Evolutionary analysis of JC polyomavirus in Misiones' population yields insight into the population dynamics of the early human dispersal in the Americas.

BACKGROUND: JC polyomavirus (JCV) has an ethno-geographical distribution across human populations. OBJECTIVE: Study the origins of the population of Misiones (Argentina) by using JCV as genetic marker. METHODS: Viral detection and characterization was conducted by PCR amplification and evolutionary analysis of the intergenic region sequences. RESULTS: 22 out of 121 samples were positive for JCV, including 5 viral lineages: MY (n = 8), Eu-a (n = 7), B1-c (n = 4), B1-b (n = 2) and Af2 (n = 1). MY sequences clustered within a branch of Native American origin that diverged from its Asian counterpart about 21,914 years ago (HPD 95% interval 15,383-30,177), followed by a sustained demographic expansion around 5000 years ago. CONCLUSIONS: JCV in Misiones reflects the multiethnic origin of the current population, with an important Amerindian contribution. Analysis of the MY viral lineage shows a pattern consistent with the arrival of early human migrations to the Americas and a population expansion by the pre-Columbian native societies.

Zoonotic RVA: State of the Art and Distribution in the Animal World.

Rotavirus species A (RVA) is a pathogen mainly affecting children under five years old and young animals. The infection produces acute diarrhea in its hosts and, in intensively reared livestock animals, can cause severe economic losses. In this study, we analyzed all RVA genomic constellations described in animal hosts. This review included animal RVA strains in humans. We compiled detection methods, hosts, genotypes and complete genomes. RVA was described in 86 animal species, with 52% (45/86) described by serology, microscopy or the hybridization method; however, strain sequences were not described. All of these reports were carried out between 1980 and 1990. In 48% (41/86) of them, 9251 strain sequences were reported, with 28% being porcine, 27% bovine, 12% equine and 33% from several other animal species. Genomic constellations were performed in 80% (32/40) of hosts. Typical constellation patterns were observed in groups such as birds, domestic animals and artiodactyls. The analysis of the constellations showed RVA's capacity to infect a broad range of species, because there are RVA genotypes (even entire constellations) from animal species which were described in other studies. This suggests that this virus could generate highly virulent variants through gene reassortments and that these strains could be transmitted to humans as a zoonotic disease, making future surveillance necessary for the prevention of future outbreaks.

Baseline prevalence and type distribution of Human papillomavirus in sexually active non-vaccinated adolescent girls from Argentina.

In 2011, Argentina launched a government-funded national Human papillomavirus (HPV) immunization program incorporating a bivalent HPV vaccine, with a 0-1-6-month schedule, for girls 11 years of age, born after January 2000. Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs. However, the data on HPV prevalence at young ages are very limited. The aim of this work was to determine the prevalence of HPV infection and type-specific distribution in sexually active 15-17-year-old non-vaccinated girls. Cervical samples from 1073 adolescents were collected for HPV detection and genotyping using the BSGP5+/GP6+PCR-reverse line blot (RLB) assay. Out of 957 specimens analyzed, 56.3% were positive for any HPV type; 42.2% harbored at least one high-risk HPV (HR-HPV) type and 30.8% low-risk HPV (LR-HPV) types. Multiple and single infections were identified in 36.3% and 20.0% of the samples respectively. The 6 most common HR-HPV types were HPV16 (11.1%), HPV52 (10.8%), HPV56 (8.3%), HPV51 (7.4%), HPV58 (7.3%) and HPV31 (7.1%). The prevalence of HR-HPV-16/18 was 15.2%. In conclusion, results confirm that HPV (particularly HR-types) are very common among sexually active adolescents, and prevalence rises quickly after their sexual debut. Our HPV type-specific prevalence baseline may be used to monitor post-vaccinal longitudinal changes in Argentina.

Multiscale environmental determinants of Leishmania vectors in the urban-rural context.

