnose acute leptospirosis infections and to detect previous exposure to leptospires in an endemic setting. In addition, to estimate the overall Leptospira spp. seroprevalence in the Wiwa indigenous population in North-East Colombia. We analysed serum samples from confirmed leptospirosis patients from the Netherlands (N = 14), blood donor sera from Switzerland (N = 20), and sera from a cross-sectional study in Colombia (N = 321). All leptospirosis ELISA-positive, and a random of negative samples from Colombia were tested by the MAT for confirmation. The ELISA performed with a sensitivity of 100% (95% CI 77% - 100%) and a specificity of 100% (95% CI 83% - 100%) based on MAT confirmed Leptospira spp. positive and negative samples. In the cross-sectional study in Colombia, the ELISA performed with a sensitivity of 100% (95% CI 2-100%) and a specificity of 21% (95% CI 15-28%). Assuming a 5% Leptospira spp. seroprevalence in this population, the positive predictive value was 6% and the negative predictive value 100%. The Leptospira spp. seroprevalence in the Wiwas tested by the ELISA was 39%; however, by MAT only 0.3%. The ELISA is suitable to diagnose leptospirosis in acutely ill patients in Europe several days after onset of disease. For cross-sectional studies it is not recommended due to its low specificity. Despite the evidence of a high leptospirosis prevalence in other study areas and populations in Colombia, the Wiwa do not seem to be highly exposed to Leptospira spp.. Nevertheless, leptospirosis should be considered and tested in patients presenting with febrile illness.

Seasonal Patterns of Enteric Pathogens in Colombian Indigenous People-A More Pronounced Effect on Bacteria Than on Parasites.

Enteric pathogens, which are frequently food- and waterborne transmitted, are highly abundant in Indigenous people living in remote rural areas of Colombia. As the frequency of gastroenteritis in the tropics shows seasonal differences, we analyzed variations of pathogen patterns in the stool samples of a Colombian Indigenous tribe called Wiwa during the dry (n = 105) and the rainy (n = 227) season, applying real-time PCR from stool samples and statistical analysis based on a multi-variable model. Focusing on bacterial pathogens, increased detection rates could be confirmed for enteropathogenic, enterotoxigenic and enteroaggregative Escherichia coli with a tendency for an increase in Campylobacter jejuni detections during the rainy season, while there was no seasonal effect on the carriage of Tropheryma whipplei. Salmonellae were recorded during the rainy season only. A differentiated pattern was seen for the assessed parasites. Entamoeba histolytica, Necator americanus and Trichuris trichiura were increasingly detected during the rainy season, but not Ascaris lumbricoides, Giardia duodenalis, Hymenolepis nana, Strongyloides stercoralis, and Taenia solium, respectively. Increased detection rates during the dry season were not recorded. Negative associations were found for Campylobacter jejuni and Giardia duodenalis with age and for Tropheryma whipplei with the body mass index, respectively. Positive associations of enteropathogenic Escherichia coli and Taenia solium detections were observed with age. In conclusion, facilitating effects of the tropical rainy season were more pronounced on bacterial enteric pathogens compared to enteropathogenic parasites.

Toxocara Seroprevalence and Risk Factor Analysis in Four Communities of the Wiwa, an Indigenous Tribe in Colombia.

The life of the indigenous Wiwa tribe in northeast Colombia is characterized by lacking access to clean drinking water and sanitary installations. Furthermore, free-roaming domestic animals and use of yucca and/or manioc as a primary food source favor the transmission of soil-transmitted helminths, e.g., Toxocara canis and Toxocara cati, the roundworms of dogs and cats. Infection may result in the clinical picture of toxocarosis, one of the most common zoonotic helminthoses worldwide. To estimate the Toxocara seroprevalence in four different villages of the Wiwa community, serum samples from 483 inhabitants were analyzed for anti-Toxocara-antibodies. Overall, 79.3% (383/483) of analyzed samples were seropositive. Statistically significant differences were observed between the four villages, as well as age groups (adults > adolescents > children), while sex had no effect. The high seropositivity rate demonstrates the risk of zoonotic roundworm infections and potential clinical disease in vulnerable indigenous inhabitants.

