SciELO - Scientific Electronic Library Online

 
vol.21 issue4Carbapenem inactivation, an alternative method to detect carbapenemase type KPC in EnterobacteriaceaBacteremia by Campylobacter fetus subsp. fetus in Colombia: Case Report author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Article

Indicators

Related links

  • On index processCited by Google
  • Have no similar articlesSimilars in SciELO
  • On index processSimilars in Google

Share


Infectio

Print version ISSN 0123-9392

Infect. vol.21 no.4 Bogotá Oct./Dec. 2017

http://dx.doi.org/10.22354/in.v21i4.689 

Artículo de revisión

First Colombian consensus on congenital Chagas and clinical approach for women of child-bearing age diagnosed with Chagas

Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas

Zulma M. Cucunubáa  , Carlos A. Valencia-Hernándeza  , Concepción J. Puertab  , Sergio Sosa-Estanic  , Faustino Torricod  , Jorge Alberto Cortése  , Juan David Ramireza  , Mauricio J. Veraf  , Belkis Xiomara Acostag  1  , Carlos Arturo Álvarezh  1  , Edith Ángel Mulleri  1  , Mauricio Beltránj  1  , María Isabel Bermúdezj  , Maritza Berríoj  , Germán Camacho Morenok  1  , Yeny Zulay Castellanosl  , Ingrid Criollom  1  , Astrid Carolina Flóreza  1  , Patricia Guerra Moralesn  1  , Rafael Antonio Herazoa  1  , Diana Carolina Hernándeza  , Cielo Maritza Leóna  1  , Manuel Medina Camargoo  1  , Mabel MedinaAlfonsoo  1  , Edwin Pachónf  1  , Bernardo Paez Fonsecan  , María Luisa Parrap  1  , Paula X. Paviab  1  , Franklin Roberto Quirózq  1  , Lyda Constanza Ríosl  , Nubia Lucía Roar  1  , Fernando Torresn  1  , Luz Marina Uribe Riveros  1 

1a Red Chagas and Parasitology Group, National Institute of Health, Bogota D.C., Colombia

b Laboratory of Molecular Parasitology, Pontificia Universidad Javeriana, Bogota D.C., Colombia

c National Institute of Parasitology, Mario Fatala Chaben, Buenos Aires, Argentina

d Faculty of Medicine, Universidad Mayor de San Simon, Cochabamba, Bolivia

e Department of Internal Medicine, National University of Colombia, Bogota D.C., Colombia

f Subdirector of Communicable Diseases, Ministry of Social Protection, Bogota D.C., Colombia

g Caprescom Entidad Promotora de Salud, Yopal, Casanare, Colombia

h Faculty of Medicine, Pontificia Universidad Javeriana, Bogota D.C., Colombia

i Department of Obstetrics and Gynecology, National University of Colombia, Bogota D.C., Colombia J National

j Red Nacional de Bancos de Sangre, National Institute of Health, Bogota D.C., Colombia

k Infectology Unit, Hospital de la Misericordia, Bogota D.C., Colombia

l Masters of Epidemiology, Industrial University of Santander, Bucaramanga, Santander, Colombia

m Secretary of Health of Casanare, Yopal, Colombia

n Grupo SaludCoop, Bogota D.C., Colombia

° Secretary of Health of Boyaca, Boyaca, Colombia

p Epidemiological Surveillance Service, Soca & Boyaca Regional Hospital, Colombia

q Cardiovascular Clinical Foundation of Colombia, San Gil, Santander, Colombia

r Clinica de Falla Cardiaca, San Ignacio University Hospital, Bogotá D.C., Colombia

s Secretary of Health of Santander, Bucaramanga, Santander, Colombia

Abstract

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. To generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: «Chagas disease/congenital», «prevention and control», «diagnosis», «therapeutics» and «pregnancy». Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-to-face discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

Resumen

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas con- génito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos Mes (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizo, clasifico y organizo en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Introduction

The congenital transmission of Chagas disease poses a challenge in the control of this parasitic disease, since it not only does it affect endemic countries in Latin America but also non-endemic countries in other continents where, because of migration, there are women of childbearing age carriers of Trypanosoma cruzi1 infection.

Comprehensive care for this disease includes not only early detection and treatment of the newborn or infant, but also new challenges in care and medical guidance for infected women. In Colombia, there is little academic production on this matter. For this reason, the country is an adequate scenario to outline a review of the strategies that have shown efficiency in countries and similar contexts and to discuss the suitability of each of these strategies in the national context. Therefore, this first consensus seeks to integrate experts on issues related to pediatrics, prenatal care and health care system stakeholder’s, daily decisions makers for this this group of women and children, along with experts in Chagas disease, so as to issue recommendations for the care of these populations in Colombia.

Objective of the consensus

To generate a series of recommendations on diagnosis, follow-up and treatment of congenital Chagas and to guide fertile women with Chagas in Colombia.

Clinical Questions answered in the consensus

  • - What is the prevalence of T. cruzi infection in pregnant women in Colombia?

  • - What is the risk of congenital transmission of T.cruzi?

  • - What are the most appropriate tests and procedures for diagnosis of T. cruzi infection in pregnant women and newborns?

  • - What are the recommended drugs for the etiological treatment of Chagas’ disease in newborns and infants?

  • - What are the basic recommendations for the etiological treatment of Chagas disease for fertile women with con- firmed diagnosis?

  • - What are the complementary public health measures for the management of congenital Chagas?

Patients to whom the consensus is addressed

Pregnant women in Colombia, newborns and women of childbearing age.

Consensus Users

Medical services, health care institutions, public health groups at municipal, departmental and national level in Colombia.

Methodology

Review of the bibliography and evaluation of the evidence

Literature search related to epidemiology, transmission, diagnosis, treatment and public health strategies for the vertical transmission of T. cruzi and congenital Chagas from 1980 to April 2013 was performed. The following Algorithms were designed within the Medline information base: («Chagas Disease/congenital»{Mesh}); («Chagas disease/ congenital»Mesh) AND «prevention and control»(Subheading); Chagas disease/congenital»Mesh) AND «Diagnosis» (Mesh) OR («Chagas disease/congenital»{Mesh} AND «Chagas disease/ diagnosis»Mesh); («Chagas disease/ congenital»Mesh) AND «Therapeutics»MeshOR («Chagas disease/ congenital»{Mesh} AND «Chagas disease/ therapy»Mesh) and («Pregnancy»Mesh) AND «Chagas disease»Mesh NOT («Chagas disease/congenital»{Mesh})

It also included the literature submitted by experts and derived from secondary research from other consensus published on the same subject. The bibliography was selected by summaries, after which the full text of the publication was evaluated. Publications with duplicate information were removed from the record for analysis. When the information of the same article was relevant for more than one topic, it was included in several searches. The data extraction from the articles was done by evidence graphs, verifying the data and the ratios reported and, in some cases, the ratios were calculated from the data provided in the text of the articles. The evaluation of each publication is carried out) through the methodology of reporting of observational studies for the evaluation of the evidence (STrengthening the Reporting of Observational studies in Epidemiology STROBE).

Development of expert consensus based on Delphi methodology

The inclusion of experts was based on the recommendations described by McGinis et al.3 Panels of 3 experts per theme were organized for each of the aspects related to decision making for the identification and management of congenital Chagas disease in the areas of: gynecology, pediatrics, infectology or public health, health promotion entities, as well as representatives of the Ministry of Health and departmental health secretariats. In addition, 2 international experts on the specific subject of congenital Chagas participated in the consensus.

