Surveillance Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015 Luca Basile¹, Pilar Ciruela1,2, Ana Requena-Méndez³, Mª José Vidal¹, Eva Dopico⁴, Andrea Martín-Nalda⁵, Elena Sulleiro⁶, Joaquim Gascon³, Mireia Jané1,2, the Working Group of Congenital Chagas disease in Catalonia⁷ 1. Public Health Agency of Catalonia, Barcelona, Spain 2. CIBER Epidemiology and Public Health CIBERESP, Carlos III Health Institute, Madrid, Spain 3. Barcelona Institute for Global Health (ISGlobal), Hospital Clínic- Universitat de Barcelona, Barcelona, Spain 4. Laboratori Clínic de l’Hospitalet, Hospitalet de Llobregat, Barcelona, Spain 5. Pediatric Infectious Diseases and Immunodeficiencies Unit, Hospital Universitari Vall d’Hebron (HUVH), Vall d’Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona (UAB), Barcelona, Spain 6. Microbiology Department, Hospital Universitari Vall d’Hebron (HUVH), PROSICS Barcelona, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain 7. The members of the network are listed at the end of the article Correspondence: Luca Basile (chagas@gencat.cat) Citation style for this article: Basile Luca, Ciruela Pilar, Requena-Méndez Ana, Vidal Mª José, Dopico Eva, Martín-Nalda Andrea, Sulleiro Elena, Gascon Joaquim, Jané Mireia, the Working Group of Congenital Chagas disease in Catalonia. Epidemiology of congenital Chagas disease 6 years after implementation of a public health surveillance system, Catalonia, 2010 to 2015. Euro Surveill. 2019;24(26):pii=1900011. https://doi.org/10.2807/1560-7917.ES.2019.24.26.19-00011 Article submitted on 21 Dec 2018 / accepted on 02 Apr 2019 / published on 27 June 2019 Background: Chagas disease is endemic in Latin Introduction America and affects 8 million people worldwide. In Chagas disease, a parasitic infection caused by the 2010, Catalonia introduced systematic public health flagellated protozoan Trypanosoma cruzi, is endemic surveillance to detect and treat congenital Chagas dis- in Latin America [1]. It is found mainly in rural areas of ease. Aim: The objective was to evaluate the health Central and South America, except on the Caribbean outcomes of the congenital Chagas disease screening islands, and coincides with the distribution of the vec- programme during the first 6 years (2010–2015) after tor that belongs to the family of triatomines and is its introduction in Catalonia. Methods: In a surveillance responsible for transmission of the parasite to humans system, we screened pregnant women and newborns [2]. Other possible mechanisms of transmission are and other children of positive mothers, and treated mother-to-child, blood transfusions, transplants of Chagas-positive newborns and children. Diagnosis infected organs and tissues and ingestion of contami- was confirmed for pregnant women and children with nated food [3]. There are an estimated 8 million people two positive serological tests and for newborns with infected worldwide, of whom up to 30% may develop microhaematocrit and/or PCR at birth or serology at heart disease, with digestive or nervous system age 9 months. Results: From 2010 to 2015, the esti- involvement in 10–20% [4-6]. mated screening coverage rate increased from 68.4% to 88.6%. In this period, 33,469 pregnant women were Following migration from endemic areas to other tested for Trypanosoma cruzi and 937 positive cases countries, the epidemiological pattern of Chagas dis- were diagnosed. The overall prevalence was 2.8 cases ease has changed in recent decades and new cases per 100 pregnancies per year (15.8 in Bolivian women). of congenital transmission and transmission by other We followed 82.8% of newborns until serological test- mechanisms are detected in non-endemic countries ing at age 9–12 months and 28 were diagnosed with [7]. The last decade (2000–2010) has seen an increase Chagas disease (congenital transmission rate: 4.17%). of people from endemic areas migrating to Europe Of 518 siblings, 178 (34.3%) were tested and 14 (7.8%) [8]. In 2009, it was estimated that between 68,000 were positive for T. cruzi. Having other children with and 122,000 people from endemic countries living in Chagas disease and the heart clinical form of Chagas Europe were infected, although the rate of underdiag- disease were maternal risk factors associated with nosis was 94–96% [8]. European prevalence rates in congenital T. cruzi infection (p < 0.05). Conclusion: The migrants from endemic areas differ greatly according increased screening coverage rate indicates consolida- to the country of origin, with an estimated prevalence tion of the programme in Catalonia. The rate of Chagas rate of 4.2%, which rises to 18.1% in migrants from disease congenital transmission in Catalonia is in Bolivia [9]. accordance with the range in non-endemic countries. www.eurosurveillance.org 1 Rates of congenital transmission in non-endemic coun- Health Care centres (Centre d’Atenció a la Salut Sexual tries are lower than those found in endemic countries I Reproductiva - ASSIR), distributed in 372 maternal [10] but the asymptomatic nature of the disease and assistance points, which form part of the network of the lack of knowledge about Chagas disease in non- public primary care centres. In addition, there are 27 endemic countries make it difficult to detect new cases microbiology laboratories able to perform diagnostic [11,12]. Screening newborns of positive mothers is key tests for Chagas disease [29]. to the early detection and treatment of possible cases in non-endemic countries [13]. Screening of pregnant women, newborns and their siblings Spain, for cultural reasons, is the European country We introduced a surveillance system to evaluate the that has received most migrants from Latin America impact of congenital Chagas disease in Catalonia. The [14]. Screening for T. cruzi in blood and tissue banks target population were pregnant women from endemic has been mandatory by Royal decree-law since 2005 countries (first or second generation) and pregnant [15] but legislation on the screening of congenital trans- women from other origins (including Spain) who have mission is still lacking [11]. lived in a rural area of an endemic country for more than one month at any point in their lives. In Catalonia, estimates of people infected with T. cruzi in 2010 were between 10,000 and 20,000, with Serological screening is carried out during the first tri- between 203 and 387 pregnant women affected and mester of pregnancy, although tests done at any time between seven and 16 children with congenital Chagas during pregnancy, delivery or after birth are included disease [16]. After confirming the cost-effectiveness of in the programme (Figure 1) [20]. The tests used for a screening programme for congenital Chagas disease screening are those recommended by the WHO [1]. [17] and following the recommendations of the World Samples are collected at the ASSIR centre during preg- Health Organization (WHO) in non-endemic countries nancy or in hospitals during or after delivery. If the first which had to take appropriate measures to prevent test is positive, a second test using a different antigen and control vertical transmission [11,18,19], the Deputy or serological technique is carried out. If the results director of public health surveillance and response to between the two tests are discrepant, a third serologi- emergencies of the Public Health Agency of Catalonia cal test, using a different technique, is carried out. All (PHAC) has since 2010 progressively introduced and tests used in the programme follow the WHO recom- coordinated a protocol to detect, treat and cure cases mendation [1] and laboratories choose recommended of congenital Chagas disease [20]. tests according to their own experience and supplier. There is no common legislation on the control of the When the diagnosis is confirmed, it is recommended congenital transmission of Chagas disease in Europe, that pregnant women start treatment with trypano- although there are regional initiatives for the early cidal drugs (benznidazole or nifurtimox) after birth detection and treatment of cases according to WHO and lactation, and before a possible new pregnancy. recommendations. Official programmes for the detec- There is no risk of transmitting Chagas disease through tion and treatment of congenital Chagas disease have breastfeeding. been introduced in the Valencia (2008) [21], Catalonia (2010) [20] and Galicia (2014) [22] regions in Spain and Immediately after a birth to a mother diagnosed with in Toscana (2012) [23] in Italy. Other regions do not Chagas disease, a clinical evaluation of the newborn have an official protocol but act locally in hospitals is made in hospital to detect symptoms compatible [19,24-26]. with Chagas disease. The parasitological tests carried out during the first 48 h of life are the microhaemato- The objective of this study was to analyse the epidemi- crit and/or PCR [20]. If there is a positive PCR at birth, ological pattern of congenital Chagas disease in preg- another PCR is carried out 4 weeks later to confirm nant women from endemic areas and their children in the diagnosis. If any parasitological test is negative or the period from 2010 to 2015 in Catalonia and to evalu- tests cannot be carried out at birth, the infant is tested ate the coverage of the screening programme. with a serological test after 9 months when maternal antibodies have waned. If this test is negative, the fol- Methods low-up ends and the child is considered not infected; if the test is positive, a second serological test with a Surveillance setting different technique is carried out. If the results of the Catalonia is an autonomous community in the north- two tests are discrepant, a third serological test, using east of Spain with more than 7.5 million inhabitants. a different technique, is carried out. If any microhaem- In the study period (2010–2015), ca 450,000 people, atocrit at birth, PCR at age 1 month or two serological 6% of the population, were born in countries where tests after 9 months old are positive, T. cruzi infection is Chagas disease is endemic [27]. There are 45 public confirmed and antiparasitic treatment is administered. and 30 private maternity hospitals in Catalonia and The programme also includes other older children from 90% of births in Latin American women occur in public positive mothers if they are living in Catalonia, using centres [28]. There are also 47 Sexual and Reproductive the same serological testing as for pregnant women. 2 www.eurosurveillance.org Figure 1 Congenital Chagas disease screening programme in Catalonia, 2010–2015 Latin American pregnant woman (first or second generation) Negative First serological test Positive Negative Second serological test Positive Third serological test Not infected Negative Infected pregnant woman • Treatment recommended after lactation Not infected Other children <18 years Newborns First serological test In the first 48 hours of life: • Clinical examination • Microhaematocrit and/or PCRa assay Positive Negative Positive Negative Second Negative serological test Positive From 9th month: • First serological test Third Positive serological test Second serological test Negative Negative Positive Third serological test Negative Infected child or newborn • Treatment Not infected • Follow-up until serological negativity Not infected a Many advances have been made in molecular biology and expert groups recommend PCR for the diagnosis in infants [28–30]. In case of positive PCR at birth, another PCR at age 1 month is necessary to confirm Chagas disease. www.eurosurveillance.org 3 When two serological tests using different technique Maternal epidemiological risk factors were evaluated are positive, T. cruziinfection is confirmed and antipar- between newborns with a definitive positive and nega- asitic treatment is administered. tive diagnosis of Chagas disease. Continuous variables (age and years living in Catalonia) were transformed The screening and follow-up of pregnant women, new- into categorical variables, choosing the mean as cut- borns and siblings are included in the public health off point. Statistical significance was established portfolio and are free of charge. assuming an α error of 0.05. Differences between groups were analysed by simple logistic regression and Epidemiological surveillance the results are shown as p value and odds ratio (OR). To implement the programme throughout the region, Multiple logistic regression was used to calculate the PHAC created the Working Group for Congenital Chagas adjusted OR (aOR) and variables with a p value < 0.20 in disease in Catalonia, enrolling a large multidisciplinary the crude analysis were entered in the model. To avoid group of Chagas disease experts who are responsible the problem of quasi-complete separation, Firth logis- for the detection, notification and follow-up of positive tic regression was used [32]. pregnant women, newborns and siblings with positive mothers [16]: midwives, obstetricians, gynaecologists, The analysis was performed using the Statistical paediatricians, microbiologists, specialists in infec- Package for Social Sciences (SPSS v.25 for Windows). tious diseases and internal medicine, community health workers and epidemiologists. Ethical statement The study was not submitted for approval by a research Surveillance includes the mandatory notification of ethics committee because the activities described confirmed T. cruzi cases through the Microbiological were conducted as part of the legislated mandate of Reporting System of Catalonia, a network of Catalonian the Health Department of Catalonia, the competent laboratories that collects and reports pathogens of authority for the surveillance of communicable dis- public health importance to the PHAC [30]. Reported eases according to Decree 203/2015 of 15 September, cases are included in the Voluntary Registry of which created the epidemiological surveillance net- Chagas Disease Congenital Cases in Catalonia (VRCH). work of Catalonia [30]. All the activities studied formed Sociodemographic, diagnostic and treatment data and part of public health surveillance and did not require epidemiological information about the mothers (years informed consent. living in Catalonia, the clinical form of Chagas disease and previous treatments for Chagas disease) are vol- Results untarily collected by the Working Group and included Table 1 shows the overall results for screened pregnant in the VRCH. women and follow-up in newborns and siblings. Laboratories report annually the number of pregnant Screening of pregnant women women screened. To calculate the coverage of the It was estimated that 40,084 pregnant women should screening of pregnant women, the denominator was have been tested in Catalonia between 2010 and 2015. estimated taking into account the number of births Of these, 33,469 (83.5%) were actually screened, an in women from endemic countries in the Register of annual mean of 5,578 tests (Table 1). No positive cases Newborns (an official regional registry linked to each were detected in pregnant women who were second- maternity hospital, public or private, which collects generation migrants or travellers. information on births in Catalonia, including the moth- ers’ country of origin [31]) and adding an estimation of A total of 818 women were diagnosed with T. cruzi during pregnancies interrupted before giving birth (miscar- pregnancy between 2010 and 2015: 707 (86%) became riages and abortions) and women who moved away pregnant once, 103 twice (13%) and eight (1%) three from Catalonia before childbirth as reported to the times. In total, 937 pregnancies in positive women VRCH (13% of total pregnancies). Prevalence rates were were followed between 2010 and 2015. calculated on pregnancies and not on pregnant women because the screening is repeated for each new preg- Screening coverage of pregnant women increased nancy. To calculate the prevalence rates by country of mainly between 2010 (68.4%) and 2011 (85.5%), when origin we applied the distribution of births by mater- the logistics of the programme were introduced in all nal country of origin in the Register of Newborns to the areas. The coverage gradually increased further until total of pregnancies screened. 2015 (88.6%) (p < 0.001 between 2010 and 2015). Statistical analysis The highest density of Chagas-positive women was All outcomes are shown in percentages and the annual seen in the Barcelona health area (717 cases; 87.7%), percentage differences between 2010 and 2015 are especially in the Baix Llobregat (270 cases; 37.7%) and shown as a relative change and evaluated using the Z Barcelona (233 cases; 32.5%) areas (Figure 2). score for two proportions of population. During the study period, the prevalence rate was 2.8 positive cases per 100 pregnancies screened (Figure 3). 