Community-based screening of Chagas disease among Latin American migrants in a non-endemic country: an observational study

Background: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. Methods: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. Results: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3-14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13-781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14-5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61-1188) or Bolivia (aOR: 1.90, 95% CI: 1.19-3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54-8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34-0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52-847) were independently associated with a lower level of knowledge. Conclusions: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals.This study was partially supported by the third call for research grants (J-M.R.-R.) from the Institute of Health and Biomedical Research of Alicante (ISABIAL)/FISABIO Foundation (III convocatoria de ayudas a proyectos de investigación del Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) – Fundación FISABIO) (UGP-16-158); and by the collaborative agreement between ISABIAL/Fundación FISABIO and Fundación Mundo Sano-Spain, in accordance with the Sponsorship Law. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Asymptomatic Strongyloidiasis among Latin American Migrants in Spain: A Community-Based Approach

Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. Aim: To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Methodology: Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Results: Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Conclusion: Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.This study was partially supported by the 3rd call for research project grants for the Institute of Health and Biometric Research of Alicante (ISABIAL)/FISABIO Foundation (UGP-16-158), and by the collaboration agreement regulated under the Law of Patronage between ISABIAL/FISABIO and the Foundation Mundo Sano, Spain.S

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

En búsqueda del parásito oculto: Trypanosoma cruzi y Strongyloides stercoralis en población inmigrante latinoamericana