Seasonal Differences in Cyclospora cayetanensis Prevalence in Colombian Indigenous People.

Fecal-orally transmitted cyclosporiasis is frequent in remote resource-limited settings in Central and South America with poor hygiene conditions. In this study, we aimed at assessing seasonal effects on the epidemiology of colonization or infection with C. cayetanensis in Colombian indigenous people living under very restricted conditions. In the rainy season between July and November and in the dry season between January and April, stool samples from indigenous people with and without gastrointestinal symptoms were collected and screened for C. cayetanensis applying in-house real-time polymerase chain reaction (PCR). In the rainy season and in the dry season, positive PCR results were observed for 11.8% (16/136) and 5.1% (15/292), respectively, with cycle threshold (Ct) values of 30.6 (±3.4) and 34.4 (±1.6), respectively. Despite higher parasite loads in the rainy season, fewer individuals (2/16, 12.5%) reported gastrointestinal symptoms compared to the dry season (6/15, 40%). In conclusion, considerable prevalence of C. cayetanensis in Colombian indigenous people persists in the dry season. Low proportions of gastrointestinal symptoms along with higher parasite loads make colonization likely rather than infection.

Prospective, historically controlled study to evaluate the efficacy and safety of a new paediatric formulation of nifurtimox in children aged 0 to 17 years with Chagas disease one year after treatment (CHICO).

Nifurtimox is a recommended treatment for Chagas disease, but data from treated children are limited. We investigated the efficacy, safety and tolerability of nifurtimox administered as divisible, dispersible 30 mg and 120 mg tablets in children with Chagas disease. In this blinded, controlled study conducted January 2016-July 2018, 330 patients aged <18 years from 25 medical centres across three South American countries were randomised 2:1 to nifurtimox 10-20 mg/kg/day (aged <12 years) or 8-10 mg/kg/day (aged ≥12 years) for 60 days (n = 219), or for 30 days plus placebo for 30 days (n = 111) (ClinicalTrials.gov NCT02625974). The primary outcome was anti-Trypanosoma cruzi serological response (negative seroconversion or seroreduction ≥20% in mean optical density from baseline determined by two conventional enzyme-linked immunosorbent assays) at 12 months in the 60-day treatment group versus historical placebo controls. Nifurtimox for 60 days achieved negative seroconversion (n = 10) and seroreduction (n = 62) in 72 patients (serological response 32.9%; 95% confidence interval [CI] 26.4%, 39.3%, of all treated patients), confirming superiority relative to the upper 95% CI of 16% for controls. In patients aged <8 months, 10/12 treated for 60 days (83.3%) and 5/7 treated for 30 days (71.4%) achieved negative seroconversion. Overall serological response was lower for 30-day than for 60-day nifurtimox (between-treatment difference 14.0% [95% CI 3.7%, 24.2%]). The frequency of T. cruzi-positive quantitative polymerase chain reactions decreased substantially from baseline levels (60-day regimen 53.4% versus 1.4%; 30-day regimen 51.4% versus 4.5%). Study drug-related treatment-emergent adverse events (TEAEs), which were observed in 62 patients (28.3%) treated for 60 days and 29 patients (26.1%) treated for 30 days, were generally mild or moderate and resolved without sequelae; 4.2% of all TEAEs led to nifurtimox discontinuation. Age- and weight-adjusted nifurtimox for 60 days achieved a serological response at 12 months post-treatment that was superior to historical placebo, was well tolerated and had a favourable safety profile in children with Chagas disease. Although, at 1 year serological follow-up, efficacy of the shorter nifurtimox treatment was not comparable to the 60-day treatment regimen for the overall study population, further long-term follow-up of the patients will provide important information about the progress of serological conversion in children treated with nifurtimox, as well as the potential efficacy difference between the two regimens over time.

Effect of Geographic Isolation on the Nasal Virome of Indigenous Children.

