[Strategies and recommendations to face respiratory syncytial virus disease in 2024]. / Estrategias y recomendaciones para enfrentar la enfermedad por virus respiratorio sincicial el año 2024.

During the winter of 2023, Chile faced a complex situation related to the respiratory syncytial virus (RSV). After experiencing a decline in RSV circulation during the years of the SARS-CoV-2 pandemic, a late outbreak was observed in the spring of 2022 and an early onset of the outbreak in 2023, with a significant increase in the number of serious cases. The ineffectiveness of strategic planning and risk communication contributed to the complexity of the situation. To avoid the above next winter, measures such as active surveillance, unification of definitions for acute respiratory infections, identification of RSV variants, public education about infections and advance preparation regarding hospital beds and health personnel are suggested. The importance of immunization and intersectoral collaboration to acquire new preventive alternatives is highlighted, as well as the need for early communication about the importance of immunization and identification of high-risk groups, improvement in training of medical personnel and strategic planning of the Ministry of Health. seeking a proactive and collaborative approach to address the complex RSV situation in future winters. The Chilean Immunization Advisory Committee has already carried out an analysis and recommendation on a new prevention alternative. This working group will support any decision of the Ministry of Health in public policies that attempt a change in the paradigm of control of this disease for the health of the children of our country.

Effects on Quality of Life of a Telemonitoring Platform amongst Patients with Cancer (EQUALITE): A Randomized Trial Protocol.

Cancer, a pervasive global health challenge, necessitates chemotherapy or radiotherapy treatments for many prevalent forms. However, traditional follow-up approaches encounter limitations, exacerbated by the recent COVID-19 pandemic. Consequently, telemonitoring has emerged as a promising solution, although its clinical implementation lacks comprehensive evidence. This report depicts the methodology of a randomized trial which aims to investigate whether leveraging a smartphone app called Contigo for disease monitoring enhances self-reported quality of life among patients with various solid cancers compared to standard care. Secondary objectives encompass evaluating the app's impact on depressive symptoms and assessing adherence to in-person appointments. Randomization will be performed independently using an allocation sequence that will be kept concealed from clinical investigators. Contigo offers two primary functions: monitoring cancer patients' progress and providing educational content to assist patients in managing common clinical situations related to their disease. The study will assess outcomes such as quality of life changes and depressive symptom development using validated scales, and adherence to in-person appointments. Specific scales include the EuroQol Group's EQ-5D questionnaire and the Patient Health Questionnaire (PHQ-9). We hypothesize that the use of Contigo will assist and empower patients receiving cancer treatment, which will translate to better quality of life scores and a reduced incidence of depressive symptoms. All analyses will be undertaken with the intention-to-treat principle by a statistician unaware of treatment allocation. This trial is registered in ClinicalTrials under the registration number NCT06086990.

Differential Effects of a Telemonitoring Platform in the Development of Chemotherapy-Associated Toxicity: A Randomized Trial Protocol.

Chemotherapy requires careful monitoring, but traditional follow-up approaches face significant challenges that were highlighted by the COVID-19 pandemic. Hence, exploration into telemonitoring as an alternative emerged. The objective is to assess the impact of a telemonitoring platform that provides clinical data to physicians overseeing solid tumor patients, aiming to enhance the care experience. The methodology outlines a parallel-group randomized clinical trial involving recently diagnosed patients with solid carcinomas preparing for curative intent chemotherapy. Eligible adult patients diagnosed with specific carcinoma types and proficient in Spanish, possessing smartphones, will be invited to participate. They will be randomized using concealed allocation sequences into two groups: one utilizing a specialized smartphone application called Contigo for monitoring chemotherapy toxicity symptoms and accessing educational content, while the other receives standard care. Primary outcome assessment involves patient experience during chemotherapy using a standardized questionnaire. Secondary outcomes include evaluating severe chemotherapy-associated toxicity, assessing quality of life, and determining user satisfaction with the application. The research will adhere to intention-to-treat principles. This study has been registered at ClinicalTrials.gov (NCT06077123).

