Chagas cardiomyopathy: Europe is not spared!

Chagas’ disease was first described in 1909 by the Brazilian physician Carlos Chagas, who named the parasite Trypanosoma cruzi after his mentor, Oswaldo Cruz.1 It causes more deaths in the Americas than any other parasitic disease.1 Due to the parasite distribution throughout Central and South America, it is commonly known as the ‘American trypanosomiasis’. As such, it is considered to be an ‘exotic’ disease in Europe, where it is virtually undiagnosed. However, thanks to free circulation of individuals and employment opportunities Europe is a magnet for millions of immigrants, many of whom are from South America. We will review the compelling arguments by which chagasic cardiomyopathy should be moved upfront in the mindset of European cardiologists, actively looked for, and appropriately recognized. Vectorial transmission of the disease is the most common form in endemic countries. This occurs through haematophagous insects (Triatominae), which become vectors for Trypanosoma cruzi by biting an infected animal or person; when infected triatominae bite, they transmit the parasite by defecating on the host's skin.2 The insects vector of the disease is present throughout most of South and Central America, their zone of distribution encompassing southern USA.2 In non-endemic countries, the disease is transmitted through blood transfusions, organ donations, and from mother to child at birth. However, besides possible occurrence of new cases of infection, substantial concern exists regarding the progressive development of cardiomyopathy in many individuals who had already become infected in their native country, and then move to Europe. The disease has three phases. The initial infection is characterized by an acute phase, which in most cases goes asymptomatic. Infection is followed by a long ‘indeterminate phase’.2 The indeterminate form of chronic Chagas’ disease is defined as chronically infected patients with positive serology but no alterations of heart, oesophagus, and colon.2 Approximately 70% of patients remain in this phase for the rest of their life, asymptomatic and in good health.2 However, they have the persistent infection with parasitaemia demonstrable more than 20 years after initial infection.3 At some point during the indeterminate phase, a substantial number of patients may develop symptoms, entering a third phase of overt disease. From 20 to 30% of infected patients will develop chronic cardiomyopathy.2 Chronic chagasic cardiomyopathy is the most serious manifestation of Chagas’ disease, and it represents the most common type of chronic myocarditis in the world.4,5 Pathophysiology and treatment of chagasic cardiomyopathy are beyond the scope of this paper. Suffice to say that ultrastructural studies have described degeneration of organelles, hypertrophy of myocytes with thickening of the basement membrane, alterations of endothelium and vascular smooth muscle cells, and increased fibrosis.4 Involvement of the parasite also in the chronic phase has been documented: T. cruzi DNA was consistently found in myocardial biopsies of patients with chagasic cardiomyopathy, but not in seropositive patients without cardiac involvement.6 Antigen stimulation would persist throughout the chronic stage, perpetuating myocardial inflammation even though parasites are not detectable in myocardial biopsies.6 In this respect, whether antiparasite therapy may be of value in the management of patients in the chronic stage, or with overt cardiomyopathy, is debated. The possible efficacy of trypanocidal therapy in patients with cardiomyopathy is currently being tested.7 Chagasic cardiomyopathy shares clinical features of ‘classical’ dilated cardiomyopathy1,2 (Figure 1), and as such it is often misdiagnosed. Right-bundle-branch block, A-V conduction delay, and altered re-polarization are commonly seen.2,6 Echocardiography may reveal LV dilatation, dyssynergic segments, aneurysm of the apex, and dilatation and dysfunction of right ventricle.2 Prevalence of symptoms and clinical signs in chronic chagasic cardiomyopathy.2,24,25 Infected patients with no evidence of myocardial damage have the same life expectancy as the general population.8 Accordingly, WHO recommends not restraining these patients from a normal lifestyle and regular jobs.2 On the other hand, patients with chagasic cardiomyopathy have a prognosis similar to or worse than that of patients with dilated cardiomyopathy; they mostly die of progressive heart failure, sudden death, or pulmonary embolism.9 Information about Latin American immigration to Europe is incomplete; illegal immigration and the fact that many Latin Americans have reclaimed the nationality of their ancestors make a precise estimation difficult.10 Knowing the prevalence of T. cruzi infection in blood donors and immigration rates, we estimated the number of infected immigrants present in those European countries for which accurate data could be gathered (Table 1). We used the data on international Latin American migration provided by the Latin American and Caribbean Demography Center,11 and by the International Organization for Migration.10 Prevalence of T. cruzi infection in blood donors was from Schmunis12 and Zeledón et al.13 For example, considering that 148/1000 blood donations in Bolivia are seropositive to T. cruzi, and that this number correlates well with the incidence of infection in the general population,12 then 249 of the 1681 