The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with very different levels of geographic isolation. Metagenomic analysis was used to characterize viral nucleic acids in nasal swabs from 63 apparently healthy young children. Sequences from human virus members of the families Anelloviridae, Papillomaviridae, Picornaviridae, Herpesviridae, Polyomaviridae, Adenoviridae, and Paramyxoviridae were detected in decreasing proportions of children. The number of papillomavirus infections detected was greater among Hispanic children most exposed to outside contacts, while anellovirus infections were more common in the isolated indigenous villages. The diversity of the other human viruses detected did not differ among the villages. Closely related variants of rhinovirus A or B were identified in 2 to 4 children from each village, reflecting ongoing transmission clusters. Genomes of viruses not currently known to infect humans, including members of the families Parvoviridae, Partitiviridae, Dicistroviridae, and Iflaviridae and circular Rep-encoding single-stranded DNA (CRESS-DNA) virus, were also detected in nasal swabs, possibly reflecting environmental contamination from insect, fungal, or unknown sources. Despite the high levels of geographic and cultural isolation, the overall diversity of human viruses in the nasal passages of children was not reduced in highly isolated indigenous villages, indicating ongoing exposure to globally circulating viruses.IMPORTANCE Extreme geographic and cultural isolation can still be found in some indigenous South American villages. Such isolation may be expected to limit the introduction of otherwise common and widely distributed viruses. Very small population sizes may also result in rapid local viral extinction due to a lack of seronegative subjects to maintain transmission chains for rapidly cleared viruses. We compared the viruses in the nasal passages of young children in three villages with increasing levels of geographic isolation. We found that isolation did not reduce the overall diversity of viral infections. Multiple infections with nearly identical rhinoviruses could be detected within each village, likely reflecting recent viral introductions and transmission clusters among epidemiologically linked members of these very small communities. We conclude that, despite their geographic isolation, remote indigenous villages show evidence of ongoing exposure to globally circulating viruses.

Modelling historical changes in the force-of-infection of Chagas disease to inform control and elimination programmes: application in Colombia.

BACKGROUND: WHO's 2020 milestones for Chagas disease include having all endemic Latin American countries certified with no intradomiciliary Trypanosoma cruzi transmission, and infected patients under care. Evaluating the variation in historical exposure to infection is crucial for assessing progress and for understanding the priorities to achieve these milestones. METHODS: Focusing on Colombia, all the available age-structured serological surveys (undertaken between 1995 and 2014) were searched and compiled. A total of 109 serosurveys were found, comprising 83 742 individuals from rural (indigenous and non-indigenous) and urban settings in 14 (out of 32) administrative units (departments). Estimates of the force-of-infection (FoI) were obtained by fitting and comparing three catalytic models using Bayesian methods to reconstruct temporal and spatial patterns over the course of three decades (between 1984 and 2014). RESULTS: Significant downward changes in the FoI were identified over the course of the three decades, and in some specific locations the predicted current seroprevalence in children aged 0-5 years is <1%. However, pronounced heterogeneity exists within departments, especially between indigenous, rural and urban settings, with the former exhibiting the highest FoI (up to 66 new infections/1000 people susceptible/year). The FoI in most of the indigenous settings remain unchanged during the three decades investigated. Current prevalence in adults in these 15 departments varies between 10% and 90% depending on the dynamics of historical exposure. CONCLUSIONS: Assessing progress towards the control of Chagas disease requires quantifying the impact of historical exposure on current age-specific prevalence at subnational level. In Colombia, despite the evident progress, there is a marked heterogeneity indicating that in some areas the vector control interventions have not been effective, hindering the possibility of achieving interruption by 2020. A substantial burden of chronic cases remains even in locations where serological criteria for transmission interruption may have been achieved, therefore still demanding diagnosis and treatment interventions.

Trypanocidal Activity of Long Chain Diamines and Aminoalcohols.

Thirteen aminoalcohols and eight diamines were obtained and tested against Trypanosoma cruzi epimastigotes strains MG, JEM and CL-B5 clone. Some of them were equal or more potent (1.0-6.6 times) than the reference compound nifurtimox. From them, three aminoalcohols and two diamines were selected for amastigotes assays. Compound 5 was as potent as the reference drug nifurtimox against amastigotes of the CL-B5 strain (IC50 = 0.6 µM), with a selectivity index of 54.