BACKGROUND: In South America, cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) are emerging diseases, expanding in the border area of Argentina, Brazil and Paraguay. Outbreaks of CL were reported since the 1990s, with Nyssomyia whitmani as the main vector in this region. Regarding VL, urban reports started in 2010 with Lutzomyia longipalpis as the main vector. The aim of this study was to evaluate environmental determinants related to the main vectors of leishmaniasis, to contribute to the prevention and control response to the emergence of VL and CL in the Argentina-Brazil-Paraguay border region. METHODS: The cross-sectional survey includes two cities and two close rural areas in the Argentinean Northeast Region, between November 2014 and January 2015, with a total of 95 sampling sites. REDILA-BL traps were set for three consecutive nights, and a total of 68 meso- and microscale environmental and landscape characteristics were surveyed. The association between vector abundance with different variables was evaluated using a generalized linear model with zero-inflated negative binomial distribution. We analyzed females for detection of Leishmania DNA. RESULTS: The analysis for Lu. longipalpis indicates an excess of absences when the mean NDWI around the sites were higher. The abundance of Lu. longipalpis at mesoscale level was higher when more urban services were present, and when blood sources such as chickens or dogs at the microscale level were present. For Ny. whitmani, no variable was found to be associated with the absences, while its abundance increased in association with the following variables: percentage of tree cover, presence of garbage collection service, hosted people and, at microscale, the presence of poultry. Leshmania infantum DNA was detected in 2/49 (4%) Lu. longipalpis. CONCLUSIONS: The abundance of both species is influenced by variables at different scales, their influence probably has a hierarchy and they are acting on different aspects of the biology of these vectors. The urban spatial segregation of Lu. longipalpis and the peri-urban and rural segregation of N. whitmani increase the risk of VL and CL. The selection of the better variables for each scale will allow the design of appropriate control strategies depending on species.

Performance of rapid tests for canine visceral leishmaniasis diagnosis in Argentina.

To diagnose dogs infected by Leishmania infantum rK39 rapid diagnosis test is widely used in the Americas, while dual path platform (DPP) was recently adopted by Brazil. In this study we assessed the performance of rK39-RDT and DPP tests in recent urban transmission scenarios of Argentina. The sensitivity and specificity were evaluated with a sera panel and field samples, taken as true infected those from parasitological and/or PCR positive tests. Since none of these tests can be taken as a gold standard, the performance was also evaluated using Latent Class Analysis, a statistical modeling technique which allows to estimating sensitivity and specificity defining a latent class variable as the reference standard. The sensitivity of both tests in the panel was around 92% (symptomatic dogs 96%, asymptomatic 83%), while the sensitivity in field samples of rK39-RDT was 77%, and DPP 98% (mean in symptomatic dogs 89%, asymptomatic 82%). The specificity was similar for both tests and samples, around 98%. Therefore, these tests are acceptable for program dog population-based studies, as spatial stratification, focus intervention and follow up, and they could be used for individual screening and confirmation of clinical presumptive diagnosis in polysymptomatic dogs. The inability to discriminate between immunity and actual infectiousness suggest that a combination with other non-immunological based tests will be required for highly sensitive/specific diagnosis in order to targeting control measures in individual reservoirs from public health perspective, as for individual management from animal health perspective.

Para diagnosticar perros infectados por Leishmania infantum, en las Américas se utiliza ampliamente la prueba rápida rK39, mientras que DPP fue adoptado recientemente por Brasil. En este estudio se evaluó el desempeño de las pruebas rK39-RDT y DPP en escenarios de transmisión urbana reciente en Argentina. La sensibilidad y especificidad se evaluaron con un panel de sueros y muestras de campo, considerando muestras infectadas verdaderas aquellas con pruebas parasitológicas y/o de PCR positivas. Como ninguna de estas pruebas puede considerarse estándar de oro, el desempeño también se evaluó mediante análisis de clases latentes, una técnica de modelado estadístico que permite estimar sensibilidad y especificidad definiendo una variable de clase latente como estándar. La sensibilidad de ambas pruebas en el panel fue de alrededor del 92% (perros sintomáticos 96%, asintomáticos 83%), mientras que la sensibilidad en muestras de campo fue rK39-RDT: 77%, y DPP 98% (media en perros sintomáticos 89%, asintomáticos 82%). La especificidad fue similar para ambas pruebas y muestras, cerca de 98%. Por lo tanto, estas pruebas son aceptables para estudios programáticos caninos de base-poblacional, como estratificación espacial, intervención de foco y seguimiento, y podrían utilizarse para el tamizaje individual y la confirmación del diagnóstico clínico presuntivo en perros poli-sintomáticos. La incapacidad de discriminar entre inmunidad e infectividad real sugiere que se requerirá una combinación con otras pruebas, de base no inmunológica, para un diagnóstico suficientemente sensible/específico que permita definir las medidas de control en reservorios individuales, tanto para salud pública, como para la gestión individual en salud animal.