4 www.eurosurveillance.org The rates were highest in women from Bolivia (15.79), had negative serological tests after treatment, with a El Salvador (1.41) and Paraguay (1.24) (Table 2). median follow-up of 4 years (range: 1–6 years) (Table 3). The mean age of positive women at pregnancy was 33 years, which increased from 32 years in 2010 to Follow-up of newborns 34 years in 2015. Bolivian women represented 92.5% Of the 812 newborns, 728 (89.7%) were tested for T. of the positive cases in whom the country of birth cruzi parasite at birth. The most frequent tests were could be identified, followed by women from Paraguay PCR (87.1%) and microhaematocrit (57.6%). In 84 of (2.5%), Argentina (1.6%), Ecuador (0.9%), Honduras 812 cases (10.3%) the newborn was not tested at birth (0.7%), Chile (0.6%), El Salvador (0.5%), Peru (0.5%), (16.8% in 2010 and 6.9% in 2015; p = 0.029). Testing Nicaragua (0.1%) and Colombia (0.1%). Almost half of after age 9 months was carried out in 672 of 812 the cases (47.6%) had arrived in Catalonia between newborns (82.8%). Of these, 95.8% (n = 644) tested 2005 and 2006, and the mean number of years from negative. The median age at screening was 10 months arrival to pregnancy was 7 years (Table 2). (Table 1). The main clinical form of Chagas disease was indeter- A total of 140 newborns (17.5%) did not complete minate (94.1%). Women with heart clinical form rep- the follow-up. The main reason was the departure of resented 3.8% of cases, while digestive and mixed the family from Catalonia before the newborn was 9 pathologies (heart and digestive) accounted for 1.6% months old (7.0%), followed by failure to attend the and 0.5% of cases, respectively. Only 26% of pregnant medical visit (6.6%) and failure of the surveillance cir- women received treatment with benznidazole or nifur- cuit (3.9%). timox before pregnancy. This percentage increased from 7.8% (7/90 cases with data about treatment) for Twenty-eight cases were diagnosed with T. pregnant women diagnosed in 2010 to 46.5% for those cruzi infection acquired through congenital diagnosed in 2015 (33/71 cases with data about treat- transmission (4.2%). In 27 cases, the mother was from ment) (p < 0.001). Bolivia and in one case from Paraguay. Twelve infants were diagnosed by parasitological tests before age 9 Pregnancies were interrupted in 9.3% (n = 87) of preg- months and 16 infants with serological tests after age nancies. More than half were miscarriages (65.5%), 9 months (Table 3). In four of 28 cases, the newborn followed by abortions (23%) and cases where the rea- presented symptoms compatible with Chagas disease, son for interruption was missing (11.5%), while 4.1% of including splenomegaly (3/4), hepatomegaly (3/4) and pregnant women left Catalonia before childbirth, which jaundice (3/4). meant that follow-up of the newborn was not possible. There were 812 births from 937 pregnancies in 818 T. All 28 positive cases were treated with benznidazole. cruzi-positive women in Catalonian maternity hospitals Treatment was suspended because of failure to attend (Table 1). follow-up visits in one case and because of an adverse reaction in one case. Overall, four of 28 newborns had Follow-up of siblings adverse reactions, including increased transaminases For 674 of the 818 T. cruzi-positive women (82.4%) (n = 1), pancytopenia (n = 1), cessation of weight gain detected by the programme, it was possible to deter- (n = 1) and anorexia (n = 1). Serology after treatment mine whether they had other children born before the was negative in 15 cases, with a mean time between current pregnancy and living in Catalonia, and 359 treatment end and serology of 8.1 months (range: 0–21 (53.3%) had at least one. The mean of other children months). Two newborns treated before age 12 months per mother was 0.8. We identified 519 children for did not become seronegative: the first was diagnosed screening. In most cases, the children had not been by PCR 1 month after birth and remained positive 1 year tested or testing information not notified by the work- after treatment. Treatment was repeated 4 years later ing group (341 cases; 65.7%), ranging from 93.1% in and the subsequent PCR was negative, but serologi- 2010 to 49.3% in 2015 (p < 0.001). Of the 178 children cal testing was not carried out. The second child had who were successfully screened and reported (34.3%), a negative PCR at birth, but positive PCR and serol- 14 were positive (7.9%) (Table 1). The median age of ogy at 9 months. Treatment was stopped after 10 days those 14 children was 10 years (range: 3–18 years) because of pancytopenia and was resumed 2 months and 12 were male. Five of them were born in Catalonia later. Two years later serology remained positive. between 2005 and 2008 but were not tested during the first year of life, while nine arrived in Catalonia during Recovery rates were 89% for newborns treated before childhood. All 14 cases started treatment with benz- 6 months of age, 80% for those treated between 6 nidazole, but treatment was interrupted in two cases and 12 months of age and 20% after 12 months of age. because of side effects such as neutropenia and toxi- Taking the serological diagnosis after 9 months as the coderma and was not resumed, although the follow-up gold standard, the sensitivity of the microhaematocrit continued. In seven of the 14 cases, the follow-up was and PCR was 29.4% and 52.6%, respectively, and the not completed with the required serological test. None specificity 100% and 99.2% (in four cases, PCR was of the seven children who continued the follow-up positive at birth but negative after 1 month). www.eurosurveillance.org 5 6 Table 1a Screening of pregnant women and follow-up of siblings and newborns for Chagas disease, Catalonia, 2010–2015 (n = 40,084) Difference Total 2010 2011 2012 2013 2014 2015 p value 2010–2015 2010 vs 2015 n % n % n % n % n % n % n % % Pregnancies follow-up To be testeda 40,084 7,656 7,145 7,099 6,348 6,005 5,831 −23.8 NA Tested 33,469 83.5 5,238 68.4 6,107 85.5 6,324 89.1 5,524 87.0 5,108 85.1 5,168 88.6 29.5 < 0.001 Positives 937 2.8 128 2.4 179 2.9 168 2.7 163 3.0 148 2.9 151 2.9 19.6 0.147 Lost before parturitionb 38 4.1 8 6.3 8 4.5 11 6.5 3 1.8 3 2.0 5 3.3 −47.0 0.381 Miscarriages/abortionsb 87 9.3 7 5.5 16 8.9 17 10.1 18 11.0 14 9.5 15 9.9 81.6 0.248 Gave birthb 812 86.7 113 88.3 155 86.6 140 83.3 142 87.1 131 88.5 131 86.8 −1.7 0.840 Other children follow-up Siblings to be tested 519 130 84 92 73 73 67 −48.5 NA Missing information/not tested 341 65.7 121 93.1 42 50 44 47.8 49 67.1 52 71.2 33 49.3 −47.1 < 0.001 Tested 178 34.3 9 6.9 42 50.0 48 52.2 24 32.9 21 28.8 34 50.7 633.0 Positives 14 7.9 2 22.2 3 7.1 2 4.2 2 8.3 2 9.5 3 8.8 −60.3 0.596 Negatives 164 92.1 7 77.8 39 92.9 46 95.8 22 91.7 19 90.5 31 91.2 17.2 Newborns follow-up 1. Parasitological control at birth Not tested 84 10.3 19 16.8 30 19.4 13 9.3 7 4.9 6 4.6 9 6.9 −59.1 0.026 Tested 728 89.7 94 83.2 125 80.6 127 90.7 135 95.1 125 95.4 122 93.1 12.0 Tested by PCR 634 87.1 83 88.3 100 80.0 110 86.6 122 90.4 111 88.8 108 88.5 0.3 0.871 Tested by MH 419 57.6 73 77.7 59 47.2 69 54.3 75 55.6 73 58.4 70 57.4 −26.1 0.003 Positives 12 1.6 2 2.1 2 1.6 1 0.8 4 3.0 3 2.4 0 0 −100.0 0.367 Negatives 716 98.4 92 97.9 123 98.4 126 99.2 131 97.0 122 97.6 122 100 2.2 NA: not Applicable. a Number of births from the Newborns Registry plus an estimation (13%) of interrupted pregnancies and women who moved away before childbirth from the Voluntary Registry of Chagas disease congenital cases in Catalonia. b Among the women who tested positive. www.eurosurveillance.org Table 1b Screening of pregnant women and follow-up of siblings and newborns for Chagas disease, Catalonia, 2010–2015 (n = 40,084) Difference Total 2010 2011 2012 2013 2014 2015 p value 2010–2015 2010 vs 2015 n % n % n % n % n % n % n % % www.eurosurveillance.org 2. Serological control at age 9–12 months To be tested 800 111 153 139 138 128 131 18.0 NA Not tested 140 17.5 21 18.9 33 21.6 31 22.3 26 18.8 12 9.4 17 13.0 −31.4 0.276 Moved away from Catalonia 56 7.0 1 0.9 13 8.5 13 9.4 17 12.3 9 7.0 3 2.3 154.2 0.735 Failure to attend the medical visit 53 6.6 15 13.5 9 5.9 9 6.5 8 5.8 2 1.6 10 7.6 −43.5 0.199 Failure of surveillance circuitc 31 3.9 5 4.5 11 7.2 9 6.5 1 0.7 1 0.8 4 3.1 −32.2 0.800 Tested 660 82.5 90 81.1 120 78.4 108 77.7 112 81.2 116 90.6 114 87.0 7.3 0.276 Mean time to test (months) 10 ± 4 10 ± 3.5 10 ± 6 10±4 10 ± 4 10 ± 3 9±4 Positives 16 2.4 4 4.4 2 1.7 1 0.9 4 3.6 2 1.7 3 2.6 −40.8 0.750 Negatives 644 97.6 86 95.4 118 98.3 107 99.1 108 96.4 114 98.3 111 97.4 1.9 3. Summary of testing Correctly tested 672 82.8 92 81.4 122 78.7 109 77.9 116 81.7 119 90.8 114 87 6.9 0.304 Positives 28 4.2 6 6.5 4 3.3 2 1.8 8 6.9 5 4.2 3 2.6 −59.6 0.318 Negatives 644 95.8 86 93.5 118 96.7 107 98.2 108 93.1 114 95.8 111 97.4 4.2 Index Pregnant women screening coverage rate (%) 83.5 68.4 85.5 89.1 87.0 85.1 88.6 29.5 < 0.001 Prevalence rate of Chagas disease (%) 2.80 2.44 2.93 2.66 2.95 2.90 2.92 19.6 0.147 Congenital transmission rate (%) 4.17 6.52 3.28 1.83 6.90 4.20 2.63 −59.6 0.318 c Missing patient referral or paediatrician’s lack of awareness about Chagas disease. 