Nuevos hallazgo de flebotomíneos (diptera: psyhodidae) en la sierra nevada dee santa marta, Colombia / New Records of Phlebotomine Sand Flies (Diptera: Psychodidae) at Sierra Nevada de Santa Marta, Colombia

Los insectos relacionados con la transmisión de los patógenos causantes de las leishmaniasis han sido poco estudiados en la Sierra Nevada de Santa Marta, Colombia, incluido el departamento de Magdalena, donde a la fecha están registradas trece especies del género Lutzomyia. En la presente nota se informa el hallazgo de tres especies y un subgénero adicionales en la región. Se recolectaron 885 flebotomíneos en Seywiaka y las veredas Las Tinajas y Calabazo, estribaciones de la Sierra Nevada de Santa Marta (117-130 m s.n.m.). El 84 % de los ejemplares se obtuvieron con trampa CDC, el 11 % con trampa Shannon y el 5 % fueron capturados, en reposo, con un dispositivo eléctrico de succión. Se identificaron nueve especies, Lu. gomezi, Lu. panamensis, Lu. trinidadensis, Lu. carpenteri, Lu. evansi, Lu. dysponeta, Lu. dubitans, Lu. shannoni, y Lu. micropyga, la más abundante fue Lu. gomezi (69 %), seguida por Lu. panamensis (14 %). También se recolectaron ejemplares de la serie Lu. osornoi del subgénero Helcocyrtomyia. Entre el material hallado sobresalen Lu. carpenteri, Lu. dubitans y Lu. dysponeta como primeros registros para el departamento del Magdalena, además de Lu. (Helcocyrtomyia) sp., que representa el primer informe del subgénero en el Caribe colombiano.

Phlebotomine sand flies, vectors of leishmaniasis, have not been well studied in the Sierra Nevada de Santa Marta, and likewise, are not well known in other regions of the Department of Magdalena, Colombia. To date only thirteen species of Lutzomyia have been recorded as occurring in the Department. The present note adds three species and includes an additional subgenus. Collections were made in the lower foothills of the Sierra Nevada de Santa Marta at elevations ranging from 117-130 m in the communities of Seywiaka, Las Tinajas and Calabazo. Eighty-four percent of the 885 phlebotomines sand flies collected were obtained from CDC light traps, 11 % from Shannon trap and 5 % from typical resting sites using an electric aspirator. The following nine species were identified from the collections: Lutzomyia gomezi, Lu. panamensis, Lu. trinidadensis, Lu. carpenteri, Lu. evansi, Lu. dysponeta, Lu. dubitans, Lu. shannoni, and Lu. micropyga. The most abundant species were Lu. gomezi and Lu. panamensis, which, respectively, accounted for 69 % and 14 % of the specimens. Of the nine species, Lu. carpenteri, Lu. dubitans and Lu. dysponeta represent new records for the Department of Magdalena. Also, a few female specimens were encountered of a species belonging to the Lu. osornoi series of the subgenus Helcocyrtomyia, which represents the first record of this subgenus in the Caribbean region of Colombia.

Genotyping of Trypanosoma cruzi in a hyper-endemic area of Colombia reveals an overlap among domestic and sylvatic cycles of Chagas disease.