Performance of rapid tests for canine visceral leishmaniasis diagnosis in Argentina

To diagnose dogs infected by Leishmania infantum rK39 rapid diagnosis test is widely used in the Americas, while dual path platform (DPP) was recently adopted by Brazil. In this study we assessed the performance of rK39-RDT and DPP tests in recent urban transmission scenarios of Argentina. The sensitivity and specificity were evaluated with a sera panel and field samples, taken as true infected those from parasitological and/or PCR positive tests. Since none of these tests can be taken as a gold standard, the performance was also evaluated using Latent Class Analysis, a statistical modeling technique which allows to estimating sensitivity and specificity defining a latent class variable as the reference standard. The sensitivity of both tests in the panel was around 92% (symptomatic dogs 96%, asymptomatic 83%), while the sensitivity in field samples of rK39-RDT was 77%, and DPP 98% (mean in symptomatic dogs 89%, asymptomatic 82%). The specificity was similar for both tests and samples, around 98%. Therefore, these tests are acceptable for program dog population-based studies, as spatial stratification, focus intervention and follow up, and they could be used for individual screening and confirmation of clinical presumptive diagnosis in polysymptomatic dogs. The inability to discriminate between immunity and actual infectiousness suggest that a combination with other non-immunological based tests will be required for highly sensitive/specific diagnosis in order to targeting control measures in individual reservoirs from public health perspective, as for individual management from animal health perspective.

Para diagnosticar perros infectados por Leishmania infantum, en las Américas se utiliza ampliamente la prueba rápida rK39, mientras que DPP fue adoptado recientemente por Brasil. En este estudio se evaluó el desempeño de las pruebas rK39-RDT y DPP en escenarios de transmisión urbana reciente en Argentina. La sensibilidad y especificidad se evaluaron con un panel de sueros y muestras de campo, considerando muestras infectadas verdaderas aquellas con pruebas parasitológicas y/o de PCR positivas. Como ninguna de estas pruebas puede considerarse estándar de oro, el desempeño también se evaluó mediante análisis de clases latentes, una técnica de modelado estadístico que permite estimar sensibilidad y especificidad definiendo una variable de clase latente como estándar. La sensibilidad de ambas pruebas en el panel fue de alrededor del 92% (perros sintomáticos 96%, asintomáticos 83%), mientras que la sensibilidad en muestras de campo fue rK39-RDT: 77%, y DPP 98% (media en perros sintomáticos 89%, asintomáticos 82%). La especificidad fue similar para ambas pruebas y muestras, cerca de 98%. Por lo tanto, estas pruebas son aceptables para estudios programáticos caninos de base-poblacional, como estratificación espacial, intervención de foco y seguimiento, y podrían utilizarse para el tamizaje individual y la confirmación del diagnóstico clínico presuntivo en perros poli-sintomáticos. La incapacidad de discriminar entre inmunidad e infectividad real sugiere que se requerirá una combinación con otras pruebas, de base no inmunológica, para un diagnóstico suficientemente sensible/específico que permita definir las medidas de control en reservorios individuales, tanto para salud pública, como para la gestión individual en salud animal.

Genetic diversity of the JC polyomavirus (JCPyV) and mitochondrial DNA ancestry in Misiones, Argentina.

BACKGROUND: The use of human and viral genetic markers offers a novel way to study human migration in multiethnic populations of Latin America. OBJECTIVES: Our goal was to characterize the genetic diversity and geographical origins of JC Polyomavirus (JCPyV) and the genetic ancestry of mitochondrial DNA (mtDNA) in inhabitants from 25 de Mayo, Misiones-Argentina, a small village of largely German ancestry located close to the border with Brazil. We also evaluated the extent of agreement between viral and mtDNA markers for the different ancestry components of this population. STUDY DESIGN: 68 individuals were analyzed for JCPyV and mtDNA diversity. JCPyV detection and typing was conducted in urine samples by PCR amplification, sequencing and phylogenetic analysis of the VP1 gene. mtDNA ancestry was assessed through HVS1 sequencing, with the resulting haplotypes being classified into haplogroups of Amerindian, European and African origin. The distribution of JCPyV diversity and mtDNA ancestry in the population was statistically evaluated by Fisher exact test and the level of agreement of both markers at the individual level was evaluated by Cohen's kappa coefficient. RESULTS: Our analysis showed that 57.4% of the samples were positive for JCPyV. Of these, the 47.6% were Asian-American Type 2, 33.3% European Type 1 and 19.1% African Type 3 in origin. The mtDNA ancestry of the study participants was 33.3% Amerindian and 66.7% European. There was a significant difference among the distribution of JCPyV diversity and mtDNA ancestry (p = 0.009) and at the individual level there was no correlation between the distribution of the both markers (κ = 0.154, p = 0.297). CONCLUSION: The apparent incongruence between JCPyV diversity and mtDNA ancestry may reflect the original settlement process and more recent migration to 25 de Mayo, the latter involving viral spread through migrants from Brazil. Some potential limitations to our interpretations are also discussed.

