Urban Chagas disease in children and women in primary care centres in Buenos Aires, Argentina

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1 644 Mem Ist Oswaldo Cruz, Rio de Jaeiro, Vol. 110(5): , August 2015 Urba Chagas disease i childre ad wome i primary care cetres i Bueos Aires, Argetia Guillermo Moscatelli 1 / +, Ada Berestei 2, Aa Tarlovsky 3, Susaa Siiawski 2, Miguel Biacardi 1, Griselda Ballerig 1, Samata Moroi 1, Marta Schwarcz 4, Susaa Herádez 4, Facudo García-Bourisse 1, Adrés Espejo Cozzi 4, Héctor Freilij 1, Jaime Altcheh 1 1 Ricardo Gutiérrez Childre s Hospital, Departmet of Parasitology ad Chagas, Bueos Aires, Argetia 2 Primary Care Cetre, Commuity Actio Cetre 15, Bueos Aires, Argetia 3 Primary Care Cetre, Commuity Actio Cetre 11, Bueos Aires, Argetia 4 Iteramerica Ope Uiversity, Cetre of Studies o Huma Sciece ad Health, Bueos Aires, Argetia The primary objective of this study was to estimate the prevalece of this disease i wome of childbearig age ad childre treated at health cetres i uderserviced areas of the city of Bueos Aires. Demographic ad Chagas disease status data were collected. Samples for Chagas disease serology were obtaied o filter paper ad the reactive results were cofirmed with covetioal samples. A total of 1,786 subjects were screeed ad 73 positive screeig results were obtaied: 17 were from childre ad 56 were from wome. The Trypaosoma cruzi ifectio risk was greater i those idividuals who had relatives with Chagas disease, who remember seeig kissig bugs, who were of Bolivia atioality or were bor i the Argetie provice of Satiago del Estero. The overall prevalece of Chagas disease was 4.08%. Due to migratio, Chagas disease is curretly predomiatly urba. The observed prevalece requires health programme activities that are aimed at urba childre ad their mothers. Most childre were ifected cogeitally, which reiforces the eed for Chagas disease screeig of all pregat wome ad their babies i Argetia. The active search for ew cases is importat because the appropriate treatmet i childre has a high cure rate. Key words: Trypaosoma cruzi - Chagas disease - cogeital trasmissio - prevalece - epidemiology - treatmet The epidemiological profile of Chagas disease has chaged. Curretly, vector trasmissio is partially cotrolled i may Souther Coe coutries (Segura et al. 1999). I Argetia, the provices of Jujuy, La Pampa, Rio Negro, Neuqué, Etre Ríos, Sata Fe ad Sa Luis ad Misioes have cotrolled domestic vector trasmissio (MSAL 2014). At preset, most of the ew cases occur i urba areas through cogeital trasmissio (Altcheh 2010). However, few studies have reported this iformatio (Luluaga & Lazzari 2002). Accordig to the 2010 Argetie cesus data, 53.3% of Argetia s populatio lives i the city of Bueos Aires ad i the provice of Bueos Aires, which explais why the largest umber of ifected cases resides i this area. The city of Bueos Aires is also the focus of a sigificat migratory flow from coutries with high ifectio rates, such as Bolivia, Paraguay ad Peru (INDEC 2010). No vectorial trasmissio is preset i the city of Bueos Aires. Primary Health Care ad Commuity Actio Cetres (CESACs) are part of the structure of the Primary Health Care of city of Bueos Aires ad are composed of multidiscipliary teams that serve primarily low-icome doi: / Fiacial support: Foudatio Buge & Bor, AJ Roemmers Foudatio, Ricardo Gutiérrez Childre s Hospital + Correspodig author: gfmoscatelli@yahoo.com.ar Received 17 March 2015 Accepted 3 July 2015 populatios, which iclude a large umber of migrats from the orth of Argetia ad eighbourig coutries. This populatio profile suggests a high probability of discoverig Trypaosoma cruzi-ifected wome ad potetial sources of ew cogeital cases. The primary objective of this study was to estimate the prevalece of Chagas disease i wome of childbearig age ad childre