BACKGROUND: Chagas disease is a neglected illness caused by the Trypanosoma cruzi parasite, which widely affects American communities. This study attempted to identify T. cruzi genotypes circulating in four indigenous communities of the Sierra Nevada of Santa Marta, Colombia, to investigate parasite transmission dynamics in these communities. In addition, some epidemiological variables to determine the risk factors for infection with this parasite, such as the prevalence of T. cruzi infection, the triatomine species, and the domestic and sylvatic mammals that act as vectors and reservoirs of the parasite in the domestic, peridomestic and sylvatic cycles, were examined. METHODS: We developed a prospective study to identify the main risk factors associated with T. cruzi infection in the region. The T. cruzi prevalence was determined by ELISA, IFA and PCR. Triatomines species and both domestic and sylvatic mammals from all communities were captured and sampled. To analyze parasite transmission dynamics in these four communities, eight DNA parasite probes were generated from insect and reservoir samples, and a DNA blot analysis were carried out. RESULTS: Serological studies revealed 37% prevalence in the four communities, and Kasakumake was the most endemic region, containing approximately 70% seropositives. Moreover, the molecular diagnosis showed a high correlation between the serological data and the T. cruzi circulating in the patients' blood. A total of 464 triatomine insects were collected in domestic, peridomestic and sylvatic environments, and these insects belonged to five different species; Rhodnius prolixus and Triatoma dimidiata were the two more important species transmitting the parasite. After studying the eco-epidemiological factors in these four communities, the most important risk factors for infection with the parasite were determined. These risk factors are a high infection rate of people and domestic animals, the construction materials of the houses, the presence of infected triatomines inside the human dwellings, the proximity between houses and a sylvatic environment with several triatomine species and wild animals. Finally, the molecular characterization of T. cruzi showed the presence of three haplotypes and complex T. cruzi mixed infections in all reservoirs. CONCLUSIONS: Active transmission of T. cruzi is present in four indigenous communities of the Sierra Nevada de Santa Marta with overlap between the domestic and the sylvatic transmission cycles of Chagas disease.

Reconstructing Native American population history.

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Incrimination of Eratyrus cuspidatus (Stal) in the transmission of Chagas' disease by molecular epidemiology analysis of Trypanosoma cruzi isolates from a geographically restricted area in the north of Colombia.

Following the report of two cases of acute Chagas' disease and the appearance of several triatomine species in human dwellings in an area considered non-endemic for domestic transmission of Trypanosoma cruzi; a epidemiological, entomological and T. cruzi molecular epidemiology analysis was performed in order to establish the transmission dynamic of the parasite in the studied area. 2 T. cruzi isolates from human patients, 5 from Eratyrus cuspidatus, 4 from Rhodnius pallescens, 4 from Panstrongylus geniculatus and 7 reference stocks were analyzed by mini-exon gene, random amplified polymorphic DNA (RAPD) and multilocus enzyme electrophoresis (MLEE). All isolates from vectors and human resulted T. cruzi group I by mini-exon, RAPD and MLEE. While mini-exon and MLEE did not showed any differences between the studied isolates, RAPD analysis identified a common T. cruzi genotype for the E. cuspidatus isolates and human isolates and distinguished different strains from R. pallescens and P. geniculatus isolates. The presence of the same T. cruzi genotype in isolates from patients and E. cuspidatus suggests that this species can be responsible for the transmission of Chagas' disease in the study area. RAPD analysis showed better resolution and discrimination of T. cruzi strains than mini-exon and MLEE and can be considered a useful tool for molecular epidemiology studies. Incrimination of sylvatic triatomine species in the transmission of Chagas' disease indicates that more knowledge about the ecology of these vectors is necessary to improve control strategies.

[Analysis of polymorphisms in the trypanothione reductase and cruzipain genes in Colombian strains of Trypanosoma cruzi]. / Análisis de polimorfismos en los genes tripanotión reductasa y cruzipaína en cepas colombianas de Trypanosoma cruzi.