Twice upon a time: The progression of canine visceral leishmaniasis in an Argentinean city.

Canine Visceral Leishmaniasis (CVL) prevalence, spatial distribution and associated factors were assessed in four locations in Iguazú department in 2014 and in Puerto Iguazú city again in 2018. The city areas were divided into a grid of 400x400m cells. All cells were sampled in 2014 and a random subsampling was developed in 2018. In each cell, five dogs clustered in a 'critical scenario' (prone to have vectors) were sampled. A rapid immunochromatographic dipstick was used to detect antibodies against Leishmania infantum, confirming by lymph node smears observation and PCR. For Puerto Iguazú, Generalized Linear Models (GLMs) were constructed considering environmental, dog and clinical variables. Pearson's Chi square and Fisher's exact tests were employed to evaluate the association between CVL, dog clinical signs and infestation with other parasites. Cartographic outputs were made and Moran's I indices were calculated as spatial autocorrelation indicators. CVL prevalence rates were 26.18% in 2014 and 17.50% in 2018. No associations were established in environmental models, but dog age and repellent use were significant when running 2014 dog models. Clinical models showed significant associations between seropositive dogs and ophthalmological, dermal signs and onychogryphosis in 2014. In 2018, only adenomegaly was associated. The results of global Moran´s I were not significant but regarding local analysis, six sites in 2014 and one in 2018 presented autocorrelation with neighboring sites. The decrease in CVL prevalence may be associated to transmission stabilization, which could explain the lack of associations with dog-related variables. Further, spatial distribution of CVL is a poor evidence for design of transmission control measures but could be important in case of intensive parasite circulation or when the first autochthonous cases appear. For control success, sensitivity of diagnostic methods, political will and adequate material resources remain critical. Modeling of multiple variables will be required to identify factors that drive disease stabilization/destabilization.

Mitochondrial DNA ancestry, HPV infection and the risk of cervical cancer in a multiethnic population of northeastern Argentina.

BACKGROUND: Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province. METHODS: Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs) adjusted by socio-demographic variables. RESULTS: The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and HPV-58 [OR of 19.0 (2.4-147.7)]. CONCLUSION: HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.

Assessment of the role of small mammals in the transmission cycle of tegumentary leishmaniasis and first report of natural infection with Leishmania braziliensis in two sigmodontines in northeastern Argentina.

To contribute to the knowledge of the role of small mammals in the transmission cycle of tegumentary leishmaniasis caused by Leishmania braziliensis, we studied the small mammal community and its temporal and spatial association with phlebotominae, as well as small mammal infection by Leishmania spp. by PCR-RFLP analyses in an endemic area of northeastern Argentina. Ten small mammal samplings were conducted (2007-2009, 7506 Sherman trap nights and 422 cage trap nights). In two of these samplings, 16 capture stations each one consisting of a CDC light trap to capture phlebotominae, two to four Sherman traps and two cage traps were placed. We found co-occurrence of phlebotominae and small mammal captures in four stations, which were all the stations with small mammal captures and yielded 97% (2295 specimens, including 21 gravid females) of the total phlebotominae captures, suggesting that small mammals may provide a potential source of blood for phlebotominae females. One Didelphis albiventris and two Rattus rattus were associated with high captures of Nyssomyia whitmani, vector of L. braziliensis in the study area. The PCR-RFLP analyses confirm the presence of L. braziliensis in two sigmodontine small mammals (Akodon sp. and Euryoryzomys russatus) for the first time in Argentina, to our knowledge.

[Retrospective eco-epidemiology as a tool for the surveillance of leishmaniasis in Misiones, Argentina, 1920-2014]. / La eco-epidemiología retrospectiva como herramienta aplicada a la vigilancia de la leishmaniasis en Misiones, Argentina, 1920-2014.