see at CESAC i uderserviced areas of the city of Bueos Aires. SUBJECTS, MATERIALS AND METHODS Betwee Jue 2005-April 2007, a multicetre crosssectioal prevalece study was performed i CESAC 11 (Balvaera eighbourhood) ad CESAC 15 (Sa Telmo eighbourhood) ad, from December 2006-December 2009, i CESAC Los Piletoes (Villa Soldati eighbourhood). The target populatio of these cetres icluded approximately 170,000 people i CESAC 11, 55,000 people i CESAC 15 ad 4,000 i Los Piletoes. Iclusio criteria - Childre > 1 year old ad wome aged years old. Coveiece samplig was coducted from groups who atteded the CESACs for healthy child visits. All of the patiets were asked to sig a writte iformed coset form. Exclusio criteria - Subjects who were ot residets i the catchmet area of the CESAC (i.e., did ot reside i the city of Bueos Aires) ad parets who did ot uderstad the ature, purpose ad possible cosequeces of the study. The subjects were erolled i the study usig the followig strategy: a iformative workshop o Chagas disease olie memorias.ioc.fiocruz.br

2 Urba Chagas disease Guillermo Moscatelli et al. 645 was performed weekly i waitig rooms i the CESACs ad the study protocol was explaied at that momet. The target populatio was ivited to participate. Demographic data were collected, icludig the erolled patiet s age, origi, place of birth, travel history ad family structure. Diagostic studies ad treatmet - Diagostic criteria - The subjects were cosidered ifected with Chagas disease whe two serological techiques for filter paper were reactive. Validatio of the dry blood spot serological method (Zicker et al. 1990, Palacios et al. 2000) - Blood samples for serological screeig were obtaied o filter paper (Schleicher & Schuell o. 903 ad 595). From each subject, six drops of blood were obtaied via figer prick. At the time of aalysis, 2.8 cm 2 of the paper was eluted with 125 µl of salie for 12 h at 4ºC (Altcheh 2010). The eluates were aalysed with idirect haemagglutiatio (IHA) (Polychaco Lab, Argetia) ad ELISA tests (Wieer Lab, Argetia). Briefly, samples from 75 subjects from the Departmet of Parasitology ad Chagas, Bueos Aires Childre s Hospital were aalysed usig covetioal serology ad dry blood spot methods. Fifty-six samples were from patiets with T. cruzi ifectio cofirmed via covetioal serology testig ad 19 samples were from oifected patiets. Based o the validatio results ad from previously published data o the method (Zicker et al. 1990, Palacios et al. 2000), the followig cut off values were chose for screeig with the filter paper method: IHA 1/8 dilutios, ELISA R 0.8 (R = optic desity of the simple/optic desity of the egative cotrol). Compariso of the dry blood spot techique vs. traditioal techiques showed a sesitivity of 96.6% [95% cofidece iterval (CI) ], a specificity of 73.7% (95% CI ), a positive predictive value of 91.5% (95% CI ) ad a egative predictive value of 87.5% (95% CI ). Additioally, the likelihood ratio was A cogeital ifectio was cosidered i idividuals bor from ifected mothers with T. cruzi ifectio who had two reactive serological tests ad had ot received trasfusios or travelled to a edemic area. I childre ad wome who were ifected, a study of the family was requested. Ifected childre were treated with 5-8 mg bezidazole (BZ)/kg/day i two doses for 60 days. Ifected adult patiets were referred to adult parasitology cetres for further evaluatio ad treatmet. Statistical aalysis - The cliical, epidemiological ad serological data were recorded ad aalysed usig Epi Ifo CDC. To estimate the Chagas disease prevalece, the proportio of childre ad wome who had two positive serological techiques was calculated. We compared the proportio of cases for each qualitative variable usig a chi square test ad Studet s t test was utilised for cotiuous variables. Uivariate regressio aalyses were performed