Chagas disease in non-endemic countries
Authors: Marianela Castillo-Riquelme
Journal: The Lancet Global Health (2017)

Globalisation can impose major public health challenges in local contexts. Because of human migration, Chagas disease—a condition endemic in Latin-American countries—has become a concern in the developed world.1Gascon J Bern C Pinazo MJ Chagas disease in Spain, the United States and other non-endemic countries.Acta Trop. 2010; 115: 22-27Crossref PubMed Scopus (447) Google Scholar, 2Jackson Y Pinto A Pett S Chagas disease in Australia and New Zealand: risks and needs for public health interventions.Trop Med Int Health. 2014; 19: 212-218Crossref PubMed Scopus (59) Google Scholar Chagas disease cannot be transmitted by direct contact with an infected person; in fact, the relevant mechanisms of transmission in non-endemic countries are transfusion with infected blood and congenital transmission from mother-to-child during pregnancy. To date, the natural history of Chagas (Trypanosoma cruzi) has been widely disseminated,3Rassi Jr, A Rassi A Marin-Neto JA Chagas disease.Lancet. 2010; 375: 1388-1402Summary Full Text Full Text PDF PubMed Scopus (1663) Google Scholar but prognosis is impossible to predict at the individual level. Most infected people (60–80%) never develop symptoms and when diagnosed symptoms-free, are considered to be in the so-called indeterminate phase. Only between 20% and 40% of people infected with Chagas disease reach the so-called chronic symptomatic phase, presenting with cardiac or digestive complications. The chronic phase occurs between 10 years and 30 years after infection and severity of pathologies varies, as do the overall presentation and prevalence of the cardiac and the digestive form across endemic countries. From a public health perspective, patients that manifest the chronic conditions are the biggest concern, because these pathologies can trigger serious disability and even death, and require the allocation of substantial recourses for treatment. But, can we avoid the chronic condition in people who are asymptomatic? Chagas disease has been considered a neglected disease, without fully effective drug treatment to avoid the chronic stage. Benznidazole and nifurtimox are the current treatment options for the indeterminate phase—with efficacy ranging from 20% to 50%. These drugs do not have accurate test of cure and have important side-effects, which affect adherence. In this landscape, are the efforts put in screening, treatment, and follow-up worthy, in terms of cost per unit of health outcome? In The Lancet Global Health, Ana Requena-Méndez and colleagues4Requena-Méndez A Bussion S Aldasoro E et al.Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis.Lancet Glob Health. 2017; (published online Feb 27.)http://dx.doi.org/10.1016/S2214-109X(17)30073-6Summary Full Text Full Text PDF PubMed Scopus (63) Google Scholar present an economic evaluation of screening for Chagas disease in adults, targeting Latin-American migrants at European primary health-care facilities, when they attend for any reason. The intervention considers treating those found to be positive with benznidazol compared with no test—ie, the situation when only symptomatic patients with Chagas disease would demand care. Economic evaluation seeks to shed light on the efficiency of resource allocation in health care, thus the analysis needs to comply with quality standards.5Drummond MJ Sculpher MJ Torrance GW O'Brien BJ Stoddart GL Methods for the Economic Evaluation of Health Care programmes. 3rd edn. Oxford University Press, Oxford2005Google Scholar The authors built a two-arm decision tree, each connected to a Marvok node that represents the natural history of Chagas disease. The study, as reported, meets the standards for good cost-effectiveness analysis. However, it is worth discussing some aspects that could be improved if better data arise in the future. In terms of efficacy, key parameters are best reported by systematic reviews. In the model, prevalence was taken from a recent systematic review,6Requena-Méndez A Aldasoro E de Lazzari E et al.Prevalence of Chagas Disease in Latin-American migrants living in Europe: a systematic review and meta-analysis.PLoS Negl Trop Dis. 2015; 9: e0003540Crossref PubMed Scopus (215) Google Scholar whereas treatment efficacy data came from one study.7Viotti R Vigliano C Lococo B et al.Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.Ann Intern Med. 2006; 144: 724-734Crossref PubMed Scopus (465) Google Scholar A recently published Cochrane review suggest that efficacy data needs to be confirmed in better designed studies.8Villar JC Perez JG Cortes OL Riarte A Pepper M Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection.Cochrane Database Syst Rev. 2014; 27 (CD003463)Google Scholar In terms of cost data, these were based on assumptions made by experts because individual data were not available for chronic treatment of Chagas disease in European settings. This limitation hampers variability analysis, and as a consequence the sensitivity analysis of parameter estimates is done with somewhat arbitrary ranges of variation that are not based on empirical data. A common misunderstanding regarding the estimation of quality-adjusted life years (QALYs) is differentiating the measurement of health states from its valuation (score from 0–1). In Requena-Méndez and colleagues' study,4Requena-Méndez A Bussion S Aldasoro E et al.Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis.Lancet Glob Health. 2017; (published online Feb 27.)http://dx.doi.org/10.1016/S2214-109X(17)30073-6Summary Full Text Full Text PDF PubMed Scopus (63) Google Scholar the so-called QALY weights were taken from a previous study that made assumptions about these. Recommendations in Europe are to use the EQ-5D questionnaire to measure health states in patients and score these states using EQ-5D valuations, elicited previously from a sample of the general population.9Brazier J Ratcliffe J Salomon JA Tsuchiya A Measuring and Valuing Health Benefits for Economic Evaluation. Oxford University Press, Oxford2007Google Scholar The question that arises in this case is whether valuations for migrants or Europeans should be used. Last, reaching screening coverage of 80% is a heroic assumption considering potential access barriers. This optimism also applies to the assumptions on the willingness to take treatment and the subsequent treatment compliance—both set as 100%. Based on the incremental cost-effectiveness ratio (ICER) of €6840·75 per QALY gained, Requena-Méndez and colleagues4Requena-Méndez A Bussion S Aldasoro E et al.Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysis.Lancet Glob Health. 2017; (published online Feb 27.)http://dx.doi.org/10.1016/S2214-109X(17)30073-6Summary Full Text Full Text PDF PubMed Scopus (63) Google Scholar conclude that the testing for Chagas is cost-effective and should be supported in Europe. This ICER falls bellow the threshold used and it was not sensitive to variation of many of the parameters. Still, the authors were cautious in interpreting the results in view of geographical variation of prevalence across countries. As an option, the authors suggest implementing the screening according to prevalence of country of origin. On the other hand, new clinical evidence suggests that patients who are prescribed biologicals should first be tested for Chagas disease and Strongyloides infestation.10González-Ramos J Alonso-Pacheco ML Mora-Rillo M Herranz-Pinto P Need to screen for Chagas disease and Strongyloides infestation in non-endemic countries prior to treatment with biologics.Actas Dermosifiliogr. 2017; 30 (i: S0001-7310(16)30368-4.)Google Scholar Further research to close the knowledge gaps in Chagas disease, as discussed in detail by Chatelain,11Chatelain E Chagas disease research and development: Is there light at the end of the tunnel?.Comput Struct Biotechnol J. 2017; 15: 98-103Crossref PubMed Scopus (95) Google Scholar is needed. More effective drugs are highly desirable but their development is slow. Whether the current treatment is effective in those individuals who otherwise would not develop chronic pathologies (60–80%) or in those who would (20–40%) would be useful to know. We need to consider that the intangible costs associated with screening programmes (anxiety, depression, or potential labour discrimination in people previously unaware of infection) have not been measured. These costs are consistently considered to outweigh treatment benefits, but hard enough evidence have not been presented. Finally, we need to take into account that Chagas disease will stay in the developed world as migration continues and the eradication of vectorial transmission in endemic countries is not achieved. Thus, entomological, social, clinical, and treatment aspects play a part in the management of this condition from a global public health perspective. I declare no competing interests. Cost-effectiveness of Chagas disease screening in Latin American migrants at primary health-care centres in Europe: a Markov model analysisScreening 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. Full-Text PDF Open Access