A retrospective analytical method is presented, based on theoretical eco-epidemiology, applied on a subnational spatial scale. This method was used here to describe scenarios for the transmission of leishmaniasis in the Argentine province of Misiones- bordering Brazil and Paraguay-and formed the basis for recommendations for surveillance and control appropriate to the subnational scale. An exhaustive search of the literature on leishmaniasis in the province was carried out. Three scenarios for the transmission of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) were found, corresponding to three periods: from 1920 to 1997, during which the transmission of CL distributed over time and space was confirmed; 1998 to 2005, during which there were focal outbreaks of CL; and 2006 to 2014, during which outbreaks were also reported and the geographical dispersion of VL was documented. To describe the risk scenarios and the anthropic processes that produce them, the results were summarized and integrated into the social, historical, and bio-ecological context of each period. Surveillance and control recommendations are based on the territory studied. They include establishing active surveillance to monitor possible rising trends in parasitic and vector circulation, conducting studies of any focal outbreak in order to confirm indigenous transmission and severity. Also, it should be a legal requirement for persons responsible for projects that alter the environment to adopt additional control measures, such as studies assessing transmission risk, risk mitigation, early detection, and timely case management.

La eco-epidemiología retrospectiva como herramienta aplicada a la vigilancia de la leishmaniasis en Misiones, Argentina, 1920-2014 / Retrospective eco-epidemiology as a tool for the surveillance of leishmaniasis in Misiones, Argentina, 1920–2014

Se presenta una metodología analítica retrospectiva, basada en el marco teórico de la eco-epidemiología, anclada en una escala espacial subnacional. Esta metodología, aplicada aquí a la caracterización de escenarios de transmisión de la leishmaniasis en la provincia argentina de Misiones —fronteriza con Brasil y Paraguay— permitió fundamentar recomendaciones de vigilancia y control apropiadas a dicha escala. Se realizó una búsqueda exhaustiva de la literatura sobre leishmaniasis en esa provincia y se determinaron tres escenarios de transmisión de leishmaniasis cutánea (LC) y visceral (LV), correspondientes a tres períodos: 1920-1997, en el que se constató la transmisión de LC, dispersa en el tiempo y el espacio; 1998-2005, en el que hubo brotes focales de LC; y 2006-2014 en el que, además, se registraron brotes y se documentó la dispersión geográfica de la LV. Para caracterizar los escenarios de riesgo y los procesos antrópicos que los producen, los resultados se sintetizaron e integraron en el contexto socio-histórico y bio-ecológico de cada período analizado. Se fundamentan recomendaciones de vigilancia y control en el territorio estudiado, entre ellas, establecer una vigilancia activa para monitorear posibles tendencias al incremento de la circulación parasitaria y vectorial y, ante la aparición de un foco, realizar estudios para verificar la transmisión autóctona y la intensidad del evento. Además, se debe establecer la obligación legal de tomar medidas adicionales de control por los responsables de los proyectos que impliquen modificación ambiental, como la realización de estudios de evaluación del riesgo de transmisión, y acciones de mitigación del riesgo, detección temprana y tratamiento oportuno de los casos.

A retrospective analytical method is presented, based on theoretical eco-epidemiology, applied on a subnational spatial scale. This method was used here to describe scenarios for the transmission of leishmaniasis in the Argentine province of Misiones—bordering Brazil and Paraguay—and formed the basis for recommendations for surveillance and control appropriate to the subnational scale. An exhaustive search of the literature on leishmaniasis in the province was carried out. Three scenarios for the transmission of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) were found, corresponding to three periods: from 1920 to 1997, during which the transmission of CL distributed over time and space was confirmed; 1998 to 2005, during which there were focal outbreaks of CL; and 2006 to 2014, during which outbreaks were also reported and the geographical dispersion of VL was documented. To describe the risk scenarios and the anthropic processes that produce them, the results were summarized and integrated into the social, historical, and bio-ecological context of each period. Surveillance and control recommendations are based on the territory studied. They include establishing active surveillance to monitor possible rising trends in parasitic and vector circulation, conducting studies of any focal outbreak in order to confirm indigenous transmission and severity. Also, it should be a legal requirement for persons responsible for projects that alter the environment to adopt additional control measures, such as studies assessing transmission risk, risk mitigation, early detection, and timely case management.

Molecular epidemiology of hepatitis B virus in Misiones, Argentina.