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study.

Background: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).

Association between salt intake and gastric atrophy by Helicobacter pylori infection: first results from the Epidemiological Investigation of Gastric Malignancy (ENIGMA).

PURPOSE: Gastric atrophy (GA), usually linked to chronic infection with Helicobacter pylori (H. pylori), may over time evolve into gastric malignancy. Besides H. pylori, high salt intake may play a role in GA development. This study evaluates cross sectionally the association between salt intake and GA in Chilean adults. METHODS: Population-based samples were recruited from two sites, Antofagasta and Valdivia, partaking in the Epidemiological Investigation of Gastric Malignancies. At recruitment, participants answered questionnaires and provided biospecimens. Salt intake (g/day) was estimated from casual spot urine samples using the Tanaka equation. GA was determined by serum pepsinogen levels. Only participants ≥ 40 to 70 years of age were considered in this analysis, n = 565. For the association between salt intake (as sex-specific quartiles) and GA, odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were estimated through multivariable logistic regression. RESULTS: In women, the multivariable-adjusted OR for GA comparing quartile 4 of the estimated salt intake (12.8 g/day) to quartile 1 (6.6 g/day) was 1.18 (95% CI 0.52-2.68, P-trend = 0.87). The corresponding OR in men was 0.49 (95% CI 0.19-1.27, P-trend = 0.17) with salt intakes of 12.8 g/day and 7.1 g/day for quartiles 4 and 1, respectively. CONCLUSION: There was little evidence for an association between salt intake estimated from spot urine and GA risk in our cross-sectional analysis of middle aged and older adults in Chile. Reverse causation bias cannot be ruled out and the sample size was limited to provide more precise estimates.

Neutralizing antibodies induced by homologous and heterologous boosters in CoronaVac vaccines in Chile.

OBJECTIVES: To determine the impact of a booster dose on the humoral response in individuals inoculated with a complete schedule of any SARS-CoV-2 vaccine, we evaluated the neutralizing antibody (NAb) titres of homologous or heterologous booster doses over a 90-days period in CoronaVac vaccinees from 3 centres in Santiago, Chile. METHODS: Individuals previously inoculated with 2 doses of CoronaVac (N = 523) were recruited in the context of the REFUERZO clinical trial (NCT04992182) and received either placebo (N = 129), or a booster dose of CoronaVac (N = 134), BNT162b2 (N = 133), or ChAdOx1 (N = 127). Pseudovirus neutralizing antibody titres (pVNT) were determined at baseline (day 0) as well as at days 14, 30, 60, and 90 after booster dose administration. RESULTS: Inoculating a booster dose increases the pVNTs titres at days 14 and 30 in all groups, (13.5- and 12.0-fold increase for the CoronaVac group; 247.0- and 212.3-fold increase for the BTN162b2 group; and 89.1- and 128.1-fold increase for ChAdOx1 at each time point, respectively) with a decline observed at days 60 and 90. However, although pVNTs remained significantly higher for the BTN162b2 and ChAdOx1 groups at days 60 and 90, NAb titres reached baseline levels in the CoronaVac group at 90 days after inoculation. DISCUSSION: A single heterologous booster (BTN162b2 or ChAdOx1) in individuals who completed the CoronaVac primary series resulted in an important increase in NAb titres remaining significantly higher at least for 90 days. These data may directly impact middle- and low-income countries currently using CoronaVac as the main vaccination strategy.

Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 spike antibodies.

BACKGROUND: Chile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters. METHODS: We compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and one homologous or heterologous booster through an ELISA assay directed against the ancestral spike protein of SARS-CoV-2. Sera were collected from individuals during the vaccination schedule and throughout the implementation of homologous and heterologous booster programs in Chile. RESULTS: Our findings demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 spike antibodies than BNT162b2 in a broad age range (median age 42 years; interquartile range (IQR) 27-61). Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher (induction fold BNT162b2: 11.2x; ChAdoX1; 12.4x; CoronaVac: 6.0x) than the responses induced by the homologous scheme. Both homologous and heterologous boosters induced persistent humoral responses (median 122 days, IQR (108-133)), although heterologous boosters remained superior in activating a humoral response after 100 days. CONCLUSIONS: Two doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous and homologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.