INTRODUCTION: Genetic studies of Trypanosoma cruzi have tried to establish relations between genetic variants and their biological characteristics, such as clinical manifestations, host or geographic origin. However, much controversy exists on the associations between the commonly used DNA markers with group, clinical characteristics and disease epidemiology. OBJECTIVE: In this study determined the variability of the genes that code for the proteins trypanothione reductase and cruzipain, both involved in the infection and survival of the parasite in the mammalian host, was studied and the association between genetic polymorphism and biological and geographic sources in Colombian T. cruzi strains was examined. MATERIALS AND METHODS: The genotypes for each of six SNPs (single nucleotide polymorphisms) for trypanothione reductase and eight SNPs for cruzipain genes were identified by polymerase chain reaction-restriction fragment length polymorphism in 36 T. cruzi Colombian stocks from several regions and biological origins. RESULTS: Three genotypes were identified for trypanothione reductase with Acy I and Hae III enzymes and six genotypes for cruzipain with the Rsa I, Ban I and Bsu 361 enzymes. CONCLUSIONS: For trypanothione reductase, an association was not established with biological or geographical origin; however, alleles at positions 102 and 210 allowed discrimination with groups I and II. For cruzipain, specific genotypes were associated with group, biological and geographic origin. The usefulness of molecular markers on these genes was demonstrated for the determination and differentiation of genetic varieties in T. cruzi.

Análisis de polimorfismos en los genes tripanotión reductasa y cruzipaína en cepas colombianas de Trypanosoma cruzi / Analysis of polymorphisms in the trypanothione reductase and cruzipain genes in Colombian strains of Trypanosoma cruzi

Introducción. Los estudios genéticos en Trypanosoma cruzi han buscado establecer asociaciones de variantes genéticas del parásito con manifestaciones clínicas de la enfermedad, origen biológico y geográfico de los aislamientos; sin embargo, los resultados de asociación con los marcadores comúnmente usados en estos estudios han generado mucha controversia, principalmente en la asociación de grupos con características clínicas y epidemiológicas de la enfermedad.Objetivo. Se planteó determinar la variabilidad de genes que codifican para las proteínas tripanotión reductasa y cruzipaína , involucradas en mecanismos de infección y supervivencia del parásito en el hospedador mamífero, y probar la asociación de variantes génicas con origen biológico y geográfico de cepas colombianas de T. cruzi. Materiales y métodos. Se tipificaron por reacción en cadena de la polimerasa- polimorfismo de longitud del fragmento de restricción seis SNPs (Single Nucleotide Polymorphisms) en tripanotión reductasa y ocho SNPs en cruzipaína en 36 cepas colombianas de T. cruzi de diferentes regiones y origen biológico.Resultados. Con las enzimas Acy I y Hae III se determinaron tres genotipos para tripanotión reductasa. Para cruzipaína se identificaron seis genotipos con las enzimas Rsa I, Ban I y Bsu 36I.Conclusiones. Para tripanotión reductasa no fue posible establecer una asociación con el origen biológico o geográfico; sin embargo los alelos producidos en las posiciones 102 y 210, permitieron discriminar los grupos tradicionales I y II. Con los genotipos obtenidos para cruzipaína se establecieron relaciones a estos grupos, origen biológico y geográfico. Los resultados sugieren la utilidad de estos genes como marcadores moleculares para determinar y diferenciar variedades genéticas en T. cruzi.

Introduction. Genetic studies of Trypanosoma cruzi have tried to establish relations between genetic variants and their biological characteristics, such as clinical manifestations, host or geographic origin. However, much controversy exists on the associations between the commonly used DNA markers with group, clinical characteristics and disease epidemiology. Objective. In this study determined the variability of the genes that code for the proteins trypanothione reductase and cruzipain, both involved in the infection and survival of the parasite in the mammalian host, was studied and the association between genetic polymorphism and biological and geographic sources in Colombian T. cruzi strains was examined. Materials and methods. The genotypes for each of six SNPs (single nucleotide polymorphisms) for trypanothione reductase and eight SNPs for cruzipain genes were identified by polymerase chain reaction-restriction fragment length polymorphism.in 36 T. cruzi Colombian stocks from several regions and biological origins. Results. Three genotypes were identified for trypanothione reductase with Acy I and Hae III enzymes and six genotypes for cruzipain with the Rsa I, Ban I and Bsu 36I enzymes. Conclusions. For trypanothione reductase ,an association was not established with biological or geographical origin; however, alleles at positions 102 and 210 allowed discrimination with groups I and II. For cruzipain, specific genotypes were associated with group, biological and geographic origin. The usefulness of molecular markers on these genes was demonstrated for the determination and differentiation of genetic varieties in T. cruzi.