Hepatitis B virus (HBV) infection is a major public health problem worldwide. The aims of this study were to describe the molecular epidemiology of HBV in the Province of Misiones, Argentina and estimate the phylodynamic of the main groups in a Bayesian coalescent framework. To this end, partial or complete genome sequences were obtained from 52 blood donor candidates. The phylogenetic analysis based on partial sequences of S/P region showed a predominance of genotype D (65.4%), followed by genotype F (30.8%) and genotype A as a minority (3.8%). At subgenotype level, the circulation of subgenotypes D3 (42.3%), D2 (13.5%), F1b (11.5%) and F4 (9.6%) was mainly identified. The Bayesian coalescent analysis of 29 complete genome sequences for the main groups revealed that the subgenotypes D2 and D3 had several introductions to the region, with ancestors dating back from 1921 to 1969 and diversification events until the late '70s. The genotype F in Misiones has a more recent history; subgenotype F4 isolates were intermixed with sequences from Argentina and neighboring countries and only one significant cluster dated back in 1994 was observed. Subgenotype F1b isolates exhibited low genetic distance and formed a closely related monophyletic cluster, suggesting a very recent introduction. In conclusion, the phylogenetic and coalescent analyses showed that the European genotype D has a higher circulation, a longer history of diversification and may be responsible for the largest proportion of chronic HBV infections in the Province of Misiones. Genotype F, especially subgenotype F1b, had a more recent introduction and its diversification in the last 20years might be related to its involvement in new transmission events.

Circulación de virus Dengue: triage clínico-laboratorial / Dengue virus circulation: clinical-laboratory triage

INTRODUCCIÓN En la infección por DENV, la mayoría de casos se refiere como SFI y requiere confirmación de laboratorio. La vigilancia laboratorial se realiza con ELISAs NS1/IgM y en laboratorios de referencia por PRNT y RT-PCR. En este contexto, las estrategias de triage basadas en evidencia que identifican primeros estadios pueden facilitar la caracterización del paciente en función del manejo clínico-laboratorial. OBJETIVO Evaluar desarrollo de triage clínico-laboratorial que facilite la caracterización de SFI por DENV. MÉTODOS Estudio prospectivo de evaluación de precisión diagnóstica de metodología clínica-laboratorial, basado en algoritmo clínico con capacidad de diferenciar al paciente con sospecha de DENV de SFI seguido de ELISA NS1/IgM, en escenario epidémico y endemo-epidémico, al efecto de evaluar la performance de prueba índice (algoritmo clínico-laboratorial) vs. prueba referencia (PRNT/PCR) por Epidat 3.1. RESULTADOS El número de casos fue menor al esperado, por lo cual no se ha evaluado aún la performance del ensayo. El tamaño muestral fue 27 pacientes. De los síntomas clínicos, eritema pos 72 horas ha sido el único diferencial en pacientes NS1/IgM-DENV (+). Otros síntomas ofrecen escasa potencialidad diagnóstica diferencial para pacientes con DENV. El caso de ZikV presentó conjuntivitis, eritema pre 72 horas y petequias. En ensayos de laboratorio (n=13) se obtuvieron 2 PCR Flavivirus (+), 1 PCR ZikaV (+) y 10 PRNT (+) para diferentes combinaciones de DenV, Ilheus, SLEV, WNV. En un paciente con NS1/IgM-DENV negativas se observó 1 PRNT DenV (+). DISCUSIÓN La escasa potencialidad diagnóstica diferencial para DENV y los resultados de PCR/PRNT acomplejan el escenario epidemiológico local, que podría estar sustentado en circulación viral por vectores en base al hallazgo reciente de otros autores. Los resultados expuestos son preliminares, el grupo de investigación asume el compromiso de proseguir con el trabajo hasta alcanzar el objetivo propuesto

First description of Migonemyia migonei (França) and Nyssomyia whitmani (Antunes & Coutinho) (Psychodidae: Phlebotominae) natural infected by Leishmania infantum in Argentina.

