article: After the United States, Spain comes second in the list of countries receiving migrants from Latin America, and, therefore, it is the European country with the highest expected number of infected patients of Chagas disease. We have studied the National Health System’s Hospital Discharge Records Database (CMBD) in order to describe the disease evolution from 1997 to 2011 in Spain. We performed a retrospective descriptive study using CMBD information on hospitalizations including Chagas disease. Data was divided in two periods with similar length in time: 1997-2004 and 2005-2011. Hospitalization rates were calculated and clinical characteristics were described. We used multivariable logistic regression to calculate adjusted odds-ratio (aOR) for the association between various conditions and being hospitalized with organ affectation. A total of 1729 hospitalization records were identified. Hospitalization rates for the two periods were 18 and 242. 8/100000 population, respectively. The median age was 35 years (range 0-87), 74% were female and the 16-45 age-group was mostly represented (69. 8%). Overall, 23. 4% hospitalizations included the diagnosis of Chagas disease with organ complications. Being male [aOR: 1. 3 (1. 00-1. 77) ], aged 45 and 64 years [aOR: 2. 59 (1. 42-4. 71) ], and a median hospitalization cost above 3,065 euro [aOR: 2. 03 (3. 73-7. 86) ] were associated with hospitalizations with organ affectation. Since 2005, the number of detected infections increased in Spain. The predominant patients’ profile (asymptomatic women at fertile age) and the conditions associated with organ affectation underlines the need for increased efforts towards the early detection of T cruzi.
  Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by the protozoan parasite, Trypanosoma cruzi (T. cruzi). This disease presents itself in two phases. The initial, acute phase lasts for about two months after infection. In most cases, symptoms are absent or mild, but can include fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling and abdominal or chest pain [1,2]. During the chronic phase, the parasites are hidden mainly in the heart and digestive muscle. Up to 30% of patients suffer from cardiac disorders (sudden death, complex arrhythmias, ventricular aneurysms, heart failure, and thromboembolism) and up to 10% suffer from digestive (typically enlargement of the esophagus or colon), neurological or mixed alterations [3]. In later years the infection can lead to sudden death or heart failure caused by progressive destruction of the heart muscle [1]. Chagas disease can be effectively treated with benznidazole and also nifurtimox. Both drugs are almost 100% effective in curing the disease if given soon after infection at the onset of the acute phase [4]. However, the efficacy of both diminishes the longer a person has been infected, thus the importance of an early diagnosis [5]. Additionally, specific treatment for cardiac or digestive manifestations may be required at latest stages of the infection [6]. Worldwide, between seven and eight million people are estimated to be infected with Chagas. The disease is endemic in 21 Latin American countries [7], where it is mostly transmitted to humans through the bite of the triatomine bug, Chagas disease natural reservoir [8]. Nevertheless, T. cruzi transmission is also possible in vector-free world regions [9]. The main non-vectorial routes are congenital transmission, blood transfusion, and solid organ transplant, these routes being characteristics but not exclusive to non-endemic countries [10]. Although most of the cases occurr in Latin America [11], Chagas disease in non-endemic countries, such as North America and the Western Pacific Region (mainly Australia and Japan), has come to light since the beginning of 2000, and only more recently in Europe [12]. In 2010, the World Health Organization (WHO) estimated that 80. 000 persons could be infected in Europe, making Chagas disease one of the predominant emerging parasitic infections in the Old World [13]. The emergence of the disease in non-endemic countries is mainly linked to population mobility, notably migration from endemic countries [12]. Beginning with 2010, Spain had the highest immigration rates from Latin America within the EU, (second after the USA worldwide) [14]. A study published by the European Center for Disease Prevention and Control (ECDC) estimated that in 2009,53% (more than 1. 7 million people) of the European migrant population coming from Latin America were living in Spain [15]. The same study indicated Spain as the country with the highest prevalence of Chagas disease in migrant population from endemic countries (2. 3–3. 8%). Estimates that take into account the prevalence of T. cruzi infection in Latin America suggest that between 40,000 and 65,000 infected people currently reside in Spain [16]. In the last decade some progress has been made regarding the management of Chagas disease in Spain. Since September 2005, in accordance with the Royal Decree RD1088/2005, serological screening of the population considered to be at risk is mandatory in all blood transfusion centers [17]. Regulations regarding screening of pregnant women from Latin American endemic countries and their newborns are in place in 4 out of 17 autonomous regions (Valencia, Catalonia, Galicia and Basque Country) [18–21]. In the rest of the country, the detection of congenital Chagas cases depends mainly on the initiative of the health professionals of the National Health System [15] (Table 1). Up to date, there is no surveillance system for Chagas disease implemented in Spain. However, hospitalized cases are recorded within the National Health System′s Hospital Discharge Records Database (CMBD in Spanish) belonging to the Spanish Ministry of Health. In this paper, we describe for the first time the Chagas disease related hospitalizations in Spain between 1997 and 2011, in terms of time, geographical distribution, and disease related individual characteristics.
