Relevance of screening for Chagas and viral hepatitis in Bolivian migrants

© 2020 Elsevier España, S.L.U. Objectives: Given the scarcity of data regarding prevalence of various infectious diseases in Latin-American countries, our study aims to assess the burden of T. cruzi, S. stercoralis, HIV and viral hepatitis in Latin-American migrants, with a focus on Bolivian migrants. Methods: We performed a retrospective observational study of 565 screening evaluations in adults (≥18 years) carried out at our International Healthcare referral service in Barcelona. We reviewed structured clinical records and microbiological results of patients attended between February 2012 and April 2015. Results: The median age was 35 years and 74% were women. Of the population screened, 87% were of Bolivian origin. We found a 48% prevalence of T. cruzi, 16% of S. stercoralis, 0.2% of HIV, 0.2% HBV and 0.2% HCV. Conclusions: These results support the relevance of screening for T. cruzi and S. stercoralis in Bolivian migrants but challenge the pertinence of systematic screening for HBV in this population

Increased expression levels of the pvcrt-o and pvmdr1 genes in a patient with severe Plasmodium vivax malaria

<p>Abstract</p> <p>Background</p> <p>There are increasing reports of severe clinical cases exclusively associated with <it>Plasmodium vivax </it>infections. Notably, this severity has been recently suggested to be associated with chloroquine resistance.</p> <p>Patients</p> <p>Two different patients presented at the Hospital Clinic in Barcelona with <it>P. vivax </it>malaria episodes. One patient had severe symptoms and the other mild symptoms. Both patients traveled through the Brazilian Amazon (Manaus) in 2007. For both patients the current diagnosis of malaria was the first. Two other patients with mild symptoms presented to the "Centro de Pesquisa em Medicina Tropical", also in the Brazilian Amazon (Rondônia) in 2000.</p> <p>Methods</p> <p>To exclude the possibility that the patient's severe symptoms were due to <it>Plasmodium falciparum</it>, a nested PCR was performed. A magnetic method was used to purify <it>P. vivax </it>free of human leukocytes. Quantitative real-time PCR was performed to compare the transcript levels of two main transporters likely to be involved in chloroquine resistance in <it>P. vivax</it>, namely the <it>P. vivax </it>chloroquine resistance transporter, <it>pvcrt-o</it>, and the <it>P. vivax </it>multidrug resistance transporter, <it>pvmdr 1</it>.</p> <p>Results</p> <p>Results demonstrated that the severe clinical symptoms were exclusively due to <it>P. vivax</it>. The patient presented acute respiratory conditions requiring admission to the intensive care unit. The magnetic method showed highly purified infected-reticulocytes with mature stages. In addition, it was found that parasites obtained from the severe patient had up to 2.9-fold increase in <it>pvmdr1 </it>levels and up to 21.9-fold increase in <it>pvcrt-o </it>levels compared to expression levels of parasites from the other patients with mild symptoms.</p> <p>Conclusion</p> <p>This is the first clinical case of severe disease exclusively associated with vivax malaria in Spain. Moreover, these findings suggest that clinical severity could be associated with increased expression levels of parasite genes likely involved in chloroquine resistance. It is necessary to further explore the potential of <it>pvmdr1 </it>and particularly <it>pvcrt-o </it>expression levels as molecular markers of severe disease in <it>P. vivax</it>.</p

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis

Background Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. Methods We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2–6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. Findings In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705–33 063 593) and €6 904 764 (6 703 258–7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6–66 459·1) and 59 875·73 (58 191·18–61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42–4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545–2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY). Interpretation Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants

Plasma-Derived Extracellular Vesicles as Potential Biomarkers in Heart Transplant Patient with Chronic Chagas Disease

Chagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.Barcelona Institute for Global Health (ISGlobal) receives support from the Spanish Ministry of Science, Innovation and Universities through the Centro de Excelencia Severo Ochoa 2019–2023 Program (CEX2018-000806-S). ISGlobal and Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP) are members of the Centres de Recerca de Catalunya (CERCA Program), Generalitat de Catalunya. Work in the laboratory of C.F.B. is funded by Fundació La Marató de TV3 (reference 566/U/2018) and Fundación Mundo Sano. This project was co-financed by the European Union through the European Regional Development Fund with the support of Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya. N.C., M.G., J.G., and M.J.P. receive funds from the Redes temáticas de investigación cooperativa en salud (RETICS), Spanish Tropical Diseases Network “RD12/0018/0010” and from the Agencia de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya; grant “2017 SGR 00924.” M.G., C.B., J.G., M.J.P., and I.C.A. belong to the Ibero-American Nuevas Herramientas para el Diagnóstico y la Evaluación del Paciente con Enfermedad de Chagas network. I.C.A. is partially supported by grants no. 2G12MD007592 and 5U54MD007592 from the National Institute on Minority Health and Health Disparities of the US National Institutes of Health. We are grateful to the Biomolecule Analysis Core Facility at University of Texas at El Paso, Border Biomedical Research Center, funded by National Institute on Minority Health and Health Disparities grants 2G12MD007592 and 5U54MD007592. M.T.M. received a PhD fellowship from the Science Without Borders Program, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil.S

Chest X-ray showing patchy infiltrates in both lungs.

<p>Chest X-ray showing patchy infiltrates in both lungs.</p

High prevalence of S. Stercoralis infection among patients with Chagas disease: A retrospective case-control study.

We evaluate the association between Trypanosoma cruzi infection and strongyloidiasis in a cohort of Latin American (LA) migrants screened for both infections in a non-endemic setting.Case-control study including LA individuals who were systematically screened for T. cruzi infection and strongyloidiasis between January 2013 and April 2015. Individuals were included as cases if they had a positive serological result for Strongyloides stercoralis. Controls were randomly selected from the cohort of individuals screened for T. cruzi infection that tested negative for S. stercoralis serology. The association between T. cruzi infection and strongyloidiasis was evaluated by logistic regression models.During the study period, 361 individuals were screened for both infections. 52 (14.4%) individuals had a positive serological result for strongyloidiasis (cases) and 104 participants with negative results were randomly selected as controls. 76 (48.7%) indiviuals had a positive serological result for T. cruzi. Factors associated with a positive T. cruzi serology were Bolivian origin (94.7% vs 78.7%; p = 0.003), coming from a rural area (90.8% vs 68.7%; p = 0.001), having lived in an adobe house (88.2% vs 70%; p = 0.006) and a referred contact with triatomine bugs (86.7% vs 63.3%; p = 0.001). There were more patients with a positive S. stercoralis serology among those who were infected with T. cruzi (42.1% vs 25%; p = 0.023). Epidemiological variables were not associated with a positive strongyloidiasis serology. T. cruzi infection was more frequent among those with strongyloidiasis (61.5% vs 42.3%; p = 0.023). In multivariate analysis, T. cruzi infection was associated with a two-fold increase in the odds of strongyloidiasis (OR 2.23; 95% CI 1.07-4.64; p = 0.030).T. cruzi infection was associated with strongyloidiasis in LA migrants attending a tropical diseases unit even after adjusting for epidemiological variables. These findings should encourage physicians in non-endemic settings to implement a systematic screening for both infections in LA individuals

Cross-reactivity of antibodies against interferon beta in multiple sclerosis patients and interference of the JAK-STAT signaling pathway

Abstract Interferon beta (IFNβ) therapy has immunogenic properties and induces the development of neutralizing antibodies (NAbs). From the extensive literature focused in the development of NAbs in multiple sclerosis (MS) patients, their ability to cross-react has been deficiently evaluated, despite having important consequences in the clinical practice. Here, the relation between the cross-reactivity and the NAbs titers has been evaluated in MS patients, by inhibition of the antiviral activity of IFNβ by bioassay and through the interference with the activation of the IFNß pathway (JAK-STAT), by phosphoflow. Thus, patients with intermediate-high titers of NAbs, determined by bioassay, had a 79-fold increased risk of cross-reactivity compared to patients with low titers. The cross-reactivity is also demonstrated because NAbs positive sera were able to decrease significantly the activation of pSTAT1 achieved by other different IFNβ molecules in the cells patients. Besides, a linear relationship between the STAT1 phosphorylation and NAbs titers was found. The study demonstrates that cross-reactivity increases with the titer of antibodies, which has important implications in clinical practice when switching the treatment. The direct relationship between the NAbs titer and the activation of STAT1 suggest that its determination could be an indirect method to identify the presence of NAbs