Bolivians known to live in Germany are estimated to have Chagas’ disease. Following this line, Europe is estimated to have from 24 001 to 38 708 (lower or upper limit of estimate, respectively) immigrants with T. cruzi infection (Table 1). Figure 2 depicts the estimated number of infected subjects in Europe. Estimated number of Chagas’ disease (infected) patients in Europe. Colour-code denotes expected frequency. Estimated number of immigrants with Chagas’ disease and chronic chagasic cardiomyopathy (ChrChC) living in Europe ChrChC, chronic chagasic cardiomyopathy; AcChC, acute chagasic cardiomyopathy; IFCD, indeterminate form of Chagas disease; M-C, mother-to-child transmission. aPrevalence of T. cruzi infection in blood donors taken from Schmunis.12 bThe number of Latin American immigrants residing in Germany and Norway was taken from Pellegrino.10 cThis field combines the data of Hungary, Finland, Luxembourg, Poland, Czech Republic, Ireland, Belgium, and Slovakia. dThe incidence of Chagas’ disease in Costa Rica was taken from a study of Zeledón13 performed in 1420 citizens. Estimated number of immigrants with Chagas’ disease and chronic chagasic cardiomyopathy (ChrChC) living in Europe ChrChC, chronic chagasic cardiomyopathy; AcChC, acute chagasic cardiomyopathy; IFCD, indeterminate form of Chagas disease; M-C, mother-to-child transmission. aPrevalence of T. cruzi infection in blood donors taken from Schmunis.12 bThe number of Latin American immigrants residing in Germany and Norway was taken from Pellegrino.10 cThis field combines the data of Hungary, Finland, Luxembourg, Poland, Czech Republic, Ireland, Belgium, and Slovakia. dThe incidence of Chagas’ disease in Costa Rica was taken from a study of Zeledón13 performed in 1420 citizens. From estimates of prevalence of seropositivity, and knowing the likelihood that individuals in the indeterminate phase progress to develop the disease (see below), we calculated the expected prevalence of chagasic cardiomyopathy in Europe. According to Basquiera et al.,14 21.4% of asymptomatic patients with chronic T. cruzi infection develop chagasic cardiomyopathy over time. Storino and Milei2 compared the evolution of the disease in patients that had been infected in endemic areas vs. patients residing in non-endemic areas. After 5–12 years follow-up, 43% of the infected patients who resided in endemic areas develop chagasic cardiomyopathy, as opposed to 7% of the patients residing in non-endemic areas,2 presumably because patients from endemic areas are exposed to re-infection. Taking into account the possibility of a lower incidence of cardiomyopathy in infected patients residing outside endemic areas, it can be estimated that in Europe from 1680 (7% of 24 001) to 8284 (21.4% of 38 708) patients may have chagasic cardiomyopathy. In spite of the alarming epidemiological considerations presented above, actual recognition of the disease in Europe is low. As of today, only 17 cases of Chagas’ cardiomyopathy have been reported,15–20 i.e. <1% of expected. Nine cases were reported in France;15 isolated cases have been reported in Norway,17 Switzerland,21 Spain,18 and Denmark.19 This latter case is particularly instructive, as it refers to a Venezuelan woman who had been residing in Denmark for 40 years; this underscores the possibility that the cardiomyopathy may become clinically evident even decades after having contracted infection. In addition to cases of imported disease, new cases can still occur in Europe. Two cases of mother-to-child transmission at birth have been reported in Spain,16,20 and it has been recommended that women of child-bearing age migrating endemic areas be routinely screened for Chagas’ disease, and that diagnostic protocols to detect the infection in neonates be established.16 The extremely low incidence of reported cases of Chagas’ disease might lead to indulgence in the consideration that the problem in Europe is negligible. However, against this seemingly reassuring view, stand the epidemiological considerations presented above, and the results of direct assessment of prevalence of seropositivity. In Berlin, 5% of apparently healthy individuals from Latin America were found seropositive to T. cruzi.22 There is a huge gap between the estimations presented above and the number of cases of Chagas' disease actually reported in Europe. The fact that Chagas' disease is usually thought of as an exotic disease restricted to South America decreases clinicians' awareness of the disease and hence, it remains undiagnosed; it is also likely that many such patients are actually being misdiagnosed as having idiopathic-dilated cardiomyopathy. Another problem is that most chagasic patients are unaware of their condition. The risk of not detecting the many individuals in the indeterminate phase is linked to their being asymptomatic, and as such they may potentially transmit the disease to others, via blood transfusions or mother-to-child transmission, or even by organ donation. The Pan-American Health Organization urges countries receiving immigrants from endemic areas to deal with Chagas’ disease, to provide appropriate treatment to affected individuals, and to prevent vertical and blood-borne transmission.23 A screening program for T. cruzi in Latin American immigrants such as the one currently in place in Spain would not only improve patients’ prognosis, but it would help diminish the economic burden of the disease in Europe. Conflict of interest: none declared.