Tanto la enfermedad de Chagas como la infección por Strongyloides stercoralis, son enfermedades consideradas "desatendidas"; ambas son endémicas en Latinoamérica, y los fenómenos migratorios han favorecido su diseminación global. Aunque cursan de manera silente, los síntomas derivados de su cronificación suponen un riesgo para la salud. La falta de consciencia de enfermedad por parte de las personas susceptibles, así como la ausencia de conocimiento sobre los riesgos por parte de los profesionales sanitarios, motivan el elevado infradiagnóstico. Objetivos: Evaluar la prevalencia de la enfermedad de Chagas y Strongyloides stercoralis en los migrantes latinoamericanos que asisten a una campaña de cribado comunitario. Además de analizar las características epidemiológicas y el nivel de conocimiento entre los participantes de dicho evento. Medir el grado de conocimiento sobre la enfermedad de Chagas entre personal sanitario y sociosanitario interesado en la cooperación internacional, mediante un cuestionario validado. Métodos: Se desarrolló una campaña de cribado comunitario en la provincia de Alicante, durante los años 2016-2018. Previa a la extracción de un análisis de sangre para la serología de Trypanosoma cruzi y Strongyloides stercoralis, los participantes asistieron a charlas informativas y completaron un cuestionario que evaluaba el conocimiento sobre los mecanismos de transmisión, la presentación de la enfermedad, el diagnóstico y el tratamiento. Por otro lado, se elaboraron dos escalas la Escala de Nivel de Conocimiento de Chagas de 10 ítems para profesionales de la salud (ChaLKS-sanitarios) y de 8 ítems para potenciales cooperantes sociosanitarios (ChaLKS-sociosanitarios). Resultados: De los 616 migrantes que acudieron al cribado, 601 fueron incluidos en el estudio de prevalencia de estrongiloidiasis (100 niños y adolescentes (< 18 años de edad) y 501 adultos); y con lo que respecta a la enfermedad de Chagas, 596 participantes fueron incluidos (490 adultos y 100 niños y adolescentes). En cuanto a la infección por Strongyloides stercoralis, dieron positivo 6 menores de edad (prevalencia 6%, intervalo de confianza [IC] del 95%: 2,5% a 13,1%) y 60 adultos (prevalencia 12%, IC del 95%: 9,3% a 15,3%). Los hombres obtuvieron con mayor frecuencia serología positiva (odds ratio ajustado [ORa] 2,28; IC del 95%: 1,289 a 4,03), al igual que aquellos nacidos en Bolivia (ORa 2,03; IC del 95%: 1,15 a 3,59). La prevalencia aumentó con la edad (ORa 1,02; IC del 95%: 0,99 a 1,05). Por el contrario, la educación universitaria tuvo un efecto protector (ORa 0,29; IC del 95%: 0,31 a 0,88). Un total de 41 (41/66; 62,1%) casos con serología positiva optó a tratamiento farmacológico. En el caso de la enfermedad de Chagas, la prevalencia en adultos fue del 11% [54/496; IC del 95%: 8,3¿14,5%] versus 0% entre los niños. Todos los casos, excepto uno, fueron en bolivianos. El diagnóstico se asoció de forma independiente con haber nacido en Bolivia (aOR: 102, IC 95%: 13-781) y una educación primaria (aOR: 2,40, IC 95%: 1,14-5,06). De las 54 personas diagnosticadas con la enfermedad de Chagas, 42 (77,7%) acudieron a consulta de revisión al menos una vez y 24 (44,4%) recibieron tratamiento. El análisis multivariable mostró que provenir de Argentina (aOR 13, IC 95%: 1,61-1188) o Bolivia (aOR 1,90, IC95%: 1,19 - 3,39) y haber recibido información sobre la enfermedad de Chagas en España (aOR 4,63, IC 95%: 2,54-8,97) se asociaron con un buen nivel de conocimiento sobre la enfermedad. Tener estudios de nivel primario (aOR 0,59, IC 95%: 0,34-0,98) y haber nacido en Ecuador (aOR 4,63, IC 95%: 2,52-847) se asoció de manera independiente a tener un bajo nivel de conocimiento. Con respecto a la escala de conocimiento, el número medio de respuestas correctas obtenido en la escala ChaLKS-sanitarios entre los encuestados de los sectores no sanitario y sanitario fue de 1,80 frente a 7,00 (P < 0,001). Las puntuaciones en ChaLKS-sociosanitarios también discriminaron entre los niveles de conocimiento de estos dos grupos (1,76 frente a 6,78, P < 0,001). El conocimiento entre los estudiantes de medicina/farmacia y los médicos residentes fue aceptable y mostró diferencias significativas (media: 5,8 y 7,4, respectivamente; P < 0,001) en ChaLKS-sanitarios. El grado de conocimiento fue mayor en aquellos con formación previa en el tema. Conclusiones: Las intervenciones comunitarias basadas en el cribado serológico de Strongyloides stercoralis y de la enfermedad de Chagas suponen una herramienta eficaz para detectar la infección asintomática entre migrantes de América Central y del Sur y una oportunidad para abordar las enfermedades tropicales desatendidas de manera trasversal. El reto es lograr la adherencia de los pacientes al seguimiento médico. El grado de conocimiento de la enfermedad de Chagas es bajo, tanto en población susceptible como entre profesionales de la salud. Las escalas ChaLKS, tanto para personal sanitario como sociosanitario, son adecuadas para su uso en el apoyo a las operaciones de ayuda en los países endémicos de Chagas o en la prestación de atención sanitaria y social a las poblaciones migrantes en los países no endémicos

ESCLEROSTINA COMO MARCADOR PRECOZ DE RIESGO CARDIOVASCULAR EN PACIENTES CON INFECCIÓN POR EL VIH

La disminución de la mortalidad por eventos SIDA en los pacientes con infección por el virus de la inmunodeficiencia humana (VIH) ha dado lugar a la aparición de numerosas complicaciones no relacionadas directamente con la inmunosupresión, entre la que se encuentra la enfermedad cardiovascular. El propio VIH, por la inflamación crónica asociada estaría implicados en el desarrollo de una arteriosclerosis acelerada en estos pacientes. Los valores séricos de esclerostina se han relacionado con el riesgo cardiovascular en otras enfermedades con arteriosclerosis precoz y acelerada, como la diabetes, por lo que nos propusimos investigar la existencia o no de una asociación entre la esclerostina y la arteriosclerosis en pacientes con VIH