Strategies to enhance access to diagnosis and treatment for Chagas disease patients in Latin America

Introduction: Chagas disease, caused by infection with the parasite Trypanosoma cruzi, represents a huge public health problem in the Americas, where millions of people are affected. Despite the availability of two drugs against the infection (benznidazole and nifurtimox), multiple factors impede their effective usage: (1) gaps in patient and healthcare provider awareness; (2) lack of access to diagnosis; (3) drug toxicity and absence of treatment algorithms to address adverse effects; (4) failures in drug supply and distribution; and (5) inconsistent drug efficacy against the symptomatic chronic stage. Areas covered: We review new approaches and technologies to enhance access to diagnosis and treatment to reduce the disease burden. We also provide an updated picture of recently published and ongoing anti-T. cruzi drug clinical trials. Although there has been progress improving the research and development (R&D) landscape, it is unclear whether any new treatments will emerge soon. Literature search methodologies included multiple queries to public databases and the use of own-built libraries. Expert opinion: Besides R&D, there is a major need to continue awareness and advocacy efforts by patient associations, local and national governments, and international agencies. Overall, health systems strengthening is essential to ensure vector control commitments, as well as patient access to diagnosis and treatment

Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis

Summary: Background: Chagas disease is currently prevalent in European countries hosting large communities from Latin America. Whether asymptomatic individuals at risk of Chagas disease living in Europe should be screened and treated accordingly is unclear. We performed an economic evaluation of systematic Chagas disease screening of the Latin American population attending primary care centres in Europe. Methods: We constructed a decision tree model that compared the test option (screening of asymptomatic individuals, treatment, and follow-up of positive cases) with the no-test option (screening, treating, and follow-up of symptomatic individuals). The decision tree included a Markov model with five states, related to the chronic stage of the disease: indeterminate, cardiomyopathy, gastrointestinal, response to treatment, and death. The model started with a target population of 100 000 individuals, of which 4·2% (95% CI 2·2–6·8) were estimated to be infected by Trypanosoma cruzi. The primary outcome was the incremental cost-effectiveness ratio (ICER) between test and no-test options. Deterministic and probabilistic analyses (Monte Carlo simulations) were performed. Findings: In the deterministic analysis, total costs referred to 100 000 individuals in the test and no-test option were €30 903 406 and €6 597 403 respectively, with a difference of €24 306 003. The respective number of quality-adjusted life-years (QALYs) gained in the test and no-test option were 61 820·82 and 57 354·42. The ICER was €5442. In the probabilistic analysis, total costs for the test and no-test option were €32 163 649 (95% CI 31 263 705–33 063 593) and €6 904 764 (6 703 258–7 106 270), respectively. The respective number of QALYs gained was 64 634·35 (95% CI 62 809·6–66 459·1) and 59 875·73 (58 191·18–61 560·28). The difference in QALYs gained between the test and no test options was 4758·62 (95% CI 4618·42–4898·82). The incremental cost-effectiveness ratio (ICER) was €6840·75 (95% CI 2545–2759) per QALY gained for a treatment efficacy of 20% and €4243 per QALY gained for treatment efficacy of 50%. Even with a reduction in Chagas disease prevalence to 0·05% and with large variations in all the parameters, the test option would still be more cost-effective than the no-test option (less than €30000 per QALY). Interpretation: Screening for Chagas disease in asymptomatic Latin American adults living in Europe is a cost-effective strategy. Findings of our model provide an important element to support the implementation of T cruzi screening programmes at primary health centres in European countries hosting Latin American migrants. Funding: European Commission 7th Framework Program

Baseline characteristics of 156 individuals included in the study, according to results on T. cruzi and strongyloidiasis serology.

<p>Baseline characteristics of 156 individuals included in the study, according to results on T. cruzi and strongyloidiasis serology.</p