Leishmania infantum is the etiological agent of the Visceral Leishmaniasis (VL) disease in America, with Lutzomyia longipalpis phlebotomine sandflies as its proven vectors in Argentina, and infected dogs as its main urban reservoir. In Puerto Iguazú City (Misiones province, Argentina), human and canine cases of VL were recorded. Additionally, in the rural area known as "2000 Hectáreas", less than 10km away from the city, several human cases of Tegumentary Leishmaniasis (TL) were registered determining an endemic area with Leishmania braziliensis as the etiological agent. Because of this, several phlebotomine captures were done in this site showing that Nyssomyia whitmani is the most abundant sandfly followed by Migonemyia migonei. In this study, three of the sandflies captured were found infected whit L. infantum parasites, detected by PCR and sequencing. Two of them were N. whitmani and the other one was a M. migonei specimen, being this the first report of L. infantum natural infection for Argentina in these sandfly species. N. whitmani is the main vector of L. braziliensis in this area, and M. migonei has been suggested as a putative vector in other locations where human and canine cases of VL where reported with L. longipalpis apparently absent. In this context, we consider necessary further studies that could define the role of M. migonei and N. whitmani as specific or permissive vectors of L. infantum, their vectorial competence and capacity, and their actual role in the transmission of both Tegumentary and Visceral Leishmaniasis in the study area.

Genetic characterization and clinical implications of human papillomavirus type 16 (HPV16) variants from northeastern Argentina.

BACKGROUND: Human papillomavirus type 16 (HPV16) plays a central role in the development of cervical cancer. Worldwide studies indicate the existence of HPV16 variants that show different geographic distributions and oncogenic potential. OBJECTIVE: Our goal was to describe the genetic variation of HPV16 isolates identified in urban women with different grades of cervical lesions living in northeastern Argentina. STUDY DESIGN: We analyzed 116 HPV16-positive cervical samples (16 NLIM, 62 L-SIL, 16 H-SIL and 22 cervical cancer) from patients attending health centers in Misiones (Argentina) during 2006-13. HPV16 isolates were genetically characterized through PCR amplification and direct sequencing of 364 bp within the long control region, and the resulting sequences classified into variants based on phylogenetic analysis (lineages A, B, C and D). A potential association between HPV16 variants and lesion grade was evaluated through an odds ratio (OR) test. A temporal framework for the origin of HPV16 variants was assessed through coalescence analysis (BEAST v 1.7.5). RESULTS: Phylogenetic analysis of HPV16 sequences showed that 92.1% of the samples clustered with lineage A, and 6.9% to lineage D. HPV16 variants from lineage D were more frequently associated with high-grade lesions and cancer (HSIL+) than lineage A variants at an OR of 13.8 (1.6-117.0). The time to most common recent ancestor (tMCRA) of all variants was 119,103 years before present (HPD 95%=48,486-197,239), a date consistent with the time frame for modern human evolution. CONCLUSION: Our results suggest that HPV16 variants from lineage D may represent an additional risk factor for the development of cervical cancer in women living in northeastern Argentina. This study provides new information about viral isolates present in Argentina that will contribute to the monitoring of HPV16 infection in the vaccine era.

Factores de riesgo asociados a la transmisión intrafamiliar del virus de la hepatitis B en la provincia de Misiones / Risk factors associated with intrafamiliar transmission of hepatitis B virus in Misiones province

INTRODUCCION: Se estima que en el mundo existen 2.000 millones de personas infectadas por el virus de la hepatitis B (VHB), de los cuales 400 millones presentan infección crónica y 1 millón muere anualmente debido a falla hepática. La transmisión del VHB entre los convivientes de un portador crónico es un evento precuente. La seroprevalencia de marcadores de infección por VHB en estos grupos de riesgo supera la esperada para la población general. La importancia de la transmisión horizontal de la hepatitis B en los núcleos familiares radica en el mayor riesgo de que sus integrantes, en particular los niños, adquieran la enfermedad y sufran graves complicaciones.OBJETIVO: Determinar la prevalencia de infección en familiares y convivientes de portadores crónicos del VHB y evaluar los posibles mecanismos de transmisión del virus de la región.METODOS: Se realizó un estudio descriptivo para determinar la prevalencia de la infección en familiares de donantes del Banco de Sangre Central de la Provincia de Misiones (BSCM) con marcadores serológicos de infección crónica (estudio transversal en 40 casos índice y 50 familiares y convivientes). Se obtuvieron datos de interés epidemiológico y muestras de sangre para detectar marcadores serológicos de infección.RESULTADOS: En los familiares y convivientes se reportaron 6% de infecciones crónicas, 22% de infecciones resueltas y 72% de individuos sin exposición al virus.CONCLUSIONES: La prevalencia total de infección por VHB fue mayor a la hallada en la población de referencia, con significancia estadística, lo que evidenció la existencia de transmisión intrafamiliar. Dado que no se logró identificar factores de riesgo, es necesario llevar a cabo más investigaciones para determinar cuáles son los mecanismos de transmisión intrafamiliar en la región y aplicar las medidas de profilaxis adecuadas.