7 Figure 2 in Italy (8.7%) [25] and Switzerland (8.8%) [24]. These Geographical distribution of Trypanosoma cruzi-positive differences may be due, in part, to methodological pregnant women and cases of congenital transmission, Catalonia, 2010–2015 (n = 818) differences in estimating the rates. The prevalence rates observed in our programme in women from other endemic countries such as Paraguay, Argentina, Ecuador, Honduras, Chile, el Salvador, Peru, Nicaragua and Colombia (range: 0.02–1.41), were much lower than those detected in other Spanish studies (range: 0.2–7.4) [36,40] or in studies from the endemic coun- tries themselves (range: 3.2–12.7) [41-45]. The rate of congenital transmission in Catalonia (4.17%) was within the range detected in endemic (range: 1.7– 5) [35,46-50] and non-endemic countries (range: 0–7.3) [25,33,34,36-38]. The estimated screening coverage rate in pregnant Barcelona women was 83.5%, which is lower than the rate found Baix Llobregat in Valencia (94.5%) [36]. This may be due, in part, to the greater centralisation and smaller number of cen- 1-5 positive pregnant women tres included in the Valencia programme (three mater- 6-15 positive pregnant women nity hospitals) compared with Catalonia (45 public 16-50 positive pregnant women maternity hospitals and 372 primary health centres 51-100 positive pregnant women with midwife care, including all public health centres). 101-200 positive pregnant women > 200 positive pregnant women Screening of the newborns’ siblings is widely neglected 1 congenital case in gestational screening programmes and there are few 2 congenital cases > 2 congenital cases studies of this subgroup [51-53]. A prevalence study conducted in Catalonia in children younger than 18 years with a Chagas disease-positive mother [53] found a slightly higher rate (10.9%) than ours (7.3%), and a Analysis of maternal risk factors clinical study of children in Catalonia and Switzerland In an analysis of maternal risk factors for vertical trans- identified a higher percentage of adverse effects dur- mission of the infection, we saw significant differences ing treatment (36%) than our programme (14.3%) and between positive and negative siblings (aOR = 22.79; a recovery rate at age 2 years of 17.2%, compared with 95% confidence interval (CI): 3.75–161.54) and between 0% in our programme [51]. Although the screening of heart and indeterminate clinical forms (aOR = 14.4; other children improved significantly between 2010 95% CI: 2.11–87.67) (Table 2). Differences between (6.9%) and 2015 (50.7%), the high percentage of miss- untreated and treated mothers showed crude statisti- ing cases (352 cases, 66.4%), and the missing follow- cal significance (p = 0.033) but significance was lost up in positive cases (50%) demonstrate a lack of a after adjusting for multivariate logistic regression well-established notification and follow-up circuit for (aOR = 6.67; 95% CI: 0.78–876.89). Other risk factors this subgroup. analysed, such as the mother’s age, country of origin or time living in Catalonia (≤ 7 years) had no significant Parasitological testing at birth improved significantly influence on the likelihood of vertical transmission. between 2010 (83.2%) and 2015 (93.1%). PCR was used more than the microhaematocrit (87.1% and 57.6%, Discussion respectively), and the microhaematocrit was less fre- The congenital Chagas disease prevention and control quent in 2015 than in 2010 (57.4% vs 77.7%). This programme in Catalonia is one of few screening pro- confirms the greater practicality of PCR in our region. grammes for the control of congenital Chagas disease Even if PCR is widely accepted for the early diagnosis launched by public health authorities in a non-endemic of Chagas disease [54-56], false positive (four cases) region [9].The observed prevalence of Chagas disease and false negative results (nine cases) indicate that a (2.8 cases/100 pregnancies) was similar to that found in standardised PCR technique with higher sensitivity is other studies in pregnant women in Catalonia [33, 34]. required [57]. Currently, it is still necessary to wait until The prevalence in Bolivian pregnant women was lower age 1 month to validate the diagnosis by PCR or to per- (15.8%) than in a similar programme in Bolivia (23.3%) form a serological test after 9 months for PCR-negative [35]. Studies in other regions in Spain show higher cases [58]. prevalence rates in Valencia (34.1%) [36] and Vizcaya (22%) [37] but lower rates in Madrid (11.4%) [38] and We detected some delay between diagnosis and start of Almeria (12.5%) [39]. Other non-endemic countries treatment for positive newborns. There are several pos- show lower rates in Bolivian pregnant women living sible explanations: the presence of other pathologies 8 www.eurosurveillance.org Figure 3 Annual number of screened women and Trypanosoma cruzi-positive pregnant women, Catalonia, 2010–2015 (n = 33,469) Screened women Positive women Prevalence 7,000 4 6,324 6,107 6,000 3.5 5,524 5,238 5,168 5,108 5,000 3 2.93 2.95 2.92 Prevalence rate 2.90 Number of women 4,000 2.66 2.5 2.44 3,000 2 2,000 1.5 1,000 128 179 168 163 148 151 0 1 2010 2011 2012 2013 2014 2015 that require other incompatible treatments, difficulty in especially in those who already have infected children obtaining the medication (there was a significant lack or those with the heart clinical form of the disease. of supply of Benznidazole a few years ago) or a deci- sion made by the patient’s family. Other studies in Catalonia found a higher proportion of the digestive clinical form (up to 21% vs 1.6%) [5,6]. The recovery rates observed in treated newborns are Our results may be an underestimate because infected provisional data because newborns with positive serol- women diagnosed during pregnancy could not undergo ogy will be followed until serology is negative and the specific radiological tests to detect possible digestive results could therefore change in the future. Sometimes disorders. problems with treatment compliance or adverse reac- tions can affect seronegativisation in post-treatment The main challenge of our programme was to calculate follow-up. However, although our results are based the coverage of screening for pregnant women and the on very few cases, the current results suggest that it prevalence rate by country of origin, because the pro- is very important to detect the infection before age tocol did not plan for quantifying the target population 12 months to achieve a probability of cure of more and collecting epidemiological information on pregnant than 80%. Schijman et al. found a 100% recovery rate women with negative results. To solve this limitation, when treatment is started before age 6 months com- we used the Register of Newborns as a source. It will be pared with 88.9% in our study [59]. necessary to involve the ASSIR centres in reporting all cases, negative or positive, or create an improved data With respect to maternal epidemiological risk factors collection system to provide this information. Another for congenital transmission, we found three studies limitation of the programme were the 10.5% missing that showed an increased risk of congenital transmis- numbers in the follow-up at age 9–12 months owing to sion in untreated women [60-62]. In our study, women failures in the follow-up circuit such as a lack of aware- untreated before pregnancy had an almost sevenfold ness about Chagas disease among paediatricians and greater probability of congenital infection but the patients, or a missing patient referral. The percentage adjusted significance was weak (p = 0.093). Having the lost to follow-up was smaller in 2013 (6.5%) and 2014 heart clinical form of Chagas disease rather than the (2.4%) because of a specific community health action indeterminate clinical form and having other infected to redirect lost cases [63]. It is therefore necessary to children increased the risk of congenital transmission improve primary healthcare circuits to control the new- 14 and 23 times, respectively. These findings demon- borns and other children of positive mothers and to strate the importance of recommending treatment of add community health actions to the surveillance of women of childbearing age before a new pregnancy, congenital Chagas disease. www.eurosurveillance.org 9 Table 2 Epidemiological characteristics, prevalence rates by endemic country of origin and maternal risk factors for congenital Chagas disease, Catalonia, 2010–2015 (n = 818) Completed Completed Positive follow-up follow-up pregnant Prevalence rates negative in positive in Crude p Crude OR Adjusted p Adjusted Maternal risk factors women for country of newborns newborns value (CI) valueb OR (CI)b (n = 818) origina (n = 644) (n = 28) n % n % n % Age 1.71 1.30 < 33 years 389 47.6 305 47.4 17 60.7 0.166 0.693 (0.79– (0.35–5.28) 3.72) ≥ 33 years 429 52.4 339 51.6 11 39.3 Ref Previous treatmentc Yes 115 26.0 107 29.9 2 8.3 Ref 3.85 6.67 No 328 74.0 251 70.1 22 91.7 0.033 0.093 (1.02– (0.78– 14.49) 876.89) Country of birthd Bolivia 755 92.5 15.79 598 92.9 27 96.4 Ref 1.30 Paraguay 20 2.5 1.24 17 2.6 1 3.6 0.801 NA (0.17– 10.15) Argentina 13 1.6 0.52 11 1.7 0 0 NA Ecuador 7 0.9 0.10 4 0.6 0 0 NA Honduras 6 0.7 0.26 4 0.6 0 0 NA Chile 5 0.6 0.50 1 0.2 0 0 NA El Salvador 4 0.5 1.41 3 0.5 0 0 NA Peru 4 0.5 0.11 4 0.6 0 0 NA Nicaragua 1 0.1 0.57 1 0.2 0 0 NA Colombia 1 0.1 0.02 1 0.2 0 0 NA Clinical form of Chagas diseasee Indeterminate 524 94.1 432 94.9 23 88.5 Ref 3.76 14.40 Heart 21 3.8 15 3.3 3 11.5 0.047 0.009 (1.02– (2.11– 13.90) 87.67) Digestive 9 1.6 8 1.8 0 0 NA Mixed 3 0.5 0 0 0 0 NA Siblings completing follow-upf Negative 131 92.3 150 97.4 4 40 Ref 56.25 22.79 Positive 11 7.7 4 2.6 6 60 < 0.001 0.001 (11.26– (3.75– 280.9) 161.54) Years living in Cataloniag 3.03 1.76 ≤ 7 years 254 57.9 186 49.7 12 75 0.059 0.453 (0.96– (0.42– 9.57) 10.05) > 7 years 185 42.1 188 50.3 4 25 Ref CI: confidence interval; NA: Not Applicable; OR: odds ratio; Ref: reference value. a Number of positive newborns per 100 births, adjusted by pregnant women screening coverage rate. b Firth multiple logistic regression. c Unknown data: n = 375 (45.8%). d Unknown data: n = 2 (0.2%). e Unknown data: n = 261 (31.9%). f Mothers without other children and with untested other children: n = 676 (82.6%). g Unknown data: n = 379 (46.3%). 10 www.eurosurveillance.org Table 3 Positive Trypanosoma cruzi diagnostic tests, treatment and follow-up in newborns and their siblings, Catalonia, 2010–2015 (n = 42) Follow-up Age at Symptoms Adverse Age at after Country Age of treatment compatible reactions Completed Serological ID Microhaematocrit PCR Serology diagnosis treatment of birth arrival start with Chagas to treatment negativisation (months) end (months) disease treatment (months) Newborns 1 + + NA 0 2 No No Yes Yes 1 2 + + NA 0 0 Yes Yes No Yes 9 3 + + NA 0 0 Yes No Yes Yes 9 4 − + NA 0 1 No No Yes Yes 1 5 + NP NA 0 0 Yes No Yes Yes 6 6 NP + NA 0 0 No No Yes Yes 21 7 − + NA 1 2 No No Yes Yes 6 8 NP + NA 1 4 No No Yes Yes 6 9 − + NA 1 1 No No Yes No 34 10 + NP NA 1 3 No No Yes Yes 3 11 − + NA 2 15 No No Yes No 11 12 NP + NA 6 6 No No Yes Yes 12 13 NP − + 9 9 No No Yes Yes 5 14 − NP + 9 10 No No Yes Losta NA NA NA 15 NP NP + 9 9 No No Yes Yes 0 16 − NP + 9 11 No No Yes Yes 9 17 NP − + 9 9 No Yes Yes No 24 18 − − + 10 11 No No Yes Losta NA 19 − − + 11 12 No No Yes No 33 20 NP NP + 11 11 No No Yes No 59 21 − − + 12 13 No Yes Yes Yes 18 22 − NP + 12 12 Yes No No Losta NA 23 − − + 13 12 No No Yes No 35 24 NP − + 15 16 No No Yes Yes 16 25 NP NP + 20 24 No No Yes No 28 26 NP NP + 20 21 No No Yes No 30 27 − − + 23 23 No No Yes No 4 28 NP − + 27 28 No Yes Yes No 27 11.5 Median (interquartile range) 9 (11) 9.5 (10.75) (21.75) Siblings 1 + Spain NA 3 3 No No Yes No 4 2 + Spain NA 4 5 No No Yes No 4 3 + Spain NA 4 4 No No Yes No 1 4 + Bolivia 7 5 5 No No Yes No 6 5 + Spain NA 7 7 No Yes No Losta NA 6 + Bolivia 1 7 8 No Yes No Losta NA 7 + Spain NA 9 9 No No Yes No 3 NA NA 8 + Bolivia 9 11 11 No No Yes Losta NA 9 + Bolivia 9 11 11 No No Yes Losta NA 10 + Bolivia 6 11 11 No No Yes No 2 11 + Bolivia 10 12 12 No No Yes Losta NA 12 + Bolivia 13 13 14 No No Yes Losta NA 13 + Bolivia 9 16 16 No No Yes No 5 14 + Bolivia 15 18 18 No No Yes Losta NA Median (interquartile range) 10 (7.5) 10 (7.5) 4 (3) +: positive; −: negative; ID: identification number; NP: not performed; NA: not applicable. a Lost to follow-up before serological control. www.eurosurveillance.org 11 Carmina Sanjosé. CLILAB Diagnòstics, Consorcio del Conclusion Laboratorio Intercomarcal. The results of the congenital Chagas disease pro- Celia Guardia. Laboratori Barcelonès Nord i Vallés Oriental. gramme in Catalonia show that systematic control of the congenital transmission of Chagas disease by an Cristina Cortes. Hospital General de l’Hospitalet. integrated public health surveillance system is pos- Cristina Gutierrez. Hospital Universitari Joan XXIII de sible in a non-endemic region and the increase in the Tarragona. estimated screening coverage rate indicates its consol- Cristina Martinez. ASSIR Barcelona Ciutat, ICS. idation in Catalonia. Cristina Riera. Facultat de Farmàcia. Universitat de Barcelona. Prevalence and congenital transmission rates were Cristina Soler. Hospital de Santa Caterina. within the ranges detected in other studies conducted Dolors Gonzalez. CAP Rambla Nova. ICS Camp de Tarragona. in non-endemic settings. Having previous children with Dolors Guix. ASSIR Granollers, ICS. Chagas disease and presenting the heart clinical dis- ease form of the disease were risk factors for the con- Eduard Solé Mir. Hospital Universitari Arnau de Vilanova, IRBLleida. genital transmission of T. cruzi. Treatment of women of childbearing age with these characteristics is recom- Eduardo Padilla. Laboratori de Referència de Catalunya. mended in order to improve the treatment of Chagas Elena Sulleiro. Hospital Universitari Vall d’Hebron. disease in non-endemic countries. Elisa Llurba. Hospital de la Santa Creu i Sant Pau. Elisabeth Del Amo. ASSIR Litoral (Barcelona ciudad), ICS. Members of the Working Group of Congenital Chagas Elisenda Moliner. Hospital de la Santa Creu i Sant Pau. disease in Catalonia Emma Padilla Esteba. Catlab-Centre Analítiques Terrassa, Alba Cebollero. CLILAB Diagnòstics, Consorci del Laboratori AIE. Intercomarcal. Engràcia Coll. ASSIR Hospital Mutua Terrassa, ICS. Alicia Carrascon. ASSIR Izquierdo (Barcelona ciudad), Institut Català de la Salut (ICS). Enrique Rodriguez. Hospital General de l’Hospitalet. Ana Moreira. Hospital Sant Joan de Déu de Martorell. Enrnesto Monaco. Hospital Residencia Sant Camil. Ana Requena-Mendez. ISGlobal, Hospital Clínic de Barcelona, Ester Muñoz. Hospital de la Cerdanya. Universitat de Barcelona. Esther Freixas. ASSIR l’Hospitalet, ICS. Ana Torres Soto. Hospital Residència Sant Camil. Eva Dopico. Laboratori Clínic L’Hospitalet. Andrea Martín. Hospital Universitari Vall d’Hebron. Eva Sardá. ASSIR Muntanya (Barcelona ciudad), ICS. Anna Ballester. Corporació de Salut del Maresme i la Selva. Federic Ballester. Hospital Universitari Sant Joan de Reus. Anna Bragulat. Hospital de la Cerdanya. Federic Gomez. Hospital Joan XXIII de Tarragona. Anna Soligó. ASSIR Consorci Sanitari de Terrassa. Ferran Barranco. Hospital de la Cerdanya. Anna Vilamala Bastarras. Consorci Hospitalari de Vic. Francesc Ripoll. Hospital Santa Caterina. Antoni Payà. Hospital del Mar. Francesc-Josep Fargas. ASSIR Camp de Tarragona, ICS. Antoni Soriano-Arandes. Hospital Universitari Vall d’Hebron. Gemma Falguera. ASSIR Direcció d’Atenció Primària Antoni Sorni. Hospital Verge de la Cinta de Tortosa. Metropolitana Nord, ICS. Antonia Calvo. Hospital Clínic de Barcelona. Gema Fernández-Rivas. Microbiology Department, Clinical Laboratory North Metropolitan Area, Hospital Universitari Antonio Mur. Hospital del Mar. Germans Trias i Pujol. Assumpta Colomer. Consorci Hospitalari de Vic. Gemma Ginovart. Hospital de la Santa Creu i Sant Pau. Begoña Carral. ASSIR Baix Llobregat Litoral, ICS. Gemma Navarro. Hospital Universitari Parc Taulí. Begoña Treviño. Unitat de Salut Internacional Drassanes, Graciano García-Pardo. Hospital Joan XXIII de Tarragona. Hospital Universitari Vall d’Hebron. Gustavo Lorenzo. Hospital de Mollet del Vallès. Borja Guarch. Hospital Universitari Dr Josep Trueta de Girona. Hakima Ouaarab. Unitat de Salut Internacional Drassanes, Carles Orta. Hospital Comarcal de l’Alt Penedès. Hospital Universitari Vall d’Hebron. Carlos Rodrigo. Hospital Universitari Germans Trias i Pujol. Imma Caubet. Espitau Vall d’Aran. Carme Gallés. Corporació de Salut del Maresme i la Selva. Isabel Claveria. Unitat de Salut Internacional Drassanes, Hospital Universitari Vall d’Hebron Carme Garrido. Hospital de la Santa Creu i Sant Pau. Isabel Sanfeliu. Hospital Universitari Parc Taulí. Carme Molina. Hospital Joan XXIII de Tarragona. Israel Molina. Hospital Universitari Vall d’Hebron. Carme Mora. Hospital de Figueres. Jesus Blanch. Hospital Residencia Sant Camil. Carmen Muñoz. Hospital de la Santa Creu i Sant Pau. Joan Agullo Martí. Hospital de Palamós. Carmina Martí. Hospital General de Granollers. Joan Farré. Hospital Universitari Arnau Vilanova de Lleida. 12 www.eurosurveillance.org Neus Prat. ASSIR Baix Llobregat, ICS. Joaquim Gascón. ISGlobal, Hospital Clínic, Universitat de Barcelona. Neus Rius. Hospital Universitario Sant Joan de Reus Jordi Costa. Hospital Universitari Parc Taulí. Nuria Prim Bosh. Laboratori de Referència de Catalunya. Jordi Gomez i Prat. Unitat de Salut Internacional Drassanes, Pablo Garcia. Hospital Comarcal Móra d’Ebre. Hospital Universitari Vall d’Hebron. Paloma Araujo. Hospital de Terrassa. Jose Fulquet. Hospital de Figueres. Pepa Solé. Hospital de Mataró. Josefa Perez Jove. Catlab-Centre Analítiques Terrassa, AIE. Pilar Ciruela. Agència de Salut Pública de Catalunya. Josep Armengol. Hospital de la Santa Creu i Sant Pau. Pilar Villalobos. Hospital de Figueres. Juan Carlos Riera. ASSIR Gironès Pla de l’Estany, ICS. Rosa Almirall. ASSIR Izquierdo (Barcelona ciudad), ICS. Judith Villar. Parc de Salut Mar. Rosa Diaz. ASSIR Mataró, ICS. Laia Sanchez Torrent. Hospital General del Parc Sanitari Sant Joan de Déu (Sant Boi de Llobregat). Rosa Puigarnau. Hospital Mútua Terrassa. Leonardo De La Torre. ISGlobal, Hospital Clínic de Barcelona. Rosa Serra. ASSIR Gironès Pla de l’Estany. Lluis Delgado. Hospital Comarcal de l’Alt Penedès. Roser Diez. Hospital de Mataró. Lluis Valerio. Unitat de Salut Internacional Metropolitana Sara Torrent Bosch. Hospital Universitario Dr Josep Trueta de Nord, ICS. Girona. Lourdes Montsant. Hospital de la Cerdanya. Silvia Franch. Hospital de Sant Pau i Santa Tecla. Luca Basile. Agència de Salut Pública de Catalunya. Sonia Vega. Hospital de Figueres. Luis Mayol. Hospital Universitario de Girona Doctor Josep Susanna Garcia Mani. ASSIR Baix Llobregat Nord, ICS. Trueta Teresa Juncosa. Hospital Maternoinfantil Sant Joan de Déu. M. Eugenia Valls. ISGlobal, Hospital Clínic de Barcelona. Valentí Pineda. Hospital Parc Taulí de Sabadell MªAngels Vives. Hospital de Terrassa. Vicky Fumado. Hospital Maternoinfantil Sant Joan de Déu. MªGoretti Sauca. Hospital de Mataró. Xavier Urquizu. Hospital Mutua de Terrassa. Maite Coll. Hospital General de Granollers. MªJesus Pinazo. ISGlobal, Hospital Clínic de Barcelona. Acknowledgements MªJosé Ferri. Hospital Universitari Dr Josep Trueta de Girona. We are grateful to Sonia Broner from the Public Health Agency MªJosé Vidal. Agència de Salut Pública de Catalunya. of Catalonia for the statistical support and recommendation. MªLuz Villegas. Hospital General de l’Hospitalet. Funding: ARM and JG belongs to the RICET, a Tropical Disease Manuel Andres Samper Anquela. PIUS Hospital de Valls. Cooperative Research Network in Spain (RD16/0027/0004) Manuel Monsonis. Hospital Maternoinfantil Sant Joan de co-funded by ISCIII and the Fondo Europeo de Desarrollo Déu. Regional (FEDER). MªPilar Blasco. ASSIR Santa Coloma de Gramenet, ICS. This work was supported by the Catalan Agency for the Mar Olga Pérez-Moreno. Hospital Verge de la Cinta de Management of Grants for University Research, Spain Tortosa. (AGAUR; grant numbers 2017/SGR 924 and 2017/SGR 1342). Margarida Curriu Sabates. Hospital Sant Bernabé. Maria Mèndez. Hospital Germans Trias i Pujol Conflict of interest Maria Navarro. Consorci Hospitalari de Vic. None declared. Marisa Urcola. Hospital de Santa Caterina. Marta Lora. Hospital Universitari Dr Josep Trueta de Girona. Authors’ contributions Marta Navarro. Hospital Universitari Parc Taulí. Programme design and implementation: LB, PC, ARM, ED, Merce Almirall. Hospital Universitari Arnau Vilanova de AMN, ES, JG, MJ and Working Group of Congenital Chagas Lleida. disease in Catalonia. Mercè Arasa. ASSIR Terres de l’Ebre, ICS. Data collection: Working Group of Congenital Chagas dis- Meritxell Vidal Alaball. ASSIR Baix Empordà, Hospital de ease in Catalonia. Palamós. Data analysis: LB. Mireia Carulla. Hospital de Sant Pau i Santa Tecla. Mireia Jané. Agència de Salut Pública de Catalunya. Original draft: LB, PC. Monica Ribell-Bachs. Hospital General de Granollers. Draft review and edition: ARM, MJV, ED, AMN, ES, JG, MJ. Montse Abella. ASSIR Sabadell, ICS. Montserrat Gallego. ISGlobal, Hospital Clínic de Barcelona. www.eurosurveillance.org 13 References 18. Organització Mundial de la Salut. Chagas disease in Latin America: an epidemiological update based on 2010 1. WHO Expert Committee. Control of Chagas disease. World estimates. Wkly Epidemiol Rec. 2015;90(6):33-43. https://doi. Health Organ Tech Rep Ser. 2002;905:i-vi, 1-109, back cover. org/10.2147/IBPC.S70402 PMID: 25671846 PMID: 12092045 19. Soriano-Arandes A, Angheben A, Serre-Delcor N, Treviño- 2. Silveira AC, Rojas de Arias A, Segura E, Guillén G, Russomando Maruri B, Gómez I Prat J, Jackson Y. Control and management G, Schenone H, et al. El control de la enfermedad de Chagas en of congenital Chagas disease in Europe and other non-endemic los países del Cono Sur de América. Historia de una iniciativa countries: current policies and practices. Trop Med Int Health. internacional 1991/2001. [The control of Chagas disease in 2016;21(5):590-6. https://doi.org/10.1111/tmi.12687 PMID: the countries of the Southern Cone of America. History of an 26932338 international initiative 1991/2001]. Washington: Pan American 20. Autonomous government of Catalonia. Protocol for screening Health Organization; 2002. Spanish. Available from: http:// and diagnosing Chagas disease in pregnant Latin American www1.paho.org/spanish/ad/dpc/cd/dch-historia-incosur.PDF women and their newborns. Barcelona: Generalitat de 3. Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet. Catalunya; 2010. Available from: https://scientiasalut. 2010;375(9723):1388-402. https://doi.org/10.1016/S0140- gencat.cat/bitstream/handle/11351/1173/protocol_cribratge_ 6736(10)60061-X PMID: 20399979 diagnostic_malaltia_chagas_embarassades_2010_ang.pdf 4. Prata A. Clinical and epidemiological aspects of Chagas 21. A Bayón Rueda, R Borrás Salvador, E Calabuig Muñoz, MT Fraile disease. Lancet Infect Dis. 2001;1(2):92-100. https://doi. Fariña, MJ Giménez Martí, E Montesinos Sanchis, Elena, et al. org/10.1016/S1473-3099(01)00065-2 PMID: 11871482 Enfermedad de Chagas importada: protocolo de actuación en 5. Pinazo MJ, Lacima G, Elizalde JI, Posada EJ, Gimeno F, Aldasoro la Comunitat Valenciana. [Imported Chagas Disease. Protocol E, et al. Characterization of digestive involvement in patients of actions in the Valencian Community]. Valencia: Conselleria with chronic T. cruzi infection in Barcelona, Spain. PLoS Negl de Sanitat. Generalitat Valenciana; 2009. Spanish. Available Trop Dis. 2014;8(8):e3105. https://doi.org/10.1371/journal. from: http://publicaciones.san.gva.es/publicaciones/ pntd.0003105 PMID: 25144648 documentos/V-5243-2008.pdf 6. Muñoz J, Gómez i Prat J, Gállego M, Gimeno F, Treviño B, López- 22. Autonomous Government of Galicia. Protocolo de cribado da Chejade P, et al. Clinical profile of Trypanosoma cruzi infection enfermidade de Chagas en mulleres embarazadas. [Chagas in a non-endemic setting: immigration and Chagas disease disease screening protocol in pregnant women]. Santiago de in Barcelona (Spain). Acta Trop. 2009;111(1):51-5. https://doi. Compostela: Xunta de Galicia; 2014. Spanish. Available from: org/10.1016/j.actatropica.2009.02.005 PMID: 19426663 https://www.sergas.es/Asistencia-sanitaria/Protocolo-de- cribado-da-enfermidade-de-chagas-en-mulleres-embarazadas- 7. Schmunis GA, Yadon ZE. Chagas disease: a Latin American Actualizacion-2014 health problem becoming a world health problem. Acta Trop. 2010;115(1-2):14-21. https://doi.org/10.1016/j. 23. Bartoloni A, Strohmeyer M, Mantella A, Zammarchi L, actatropica.2009.11.003 PMID: 19932071 Trotta M, Rossolini GM, et al. Programma regionale per la prevenzione e il controllo della malattia di Chagas 8. Basile L, Jansa JM, Carlier Y, Salamanca DD, Angheben A, congenita: indicazioni per l’assistenza in gravidanza. Bartoloni A, et al. Chagas disease in European countries: [Regional program for the prevention and control of the challenge of a surveillance system. Euro Surveill. congenital Chagas disease: indications for assistance 2011;16(37):19968. PMID: 21944556 during pregnancy]. Firenze: Regione Toscana; 2012. 9. Requena-Méndez A, Aldasoro E, de Lazzari E, Sicuri E, Brown Italian. Available from: http://www.regione.toscana.it/ M, Moore DA, et al. Prevalence of Chagas disease in Latin- documents/10180/13329059/Allegato+parere+n.+46- American migrants living in Europe: a systematic review and 2015+Prev+e+conrollo+malattia+di+Chagas. meta-analysis. PLoS Negl Trop Dis. 2015;9(2):e0003540. pdf/6e153700-0d7b-4d70-b098-faba975c6de8?version=1.0 https://doi.org/10.1371/journal.pntd.0003540 PMID: 24. Martinez de Tejada B, Jackson Y, Paccolat C, Irion OGroupe 25680190 Chagas Congénital Genéve. [Congenital Chagas disease in 10. Howard EJ, Xiong X, Carlier Y, Sosa-Estani S, Buekens P. Geneva: diagnostic and clinical aspects]. Rev Med Suisse. Frequency of the congenital transmission of Trypanosoma 2009;5(222):2091-2, 2094-6. French. PMID: 19947451 cruzi: a systematic review and meta-analysis. BJOG. 25. Rodari P, Angheben A, Gennati G, Trezzi L, Bargiggia G, Maino 2014;121(1):22-33. https://doi.org/10.1111/1471-0528.12396 M, et al. Congenital Chagas disease in a non-endemic area: PMID: 23924273 Results from a control programme in Bergamo province, 11. Requena-Méndez A, Albajar-Viñas P, Angheben A, Chiodini Northern Italy. Travel Med Infect Dis. 2018;25:31-4. https:// P, Gascón J, Muñoz J, et al. Health policies to control Chagas doi.org/10.1016/j.tmaid.2018.04.011 PMID: 29680285 disease transmission in European countries. PLoS Negl Trop 26. Merino FJ, Martínez-Ruiz R, Olabarrieta I, Merino P, García- Dis. 2014;8(10):e3245. https://doi.org/10.1371/journal. Bujalance S, Gastañaga T, et al. [Control of Chagas disease pntd.0003245 PMID: 25357193 in pregnant Latin-American women and her children]. Rev Esp 12. Oliveira I, Torrico F, Muñoz J, Gascon J. Congenital transmission Quimioter. 2013;26(3):253-60. Spanish. PMID: 24080893 of Chagas disease: a clinical approach. Expert Rev Anti Infect 27. Institut d’Estadística de Catalunya. [Statistical Institute of Ther. 2010;8(8):945-56. https://doi.org/10.1586/eri.10.74 Catalonia]. Població estrangera resident a Catalunya segons PMID: 20695749 la seva nacionalitat 2016. [Foreign population resident in 13. Carlier Y, Torrico F, Sosa-Estani S, Russomando G, Luquetti A, Catalonia by nationality]. Barcelona: Generalitat de Catalunya. Freilij H, et al. Congenital Chagas disease: recommendations [Accessed: 13/06/2019]. Catalan. Available from: http://www. for diagnosis, treatment and control of newborns, siblings idescat.cat/poblacioestrangera/ and pregnant women. PLoS Negl Trop Dis. 2011;5(10):e1250. 28. Agència de Salut Pública de Catalunya. [Public Health https://doi.org/10.1371/journal.pntd.0001250 PMID: 22039554 Agency of Catalonia]. Xifres i dades de salut maternoinfantil 14. Jackson Y, Angheben A, Carrilero Fernandez B, Jansa i Lopez 2018. [Figures and data on maternal and child health 2018]. del Vallado JM, Jannin JG, Albajar-Viñas P. [Management Barcelona: Generalitat de Catalunya. [Accessed: 13 Jun of Chagas disease in Europe. Experiences and challenges 2019]. Catalan. Available from: http://salutpublica.gencat. in Spain, Switzerland and Italy]. Bull Soc Pathol Exot. cat/ca/ambits/promocio_salut/Embaras-part-i-puerperi/ 2009;102(5):326-9. French. PMID: 20131427 Xifres-i-dades/ 15. Ministry of Health. Real Decreto 1088/2005, de 16 de 29. Subdirecció general de vigilància i resposta a emergencies septiembre, por el que se establecen los requisitos técnicos en salut pública, Agència de Salut Pública de Catalunya. y condiciones mínimas de la hemodonación y de los centros [Deputy director of public health surveillance and response y servicios de transfusión. [Royal decree 1088/2005 of to emergencies, Public Health Agency of Catalonia]. Centres September 16 which establishes the technical requirements collaboradors del Programa de prevenció i control de la and minimum conditions of blood donation and of transfusion malaltia de Chagas congènita a Catalunya. [Collaborating centres and services]. Madrid: Ministeri de Sanitat y Consum; Centers of the Congenital Chagas disease Screening Program 2005:31288-304. Spanish. Available from: http://www.boe.es/ in Catalonia]. Barcelona: Generalitat de Catalunya; 2019. boe/dias/2005/09/20/pdfs/A31288-31304.pdf Catalan. Available from: http://canalsalut.gencat.cat/web/. 16. Basile L, Oliveira I, Ciruela P, Plasencia AWorking Group content/_A-Z/C/chagas/arxius/llistatcentres.pdf For Developing The Catalonian Screening Programme For 30. Departament de Salut. [Department of Health]. Decret Congenital Transmission Of Chagas Disease. The current 203/2015, de 15 de setembre, pel qual es crea la Xarxa screening programme for congenital transmission of Chagas de Vigilància Epidemiológica i es regulen els sistemes de disease in Catalonia, Spain. Euro Surveill. 2011;16(38):19972. notificació de malalties de declaració obligatòria i brots https://doi.org/10.2807/ese.16.38.19972-en PMID: 21958532 epidémics. [Decree 203/2015, of September 15, which creates 17. Sicuri E, Muñoz J, Pinazo MJ, Posada E, Sanchez J, Alonso the Epidemiological Surveillance Network and regulates the PL, et al. Economic evaluation of Chagas disease screening reporting systems for compulsory declaration diseases and of pregnant Latin American women and of their infants in a epidemic outbreaks]. Barcelona: Generalitat de Catalunya; non endemic area. Acta Trop. 2011;118(2):110-7. https://doi. 2015. Catalan. Available from: http://dogc.gencat.cat/ca/ org/10.1016/j.actatropica.2011.02.012 PMID: 21396345 14 www.eurosurveillance.org pdogc_canals_interns/pdogc_resultats_fitxa/?action=fitxa&d 46. Martins-Melo FR, Lima M da S, Ramos ANJ Jr, Alencar CH, ocumentId=702922&language=ca_ES Heukelbach J. Prevalence of Chagas disease in pregnant 31. Jané M, Vidal MJ, Tomas Z, Maresma M, Mayoral LK. Indicators women and congenital transmission of Trypanosoma cruzi in of perinatal health in Catalonia 2016. Executive Report. Brazil: a systematic review and meta-analysis. Trop Med Int Barcelona: Sub-directorate General for Epidemiological Health. 2014;19(8):943-57. https://doi.org/10.1111/tmi.12328 Surveillance and Public Health Emergency Response. PMID: 24815954 Secretariat for Public Health; 2018. Available from: http:// 47. Howard EJ, Xiong X, Carlier Y, Sosa-Estani S, Buekens P. canalsalut.gencat.cat/web/.content/_Professionals/ Frequency of the congenital transmission of Trypanosoma Vigilancia_epidemiologica/documents/arxius/Perinatal_ cruzi: a systematic review and meta-analysis. BJOG. Indicator_Catalonia_2016.pdf 2014;121(1):22-33. https://doi.org/10.1111/1471-0528.12396 32. Firth D. Bias reduction of maximum likelihood estimates. PMID: 23924273 Biometrika. 1993;80(1):27-38. https://doi.org/10.1093/ 48. Salas Clavijo NA, Postigo JR, Schneider D, Santalla JA, Brutus biomet/80.1.27 L, Chippaux J-P. Prevalence of Chagas disease in pregnant 33. Muñoz J, Coll O, Juncosa T, Vergés M, del Pino M, Fumado V, et women and incidence of congenital transmission in Santa Cruz al. Prevalence and vertical transmission of Trypanosoma cruzi de la Sierra, Bolivia. Acta Trop. 2012;124(1):87-91. https://doi. infection among pregnant Latin American women attending org/10.1016/j.actatropica.2012.06.012 PMID: 22772023 2 maternity clinics in Barcelona, Spain. Clin Infect Dis. 49. Torrico F, Alonso-Vega C, Suarez E, Rodriguez P, Torrico M-C, 2009;48(12):1736-40. https://doi.org/10.1086/599223 PMID: Dramaix M, et al. Maternal Trypanosoma cruzi infection, 19438393 pregnancy outcome, morbidity, and mortality of congenitally 34. Otero S, Sulleiro E, Molina I, Espiau M, Suy A, Martín-Nalda infected and non-infected newborns in Bolivia. Am J Trop A, et al. Congenital transmission of Trypanosoma cruzi Med Hyg. 2004;70(2):201-9. https://doi.org/10.4269/ in non-endemic areas: evaluation of a screening program ajtmh.2004.70.201 PMID: 14993634 in a tertiary care hospital in Barcelona, Spain. Am J Trop 50. Luquetti AO, Tavares SB, Siriano LR, Oliveira RA, Campos DE, Med Hyg. 2012;87(5):832-6. https://doi.org/10.4269/ de Morais CA, et al. Congenital transmission of Trypanosoma ajtmh.2012.12-0152 PMID: 22987653 cruzi in central Brazil. A study of 1,211 individuals born to 35. Alonso-Vega C, Billot C, Torrico F. Achievements and infected mothers. Mem Inst Oswaldo Cruz. 2015;110(3):369-76. challenges upon the implementation of a program for national https://doi.org/10.1590/0074-02760140410 PMID: 25993506 control of congenital Chagas in Bolivia: results 2004-2009. 51. Rodriguez-Guerineau L, Posfay-Barbe KM, Monsonis-Cabedo PLoS Negl Trop Dis. 2013;7(7):e2304. https://doi.org/10.1371/ M, Juncosa-Morros T, Diana A, Wyler-Lazarevic CA, et al. journal.pntd.0002304 PMID: 23875039 Pediatric Chagas disease in Europe: 45 cases from Spain and 36. Barona-Vilar C, Giménez-Martí MJ, Fraile T, González- Switzerland. Pediatr Infect Dis J. 2014;33(5):458-62. https:// Steinbauer C, Parada C, Gil-Brusola A, et al. Prevalence of doi.org/10.1097/INF.0000000000000139 PMID: 24153010 Trypanosoma cruzi infection in pregnant Latin American 52. Russomando G, Cousiño B, Sanchez Z, Franco LX, Nara women and congenital transmission rate in a non-endemic EM, Chena L, et al. Chagas disease: national survey of area: the experience of the Valencian Health Programme seroprevalence in children under five years of age conducted (Spain). Epidemiol Infect. 2012;140(10):1896-903. https://doi. in 2008. Mem Inst Oswaldo Cruz. 2017;112(5):348-53. https:// org/10.1017/S0950268811002482 PMID: 22129521 doi.org/10.1590/0074-02760160407 PMID: 28443980 37. Avila Arzanegui O, Liendo Arenaza P, Martinez Indart L, 53. Fumadó V, Juncosa T, Posada E, Fisa R, Gállego M, Gascón Martinez Astorkiza T, Pocheville Guruceta MI, Egurbide Arberas J. [Paediatric Chagas in a non-endemic area.] Enferm Infecc MV. [Prevalence of Trypanosoma cruzi infection and vertical Microbiol Clin. 2014;32(5):293-6. Spanish. https://doi. transmission in Latin-American pregnant women in a health org/10.1016/j.eimc.2013.04.024 PMID: 24491481 area of Biscay.] Enferm Infecc Microbiol Clin. 2013;31(4):210-6. 54. Virreira M, Torrico F, Truyens C, Alonso-Vega C, Solano Spanish. https://doi.org/10.1016/j.eimc.2012.01.029 PMID: M, Carlier Y, et al. Comparison of polymerase chain 22621813 reaction methods for reliable and easy detection of 38. Flores-Chavez MD, Merino FJ, Garcia-Bujalance S, Martin- congenital Trypanosoma cruzi infection. Am J Trop Med Rabadan P, Merino P, Garcia-Bermejo I, et al. Surveillance of Hyg. 2003;68(5):574-82. https://doi.org/10.4269/ Chagas disease in pregnant women in Madrid, Spain, from ajtmh.2003.68.574 PMID: 12812349 2008 to 2010. Euro Surveill. 2011;16(38):19974. https://doi. 55. Schijman AG, Bisio M, Orellana L, Sued M, Duffy T, Mejia org/10.2807/ese.16.38.19974-en PMID: 21958533 Jaramillo AM, et al. International study to evaluate PCR 39. Muñoz-Vilches MJ, Salas J, Cabezas T, Metz D, Vázquez J, methods for detection of Trypanosoma cruzi DNA in blood Soriano MJ. [Chagas screening in pregnant Latin-American samples from Chagas disease patients. PLoS Negl Trop Dis. women. Experience in Poniente Almeriense (Almeria, Spain)]. 2011;5(1):e931. https://doi.org/10.1371/journal.pntd.0000931 Enferm Infecc Microbiol Clin. 2012;30(7):380-2. Spanish. PMID: 21264349 https://doi.org/10.1016/j.eimc.2011.11.012 PMID: 22277372 56. Bua J, Volta BJ, Perrone AE, Scollo K, Velázquez EB, Ruiz AM, 40. Ramos JM, Milla A, Rodríguez JC, López-Chejade P, Flóres M, et al. How to improve the early diagnosis of Trypanosoma Rodríguez JM, et al. Chagas disease in Latin American pregnant cruzi infection: relationship between validated conventional immigrants: experience in a non-endemic country. Arch diagnosis and quantitative DNA amplification in congenitally Gynecol Obstet. 2012;285(4):919-23. https://doi.org/10.1007/ infected children. PLoS Negl Trop Dis. 2013;7(10):e2476. s00404-011-2081-9 PMID: 21927962 https://doi.org/10.1371/journal.pntd.0002476 PMID: 24147166 41. Russomando G, Almirón M, Candia N, Franco L, Sánchez Z, 57. Abras A, Muñoz C, Ballart C, Berenguer P, Llovet T, Herrero de Guillen I. [Implementation and evaluation of a locally M, et al. Towards a new strategy for diagnosis of congenital sustainable system of prenatal diagnosis to detect cases of Trypanosoma cruzi infection. J Clin Microbiol. 2017;55(5):1396- congenital Chagas disease in endemic areas of Paraguay]. Rev 407. https://doi.org/10.1128/JCM.02248-16 PMID: 28202792 Soc Bras Med Trop. 2005;38(Suppl 2):49-54. Spanish. PMID: 58. Volta BJ, Perrone AE, Rivero R, Scollo K, Bustos PL, Bua J. Some 16482814 limitations for early diagnosis of congenital Chagas infection 42. Kolliker-Frers RA, Insua I, Razzitte G, Capani F. Chagas by PCR. Pediatrics. 2018;141(Suppl 5):S451-5. https://doi. disease prevalence in pregnant women: migration and risk of org/10.1542/peds.2016-3719 PMID: 29610170 congenital transmission. J Infect Dev Ctries. 2016;10(9):895- 59. Schijman AG, Altcheh J, Burgos JM, Biancardi M, Bisio M, Levin 901. https://doi.org/10.3855/jidc.7118 PMID: 27694720 MJ, et al. Aetiological treatment of congenital Chagas’ disease 43. Castellanos-Domínguez YZ, Cucunubá ZM, Orozco LC, diagnosed and monitored by the polymerase chain reaction. Valencia-Hernández CA, León CM, Florez AC, et al. Risk J Antimicrob Chemother. 2003;52(3):441-9. https://doi. factors associated with Chagas disease in pregnant women org/10.1093/jac/dkg338 PMID: 12917253 in Santander, a highly endemic Colombian area. Trop Med Int 60. Álvarez MG, Vigliano C, Lococo B, Bertocchi G, Viotti R. Health. 2016;21(1):140-8. https://doi.org/10.1111/tmi.12634 Prevention of congenital Chagas disease by Benznidazole PMID: 26578246 treatment in reproductive-age women. An observational 44. Apt W, Zulantay I, Arnello M, Oddó D, González S, Rodríguez J, study. Acta Trop. 2017;174:149-52. https://doi.org/10.1016/j. et al. Congenital infection by Trypanosoma cruzi in an endemic actatropica.2017.07.004 PMID: 28720492 area of Chile: a multidisciplinary study. Trans R Soc Trop Med 61. Fabbro DL, Danesi E, Olivera V, Codebó MO, Denner S, Heredia Hyg. 2013;107(2):98-104. https://doi.org/10.1093/trstmh/ C, et al. Trypanocide treatment of women infected with trs013 PMID: 23222947 Trypanosoma cruzi and its effect on preventing congenital 45. Carrera Vargas C, Narváez AO, Muzzio Aroca J, Shiguango G, Chagas. PLoS Negl Trop Dis. 2014;8(11):e3312. https://doi. Robles LM, Herrera C, et al. Seroprevalence of Trypanosoma org/10.1371/journal.pntd.0003312 PMID: 25411847 cruzi infection in schoolchildren and in pregnant women 62. Murcia L, Simón M, Carrilero B, Roig M, Segovia M. Treatment from an Amazonian region in Orellana Province, Ecuador. Am of infected women of childbearing age prevents congenital J Trop Med Hyg. 2015;93(4):774-8. https://doi.org/10.4269/ Trypanosoma cruzi infection by eliminating the parasitemia ajtmh.14-0807 PMID: 26283751 detected by PCR. J Infect Dis. 2017;215(9):1452-8. https://doi. org/10.1093/infdis/jix087 PMID: 28201741 www.eurosurveillance.org 15 63. Soriano-Arandes A, Basile L, Ouaarab H, Clavería I, Gómez i Prat J, Cabezos J, et al. Controlling congenital and paediatric chagas disease through a community health approach with active surveillance and promotion of paediatric awareness. BMC Public Health. 2014;14(1):1201. https://doi. org/10.1186/1471-2458-14-1201 PMID: 25416081 License, supplementary material and copyright This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) Licence. You may share and adapt the material, but must give appropriate credit to the source, provide a link to the licence and indicate if changes were made. Any supplementary material referenced in the article can be found in the online version. This article is copyright of the authors or their affiliated in- stitutions, 2019. 16 www.eurosurveillance.org