The participation of the consultants was administered in 3 rounds, being the first 2 virtual and the last one, face-to- face. These were carried out from December 2012 to May 2013. The questionnaires were sent by electronic mail with hidden carbon copy and reminders for completion. During all the rounds participants were submitted a text with the best available evidence for each topic, accompanied by questions leading to decision making with the patient. During the first round, she asked about general aspects related to epidemiology, diagnosis and clinical guidance for children, pregnant women and women of childbearing age with Chagas disease through 15 questions questionnaire. During the second round, the results of the first round were presented and evidence was included for questions in which there was no consensus in the first round; In addition, 10 more specific questions were included. During the third round, in person, consolidated results of the previous rounds were presented, disagreements were resolved based on the points of view of the experts from each area and the final version of the document was approved. Throughout the process participants could suggest adding other studies to the searches (Figure 1)

Graph 1 Flowchart for the phases of the consensus 

Consensus data analysis

Since the questionnaires were in some cases based on open- ended questions, the responses were analyzed at a qualitative level and similar response groups were organized over the total to establish the percentage agreement. It was considered as a consensus based on a 60% agreement percentage plus the validation of the responses during the third round. In cases where the agreement was below 60%, a new question was drafted related to the same topic in the following round and, if no consensus was reached, it was recorded as a lack agreement (Graph 1).

Table 1 Classification of Degrees of Consensus 

Classification of evidence and formulation of recommendations

The level of evidence and the degrees of recommendation were assessed and cataloged per the Strength of Recommendation Taxonomy (SORT).

Thus, the quality of evidence was classified into three levels: good, limited, and other. Similarly, the recommendations were classified into 3 categories per the quality of the evidence and the degree of consensus (Graph 2).

Graph 2 Classification about the quality of the evidence and level of recommendation contributed by studies, per SORT 

RCT: Randomized Clinical Trials

Results

In total, 545 titles under the algorithms designed were found, the information provided by the researchers and the review of the gray literature. With the reading of the summaries, 172 texts were chosen for full text reading, of which, finally, 81 texts were included to contribute the evidence presented in the 3 rounds questionnaires. The relevant results of each aspect are shown below:

Section 1. Epidemiology

Prevalence of Chagas in women of childbearing age in Colombia

According to estimates by the Pan American Health Organization, the prevalence of Chagas’ disease in Colombia is 437,960 infected and approximately 107,800 women of fertile age (15 to 44 years) suffer from disease4.There is a lack of precise data on the prevalence of infection in women, both in the general population and in areas where Chagas disease is considered endemic. One of the possible reasons for this lack of knowledge is that screening for diseases such as HIV, toxoplasmosis, syphilis and hepatitis B, but not for Chagas disease, is included during mandatory prenatal care 5,6. It is estimated that in Colombia there were 665,499 births in 20117, and, per estimates of the population at risk of transmission (10.5%), it can be reasoned that about 69,877 of these pregnant women lived in endernic areas.

Since there is no information on the prevalence of Chagas disease among pregnant women in the general population, it was decided to consider the prevalence of seropositive individuals in blood bank donors as a reference data to obtain an estimate of the magnitude. However, it is also known that prevalence is usually lower in blood banks8. This would be explained by the selection of healthy patients and the repetitive stimulation of the donation by suitable donors9. There- fore, considering that estimates of reactivity prevalence for IgG. anti-T Cruzi in blood banks vary amongst departments between 0.3 and 0.8% 4,10, it could be gathered that the prevalence in pregnant women is higher than these figures and could be close to 1%.

Prevalence of Chagas’ disease in pregnant women in en- demic populations

A recent study determined that the overall prevalence of T. cruzi infection in pregnant women from 5 endernic departments was 2.7%, as follows for each department: Casanare: 4.0%; Santander: 3,3%; Boyacá: 3.2%; Arauca: 2.1% and Meta 0.2%, while the range among the 63 participating municipalities oscillated between 0.0 and 20.2%11. In addition, a study carried out in 2 municipalities of Boyacá during 2006 and 2007 indicated that the prevalence for Miraflores 4.0% and for Moniquira 2.8%. In conclusion, considering the few local data, it could be estimated that the prevalence of T. cruzi infection in pregnant women in endemic Colombian departments ranges from 2% to 4%, while in some municipalities it may reach 20%.

Magnitude of Congenital Chagas Disease

There is confirmed evidence of the congenital transmission of T. cruzi in at least 9 cases in Colombia. Six of these were diagnosed by blood culture a study about the endemic area of Boyacá 12,13; Another 2 cases were diagnosed in the department of Santander; and a case of a premature newborn (28 weeks) in the department of Caldas, who was diagnosed by thick blood smear and 8 days after birth and died due to the infection before receiving treatment. On the other hand, in acute Chagas outbreaks, 2 cases of pregnant women have been reported: one occurred before 20 weeks’ pregnancy and led to an abortion and the other in Villanueva Bolivar in a 32 weaker, causing the death of the mother and the child.

In terms of population, the Pan American Health Organization estimates that the annual incidence of congenital Chagas congenital in Colombia is 0.104 and causes an average of 1,000 cases per year4. However, there are only two studies in the literature aimed at estimating the magnitude of the problem. The first of one was developed in an endemic area of the department of Boyacá, with a frequency of transmission of 27.3% (6/22) by blood culture, which has been one of the highest frequencies reported in the literature15. In contrast, the second study, per preliminary results, has followed done a follow up of 114 children of seropositive mothers in endemic areas from birth and every 3 months up to 12 months of age, and so far, has not shown the presence of cases with the use of parasitological or serological methods11. Thus, although in Colombia there is evidence of the frequency of transmission of congenital T. cruzi, it is considered that more studies are required and research in grey literature to establish the magnitude of the problem in the country. For now, in the only 2 studies available in Colombia, the frequency of congenital T. cruzi transmission ranges from 0 to 27.3%. Graph 3 summarizes the estimates of transmission rates of congenital Chagas based on data from Colombia and other countries.

Graph 3 

ELISA: Enzyme linked immunosorbent assays; FC: complement fixation test; HAI: Indirect Hemagglutination; HC: blood culture; IgM: immunoglobulin M; IIF (IFI) indirect immunofluorescence; MH: microhematocrit; NA: not applicable; NI: no information; PCR polymerase reaction chain; Stat-Pack immunochromatographic rapid test; XD xeno diagnosis. a: as there were twins. b: historical data from local hospital from 2005-2006

Cost effectiveness of strategies

Some studies of cost-effectiveness of screening in endemic countries such as Chile, 16 and Bolivia17, and in non-endemic countries such as Spain2, indicate a good cost-effectiveness ratio for screening and subsequent follow-up of newborns born to infected mothers and to the women themselves to reduce the burden of disease in both endemic and non-endemic areas compared to not performing the diagnosis. In addition, in other countries, strategies for the active search of cases have been suggested for cases in door to door pregnant women in rural areas difficult to access to improve the coverage of the diagnosis18. Preliminary results from a study in Colombia show that the inclusion of a congenital Chagas’ surveillance program is a cost-effective strategy, being more cost-effective in endemic areas19.

Recommendation 1: Although there is no precise data on the magnitude of Chagas disease in women in pregnant women and newborns in Colombia, estimates suggest that the magnitude is potentially sufficient to consider the inclusion of screening for T. cruzi infection in women during pregnancy as part of the test suite during prenatal control. This strategy would potentially be more cost-effective in areas where the disease is considered endemic. Screening is recommended for pregnant women who have lived in recognized endemic areas or have been in contact with risk factors at any point in life. The most widely recognized risk factors are: knowledge of the “pito” vector, ground floor dwelling, palm roof or bahareque wall located less than 2,000 m above sea level, and having relatives diagnosed Chagas. (perfect Consensus). Level of evidence 3. (Degree of recommendation B).