INTRODUCTION: Hepatitis B virus (HBV) affecs an estimated 2 billion persons worldwide, of which 400 million remain chronically infected, and 1 million die of HBV-related liver diseases annually. HBV transmission between household contacts of a chronic carrier is a frequent event. The serological prevalence of HBV infection markeris in these risk groups is higher than the one observed in general population. The horizontal transmission risk is related to the severe forms of the disease, particularly in children.OBJECTIVE: To evaluate the prevalence and the modes of transmission of HBV, within infected subjects and their household in the region.METHODS: A descriptive study was conducted to determine the prevalence of infection in family members of donors of the Central Blood Bank of Misiones Province (BSCM) with serological markers of chronic infection (cross-sectional study performed in 40 index cases and 50 household contacts). Data of epidemiological interest and blood samples were collected to detect serological markers of infection.RESULTS: The prevalence in household contacts was 6% of chronic infections, 22% of resolved infections and 72% of individuals without previous virus exposure.CONCLUSIONS: The overall prevalence of HBV infection was higher than for the reference population, with statistical significance, showing intrafamiliar transmission. Since no risk factors were identified, it is necessary to do more research to clarify the intrafamiliar impact and transmission mechanisms in the region.

Factores de riesgo asociados a la transmisión intrafamiliar del virus de la hepatitis B en la provincia de Misiones / Risk factors associated with intrafamiliar transmission of hepatitis B virus in Misiones province

INTRODUCCION: Se estima que en el mundo existen 2.000 millones de personas infectadas por el virus de la hepatitis B (VHB), de los cuales 400 millones presentan infección crónica y 1 millón muere anualmente debido a falla hepática. La transmisión del VHB entre los convivientes de un portador crónico es un evento precuente. La seroprevalencia de marcadores de infección por VHB en estos grupos de riesgo supera la esperada para la población general. La importancia de la transmisión horizontal de la hepatitis B en los núcleos familiares radica en el mayor riesgo de que sus integrantes, en particular los niños, adquieran la enfermedad y sufran graves complicaciones.OBJETIVO: Determinar la prevalencia de infección en familiares y convivientes de portadores crónicos del VHB y evaluar los posibles mecanismos de transmisión del virus de la región.METODOS: Se realizó un estudio descriptivo para determinar la prevalencia de la infección en familiares de donantes del Banco de Sangre Central de la Provincia de Misiones (BSCM) con marcadores serológicos de infección crónica (estudio transversal en 40 casos índice y 50 familiares y convivientes). Se obtuvieron datos de interés epidemiológico y muestras de sangre para detectar marcadores serológicos de infección.RESULTADOS: En los familiares y convivientes se reportaron 6% de infecciones crónicas, 22% de infecciones resueltas y 72% de individuos sin exposición al virus.CONCLUSIONES: La prevalencia total de infección por VHB fue mayor a la hallada en la población de referencia, con significancia estadística, lo que evidenció la existencia de transmisión intrafamiliar. Dado que no se logró identificar factores de riesgo, es necesario llevar a cabo más investigaciones para determinar cuáles son los mecanismos de transmisión intrafamiliar en la región y aplicar las medidas de profilaxis adecuadas.

INTRODUCTION: Hepatitis B virus (HBV) affecs an estimated 2 billion persons worldwide, of which 400 million remain chronically infected, and 1 million die of HBV-related liver diseases annually. HBV transmission between household contacts of a chronic carrier is a frequent event. The serological prevalence of HBV infection markeris in these risk groups is higher than the one observed in general population. The horizontal transmission risk is related to the severe forms of the disease, particularly in children.OBJECTIVE: To evaluate the prevalence and the modes of transmission of HBV, within infected subjects and their household in the region.METHODS: A descriptive study was conducted to determine the prevalence of infection in family members of donors of the Central Blood Bank of Misiones Province (BSCM) with serological markers of chronic infection (cross-sectional study performed in 40 index cases and 50 household contacts). Data of epidemiological interest and blood samples were collected to detect serological markers of infection.RESULTS: The prevalence in household contacts was 6% of chronic infections, 22% of resolved infections and 72% of individuals without previous virus exposure.CONCLUSIONS: The overall prevalence of HBV infection was higher than for the reference population, with statistical significance, showing intrafamiliar transmission. Since no risk factors were identified, it is necessary to do more research to clarify the intrafamiliar impact and transmission mechanisms in the region.