  This study involves use of patient medical data from The Spanish National Hospital Database (CMBD). These data, are hosted by the Ministry of Health Social Services and Equality (MSSSI). Researchers working in public and private institutions can request the databases by filling, signing and sending a questionnaire available at the MSSSI website. In this questionnaire a signed Confidentiality Commitment is required. All data is anonymized and de-identified by the MSSII before it is provided to applicants. According to this Confidentiality Commitment signed with the MSSSI, researchers cannot provide the data to other researchers, thus other researchers must request the data directly to the MSSSI [22].
  Between 1997 and 2011,1729 hospitalizations including Chagas disease in any diagnosis position were recorded in Spain, out of which 546 (31. 6%) were re-admissions. Up to 90% (1630/1729) of these cases were notified between 2005 and 2011. For the two study periods (1998–2004 and 2005–2011), we obtained hospitalization rates of 18 and 242. 8/100000 population, respectively. While the Latin American population migrating form Chagas disease endemic countries began to increase steadily from 2001, the hospitalization rate showed a stationary tendency in the first time period. In the second time interval (2005–2011), this rate increased while the Latin American population began a slow decrease, starting with 2009 (Fig 1). The increase in hospitalization rate was registered in all but two autonomous regions (Fig 2 and S2 Table). For eight autonomous regions the hospitalization rate increased more for women, in two increased more for men, while in seven autonomous regions there was no difference among sexes (Fig 3). The median age of the 1729 hospitalizations was 35 years (range 0–87) with the 16–45 age-group being mostly represented with 1207/1729 (69. 8%). A total of 74% hospitalized were female, predominating in all age-groups (Fig 4). For 206/1729 (11. 9%) records, Chagas disease was registered as the first diagnosis while for 878/1729 (50. 7%) appeared as second diagnosis. Other diagnoses in first position are summarized in S1 Table. In the remaining 37. 4% records, Chagas disease appeared in any of the last 12 positions. The most frequent main diagnostics associated with Chagas disease were related to pregnancy, giving birth or postpartum complications (36. 6%), heart and circulatory conditions (15. 3%) and digestive system conditions (9. 1%). The hospital departments with higher number of Chagas related admissions were Obstetrics-Gynecology (37. 1%), Cardiology (13. 1%), Internal Medicine (11. 2%) and Digestive Diseases (7. 9%) (S3 Table). Overall, 1302/1792 (75. 3%) hospitalizations were related to Chagas disease without organ complications, while 388/1792 (23. 4%) hospitalizations were recorded as Chagas disease with organ complications, of which 317/388 (81. 7%) were due to heart complications and 71/388 (17. 9%) were due to another organ complications. Invasive or non-invasive medical procedures were documented for 1463/1729 (84. 6%) hospitalizations. We identified 290 different types of medical procedures; 579/1463 (33. 5%) procedures were related to obstetrical surgery, 375/1463 (21. 7%) were diagnosis or therapy procedures and 190/1463 (11%) were related to heart surgery. Of the total 1729 hospitalizations, 487 (28. 2%) had registered a surgical intervention. The admission period was inferior to one week in 71% of Chagas related hospitalizations. The predominant admission type was urgent (76. 6%) and 61. 5% had a severity level of 2 (out of 4). Around 95% of them were discharged at home, decease occurring in 1. 2% of overall Chagas related hospitalizations. The hospitalization median cost was 3,064. 9 euros (range 287. 3–939,324. 1). Costs were covered by social security health care service for 95% of the cases (Table 2). A total of 55. 6% (114/206) hospitalized were female, with the 16–45 and 46–65 age-groups being mostly represented (49. 3% and 32. 7%, respectively). Around 50% of the hospitalizations were related to Chagas disease with organ complication. Surgical intervention was documented for 25/206 (12. 2%) hospitalizations and invasive or non-invasive medical procedures were documented for 147/206 (71. 4%) hospitalizations. The predominant admission type was urgent (58. 5%) followed by programmed (41. 5%). Median time of hospitalization was 7 days, and up to 40% stayed more than one week. Around 90% (184/206) were discharged at home; decease occurred in 2. 4% of these hospitalizations. The hospitalization median cost was 4195. 6 euros. From 1997 to 2011,614 hospitalizations related to Chagas disease with child delivery as first diagnosis occurred. The 16–45 age-group was predominant with 612/614 (99. 7%) and heart and other organ complications were present in 23/614 (3. 8%) and 4/614 (0. 6%) of these hospitalizations, respectively. Surgical intervention was recorded for 43. 8% of them, and they were mostly urgent admissions (93. 2%). Invasive or non-invasive medical procedures were documented for all the hospitalizations, mainly obstetrical procedures. Up to 95% stayed less than one week in the hospital, being the median average time of 3 days. Around 99% hospitalizations were discharged at home, only 30/614 (4. 9%) need to be re-admitted. The hospitalization median cost was 2,207. 9 euros. Through bivariate analysis, we identified several conditions associated with hospitalization due to Chagas disease with organ affectation. Being male, aged over 45 years, Chagas disease as main diagnosis, a history of re-admission in the hospital, and hospitalization’s cost higher than the median (3,065 euros), were significantly associated with Chagas disease with organ affectation. On the other hand, being aged between 16 and 45 years, hospitalization stay up to one week, a history surgery, the urgent admission type and the medium level of disease severity where inversely associated with organ affectation (Table 3). All these significant variables where included in the final multivariable logistic regression model. Results indicated that the patients being hospitalized with organ affectation Chagas disease were 1. 3 times more likely to be male, 2. 6 times more likely to be aged between 45 and 64 years, 5. 4 times more likely to be admitted with Chagas disease as main diagnosis, and almost 3 times more likely to be admitted for the first time in the hospital, compared to those admitted with Chagas disease without organ affectation. Also, hospitalizations with organ affectation were two times more likely to cost above the median cost of 3065 euro that the hospitalizations of asymptomatic Chagas disease. Not having a personal surgery history and medium severity level appeared to have a negative association with Chagas disease with organ affectation (Table 3).
  We calculated the hospitalization rate using as denominators Latin American immigrants officially registered in Spain. Non-registered immigrants could enlarge both the population denominator and the number of cases, thus the results should be interpreted with caution. Another limitation when using the CMBD database is that the country of origin is not recorded, therefore the hospitalization rates can be calculated only as overall figures. This is an important aspect being known that the endemicity levels varies widely among Latin American countries [40]. On the other hand, the estimation of the risk factors for hospitalizations with organ complications might be influenced by this and other factors not present in the CMBD database. One of the strong points of CMBD is that it provides the total number of hospitalizations records without being subject to the limitations of outpatient surveillance systems, such as under-diagnosis or reporting deficiencies. It remains dependent only by the population’s health seeking behavior and healthcare accessibility. The Spanish Government enacted a Royal Decree in 2012 which basically limits access to free services at the point of delivery for all population (including non-residents migrants), undermining the principle of universal coverage which exist in this country since 1986 [41]. This can have as consequence a decrease in the number of Latin American immigrants attending to the healthcare services. Subsequently, and in the absence of systematic and coordinated actions towards early detection of T. cruzi, a larger number of asymptomatic infections might remain under-diagnosed, increasing the number of patients suffering from Chagas disease chronic conditions in the future. In conclusion, using hospitalized cases discharge database can be a useful tool when describing the Chagas disease epidemiology. However, our work underlines the need of a nationwide systematic approach towards T. cruzi early detection, especially targeting fertile aged women and relatives from endemic Latin American countries. Health inequalities on immigrants health status might exist across our country if screening programs differ from one region to another and, furthermore, are not nationwide implemented. Moreover, a national surveillance system that would allow a more accurate data collection, analyzing and interpretation, could be of added value in completing a more accurate picture of Chagas disease in Spain, resulting useful both in gaining extended disease knowledge, but especially in evaluating implemented control actions.
summary: Chagas disease, caused by the protozoa Trypanosoma cruzi, is endemic in most Latin American countries and it is considered a neglected tropical disease (NTD). T. cruzi transmission is feasible in vector-free world regions. The main non-vectorial routes are congenital transmission, blood transfusion, and solid organ transplant. According to WHO, in Spain, which is the second country in the world receiving migrant population from endemic countries, there are up to 40. 000 persons at risk of developing symptomatic Chagas disease. Since 2005, serological screening for at-risk blood and solid organ donors is mandatory. Lately, some regulations regarding screening of pregnant women from Latin American endemic countries have also been implemented, but only in some autonomous regions. Up to date, there is no surveillance system in place. Thus, the Chagas disease burden remains unknown. In this paper we use hospitalized Chagas disease discharge data, in order to describe Chagas disease’s geographical and temporal trends before and after the implementation of control measures in Spain from 1997 to 2011. We also assess patients’ main clinical characteristics by organ affectation.
title: Using Hospital Discharge Database to Characterize Chagas Disease Evolution in Spain: There Is a Need for a Systematic Approach towards Disease Detection and Control