to establish the relatioship betwee positive serological ad explaatory variables. Sample size calculatio - Cosiderig a estimated prevalece of 2.5% with a error of 30% ad a 95% CI, 1,500 subjects were required, cosiderig a 20% rejectio. Ethics - The Ethical ad Research Review Boards of the Ricardo Gutierrez Childre s Hospital approved the study. Writte iformed coset was required from the patiets legal represetatives, as well as asset from the patiets as appropriate. RESULTS Populatio - A total of 1,786 subjects were icluded i the study. The mea age was 19.2 years (rage 1-40 years), 73% were uder 20 years of age ad 68.6% were female. More tha half of the subjects (58.7%) were of Argetie origi, followed by atives of Bolivia, Peru ad Paraguay (Table I). All of the patiets resided i the city of Bueos Aires. Oly 56.1% of the subjects had a history of travel to edemic areas of Argetia or eighbourig coutries. The edemic areas that were visited icluded Argetia (50.1%), Bolivia (21.7%), Paraguay (15.6%), Peru (9.5%), Brazil (< 2%), Uruguay (< 2%) ad Chile (< 2%). Twety-six per cet of patiets reported havig see kissig bugs ad 6.4% had received trasfusios. TABLE I Hometow of childre ad wome i the study Coutry CESAC 11 ( = 380) CESAC 15 ( = 608) Los Piletoes ( = 798) Total ( = 1,786) (%) Argetia ,049 (58.7) Bolivia (17) Peru (12.4) Paraguay (10) Uruguay (0.8) Brazil (0.4) Chile (0.2) Otros (0.2) CESAC: Commuity Actio Cetre.

3 646 Mem Ist Oswaldo Cruz, Rio de Jaeiro, Vol. 110(5), August 2015 Twety per cet had relatives with Chagas disease ad this percetage icreased to 49.3% i ifected patiets. A total of 82.9% of the subjects mothers lived i orther Argetia or eighbourig coutries; i ifected subjects this percetage rose to 94.5%. Results of the Chagas serology testig - Study results o filter paper - A total of 1,786 blood samples were collected for screeig (o filter paper): 380 from CESAC 11, 608 from CESAC 15 ad 798 from CESAC Los Piletoes. Screeig was reactive i 73 subjects (4.1%). Accordig to the age groups, we observed that the higher the age, the higher the prevalece (Table II) Data from ifected childre ad wome - Of the 73 reactive subjects, 17 were childre ad 56 were wome (Fig. 1) Their average age was 27.7 years (iterquartile rage ). The ifected patiets were from Bolivia (42.5%), Argetia (41.1%) ad Paraguay (16.4%). The patiets from Argetia were from Bueos Aires (33.3%), Satiago del Estero (13.3%) ad Salta (13.3%). The majority (76.7%) had a history of travel to edemic areas (Bolivia 48.9%, Argetia 36.2% ad Paraguay 14.9%), with 61.7% visitig rural areas. Half of the patiets recalled seeig the vector (kissig bugs) ad 9.5% had received trasfusios. Approximately half of the patiets (51.4%) reported havig relatives with Chagas disease. The followig factors were associated with a greater risk of T. cruzi ifectio: havig a relative with Chagas, havig see kissig bugs or beig bor i Satiago del Estero (Argetia) (Table III). Study of the family group - We studied 18 idividuals from eight families with positive cases; as a result, we idetified six ew positive cases (Fig. 1). Two cases were childre (4 ad 10 years old) who were bor i Bueos Aires to mothers with Chagas disease who had ot received trasfusios or travelled to edemic areas. Therefore, we assume that the route of ifectio was cogeital i both cases. Treatmet - All of the reactive childre were recalled ad a secod blood sample was obtaied via veipucture to cofirm the ifectio (Fig. 2) These TABLE II Prevalece by fractios rages a Age (years) Reactive (%) (0.36) (1.64) (5.26) (4.46) (10.08) (4.28) Total 73 1,786 (4.08) a: childre ad wome icluded. Fig. 1: patiets with both positive techiques by filter paper. samples were cosidered reactive whe the IHA titres were 1/16 ad the ELISA R 1.2. Five-8 mg BZ/kg/day was prescribed. All completed 60 days