Section 2. Diagnosis in pregnant women

As for the diagnostic tests for Chagas’ disease in chronic phase, the most appropriate are the serological tests such as the immunoenzymatic test (ELISA) and indirect immunofluorescence (IFI). The reported sensitivity for the ELISA test is 97 to 100%, while its specificity is 96.3 to 100% 20-22. Regarding the IFI test, it is estimated that it has sensitivity from 93.3 to 100% and specificity from 99 to 100% 21,23. These results are like those reported in Colombia from both serum and filter paper samples24. Furthermore, a recent study in Colombia compared the intra-reproducibility of serological tests for identifi- cation of T. cruzi infection in pregnant women (ELISA, IFI and indirect hemagglutination-HAI in serum and ELISA on filter paper). This study concluded that the ELISA reproducibility in serum was 0.98, higher than the reproducibility of the other serological tests and well above the ELISA reproducibility on filter paper, which was 0.5525.

Recommendation 2: ELISA is recommended for serological screening in pregnant women. In a reactive case, confirmation must be made through another conventional serological test with a different principle or with a different antigen, such as IFI or HAI, which has been previously validated in Colombia. (Good consensus). Level of evidence 1. (Level of recom- mendation A).

On the other hand, some researchers have evaluated the usefulness of rapid immunochromatographic tests for chronic Chagas’ screening with good results in both sensitivity and specificity in the general population, with values above 95% 26-30. In Colombia, there is only one evaluation report of the Stat-Pack test in population from 5 to 18 years of age in the department of Casanare, with a sensitivity of 85.4% and specificity of 98% when compared with conventional serological tests and 46.7% when compared to ELISA on filter paper, showing a lower sensitivity in relation to the studies31. A population study of pregnant women from Argentina, Bolivia, Honduras, and Mexico, using umbilical cord blood samples, found that the rapid test on average sensitivity and specificity of 94.6 and 99,0%, respectively, suggesting the use of this test as alternative screening during childbirth32. Finally, some studies show that the sensitivity of rapid tests could be affected using whole blood samples, since sensitivity values increase when serum samples are analyzed33,34. Although there are limitations are identified in terms of reproducibility, in certain regions, rapid tests could be useful in special situations where there is no alternative, by allowing quick decisions.

Recommendation 3. In cases where the pregnant woman is in labor and there is no previous standard serology for T. Cruzi antibodies, an alternative would be the use of rapid test for Chagas on admission to labor. Since the rapid test could have a low sensitivity, in case of a negative result and there are risk factors, the serum test should be administered. A positive test result would lead to the immediate assessment of the newborn, but it will also have to perform confirmatory serological tests on the mother. The use of rapid tests would facilitate the screening strategies; thus, it is necessary to en- courage validation studies in the national and especially rural context. (Good consensus). Level of evidence 2. (Degree of re- commendation B).

Section 3. Diagnosis in the newborn

Microhematocrit in the newborn. This parasitological method of blood concentration from capillaries allows the microscopic identification of T. cruzi in movement, by reading the leukocyte phase in the slide, a procedure that includes the rupture of the capillary. Its main advantage is that it can be performed on the first level settings and requires a low volume of blood, which is ideal for newborns35. In classical studies, it is estimated that the sensitivity of this test varies between 80 and 90%36. Later in Bolivia the so-called modified microhematocrit was introduced, which consists on the direct visualization of the capillary without requiring its rupture, generating better biosafety conditions in the procedure and additionally allowing the estimation of the parasitic load. The quantification of the load has allowed to determine a direct relation of the level of parasitemia, detected by modified microhematocrit, with the severity and lethality of congenital Chagas disease. There is a recent modification to this method called “Eppendorf” micro method, which consists of taking the sample in conical plastic vials (“Eppendorf”) of 1.5 ml, in place of capillaries. This test has shown excellent operational characteristics compared to xenodiagnostics in Argentina. These 3 concentration techniques (microhematocrit, modified microhematocrit modified and “Eppendorf ” micro method) have been widely recommended at international level, as a routine test for the diagnosis of congenital Chagas during the first months of life39. These tests can be performed from cord blood or peripheral blood, having a better performance during the first months of the child’s life and increasing the possibility of detection with the repetition of the test and with an optimal training of the reader40. In Colombia, this method has been used for the diagnosis of acute Chagas in endemic areas and for research of congenital Chagas, in reference centers.

Recommendation 4. It is recommended to carry out concentration parasitological tests (microhematocrit and modi- fied microhematocrit and “Eppendorf ” micro method for the diagnosis of congenital T cruzi infection in the newborn and during the first months of life. (Excellent consensus). Level of evidence 2. (Degree of recommendation B).

Recommendation 5. Given that the performance of the con- centration tests depend to a large extent on the skill of the operator, it is recommended to train health service personnel so they are administered properly, especially in institutions where deliveries take place. (Very good consensus). Level of evidence 2. (Degree of recommendation B).

Serological tests in infants. It is known that serological tests for the detection of anti-T cruzi IgG are useful for the diag- nosis of congenital Chagas only after enough time has elapsed that allows the removal of passive IgG antibodies from the mother, so that the detected antibodies do correspond to the the baby39. According to different investigations, the time for the removal of maternal IgG antibodies varies. While a study in Santa Fe, Argentina, evidenced the elimination of maternal antibodies to at 6 months,41 other investigators have proposed a threshold of 839.,42 or 9 months, 43,44 for the performance of these tests. Finally, there are some proposals to perform the serological tests at month 12 as it coincides with the date of application of vaccines and other public health interventions45. Alternatively, the Shed Acute Phase Antigen (SAPA) antigen, expressed mainly in the acute phase of the disease, has been proposed for the diagnosis in infants as of 3 months of age. This is because anti-SAPA IgG class specific antibodies transferred from the mother to the baby transplacentally are eliminated from the baby between days 30 and 90. Different studies performed using SAPA antigen in an ELISA test showed their potential for the diagnosis of congenital infection. A limitation for the use of this test is the low availability of the antigen.

Recommendation 6. It is recommended that in situations where the initial parasitological tests are negative, the determination of congenital infection by means of conventional T-cruzi anti- IgG serological tests is administered at 8 months of age. Any negative test at that time discards congenital transmission. Any positive test at 8 months should be con- firmed after 10 months by 2 serological tests with different principles. (Very good consensus). Level of evidence 2. (Degree of recommendation B).

PCR: In a Colombian study, the polymerase chain reaction (PCR) displayed a sensitivity of 88.8% and specificity of 92.5% for chronic Chagas’ disease in an adult population50. In addition, other studies in Colombia have shown 80% sensitivity and 100% specificity in adult patients51, it is recommended to take serial samples at different times to increase the likelihood of detecting parasites in the sample. However, there are no local studies that allow to have these estimates about the use of this test for diagnosis of congenital Chagas in Colombia. On the other hand, international publications show that PCR could have a great diagnostic value of the congenital infection and especially the real-time PCR (qPCR) given its: sensitivity higher than that of parasitological tests, early detection of congenital infection, quantitative result (parasite load) and information of epidemiological interest as the determination of lineages of the parasite53-56. However, in the latter years it has been reported that T cruzi DNA can be transferred transplacentally, being able to circulate for a time in the baby without infection and suggesting that the use of the PCR test is should be after 3 months old to avoid false positives57. Despite the potential benefits of the test, it must be considered that it requires a specialized infrastructure and that it is still in the process of standardization and validation in the different laboratories of the endemically countries68,59. Therefore, PCR is not recommended as a routine method for diagnosis33,39.

Recommendation 7. Polymerase chain reaction (PCR) test has shown its potential for the detection of T. cruzi congenital infection. However, this test requires more laboratory infras- tructure than conventional tests and additionally it needs to be validated specifically for the newborn population. On this basis, it is not recommended to incorporate this test into the routine diagnosis until the above criteria are met. (Good consensus). Level of Evidence 2. (Degree of recommendation B).

