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Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected tropical disease (NTD) with a high disease burden in the Americas. It is transmitted primarily by hematophagous triatomine bugs, but alternate transmission routes such as congenital, oral, and transfusional transmission are becoming more relevant in many regions. After a short acute phase, infected patients enter an asymptomatic chronic phase, which can become symptomatic in 20% to 40% of the cases, characterized by a chronic chagasic cardiomyopathy and less frequently by a digestive form of the disease. Current control is mostly focused on vector control with indoor spraying of residual pyrethroids and to a lesser extent with housing improvement. Treatment of infected patients remains challenging due to the limited efficacy of the two available drugs during the chronic phase and their side effects but also because of limited access to treatment for patients. Over the past ten years, PLOS Neglected Tropical Diseases has been a key journal for the diffusion of some of the major achievements to better understand and control Chagas disease. With a total of 390 published studies during that time, Chagas disease research represented about 8% of the published material by the journal. Some of the key issues addressed have been related to the evaluation of disease burden, improvement in serological and molecular diagnostics, drug development, patient care, and vector control (Table 1). New estimates of Chagas disease burden and its epidemiological impact provide the basis for health interventions in both endemic and nonendemic countries. Indeed, Chagas disease is responsible for one of the largest disease burden in the Americas where it is endemic, with over 6 million cases. It also has the peculiarity of being one of the few NTDs to cause most of its burden in upper-middle income countries [1], including in the United States where an estimated 300,000 cases are present, and a growing number of autochthonous cases are being identified [2,3]. In nonendemic regions such as in Europe, Chagas disease is a growing concern as well, with an estimated 68,000–120,000 patients [4]. However, the identification of infected patients remains challenging in many countries, and underreporting is still a major issue. Contrary to most, if not all, other infectious diseases, at least two serological tests are still needed for a reliable serological diagnostic of T. cruzi infection, and additional tests need to be performed in case of discordance among tests. Cases of individuals who are seronegative with conventional serological tests but seropositive with alternative tests or T. cruzi PCR-positive have been reported [5]. Part of the discordances may be attributed to the very large genetic and antigenic diversity of T. cruzi, which has been divided into seven discrete typing units (DTUs) TcI–TcVI and Tcbat [6,7]. Current serological tests are thus based on limited sets of

Ten years of Chagas disease research: Looking back to achievements, looking ahead to challenges