with good tolerace, presetig a steady decrease or disappearace of specific T. cruzi atibodies. The ifected adults were referred for follow-ups to hospitals i the area of the CESACs. DISCUSSION To develop ad implemet effective itervetios to cotrol Chagas disease trasmissio ad establish a effective surveillace system, particularly i paediatric patiets, it is ecessary to broade the kowledge regardig the T. cruzi epidemiology ad ifectio risk factors. Migratory pheomea have geerated a major chage i the epidemiological Chagas disease profile (Moscatelli et al. 2013). Accordig to the 2010 Argetie cesus, 550,713 Paraguayas, 345,272 Bolivias ad 157,514 Peruvias live i Argetia. Compared with the 2001 cesus, there was a marked icrease i the arrival of immigrats from Bolivia, Paraguay ad Peru to city of Bueos Aires ad the greater Bueos Aires area. The largest icrease i the umber of foreig immigrats i city of Bueos Aires sice 2001 was observed i the Flores, Lugao ad Retiro eighbourhoods. These eighbourhoods coicide with the areas covered by the cetres participatig i the study (INDEC 2010). We observed that 41.3% of the subjects i the study were immigrats, mostly from Bolivia, Paraguay ad Peru. This pheomeo was also observed i oedemic coutries, such as Australia, Caada, Spai ad the Uited States of America (Schmuis 2007). Most of our study subjects were female adolescets, which coicided with the 2010 cesus data that showed a high proportio of youg wome amogst the reported immigrats. The high birth rate of the populatio helps explai the cogeital case icrease i our coutry i recet years. It was estimated that betwee 1,000-1,300 ifected childre are bor i Argetia every year (MSAL 2010).

4 Urba Chagas disease Guillermo Moscatelli et al. 647 TABLE III Risk factors for ifectio with Trypaosoma cruzi i the subjects studied Risk factors + /ifected () Risk factors + /ot ifected () Odds ratio (CI 95%) p Female sex 58/73 1,236/1, ( ) Travel to edemic area 55/71 931/1, ( ) Travel to rural area 28/47 480/ (0.6-2) Seeig kissig bugs 37/73 300/1, ( ) < Received trasfusios 7/73 107/1, ( ) Familiar with Chagas 36/73 265/1, ( ) < Bor from a mother who travel to edemic zoe 69/73 1,402/1, ( ) Natioality vs. others Argetia 31/73 1,027/1, ( ) Bolivia 30/73 297/1, ( ) Paraguay 12/73 167/1, ( ) Argetie-bor i Satiago del Estero vs. other provices 5/31 46/1, ( ) < 0.01 CI: cofidece iterval. The majority of the ifected idividuals who were idetified i our study were of Bolivia atioality. I Argetia, the provices with the highest Chagas disease prevalece were the orther provices of Chaco, Satiago del Estero, Formosa, La Rioja, Salta ad Jujuy (MSAL 2014) ad this was reflected i our study populatio. There are few studies that evaluated the T. cruzi ifectio prevalece i city of Bueos Aires, i which the estimated umber of births was 44,796 ad 1.71% were from T. cruzi ifected pregat wome (Spillma et al. 2013). Almost half (41%) of these wome were from Argetia (most were origially bor i the Chaco ad Satiago del Estero provices), 29% were from Bolivia, 18% were from Peru ad 9% were from Paraguay. I our study, we foud a 4.08% Chagas disease prevalece, which icluded the followig risk factors: beig a relative i a family with Chagas, havig see kissig bugs or beig bor i Satiago del Estero (Argetia). We observed a higher prevalece i childre tha what was reported i a 2002 survey of healthy school childre i city of Bueos Aires that showed a prevalece of Fig. 2: populatio surveyed. 