Effectiveness of CoronaVac in children 3-5 years of age during the SARS-CoV-2 Omicron outbreak in Chile.

The outbreak of the B.1.1.529 lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Omicron) has caused an unprecedented number of Coronavirus Disease 2019 (COVID-19) cases, including pediatric hospital admissions. Policymakers urgently need evidence of vaccine effectiveness in children to balance the costs and benefits of vaccination campaigns, but, to date, the evidence is sparse. Leveraging a population-based cohort in Chile of 490,694 children aged 3-5 years, we estimated the effectiveness of administering a two-dose schedule, 28 days apart, of Sinovac's inactivated SARS-CoV-2 vaccine (CoronaVac). We used inverse probability-weighted survival regression models to estimate hazard ratios of symptomatic COVID-19, hospitalization and admission to an intensive care unit (ICU) for children with complete immunization over non-vaccination, accounting for time-varying vaccination exposure and relevant confounders. The study was conducted between 6 December 2021 and 26 February 2022, during the Omicron outbreak in Chile. The estimated vaccine effectiveness was 38.2% (95% confidence interval (CI), 36.5-39.9) against symptomatic COVID-19, 64.6% (95% CI, 49.6-75.2) against hospitalization and 69.0% (95% CI, 18.6-88.2) against ICU admission. The effectiveness against symptomatic COVID-19 was modest; however, protection against severe disease was high. These results support vaccination of children aged 3-5 years to prevent severe illness and associated complications and highlight the importance of maintaining layered protections against SARS-CoV-2 infection.

Effectiveness of homologous and heterologous booster doses for an inactivated SARS-CoV-2 vaccine: a large-scale prospective cohort study.

BACKGROUND: Several countries have authorised or begun using a booster vaccine dose against COVID-19. Policy makers urgently need evidence of the effectiveness of additional vaccine doses and its clinical spectrum for individuals with complete primary immunisation schedules, particularly in countries where the primary schedule used inactivated SARS-CoV-2 vaccines. METHODS: Using individual-level data, we evaluated a prospective, observational, national-level cohort of individuals (aged ≥16 years) affiliated with the Fondo Nacional de Salud insurance programme in Chile, to assess the effectiveness of CoronaVac (Sinovac Biotech), AZD1222 (Oxford-AstraZeneca), or BNT162b2 (Pfizer-BioNTech) vaccine boosters in individuals who had completed a primary immunisation schedule with CoronaVac, compared with unvaccinated individuals. Individuals administered vaccines from Feb 2, 2021, to the prespecified study end date of Nov 10, 2021, were evaluated; we excluded individuals with a probable or confirmed SARS-CoV-2 infection (RT-PCR or antigen test) on or before Feb 2, 2021, and individuals who had received at least one dose of any COVID-19 vaccine before Feb 2, 2021. We estimated the vaccine effectiveness of booster doses against laboratory-confirmed symptomatic COVID-19 (symptomatic COVID-19) cases and COVID-19 outcomes (hospitalisation, admission to the intensive care unit [ICU], and death We used inverse probability-weighted and stratified survival regression models to estimate hazard ratios, accounting for time-varying vaccination status and adjusting for relevant demographic, socioeconomic, and clinical confounders. We estimated the change in hazard from unvaccinated status to vaccinated status associated with the primary immunisation series and a booster vaccine. FINDINGS: 11 174 257 individuals were eligible for this study, among whom 4 127 546 completed a primary immunisation schedule (two doses) with CoronaVac and received a booster dose during the study period. 1 921 340 (46·5%) participants received an AZD1222 booster, 2 019 260 (48·9%) received a BNT162b2 booster, and 186 946 (4·5%) received a homologous booster with CoronaVac. We calculated an adjusted vaccine effectiveness (weighted stratified Cox model) in preventing symptomatic COVID-19 of 78·8% (95% CI 76·8-80·6) for a three-dose schedule with CoronaVac, 96·5% (96·2-96·7) for a BNT162b2 booster, and 93·2% (92·9-93·6) for an AZD1222 booster. The adjusted vaccine effectiveness against COVID-19-related hospitalisation, ICU admission, and death was 86·3% (83·7-88·5), 92·2% (88·7-94·6), and 86·7% (80·5-91·0) for a homologous CoronaVac booster, 96·1% (95·3-96·9), 96·2% (94·6-97·3), and 96·8% (93·9-98·3) for a BNT162b2 booster, and 97·7% (97·3-98·0), 98·9% (98·5-99·2), and 98·1% (97·3-98·6) for an AZD1222 booster. INTERPRETATION: Our results suggest that a homologous or heterologous booster dose for individuals with a complete primary vaccination schedule with CoronaVac provides a high level of protection against COVID-19, including severe disease and death. Heterologous boosters showed higher vaccine effectiveness than a homologous booster for all outcomes, providing additional support for a mix-and-match approach. FUNDING: Agencia Nacional de Investigación y Desarrollo through the Fondo Nacional de Desarrollo Científico y Tecnológico, Millennium Science Initiative Program, and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias.

Effectiveness of an Inactivated SARS-CoV-2 Vaccine in Chile.

BACKGROUND: Mass vaccination campaigns to prevent coronavirus disease 2019 (Covid-19) are occurring in many countries; estimates of vaccine effectiveness are urgently needed to support decision making. A countrywide mass vaccination campaign with the use of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (CoronaVac) was conducted in Chile starting on February 2, 2021. METHODS: We used a prospective national cohort, including participants 16 years of age or older who were affiliated with the public national health care system, to assess the effectiveness of the inactivated SARS-CoV-2 vaccine with regard to preventing Covid-19 and related hospitalization, admission to the intensive care unit (ICU), and death. We estimated hazard ratios using the extension of the Cox proportional-hazards model, accounting for time-varying vaccination status. We estimated the change in the hazard ratio associated with partial immunization (≥14 days after receipt of the first dose and before receipt of the second dose) and full immunization (≥14 days after receipt of the second dose). Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. RESULTS: The study was conducted from February 2 through May 1, 2021, and the cohort included approximately 10.2 million persons. Among persons who were fully immunized, the adjusted vaccine effectiveness was 65.9% (95% confidence interval [CI], 65.2 to 66.6) for the prevention of Covid-19 and 87.5% (95% CI, 86.7 to 88.2) for the prevention of hospitalization, 90.3% (95% CI, 89.1 to 91.4) for the prevention of ICU admission, and 86.3% (95% CI, 84.5 to 87.9) for the prevention of Covid-19-related death. CONCLUSIONS: Our results suggest that the inactivated SARS-CoV-2 vaccine effectively prevented Covid-19, including severe disease and death, a finding that is consistent with results of phase 2 trials of the vaccine. (Funded by Agencia Nacional de Investigación y Desarrollo and others.).

Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes.

BACKGROUND: Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS. METHODS: DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs. RESULTS: In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate. CONCLUSIONS: Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.

Performance of SARS-CoV-2 rapid antigen test compared with real-time RT-PCR in asymptomatic individuals.

Screening, testing and contact tracing plays a pivotal role in control of the COVID-19 pandemic. To enable this it is necessary to increase the testing capacity. This study compared a SARS-CoV-2 rapid antigen test (RAT) and RT-PCR in 842 asymptomatic individuals from Tarapacá, Chile. A sensitivity of 69.86%, specificity of 99.61%, PPV of 94.44% and NPP of 97.22% with Ct values (Ct > 27) that were significantly higher among individuals with false-negative RAT were reported. These results support the fact that RAT might have a significant impact on the identification of asymptomatic carriers in areas that lack suitable laboratories to perform SARS-CoV-2 real-time RT-PCR diagnostics, or the results take more than 24-48 h, as well as zones with high traffic of individuals such as border/customs, airports, interregional bus, train stations or in any mass testing campaign requiring rapid results.

National Seroprevalence of Coxiella burnetii in Chile, 2016-2017.

Coxiella burnetii is an intracellular bacterium and the cause of the zoonotic infection, Q fever. National surveillance data on C. burnetii seroprevalence is currently not available for any South American country, making efforts of public health to implement strategies to mitigate infections in different at-risk groups within the population extremely challenging. In the current study, we used two commercial anti-C. burnetii immunoassays to screen sera collected from a sample of the Chilean population as part of a 2016-2017 national health survey (n = 5166), nationwide and age-standardized. The seroprevalence for C. burnetii for persons ≥ 15 years was estimated to be 3.0% (95% CI 2.2-4.0), a level similar to national surveys from The Netherlands (2.4%) and USA (3.1%), but lower than Australia (5.6%). A linear increase of C. burnetii seropositivity was associated with an individual's age, with the peak seroprevalence 5.6% (95% CI 3.6-8.6) observed in the ≥65 years' group. C. burnetii seropositivity was significantly higher in the southern macro-zone 6.0% (95% CI 3.3-10.6) compared to metropolitan region 1.8% (95% CI 0.9-3.3), the former region being home to significant livestock industries, particularly dairy farming. These data will be useful to inform targeted strategies for the prevention of Q fever in at-risk populations in Chile.

[Molecular detection of gastrointestinal pathogens among children under 5 years old with diarrhea in a hospital center for rotavirus sentinel surveillance in Chile]. / Detección molecular de patógenos entéricos en niños con diarrea en un hospital centinela de vigilancia de rotavirus en Chile.

BACKGROUND: Infectious diarrhea is still a major problem in public health, especially in children under 5 years of age. The identification of the etiologic agent is important for the clinical management of the diarrhea episode and, from the epidemiological point of view, to implement control measures. AIM: To determine the presence of gastrointestinal pathogens in children under five years of age with diarrhea in a Chilean rotavirus surveillance center. METHODS: Observational study in children under five years of age who were hospitalized for diarrhea at the Dr. Luis Calvo Mackenna Hospital from December 2015 to December 2019. Molecular detection was performed using the FilmArray gastrointestinal (FilmArray GI®) panel. RESULTS: We analyzed 493 diarrheal stool samples of children, 427 samples (87%) were positive and 66 samples (13%) were negative. Of positive samples, 174 samples (41%) and 253 samples (59%) were positive for one or more pathogen, respectively. In children under one year and the group between one and four years there was a predominance of infections caused by enteric virus. Rotavirus and norovirus were the most common virus in both age groups. The most frequent bacteria were EPEC (27%), C. difficile (17%), EAEC (14%) and Campylobacter (9%). In parasites, Giardia lamblia and Cryptosporidium were identified, in 3% and 1% of the total samples, respectively. CONCLUSIONS: The molecular detection system used allowed an increase in the detection of enteropathogens in children under five years of age. The information generated by this type of surveillance could help to characterize the episodes of diarrhea in the population and might be a tool to technically advise the authorities in the decision-making process for the implementation of control measures.

Detección molecular de patógenos entéricos en niños con diarrea en un hospital centinela de vigilancia de rotavirus en Chile / Molecular detection of gastrointestinal pathogens among children under 5 years old with diarrhea in a hospital center for rotavirus sentinel surveillance in Chile

INTRODUCCIÓN: Las diarreas de causa infecciosa son un problema de salud pública, especialmente en niños bajo los cinco años. La identificación de los agentes etiológicos puede ser relevante para el manejo del cuadro clínico y, desde el punto de vista epidemiológico, para la implementación de medidas de control. OBJETIVO: Determinar la presencia de patógenos entéricos en niños bajo los cinco años que se hospitalizaron por diarrea aguda en uno de los centros centinelas de la red de vigilancia de rotavirus en Chile. PACIENTES Y MÉTODOS: Estudio observacional en niños menores de cinco años que se internaron por cuadros de diarrea en el Hospital Dr. Luis Calvo Mackenna, durante diciembre del 2015 a diciembre del 2019, el que forma parte de la red de vigilancia de rotavirus del Ministerio de Salud de Chile. Las muestras fecales se analizaron mediante un test molecular, FilmArray GI® panel, que permite la detección de 22 patógenos entéricos virales, bacterianos y parasitarios. RESULTADOS: Se analizaron 493 muestras fecales de niños con episodios de diarrea infecciosa, detectando al menos un patógeno en 427 muestras (87%). De estas muestras positivas, se detectó solo un patógeno en 174 muestras (41%) y dos o más patógenos en 253 muestras (59%). En el grupo de niños bajo un año y el grupo entre uno y cuatro años hubo un predominio de infecciones causadas por virus gastroentéricos, siendo rotavirus y norovirus los virus más detectados en ambos grupos de edad. Las bacterias más frecuentes fueron EPEC (27%), C. difficile (17%), EAEC (14%) y Campylobacter (9%). Respecto a los parásitos, se identificó Giardia lamblia y Cryptosporidium, en el 3 y 1% del total de las muestras, respectivamente. CONCLUSIÓN: La detección molecular utilizada permitió detectar un alto número de enteropatógenos en niños bajo los cinco años. La información generada por este tipo de vigilancia, podría ayudar a caracterizar en la población los episodios de diarrea causados por los principales patógenos entéricos y podría ser una herramienta para asesorar técnicamente a las autoridades en la toma de decisión para la implementación de medidas de control contra estos patógenos.

BACKGROUND: Infectious diarrhea is still a major problem in public health, especially in children under 5 years of age. The identification of the etiologic agent is important for the clinical management of the diarrhea episode and, from the epidemiological point of view, to implement control measures. AIM: To determine the presence of gastrointestinal pathogens in children under five years of age with diarrhea in a Chilean rotavirus surveillance center. METHODS: Observational study in children under five years of age who were hospitalized for diarrhea at the Dr. Luis Calvo Mackenna Hospital from December 2015 to December 2019. Molecular detection was performed using the FilmArray gastrointestinal (FilmArray GI®) panel. RESULTS: We analyzed 493 diarrheal stool samples of children, 427 samples (87%) were positive and 66 samples (13%) were negative. Of positive samples, 174 samples (41%) and 253 samples (59%) were positive for one or more pathogen, respectively. In children under one year and the group between one and four years there was a predominance of infections caused by enteric virus. Rotavirus and norovirus were the most common virus in both age groups. The most frequent bacteria were EPEC (27%), C. difficile (17%), EAEC (14%) and Campylobacter (9%). In parasites, Giardia lamblia and Cryptosporidium were identified, in 3% and 1% of the total samples, respectively. CONCLUSIONS: The molecular detection system used allowed an increase in the detection of enteropathogens in children under five years of age. The information generated by this type of surveillance could help to characterize the episodes of diarrhea in the population and might be a tool to technically advise the authorities in the decision-making process for the implementation of control measures.

Genetic Population Structure of Wild Pigs in Southern Texas.

Wild pigs (Sus scrofa) alter ecosystems, affect the economy, and carry diseases that can be transmitted to livestock, humans, and wildlife. Understanding wild pig movements and population structure data, including natural population boundaries and dispersal, may potentially increase the efficiency and effectiveness of management actions. We trapped, conducted aerial shootings, and hunted wild pigs from 2005 to 2009 in southern Texas. We used microsatellites to assist large-scale applied management. We quantify broad-scale population structure among 24 sites across southern Texas by computing an overall Fst value, and a Bayesian clustering algorithm both with and without considering the spatial location of samples. At a broad geographic scale, pig populations displayed a moderate degree of genetic structure (Fst = 0.11). The best partition for number of populations, based on 2nd order rate of change of the likelihood distribution, was K = 10 genetic clusters. The spatially explicit Bayesian clustering algorithm produced similar results, with minor differences in designation of admixed sites. We found evidence of past (and possibly ongoing) translocations; many populations were admixed. Our original goal was to identify landscape features, such as barriers or dispersal corridors, that could be used to aid management. Unfortunately, the extensive admixture among clusters made this impossible. This research shows that large-scale management of wild pigs may be necessary to achieve control and ameliorate damages. Reduction or cessation of translocations is necessary to prevent human-mediated dispersion of wild pigs.

The Association between Fasting Glucose and Sugar Sweetened Beverages Intake Is Greater in Latin Americans with a High Polygenic Risk Score for Type 2 Diabetes Mellitus.

Chile is one of the largest consumers of sugar-sweetened beverages (SSB) world-wide. However, it is unknown whether the effects from this highly industrialized food will mimic those reported in industrialized countries or whether they will be modified by local lifestyle or population genetics. Our goal is to evaluate the interaction effect between SSB intake and T2D susceptibility on fasting glucose. We calculated a weighted genetic risk score (GRSw) based on 16 T2D risk SNPs in 2828 non-diabetic participants of the MAUCO cohort. SSB intake was categorized in four levels using a food frequency questionnaire. Log-fasting glucose was regressed on SSB and GRSw tertiles while accounting for socio-demography, lifestyle, obesity, and Amerindian ancestry. Fasting glucose increased systematically per unit of GRSw (ß = 0.02 ± 0.006, p = 0.00002) and by SSB intake (ß[cat4] = 0.04 ± 0.01, p = 0.0001), showing a significant interaction, where the strongest effect was observed in the highest GRSw-tertile and in the highest SSB consumption category (ß = 0.05 ± 0.02, p = 0.02). SNP-wise, SSB interacted with additive effects of rs7903146 (TCF7L2) (ß = 0.05 ± 0.01, p = 0.002) and with the G/G genotype of rs10830963 (MTNRB1B) (ß = 0.19 ± 0.05, p = 0.001). Conclusions: The association between SSB intake and fasting glucose in the Chilean population without diabetes is modified by T2D genetic susceptibility.

Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile.

BACKGROUND: Regional variations in gastric cancer incidence are not explained by prevalence of Helicobacter pylori, the main cause of the disease, with several areas presenting high H. pylori prevalence but low gastric cancer incidence. The IARC worldwide H. pylori prevalence surveys (ENIGMA) aim at systematically describing age and sex-specific prevalence of H. pylori infection around the world and generating hypotheses to explain regional variations in gastric cancer risk. METHODS: We selected age- and sex-stratified population samples in two areas with different gastric cancer incidence and mortality in Chile: Antofagasta (lower rate) and Valdivia (higher rate). Participants were 1-69 years old and provided interviews and blood for anti-H. pylori antibodies (IgG, VacA, CagA, others) and atrophy biomarkers (pepsinogens). RESULTS: H. pylori seroprevalence (Age-standardized to world population) and antibodies against CagA and VacA were similar in both sites. H. pylori seroprevalence was 20% among children <10 years old, 40% among 10-19 year olds, 60% in the 20-29 year olds and close to or above 80% in those 30+ years. The comparison of the prevalence of known and potential H. pylori cofactors in gastric carcinogenesis between the high and the low risk area showed that consumption of chili products was significantly higher in Valdivia and daily non-green vegetable consumption was more common in Antofagasta. Pepsinogen levels suggestive of gastric atrophy were significantly more common and occurred at earlier ages in Valdivia, the higher risk area. In a multivariate model combining both study sites, age, chili consumption and CagA were the main risk factors for gastric atrophy. CONCLUSIONS: The prevalence of H. pylori infection and its virulence factors was similar in the high and the low risk area, but atrophy was more common and occurred at younger ages in the higher risk area. Dietary factors could partly explain higher rates of atrophy and gastric cancer in Valdivia. IMPACT: The ENIGMA study in Chile contributes to better understanding regional variations in gastric cancer incidence and provides essential information for public health interventions.