Section 4. Clinical Manifestations of Congenital Chagas Disease

Between 60 and 90% of cases with congenital Chagas disease may be asymptomatic. Symptoms may appear at an early stage if be it appears during the first 30 days of life, or later, if it appears after this period36. There are no pathognomonic symptoms, but some authors have reported that clinically some of the most severe forms of the disease do not differ greatly from infections of the TORCH group (to- xoplasmosis, rubella, cytomegalovirus, herpes, and others) Such as low birth weight, prematurity, generalized edema, hepatosplenomegaly, respiratory distress and some more severe cases of hydrops fetalis and death 37,60. With regards to the association of prematurity with congenital infection evidence is disparate, as some authors have reported a de- crease in the gestational age of infected infants compared to healthy infants61, there are other investigators who do not find any difference regarding the age at birth between the children of infected and non-infected mothers 48. -hepatomegaly and splenomegaly are among the most commonly reported signs in congenital cases48,60,62 and there are also low frequency symptoms, such as anasarca, petechia, myocardi tis and meningoencephalitis60,62,63. Although the presence of symptoms and signs does not usually reach high percentages, the presence of them should warn the treating physician to the possibility of congenital Chagas57.

Recommendation 8. It is recommended that newborns with clinical signs such as low birth weight, prematurity, respiratory distress, hepatomegaly, splenomegaly, neurological anomalies, cardiomegaly, hydrops fetalis, fetal death and with an epidemiological history associated with T. cruzi infection are discarded the diagnosis of congenital Chagas, using the appropriate technique given the case. (Excellent consensus). Level of evidence 2. (Degree of recommendation A).

Section 5. Etiological treatment of newborns

The effectiveness of the etiological treatment in children with congenital infection during the first year of life is considered to be close to 100%, with disappearance of parasitemia and seronegativization after a few months’ posttreatment. These findings have been consistently published in studies conducted in Paraguay, Argentina53 ’64-66 and Botivia40, 42,45 among others. Thus, the goal of etiological treatment in the baby is clearly the cure, as evidenced by all methods.

Recommendation 9. The efficacy of trypanocides treatment for children with congenital Chagas’ disease is close to 100% before the first year of life and, therefore, etiological treatment at an early stage is recommended for all cases. The criteria for healing is the negative results in parasitological and serological tests. (Very good consensus). Level of evidence

1. (Degree of recognition A).

Per international recommendations and although there are no comparative clinical trials between the two available drugs (benznidazole and nifurtimox), both are used to treat congenital cases39. Recommended dosage is specified in Table 4.

Graph 4 Dosing of etiological treatment for children with congenital Chagas 

Section 6. Etiological treatment of women in child- bearing age

The objectives of etiological treatment are to eliminate infection, reduce parasitic burden and reduce the likelihood of complications and death 67,68. In observational studies there is evidence of the positive effect of etiological treatment on the elimination or reduction of parasitaemia69 and there is some evidence of its effect on the reduction of morbidity and mortality in adult patients treated with benznidazole70-72. To reach the highest levels of evidence, clinical trials such as: Adult Treatment (TRAENA) in Argentina and the Benznidazole Evaluation for Interrupting Trypanosomiasis (BENEFIT) clinical trial are being developed in a multi-centered way in 5 endernic countries74. On its side, the Colombian guideline for the integral treatment of Chagas disease recommends that etiological treatment should be offered to all patients under 18 and, per medical criteria, for adults in the chronic phase6. Therefore, etiological treatment for fertile women is indicated with different levels of evidence and strength of recommendation, being a population that could benefit for it as they are mainly young and asymptomatic.

Moreover, there is increasing evidence of the benefit of etiological treatment in women for prevention of congenital transmission in future pregnancies75. Etiological treatment is clearly contraindicated during pregnancy. During the chronic phase of the disease, it is recommended to postpone the initiation of etiological treatment during nursing, in order not to alter the mother-child bond in the event of adverse effects of the medication on the mother. When prescribed in fertile women, contraception should be provided because trypanocides drugs have teratogenic potential.

Recommendation 10. It is recommended to provide etiological treatment with benznidazole or nifurtimox to fertile women. It is contraindicated during pregnancy and it is recommended to delay the start of treatment until the end of nursing. In all cases, contraception is recommended for fertile women during the administration of etiological treatment for Chagas. (Very good consensus). Level of Evidence 2. (Degree of recommendation B).

Adverse effects of etiological treatment

Etiological treatment with available trypanocides (benznidazole or nifurtimox) may generate some adverse effects; However, these drugs are always better tolerated in children than in adults76. Adverse effects can be well controlled through appropriate symptomatic management and the possibility of rigorous medical follow-up allows the completion of treatment in more than 85% of patients.

Recommendation 11. It is recommended that the patient be informed in advance about the possibility of adverse effects of the etiological treatment of the Chagas disease. It is also recommended that patients receive constant medical follow- up during the treatment period, to promote good adherence to treatment, as well as the end of treatment. (Very good consensus). Level of evidence 2. (Degree of recommendation B).

Section 7. Considerations about activities in the family of the pregnant woman

The recommendation to study the relatives of patients with congenital Chagas ‘disease and pregnant women with Chagas’ disease is widely disseminated39,45,67. Since congenital infection can occur in one or more children of seropositive pregnant women, it is possible that there are children older than the neonate with an undiagnosed congenital infection77. In addition, in a local study in Casanare, Colombia, the prevalence of Chagas disease in relatives of positive pregnant women was 9.8%. Other studies in Argentina have found that being a sibling of a child infected with T. cruzi is a risk factor for acquiring the infection, which indicates that family members should be targeted by screening programs33.

Recommendation 12. Diagnostic activities for the family group of HIV-positive mothers (with emphasis on children) are recommended to confirm other possible cases and en- sure access to treatment and follow-up. (Excellent consensus). (Level of Evidence 1). (Grade of recommendation A).

Recommendation 13. Comprehensive counseling is recommended at the time of diagnosis to both the pregnant woman and her family, with a clear orientation regarding comprehensive treatment and mental health support to minimize the impact of the diagnosis. (Excellent consensus). (Level of Evidence 3). (Degree of recommendation C).

Section 8. Considerations on vector control and other public health measures

Vector control, not only has an impact on the most important transmission route (vectorially), but it is also an indirect control tool for congenital Chagas79 because it reduces the likelihood of new infected mothers or seropositive mothers who have been reinfected, avoiding parasitemias that make mother-child transmission more likely80. Some studies in Bolivia have shown that the children of mothers from areas with higher exposure to reinfection, caused by a higher vector presence, are more likely to have worse outcomes at birth, such as lower birth weight or postpartum complications81. Similar findings in Bolivia confirm that there is less severity of congenital disease in the absence of reinfection of the mother during pregnancy.

Recommendation 14. Home visits for vector control is recommended and sustained surveillance activities in areas where of HIV-positive pregnant women and persons undergoing etiological treatment for Chagas disease are at risk Vector transmission live. (Excellent consensus). Level of evidence 1. (Degree of recommendation A).

Recommendation 15. Given the logistical difficulties of monitoring the mother-child binomial as well as the family back- ground, it is recommended that vector-borne disease control programs integrate efforts and platforms with strategies al- ready in place, such as sexual and reproductive health, indi- genous communities and programs for the care of children. (Excellent consensus). Level of evidence 3. (Degree of recommendation C).

The consensus recommendations are summarized in Figure 2.

As indicators of the implementation of these recommendations, the following are proposed:

  • % of pregnant women with screening tests for T. cruzi infection

  • % of pregnant women with confirmatory tests for T. cruzi infection

  • % of children of HIV-positive mothers with parasitological tests the first month of life

  • % of children of seropositive mothers with serological tests between 9 and 12 months

  • % of children with confirmed diagnosis receiving etiological treatment

Updating process for the consensus

It is suggested to update the consensus every 3 years.

Figure 2: Algorithm recommended by the consensus for diagnostic and treatment of congenital Chagas. 

Potential barriers to implementation of recommendations

There are potential barriers, first, the acceptance of the recommendations by health professionals. Second, the dissemination of recommendations in the national territory. Thirdly, the reforms to the health system that eventually modify the roles of the stakeholders or that limit the opportunity of the processes.

Limitations

In Colombia, there is little information about this topic, since most of the evidence presented comes from studies performed in other Latin American countries. Although the consensus was reached with representatives from all sectors of in health care it did not include patients. In addition, the possible limitations due to health reforms generated or implemented after the consensus was drafted, that modify the itinerary of care and responsibilities of the different stakeholder of the system, are not considered.

Conclusion

The methodology for the elaboration of this consensus is based on the compilation and organization of the abundant international experience, in comparison to domestic experience, to establish common points and potential applications to the Colombian context. The recommendations are based on a collective construction from stakeholders from the scientific, clinical and public health care fields of various levels of care related to decision making in this population group. This consensus constitutes the first effort to generate a tool to base the application of practices in the health system that optimize the opportunity of diagnosis and treatment of people infected with T cruzi, with emphasis on women and children. Additional efforts on the part of the authorities should be carried out to guarantee the dissemination and application of the recommendations in the national territory. Finally, the consensus update should be given once the evidence on new or better procedures is identified.

Acknowledgements

The Consensus Coordinating Group is part of the Pilot Pro- gram for the Surveillance of Congenital Chagas Colombia Colciencias code: 1203-459-21581. This work has the sup- port and sponsorship of the Pan American Health Organi- zation, the Pontificia Universidad Javeriana, the Ministry of Social Protection, the National Institute of Health and the Red Chagas Program (Cont. Colciencias 080-2011). Special acknowledgement to the professionals invited and to the participating institutions.

Bibliography

1. Schmunis GA. Epidemiology of Chagas disease in non endemic countries: The role of international migration. Memorias Inst Oswaldo Cruz. 2007;102:75-86. [ Links ]

2. Sicuri E, Munoz J, Pinazo MJ, Posada E, Sanchez J, Alonso PL, et al. Economic evaluation of Chagas disease screening of pregnant Latin American women and of their infants in a non endemic area. Acta Trop. 2011;118:110-7. [ Links ]

3. McGinnis PQ, Wainwright SF, Hack LM, Nixon-Cave K, Michlovitz S. Use of a Delphi panel to establish consensus for recommended uses of selected balance assessment approaches. Physiother Theory Pract. 2010;26:358-73. [ Links ]

4. OPS. Estimacion cuantitativa de la enfermedad de Chagas en las Americas. 2006 consultado 2 May 2013. Disponible en: http://www.bvsops.org.uy/pdf/chagas19.pdfLinks ]

5. Ministerio de Salud. Resolucion 00412 de 2000 consultado 2 May 2013. Disponible en: http://www.saludcolombia.com/actual/htmlnormas/Res412_00.htm [ Links ]

6. Ministerio de Proteccion Social. Guia colombiana de tratamiento integral de la enfermedad de Chagas 2010 consultado 9 May 2013. Disponible en: http://www.nacer.udea.edu.co/ pdf/libros/guiamps/guias02.pdf [ Links ]

7. Departamento Nacional de Estadistica DANE. Nacimientos por area de ocurrencia y sexo, segan grupos de edad de la madre, total nacional. 2013 consultado 3 May 2013. Disponible en: http://www.dane.gov.co/index.php/poblacion-ydemografia/nacimientos-y-defunciones/118-demograficas/estadisticasvitales/2879-nacimientosLinks ]

8. Sedyaningsih-Mamahit E, Schinaia N, Lazzari S, Walker N, Vercauteren G. The use of blood donor data for HIV surveillance purposes. AIDS. 2004;18:1849-51. [ Links ]

9. Atsma F, Veldhuizen I, Verbeek A, de Kort W, de Vegt F. Healthy donor effect: Its magnitude in health research among blood donors. Transfusion (Paris). 2011;51: 1820-8. [ Links ]

10. Beltran M, Bermudez MI, Forero MC, Ayala M, Rodriguez MJ. Control of Trypanosoma cruzi infection in blood donors in Colombia, 2003. Biomedica. 2005;25:527-32. [ Links ]

11. Cucunuba Z, Valencia C, Florez C, Leon C, Castellanos Y, Cardenas A, et al. Pilot program for surveillance of congenital Chagas disease in Colombia 2010-2011. Int J Infect Dis. 2012;16:e343. [ Links ]

12. Manrique F, Herrera G, Ospina J, Pavia PX, Montilla M, Puerta CJ, et al. Prevalencia de enfermedad de Chagas en maternas e incidencia transplacentaria en Boyaca. Biomedica. 2014;29:315-6. [ Links ]

13. Pavia PX, Montilla M, Florez C, Herrera G, Ospina JM, Manrique F, et al. The first case of congenital Chagas' disease analyzed by AP-PCR in Colombia. Biomedica. 2009;29:513-22. [ Links ]

14. Instituto Nacional de Salud. Grupo ETV. Informe Vigilancia epidemiologica, enfermedad de Chagas. 2011 consultado 3 May 2013. Disponible en: http://www.ins.gov.co/lineasde-accion/Subdireccion-Vigilancia/ Informe%20de%20Evento %20Epidemiolgico/Forms/AllItems.aspx [ Links ]

15. Manrique-Abril F, Ospina JM, Herrera AG, Florez C, Buia CP. Diagn6stico de enfermedad de Chagas en maternas y recien nacidos de Moniquira y Miraflores, Boyaca, Colombia. Infectio. 2013;17:28-34. [ Links ]

16. Castillo Riqueime M, Loayza S, Castillo C, Freile B. Costo-efectividad del screening y tratamiento de mujeres embarazadas y recien nacidos por transmision de Chagas congenito. 2012 consuitado 5 May 2013. Disponible en: http: / /desal. minsal.cl/ DOCUMENTOS/ PDF/2012 /chagas %20congenito.pdfLinks ]

17. Billot C, Torrico F, Cartier Y. Cost effectiveness study of a control program of congenital Chagas disease in Bolivia. Rev Soc Bras Med Trop. 2005;38 Suppi 2:108-13. [ Links ]

18. Romero M, Postigo J, Schneider D, Chippaux J-P, Santalla JA, Brutus L. Door-to-door screening as a strategy for the detection of congenital Chagas disease in rural Bolivia. Trop Med Int Heal TM IH. 2011;16:562-9. [ Links ]

19. Cucunuba Z, Puerta CJ, Florez AC, Valencia CA, Leon C, Pavia PX et al. Informe tecnico final. Proyecto de desarrollo e implementacion de un programa piloto de vigilancia de Chagas congenito en Colombia, Bogota, Colombia; 2013 reporte no publicado. [ Links ]

20. Enciso C, Montilla M, Santacruz MM, Nicholls RS, Rodriguez A, Mercado M, et al. Comparison of the indirect immunofluorescent (IFAT), ELISA test and the comercial Chagatek test for anti-Trypanosoma cruzi antibodies detection. Biomedica. 2004;24:104-8. [ Links ]

21. Malan AK, Aveiar E, Litwin SE, Hill HR, Litwin CM. Serological diagnosis of Trypanosoma cruzi: Evaluation of three enzyme immunoassays and an indirect immunofluorescent assay. J Med Microbiol. 2006;55:171-8. [ Links ]

22. Brasil PEAA, de Castro L, Hassiocher-Moreno AM, Sangenis LHC, Braga JU. ELISA versus PCR for diagnosis of chronic Chagas disease: Systematic review and meta-analysis. BMC Infect Dis. 2010;10:337. [ Links ]

23. De Andrade AQ, Gontijo ED. Neonatal screening for congenital Chagas infection: Application of latent class analysis for diagnostic test evaluation. Rev Soc Bras Med Trop. 2008;41:615-20. [ Links ]

24. Orozco LC, Camargo D, Lopez C, Duque S, Guaidron L, Caceres E. Inmunodiagnostico de la infection en humanos por Trypanosoma cruzi mediante ELISA utilizando sangre recoiectada en papel filtro. Biomedica. 1999;19:164-8. [ Links ]

25. Castellanos YZ, Cucunuba ZM, Florez AC, Orozco-Vargas LC. Reproducibilidad de pruebas serologicas para el diagn6stico de infeccion por Trypanosoma cruzi en gestantes de zona endemica de Santander, Colombia. Biomedica. 2014;34(2). [ Links ]

26. Barfield CA, Barney RS, Crudder CH, Wilmoth JL, Stevens DS, Mora-Garcia S, et al. A highly sensitive rapid diagnostic test for Chagas disease that utilizes a recombinant Trypanosoma cruzi antigen. IEEE Trans Biomed Eng. 2011;58:814-7. [ Links ]

27. Ponce C, Ponce E, Vinelli E, Montoya A, de Aguilar V, Gonzalez A, et al. Validation of a rapid and reliable test for diagnosis of Chagas' disease by detection of Trypanosoma cruzi-specific antibodies in blood of donors and patients in Central America. J Clin Microbiol. 2005;43:5065-8. [ Links ]

28. Lorca M, Contreras MD, Salinas P, Guerra A, Raychaudhuri S. Evaluacion de una prueba rapida para el diagn6stico de la infection por Trypanosoma cruzi en suero. Parasitol Latinoam. 2008;63:29-33. [ Links ]

29. Luquetti AO, Ponce C, Ponce E, Esfandiari J, Schijman A, Revollo S, et al. Chagas' disease diagnosis: A multicentric evaluation of Chagas Stat-Pack, a rapid immunochromatographic assay with recombinant proteins of Trypanosoma cruzi. Diagn Microbiol Infect Dis. 2003;46:265-71. [ Links ]

30. Chappuis F, Mauris A, Hoist M, Aibajar-Vinas P, Jannin J, Luquetti AO, et al. Validation of a rapid immunochromatographic assay for diagnosis of Trypanosoma cruzi infection among Latin-American migrants in Geneva, Switzerland. J Clin Microbiol. 2010;48:2948-52. [ Links ]

31. Florez AC, Gonzalez L, Guasmayan L, Cucunuba ZM, Silva N, Guhl F. Evaluacion del rendimiento de una prueba rapida de diagnostico para la enfermedad de Chagas y estimacion de la seroprevaiencia en escoiares de una zona endemica de Colombia. Ponencia presentada en: XLV Congreso Nacional de Ciencias Biologicas; Octubre 5-8 de 2010. Armenia, Colombia. [ Links ]

32. Sosa-Estani S, Gamboa-Leon MR, del Cid-Lemus J, Aithabe F, Alger J, Aimendares 0, et al. Use of a rapid test on umbilical cord blood to screen for Trypanosoma cruzi infection in pregnant women in Argentina, Bolivia, Honduras, and Mexico. Am J Trop Med Hyg. 2008;79:755-9. [ Links ]

33. Sanchez LV, Ramirez JD. Congenital and oral transmission of American trypanosomiasis: An overview of physiopathogenic aspects. Parasitology. 2013;140:147-59. [ Links ]

34. Roddy P, Goiri J, Fievaud L, Palma PP, Morote S, Lima N, et al. Field evaluation of a rapid immunochromatographic assay for detection of Trypanosoma cruzi infection by use of whole blood. J Clin Microbiol. 2008;46:2022-7. [ Links ]

35. Feilij H, Muller L, Gonzalez Cappa SM. Direct micromethod for diagnosis of acute and congenital Chagas' disease. J Clin Microbiol. 1983;18:327-30. [ Links ]

36. Freilij H, Aitcheh J. Congenital Chagas' disease: Diagnostic and clinical aspects. Clin Infect Dis Off Pubi Infect Dis Soc Am. 1995;21:551-5. [ Links ]

37. Torrico MC, Soiano M, Guzman JM, Parrado R, Suarez E, Alonzo-Vega C, et al. Estimation of the parasitemia in Trypanosoma cruzi human infection: High parasitemias are associated with severe and fatal congenital Chagas disease. Rev Soc Bras Med Trop. 2005;38 Suppi 2:58-61. [ Links ]

38. De Rissio AM, Riarte AR, Garcia MM, Esteva MI, Quaglino M, Ruiz AM. Congenital Trypanosoma cruzi infection. Efficacy of its monitoring in an urban reference health center in a non-endemic area of Argentina. Am J Trop Med Hyg. 2010;82:838-45. [ Links ]

39. Cartier Y, Torrico F, Sosa-Estani S, Russomando G, Luquetti A, Freilij H, et al. Congenital Chagas disease: Recommendations for diagnosis, treatment and control of newborns, siblings and pregnant women. PLoS Negi Trop Dis. 2011;5:e1250. [ Links ]

40. Torrico F, Alonzo-Vega C, Suarez E, Rodriguez P, Torrico M-C, Dramaix M, et al. Endemic level of congenital Trypanosoma cruzi infection in the areas of maternal residence and the development of congenital Chagas disease in Bolivia. Rev Soc Bras Med Trop. 2005;38 Suppi 2:17-20. [ Links ]

41. Streiger M, Fabbro D, del Barco M, Beitramino R, Bovero N. Congenital Chagas disease in the city of Santa Fe. Diagnosis and treatment. Medicina (Mex). 1995;55:125-32. [ Links ]

42. Chippaux JP, Ciavijo AN, Santalla JA, Postigo JR, Schneider D, Brutus L. Antibody drop in newborns congenitally infected by Trypanosoma cruzi treated with benznidazoie. Trop Med Int Heal TM IH. 2010;15:87-93. [ Links ]

43. Bern C, Verastegui M, Gilman RH, Lafuente C, Gaidos-Cardenas G, Calderon M, et al. Congenital Trypanosoma cruzi transmission in Santa Cruz, Bolivia. Clin Infect Dis. 2009;49:1667-74. [ Links ]

44. Mallimaci MC, Sosa-Estani S, Russomando G, Sanchez Z, Sijvarger C, Alvarez IM, et al. Early diagnosis of congenital Trypanosoma cruzi infection, using shed acute phase antigen, in Ushuaia, Tierra del Fuego, Argentina. Am J Trop Med Hyg. 2010;82:55-9. [ Links ]

45. Cartier Y, Torrico F. Congenital infection with Trypanosoma cruzi: From mechanisms of transmission to strategies for diagnosis and control. Rev Soc Bras Med Trop. 2003;36:767-71. [ Links ]

46. Reyes MB, Lorca M, Munoz P, Frasch AC. Fetal IgG specificities against Trypanosoma cruzi antigens in infected newborns. Proc Nati Acad Sci U S A. 1990;87:2846-50. [ Links ]

47. Umezawa ES, Nascimento MS, Kesper Jr N, Coura JR, Borges-Pereira J, Junqueira AC, et al. Immunoblot assay using excreted-secreted antigens of Trypanosoma cruzi in serodiagnosis of congenital, acute, and chronic Chagas' disease. J Clin Microbiol. 1996;34:2143-7. [ Links ]

48. Torrico F, Alonso-Vega C, Suarez E, Rodriguez P, Torrico M-C, Dramaix M, et al. Maternal Trypanosoma cruzi infection, pregnancy outcome, morbidity, and mortality of congenitally infected and non-infected newborns in Bolivia. Am J Trop Med Hyg. 2004;70:201-9. [ Links ]

49. Russomando G, Almiron M, Candia N, Franco L, Sanchez Z, de Gulllen I. Implementation and evaluation of a locally sustainable system of prenatal diagnosis to detect cases of congenital Chagas disease in endemic areas of Paraguay. Rev Soc Bras Med Trop. 2005;38 Suppl 2:49-54. [ Links ]

50. Gil J, Pavia P, Montilla M, Florez AC, Quintero C, Mercado M, et al. Comparison of a PCR test based on the histone H2A/SIRE genes with classical serological tests for the diagnosis of chronic Chagas disease in Colombian patients. Biomedica. 2007;27 Suppl 1:83-91. [ Links ]

51. Ramirez JD, Guhl F, Umezawa ES, MoriIto CA, Rosas F, MarinNeto JA, et al. Evaluation of adult chronic Chagas' heart disease diagnosis by molecular and serological methods. J Clin Microbiol. 2009;47:3945-51. [ Links ]

52. Avila HA, Sigman DS, Cohen LM, Millikan RC, Simpson L. Polymerase chain reaction amplification of Trypanosoma cruzi kinetoplast minicircle DNA isolated from whole blood lysates: Diagnosis of chronic Chagas' disease. Mol Biochem Parasitol. 1991;48:211-21. [ Links ]

53. Diez CN, Manattini S, Zanuttini JC, Bottasso 0, Marcipar I. The value of molecular studies for the diagnosis of congenital Chagas disease in northeastern Argentina. Am J Trop Med Hyg. 2008;78:624-7. [ Links ]

54. Gonzalez-Granado LI, Guillen-Fief G, Rojo-Conejo R In nonendemic areas, is microscopy better than polymerase chain reaction for diagnosis of congenital chagas disease? Clin Infect Dis. 2010;50:279-80, author reply [ Links ]

55. Russomando G, de Tomassone MM, de Gulllen I, Acosta N, Vera N, Almiron M, et al. Treatment of congenital Chagas' disease diagnosed and followed up by the polymerase chain reaction. Am J Trop Med Hyg. 1998;59:487-91. [ Links ]

56. Mora MC, Sanchez Negrette 0, Marco D, Barrio A, Ciaccio M, Segura MA, et al. Early diagnosis of congenital Trypanosoma cruzi infection using PCR, hemoculture, and capillary concentration, as compared with delayed serology. J Parasitol. 2005;91:1468-73. [ Links ]

57. Oliveira I, Torrico F, Munoz J, Gascon J. Congenital transmission of Chagas disease: A clinical approach. Expert Rev Anti Infect Then 2010;8:945-56. [ Links ]

58. Duffy T, Cura CI, Ramirez JC, Abate T, Cayo NM, Parrado R, et al. Analytical performance of a multiplex Real-Time PCR assay using TaqMan probes for quantification of Trypanosoma cruzi satellite DNA in blood samples. PLoS Negl Trop Dis. 2013;7:e2000. [ Links ]

59. Schijman AG, Bisio M, Oreliana L, Sued M, Duffy T, Mejia Jaramillo AM, et al. International study to evaluate PCR methods for detection of Trypanosoma cruzi DNA in blood samples from Chagas disease patients. PLoS Negl Trop Dis. 2011;5: e931. [ Links ]

60. Munoz CV, Thiermann E, Atlas M, Acevedo C. Enfermedad de Chagas congenita sintomatica en recten nacidos y lactantes. Rev Chit Pediatr. 1992;63:196-202. [ Links ]

61. Brutus L, Schneider D, Postigo J, Romero M, Santalla J, Chippaux JP. Congenital Chagas disease: Diagnostic and clinical aspects in an area without vectorial transmission, Bermejo, Bolivia. Acta Trop. 2008;106:195-9. [ Links ]

62. Blanco SB, Segura EL, Cura EN, Chuit R, Tulian L, Flores I, et al. Congenital transmission of Trypanosoma cruzi: An operational outline for detecting and treating infected infants in north- western Argentina. Trop Med Int Heal TM IH. 2000;5:293-301. [ Links ]

63. Shikanai-Yasuda MA, Lopes MH, Tolezano JE, Umezawa E, Amato Neto V, Barreto AC, et al. Acute Chagas' disease: Transmission routes, clinical aspects and response to specific therapy in diagnosed cases in an urban center. Rev Inst Med Trop Sao Paulo. 1990;32:16-27. [ Links ]

64. Burgos JM, Altcheh J, Petrucelli N, Bisio M, Levin MJ, Freilij H, et al. Molecular diagnosis and treatment monitoring of congenital transmission of Trypanosoma cruzi to twins of a triplet delivery. Diagn Microbiol Infect Dis. 2009;65:58-61. [ Links ]

65. Schijman AG, Altcheh J, Burgos JM, Biancardi M, Bisio M, Levin MJ, et al. Aetiological treatment of congenital Chagas' disease diagnosed and monitored by the polymerase chain reaction. J Antimicrob Chemother. 2003;52:441-9. [ Links ]

66. Moya P, Basso B, Moretti E. Congenital Chagas disease in Cordoba. Argentina: Epidemiological, clinical, diagnostic, and therapeutic aspects. Experience of 30 years of follow up. Rev Soc Bras Med Trop. 2005;38 Suppl 2:33-40. [ Links ]

67. Organizacio'n Mundial de la Salud. Control de la enfermedad de Chagas: Segundo informe del Comite de Expertos de la OMS. Ginebra: Organizacion Mundial de la Salud; 2002. [ Links ]

68. Coura JR. Present situation and new strategies for Chagas disease chemotherapy: A proposal. Memorias Inst Oswaldo Cruz. 2009;104:549- [ Links ]

54. 69. Villar JC, Perez JE, Cortes OL, Riarte A, Pepper ML, Guyatt GH. Trypanocidal agents for chronic asymptomatic T. cruzi infections. En: An updated systematic review and meta-analysis. Rio de Janeiro: Memories XVIII International Congress for Tropical Medicine and Malaria; 2012. p. 561. [ Links ]

70. Fabbro de Suasnabar D, Arias E, Streiger M, Piacenza M, Ingaramo M, del Barco M, et al. Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients. Rev Inst Med Trop Sao Paulo. 2000;42:99-109. [ Links ]

71. Viotti R, Vigliano C, Lococo B, Bertocchi G, Petti M, Alvarez MG, et al. Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: A nonrandomized trial. Ann Intern Med. 2006;144:724-34. [ Links ]

72. Viotti R, Vigliano C, Alvarez MG, Lococo B, Petti M, Bertocchi G, et al. Impact of aetiological treatment on conventional and multiplex serology in chronic Chagas disease. PLoS Negl Trop Dis. 2011;5:e1314. [ Links ]

73. Riarte A, Velazquez E, Prado N, Schijman AG, Ramirez JC, de Rissio A. Actualizacion de los estudios con benznidazol: BENEFIT y TRAENA. VIII taller sobre la enfermedad de Chagas importada. Barcelona, Espana. 5 de marzo de 2012 consultado 2 May 2013. Disponible en: http: / /www.isglobal. org/ documents/10179/25254 /VI II+taller+sobre+la+enfermedad+ de+Chagas+importada. pdf/c3abO8f9-d161-412e-b6b0- f7e65c7e0f55 [ Links ]

74. Marin-Neto JA, Rassi Jr A, Avezum Jr A, Mattos AC, Rassi A, Morillo CA, et al. The BENEFIT trial: Testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease. Memorias Inst Oswaldo Cruz. 2009;104 Suppl 1:319-24. [ Links ]

75. Sosa-Estani S, Cura E, Velazquez E, Yampotis C, Segura EL. Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission. Rev Soc Bras Med Trop. 2009;42:484-7. [ Links ]

76. Castro JA, de Mecca MM, Bartel LC. Toxic side effects of drugs used to treat Chagas' disease (American trypanosomiasis). Hum Exp Toxicol. 2006;25:471-9. [ Links ]

77. Zulantay I, Apt W, Ramos D, Godoy L, Valencia C, Molina M, et al. The epidemiological relevance of family study in Chagas disease. PLoS Negl Trop Dis. 2013;7:e1959. [ Links ]

78. Cucunuba ZM, Florez AC, Cardenas A, Pavia P, Montilla M, Aldana R, et al. Prevalence and risk factors for Chagas disease in pregnant women in Casanare, Colombia. Am J Trop Med Hyg. 2012;87:837-42. [ Links ]

79. Wort Health Organization. WHA63.20 Chagas disease: Control and elimination. 2010 consultado 10 May 2013. Disponible en: http: / /www. who.int/neglected_diseases/mediacentre/WHA_ 63.20_Eng.pdf [ Links ]

80. Dias JCP, Coura JR. Cli'nica e terape-utica da doenca de Chagas: Um abordagem pratica para o cli'nico geral. Rio de Janeiro: Editora FIOCRUZ; [ Links ]

1997 81. Torrico F, Vega CA, Suarez E, Tellez T, Brutus L, Rodriguez P, et al. Are maternal re-infections with Trypanosoma cruzi associated with higher morbidity and mortality of congenital Chagas disease? Trop Med Int Health. 2006;11:628-35. [ Links ]

82. Zaidenberg M. Congenital Chagas' disease in the province of Salta, Argentina, from 1980 to 1997. Rev Soc Bras Med Trop. 1999;32:689-95. [ Links ]

83. Contreras S, Fernandez MR, Agliero F, Desse Desse J, Orduna T, Martino 0. Congenital Chagas-Mazza disease in Salta, Argentina. Rev Soc Bras Med Trop. 1999;32:633-6. [ Links ]

84. Basombrio MA, Nasser J, Segura MA, Marco D, Sanchez Negrette 0, Padilla M, et al. The transmission de Chagas disease in Salta and the detection of congenital cases. Medicina (Mex). 1999;59 Suppl 2:143-6. [ Links ]

85. Zaidenberg M, Segovia A. Congenital Chagas disease in the city of Salta, Argentina. Rev Inst Med Trop Sao Paulo. 1993;35:35-43. [ Links ]

86. Arcavi M, Orfus G, Griemberg G. Incidence of Chagas infection in pregnant women and newborn infants in a non-endemic area. Medicina (Mex). 1993;53:217-22. [ Links ]

87. Sanchez Negrette 0, Mora MC, Basombrio MA. High prevalence of congenital Trypanosoma cruzi infection and family clustering in Salta, Argentina. Pediatrics. 2005;115:e668-72. [ Links ]

88. Sosa-Estani S, Dri L, Touris C, Abalde S, dell'Arciprete A, Braunstein J. Vectorial and congenital transmission of Trypanosoma cruzi in Las Lomitas, Formosa. Medicina (Mex). 2009;69:424-30. [ Links ]

89. Azogue E, la Fuente C, Darras C. Congenital Chagas' disease in Bolivia: Epidemiological aspects and pathological findings. Trans R Soc Trop Med Hyg. 1985;79:176-80. [ Links ]

90. Azogue E, Darras C. Prospective study of Chagas disease in newborn children with placental infection caused by Trypanosoma cruzi (Santa Cruz-Bolivia). Rev Soc Bras Med Trop. 1991;24:105-9. [ Links ]

91. Brutus L, Castillo H, Bernal C, Salas NA, Schneider D, Santalla J-A, et al. Detectable Trypanosoma cruzi parasitemia during pregnancy and delivery as a risk factor for congenital Chagas disease. Am J Trop Med Hyg. 2010;83:1044-7. [ Links ]

92. Salas Clavijo NA, Postigo JR, Schneider D, Santalla JA, Brutus L, Chippaux J-P. Prevalence of Chagas disease in pregnant women and incidence of congenital transmission in Santa Cruz de la Sierra, Bolivia. Acta Trop. 2012;124:87-91. [ Links ]

93. Salas NA, Cot M, Schneider D, Mendoza B, Santalla JA, Postigo J, et al. Risk factors and consequences of congenital Chagas disease in Yacuiba, South Bolivia. Trop Med Int Health. 2007;12:1498-505. [ Links ]

94. Brutus L, Schneider D, Postigo J, Delgado W, Mollinedo S, Chippaux J-P. Evidence of congenital transmission of Trypanosoma cruzi in a vector-free area of Bolivia. Trans R Soc Trop Med Hyg. 2007;101:1159-60. [ Links ]

95. Arteaga-Fernandez E, Pereira Barretto AC, lanni BM, Vianna C de B, Mady C, Bellotti G, et al. Incidence of congenital transmission of Chagas' disease. Arq Bras Cardiol. 1987;49: 47-9. [ Links ]

96. Nisida IV, Amato Neto V, Braz LM, Duarte MI, Umezawa ES. A survey of congenital Chagas' disease, carried out at three health institutions in Sao Paulo City, Brazil. Rev Inst Med Trop Sao Paulo. 1999;41:305-11. [ Links ]

97. Araajo AB, Castagno VD, Gallina T, Berne ME. Prevalence of Chagas disease among pregnant women in the southern region of Rio Grande do Sul. Rev Soc Bras Med Trop. 2009;42: 732-3. [ Links ]

98. Jercic MI, Mercado R, Villarroet R. Congenital Trypanosoma cruzi infection in neonates and infants from two regions of Chile where Chagas' disease is endemic. J Clin Microbiol. 2010;48:3824-6. [ Links ]

99. Apt W, Zulantay I, Arnetto M, Oddo D, Gonzalez S, Rodriguez J, et al. Congenital infection by Trypanosoma cruzi in an endemic area of Chile: A multidisciplinary study. Trans R Soc Trop Med Hyg. 2013;107:98-104. [ Links ]

100. Murcia L, Carritero B, Munoz-Davila MJ, Thomas MC, Lopez MC, Segovia M. Risk factors and primary prevention of congenital Chagas disease in a nonendemic country. Clin Infect Dis. 2013;56:496-502. [ Links ]

101. Cardoso EJ, Valdez GC, Campos AC, de la Luz Sanchez R, Mendoza CR, Hernandez AP, et al. Maternal fetal transmission of Trypanosoma cruzi: A problem of public health little studied in Mexico. Exp Parasitol. 2012;131:425-32. [ Links ]

102. Velarde CN. Chagas disease in Peru: Congenital transmission. Rev Soc Bras Med Trop. 2005;38 Suppl 2:55-7. [ Links ]

103. Mendoza Ticona CA, Cordova Benzaquen E, Ancca Juarez J, Saldafia Diaz J, Torres Choque A, Velasquez Talavera R, et al. The prevalence of Chagas' disease in puerperal women and congenital transmission in an endemic area of Peru. Rev Panam Salud Publica. 2005;17:147-53. [ Links ]

104. Yadon ZE, Schmunis GA. Congenital Chagas disease: Estimating the potential risk in the United States. Am J Trop Med Hyg. 2009;81:927-33. [ Links ]

105. Martinez de Tejada B, Jackson Y, Paccolat C, Ilion 0, Groupe Chagas Congenital Geneve. Congenital Chagas disease in Geneva: Diagnostic and clinical aspects. Rev Medicate Suisse. 2009;5:2094-6. [ Links ]

2Cómo citar este artículo: Z.M. Cucunubá, et al. First Colombian consensus on recommendations for diagnosis and treatment of congenital Chagas and clini- cal approach for diagnosis in child-bearing age women diagnosed with Chagas. Infectio 2017; 21(4): 255-266

1Conflicts of interest It is considered that there is no conflict of interest between the proponents and participants of this consensus.

Received: September 28, 2013; Accepted: February 14, 2014

* Autor para correspondencia: Correo electrónico: zcucunuba@gmail.com (Z.M. Cucunubá).

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License