Chagas Disease-Related Mortality in Spain, 1997 to 2018

Background. Chagas disease (CD) is associated with excess mortality in infected people in endemic countries, but little information is available in non-endemic countries. The aim of the study was to analyze mortality in patients admitted to the hospital with CD in Spain. Methods. A retrospective, observational study using the Spanish National Hospital Discharge Database. We used the CD diagnostic codes of the 9th and 10th International Classification of Diseases to retrieve CD cases from the national public registry from 1997 to 2018. Results. Of the 5022 hospital admissions in people with CD, there were 56 deaths (case fatality rate (CFR) 1.1%, 95% confidence interval (CI) 0.8%, 1.4%), 20 (35.7%) of which were considered directly related to CD. The median age was higher in those who died (54.5 vs. 38 years; p &lt; 0.001). The CFR increased with age, peaking in the 70–79-year (7.9%, odds ratio (OR) 6.27, 95% CI 1.27, 30.90) and 80–89-year (16.7%, OR 14.7, 95% CI 2.70, 79.90) age groups. Men comprised a higher proportion of those who died compared to survivors (50% vs. 22.6%; p &lt; 0.001). Non-survivors were more likely to have neoplasms (19.6% vs. 3.4%; p &lt; 0.001), heart failure (17.9% vs. 7.2%; p = 0.002), diabetes (12.5% vs. 3.7%; p = 0.001), chronic kidney failure (8.9% vs. 1.6%; p &lt; 0.001), and HIV (8.9% vs. 0.8%; p &lt; 0.001). In the multivariable analysis, the variables associated with mortality were age (adjusted OR (aOR) 1.05; 95% CI: 1.03, 1.07), male sex (aOR 1.79, 95% CI 1.03, 3.14), cancer (aOR: 4.84, 95% CI 2.13, 11.22), and HIV infection (aOR 14.10 95% CI 4.88, 40.73). Conclusions. The case fatality rate of CD hospitalization was about 1%. The mortality risk increased with age, male sex, cancer, and HIV infection

Chagas disease screening in pregnant Latin American women: Adherence to a systematic screening protocol in a non-endemic country.

BackgroundChagas disease (CD) is a chronic parasitic disease caused by Trypanosoma cruzi and is endemic to continental Latin America. In Spain, the main transmission route is congenital. We aimed to assess adherence to regional recommendations of universal screening for CD during pregnancy in Latin American women in the province of Alicante from 2014 to 2018.Methodology/principal findingsRetrospective quality study using two data sources: 1) delivery records of Latin American women that gave birth in the 10 public hospitals of Alicante between January 2014 and December 2018; and 2) records of Chagas serologies carried out in those centers between May 2013 and December 2018. There were 3026 deliveries in Latin American women during the study period; 1178 (38.9%) underwent CD serology. Screening adherence ranged from 17.2% to 59.3% in the different health departments and was higher in Bolivian women (48.3%). Twenty-six deliveries (2.2%) had a positive screening; CD was confirmed in 23 (2%) deliveries of 21 women. Bolivians had the highest seroprevalence (21/112; 18.7%), followed by Colombians (1/333; 0.3%) and Ecuadorians (1/348; 0.3%). Of 21 CD-positive women (19 Bolivians, 1 Colombian, 1 Ecuadorian), infection was already known in 12 (57.1%), and 9 (42.9%) had already been treated. Only 1 of the 12 untreated women (8.3%) was treated postpartum. Follow-up started in 20 of the 23 (87.0%) neonates but was completed only in 11 (47.8%); no cases of congenital transmission were detected. Among the 1848 unscreened deliveries, we estimate 43 undiagnosed cases of CD and 1 to 2 undetected cases of congenital transmission.Conclusions/significanceAdherence to recommendations of systematic screening for CD in Latin American pregnant women in Alicante can be improved. Strategies to strengthen treatment of postpartum women and monitoring of exposed newborns are needed. Currently, there may be undetected cases of congenital transmission in our province