0.36% (Luluaga & Lazzari 2002). The almost five-fold differece i the observed prevalece i our study ca be explaied by the characteristics of the erolled populatios, with a high percetage of the migrat populatio beig from edemic areas i our study. The high prevalece foud i our study could be biased because it was coducted i a area of the city with a large compoet of a migrat populatio that was from edemic areas. This study led to the diagosis of seve cogeitally ifected childre, five from the iitial cohort ad two from the active screeig withi family groups of positive subjects for both techiques o filter paper. All of the childre ifected that were treated with BZ had good tolerace ad resposes. This showed that it is importat to diagose ad treat childre with Chagas disease to prevet the developmet of cardiac complicatios ad ew cogeital cases. Give that treatig childre with BZ or ifurtimox has high cure rates with low adverse evets, ulike these treatmets i adults (Altcheh et al. 2011), it should be a public health priority to scree for Chagas disease i pregat wome for further study ad treatmet of their childre if they are ifected (Altcheh et al. 2011). Fially, the (albeit limited) presece of uifected vectors i some areas of the city of Bueos Aires highlights the importace of cotiuous surveillace ad elimiatio efforts to prevet ifectio of the vectors from ifected patiets ad potetial reitroductio of vectorial trasmissio. Due to migratio, as evideced i this study, Chagas disease has become a predomiatly urba disease. The observed ifected subject prevalece rate requires health activities that are aimed at this group of patiets. A ifected idividual that is udiagosed ito adulthood may become a blood door or, i the case of wome, geerate ew potetial cases by trasplacetal tras-

5 648 Mem Ist Oswaldo Cruz, Rio de Jaeiro, Vol. 110(5), August 2015 missio, which may thus help perpetuate the edemic. I migratio cases, the disease may spread to other regios as with the mothers of the subjects who were studied. Progress i the cotrol of vector-bore ad blood i blood baks reiforces the eed to implemet active search programmes for the detectio of pregat wome ad childre with Chagas disease. REFERENCES Altcheh J La efermedad de Chagas a 100 años de su descubrimieto. Arch Arget Pediatr 108: 4-5. Altcheh J, Moscatelli G, Moroi S, García-Bourisse F, Freilij H Adverse evets after the use of bezidazole i ifats ad childre with Chagas disease. Pediatrics 127: e212-e218. INDEC - Istituto Nacioal de Estadística y Cesos Ceso acioal de població, hogares y viviedas, Argetia, Available from: ceso2010.idec.gov.ar/. Luluaga I, Lazzari J Prevalecia de la efermedad de Chagas e escolares de la ciudad de Bueos Aires. Rev Arge Cardiol 70: Moscatelli G, García-Bourisse F, Freilij H, Berestei A, Tarlovsky A, Moroi S, Ballerig G, Biacardi M, Siiawski S, Schwarrcz M, Herádez S, Cozzi AE, Altcheh J Impact of migratio o the occurrece of ew cases of Chagas disease i Bueos Aires city, Argetia. J Ifect Dev Ctries 157: MSAL - Miisterio de Salud de la Nació Argetia Boletí epidemiológico aual Available from: msal.gov.ar/saladesituacio/boleties_epidemiologia/pdfs/bepanual_2010.pdf. MSAL - Miisterio de Salud de la Nació Argetia Programa Nacioal de Chagas. Available from: presa.argetia. ar/2014/08/27/52387-salud-aprobo-u-aumeto-del-accesoetareo-al-tratamieto-por-mal-de-chagas.php. Palacios X, Belli A, Espio A Detectio of atibodies agaist Trypaosoma cruzi i Somoto, Nicaragua, usig idirect ELISA ad IFI o blood samples o filter paper. Rev Paam Salud Publica 8: Schmuis GA Epidemiology of Chagas disease i o-edemic coutries: the role of iteratioal migratio. Mem Ist Oswaldo Cruz 102 (Suppl. I): Segura E, Sosa-Estai S, Esquivel M, Gómez A, Salomo O Cotrol of the trasmissio of Trypaosoma cruzi i Argetia. Medicia (Bueos Aires) 59 (Suppl. 2): Spillma C, Burroe S, Coto H Aálisis de la situació epidemiológica de la efermedad de Chagas e Argetia: avaces e el cotrol, Rev Arget Salud Pública 4: Zicker F, Smith P, Luquetti A, Oliveira O Mass screeig for Trypaosoma cruzi ifectios usig the immuofluorescece, ELISA ad haemagglutiatio test o serum samples ad o blood eluates from filter-paper. Bull World Health Orga 68: