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  1. Article ; Online: Transmisión congénita de Trypanosoma cruzi. Argentina 2002-2014.

    Danesi, Emmaría / Codebó, María Olenka / Sosa-Estani, Sergio

    Medicina

    2019  Volume 79, Issue 2, Page(s) 81–89

    Abstract: In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information ...

    Title translation Congenital transmission of Trypanosoma cruzi. Argentina 2002-2014.
    Abstract In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information available on congenital T. cruzi infection, to analyze its evolution and its relation with the index of maternal infection and the risk for vector-borne infection by province of Argentina. Data concerning the public health sector for the period 1997-2014 were retrieved from national and local records. An increase in the number and proportion of pregnant women examined for Chagas was observed, reaching 60.3% coverage in 2014. The prevalence of maternal infection dropped from 9.0% to 2.6%. The control of newborns from infected women was highly variable (23.3%-93.6%), and data quality was deficient, varying amply by province and year. The rate of congenital infection had an irregular evolution and its national average fluctuated between 1.9 and 8.2%. An association was observed between the risk for vector-borne infection and the prevalence of maternal infection by province (Wilcoxon test p = 0.017). The rate of congenital transmission by province was neither associated with the rate of maternal infection (linear regression p = 0.686) nor with the risk for vectorial infection (Kruskal-Wallis test p = 0.3154). The available data show insufficient control of children born from infected mothers, as well as deficient recording of these procedures. Both aspects must be improved to achieve better epidemiological information and to enable timely access of infected children to treatment.
    MeSH term(s) Argentina/epidemiology ; Chagas Disease/congenital ; Chagas Disease/epidemiology ; Chagas Disease/transmission ; Female ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical/statistics & numerical data ; Linear Models ; Male ; Pregnancy ; Pregnancy Complications, Parasitic/epidemiology ; Prevalence ; Risk Assessment ; Risk Factors ; Statistics, Nonparametric ; Time Factors
    Language Spanish
    Publishing date 2019-04-25
    Publishing country Argentina
    Document type Journal Article ; Observational Study
    ZDB-ID 411586-7
    ISSN 1669-9106 ; 0025-7680 ; 0325-951X
    ISSN (online) 1669-9106
    ISSN 0025-7680 ; 0325-951X
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Benznidazole in Chagas disease study: do the data justify progression to phase 3? - Authors' reply.

    Torrico, Faustino / Barreira, Fabiana / Strub-Wourgaft, Nathalie / Ribeiro, Isabella / Sosa-Estani, Sergio

    The Lancet. Infectious diseases

    2021  Volume 21, Issue 8, Page(s) 1067

    MeSH term(s) Chagas Disease/drug therapy ; Humans ; Nitroimidazoles/therapeutic use
    Chemical Substances Nitroimidazoles ; benzonidazole (YC42NRJ1ZD)
    Language English
    Publishing date 2021-07-27
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(21)00336-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The translational challenge in Chagas disease drug development.

    Kratz, Jadel M / Gonçalves, Karolina R / Romera, Lavínia Md / Moraes, Carolina Borsoi / Bittencourt-Cunha, Paula / Schenkman, Sergio / Chatelain, Eric / Sosa-Estani, Sergio

    Memorias do Instituto Oswaldo Cruz

    2022  Volume 117, Page(s) e200501

    Abstract: Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development ... ...

    Abstract Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.
    MeSH term(s) Chagas Disease/drug therapy ; Chagas Disease/parasitology ; Drug Development ; Drug Discovery ; Humans ; Neglected Diseases/drug therapy ; Trypanocidal Agents/pharmacology ; Trypanocidal Agents/therapeutic use ; Trypanosoma cruzi
    Chemical Substances Trypanocidal Agents
    Language English
    Publishing date 2022-05-23
    Publishing country Brazil
    Document type Journal Article ; Review
    ZDB-ID 953293-6
    ISSN 1678-8060 ; 0074-0276
    ISSN (online) 1678-8060
    ISSN 0074-0276
    DOI 10.1590/0074-02760200501
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Higher congenital transmission rate of Trypanosoma cruzi associated with family history of congenital transmission.

    Danesi, Emmaría / Fabbro, Diana Lucrecia / Segura, Elsa Leonor / Sosa-Estani, Sergio

    Revista da Sociedade Brasileira de Medicina Tropical

    2020  Volume 53, Page(s) e20190560

    Abstract: Introduction: Congenital transmission (CT) of Trypanosoma cruzi has led to globalization of Chagas disease and its growing relevance as a public health problem. Although the occurrence of CT has been associated with several factors, its mechanisms are ... ...

    Abstract Introduction: Congenital transmission (CT) of Trypanosoma cruzi has led to globalization of Chagas disease and its growing relevance as a public health problem. Although the occurrence of CT has been associated with several factors, its mechanisms are still unknown. This study aimed to analyze the geographical and familiar variables of mothers and their association with CT of Chagas disease in a population living in non-endemic areas of Argentina for the last decades.
    Methods: We developed a retrospective cohort study in a sample of 2120 mother-child pairs who attended three reference centers in the cities of Buenos Aires, Santa Fe, and Salta between 2002 and 2015.
    Results: The highest CT rates were observed in children born to Argentinean mothers (10.7%) and in children born to mothers from Buenos Aires (11.7%). Considering the areas of origin of the mothers, those from areas of null-low risk for vector-borne infection had higher CT rates than those from areas of medium-high risk (11.1% vs 8.2%). We also observed a significant intra-familiar "cluster effect," with CT rates of 35.9% in children with an infected sibling, compared to 8.2% in children without infected siblings (RR=4.4 95% CI 2.3-8.4).
    Conclusions: The associations observed suggest a higher CT rate in children born to mothers who acquired the infection congenitally, with familiar antecedents, and from areas without the presence of vectors. These observations are considered new epidemiological evidence about Chagas disease in a contemporary urban population, which may contribute to the study of CT and may also be an interesting finding for healthcare professionals.
    MeSH term(s) Adolescent ; Adult ; Animals ; Argentina/epidemiology ; Chagas Disease/epidemiology ; Chagas Disease/transmission ; Female ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/statistics & numerical data ; Male ; Middle Aged ; Pregnancy ; Pregnancy Complications, Parasitic/epidemiology ; Retrospective Studies ; Risk Factors ; Urban Population ; Young Adult
    Language English
    Publishing date 2020-04-27
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 1038126-0
    ISSN 1678-9849 ; 0037-8682
    ISSN (online) 1678-9849
    ISSN 0037-8682
    DOI 10.1590/0037-8682-0560-2019
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Critical analysis of Chagas disease treatment in different countries.

    Mendes, Fernanda de Souza Nogueira Sardinha / Perez-Molina, Jose Antonio / Angheben, Andrea / Meymandi, Sheba K / Sosa-Estani, Sergio / Molina, Israel

    Memorias do Instituto Oswaldo Cruz

    2022  Volume 117, Page(s) e210034

    Abstract: As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In ... ...

    Abstract As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.
    MeSH term(s) Americas ; Chagas Disease/drug therapy ; Europe ; Humans
    Language English
    Publishing date 2022-07-08
    Publishing country Brazil
    Document type Journal Article ; Review
    ZDB-ID 953293-6
    ISSN 1678-8060 ; 0074-0276
    ISSN (online) 1678-8060
    ISSN 0074-0276
    DOI 10.1590/0074-02760210034
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Human Trypanosoma cruzi chronic infection leads to individual level steady-state parasitemia: Implications for drug-trial optimization in Chagas disease.

    De Salazar, Pablo M / Sosa-Estani, Sergio / Salvador, Fernando / Sulleiro, Elena / Sánchez-Montalvá, Adrián / Ribeiro, Isabela / Molina, Israel / Buckee, Caroline O

    PLoS neglected tropical diseases

    2022  Volume 16, Issue 11, Page(s) e0010828

    Abstract: Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite ... ...

    Abstract Currently available drugs against Trypanosoma cruzi infection, which causes 12000 deaths annually, have limitations in their efficacy, safety and tolerability. The evaluation of therapeutic responses to available and new compounds is based on parasite detection in the bloodstream but remains challenging because a substantial proportion of infected individuals have undetectable parasitemia even when using diagnostic tools with the highest accuracy. We characterize parasite dynamics which might impact drug efficacy assessments in chronic Chagas by analyzing pre- and post-treatment quantitative-PCR data obtained from blood samples collected regularly over a year. We show that parasitemia remains at a steady-state independently of the diagnostic sensitivity. This steady-state can be probabilistically quantified and robustly predicted at an individual level. Furthermore, individuals can be assigned to categories with distinct parasitological status, allowing a more detailed evaluation of the efficacy outcomes and adjustment for potential biases. Our analysis improves understanding of parasite dynamics and provides a novel background for optimizing future drug efficacy trials in Chagas disease. Trial Registration: original trial registered with ClinicalTrials.gov, number NCT01489228.
    MeSH term(s) Humans ; Chagas Disease/parasitology ; Parasitemia/parasitology ; Persistent Infection ; Real-Time Polymerase Chain Reaction ; Trypanosoma cruzi/genetics ; Clinical Trials as Topic
    Language English
    Publishing date 2022-11-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2429704-5
    ISSN 1935-2735 ; 1935-2735
    ISSN (online) 1935-2735
    ISSN 1935-2735
    DOI 10.1371/journal.pntd.0010828
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Chagas disease control-surveillance in the Americas: the multinational initiatives and the practical impossibility of interrupting vector-borne Trypanosoma cruzi transmission.

    de Arias, Antonieta Rojas / Monroy, Carlota / Guhl, Felipe / Sosa-Estani, Sergio / Santos, Walter Souza / Abad-Franch, Fernando

    Memorias do Instituto Oswaldo Cruz

    2022  Volume 117, Page(s) e210130

    Abstract: Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis ... ...

    Abstract Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis and medical care, however, is far from universal. Starting in the 1990s, CD-endemic countries and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for CD control-surveillance. An overview of the initiatives' aims, achievements, and challenges reveals some key common themes that we discuss here in the context of the WHO 2030 goals for CD. Transmission of T. cruzi via blood transfusion and organ transplantation is effectively under control. T. cruzi, however, is a zoonotic pathogen with 100+ vector species widely spread across the Americas; interrupting vector-borne transmission seems therefore unfeasible. Stronger surveillance systems are, and will continue to be, needed to monitor and control CD. Prevention of vertical transmission demands boosting current efforts to screen pregnant and childbearing-aged women. Finally, integral patient care is a critical unmet need in most countries. The decades-long experience of the initiatives, in sum, hints at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas. The concept of disease control seems to provide a more realistic description of what can in effect be achieved by 2030.
    MeSH term(s) Aged ; Americas/epidemiology ; Animals ; Chagas Disease/epidemiology ; Chagas Disease/prevention & control ; Disease Vectors ; Female ; Humans ; Infectious Disease Transmission, Vertical/prevention & control ; Pregnancy ; Trypanosoma cruzi
    Language English
    Publishing date 2022-07-06
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 953293-6
    ISSN 1678-8060 ; 0074-0276
    ISSN (online) 1678-8060
    ISSN 0074-0276
    DOI 10.1590/0074-02760210130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Congenital transmission of Trypanosoma cruzi. Argentina 2002-2014

    Emmaría Danesi / María Olenka Codebó / Sergio Sosa-Estani

    Medicina (Buenos Aires), Vol 79, Iss 2, Pp 81-

    2019  Volume 89

    Abstract: In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information ...

    Abstract In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information available on congenital T. cruzi infection, to analyze its evolution and its relation with the index of maternal infection and the risk for vector-borne infection by province of Argentina. Data concerning the public health sector for the period 1997-2014 were retrieved from national and local records. An increase in the number and proportion of pregnant women examined for Chagas was observed, reaching 60.3% coverage in 2014. The prevalence of maternal infection dropped from 9.0% to 2.6%. The control of newborns from infected women was highly variable (23.3%-93.6%), and data quality was deficient, varying amply by province and year. The rate of congenital infection had an irregular evolution and its national average fluctuated between 1.9 and 8.2%. An association was observed between the risk for vector-borne infection and the prevalence of maternal infection by province (Wilcoxon test p = 0.017). The rate of congenital transmission by province was neither associated with the rate of maternal infection (linear regression p = 0.686) nor with the risk for vectorial infection (Kruskal-Wallis test p = 0.3154). The available data show insufficient control of children born from infected mothers, as well as deficient recording of these procedures. Both aspects must be improved to achieve better epidemiological information and to enable timely access of infected children to treatment.
    Keywords Chagas disease ; congenital ; epidemiological monitoring ; public health ; Medicine ; R ; Immunologic diseases. Allergy ; RC581-607 ; Infectious and parasitic diseases ; RC109-216
    Subject code 610
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher Fundación Revista Medicina
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Geographic Variations in Test Reactivity for the Serological Diagnosis of Trypanosoma cruzi Infection.

    Truyens, Carine / Dumonteil, Eric / Alger, Jackeline / Cafferata, Maria Luisa / Ciganda, Alvaro / Gibbons, Luz / Herrera, Claudia / Sosa-Estani, Sergio / Buekens, Pierre

    Journal of clinical microbiology

    2021  Volume 59, Issue 12, Page(s) e0106221

    Abstract: Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples ... ...

    Abstract Chagas disease is a neglected disease caused by Trypanosoma cruzi parasites. Most diagnosis is based on serological tests, but the lack of a gold standard test complicates the measurement of test performance. To overcome this limitation, we used samples from a cohort of well-characterized T. cruzi-infected women to evaluate the reactivity of two rapid diagnostic tests and one enzyme-linked immunosorbent assay (ELISA). Our cohort was derived from a previous study on congenital transmission of T. cruzi and consisted of 481 blood/plasma samples from Argentina (
    MeSH term(s) Antibodies, Protozoan ; Chagas Disease/diagnosis ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Serologic Tests ; Trypanosoma cruzi
    Chemical Substances Antibodies, Protozoan
    Language English
    Publishing date 2021-09-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.01062-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial.

    Pinazo, Maria-Jesus / Forsyth, Colin / Losada, Irene / Esteban, Elena Trigo / García-Rodríguez, Magdalena / Villegas, Maria Luz / Molina, Israel / Crespillo-Andújar, Clara / Gállego, Montserrat / Ballart, Cristina / Ramirez, Juan Carlos / Aden, Tilman / Hoerauf, Achim / Pfarr, Kenneth / Vaillant, Michel / Marques, Tayná / Fernandes, Jayme / Blum, Bethania / Ribeiro, Isabela /
    Sosa-Estani, Sergio / Barreira, Fabiana / Gascón, Joaquim

    The Lancet. Infectious diseases

    2024  Volume 24, Issue 4, Page(s) 395–403

    Abstract: Background: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both ... ...

    Abstract Background: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both drugs used to treat this chronic, neglected infection, benznidazole and nifurtimox, were developed more than 50 years ago, and adverse drug reactions during treatment pose a major barrier, causing 20% of patients to discontinue therapy. Fexinidazole proved efficacious in an earlier, interrupted clinical trial, but the doses evaluated were not well tolerated. The present study evaluated fexinidazole at lower doses and for shorter treatment durations.
    Methods: In this randomised, double-blind, phase 2 trial, we included adult patients (18-60 years old) with confirmed T cruzi infection by serology and PCR and without signs of organ involvement. We evaluated three regimens of fexinidazole-600 mg once daily for 10 days (6·0 g total dose), 1200 mg daily for 3 days (3·6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (6·6 g)-and compared them with a historical placebo control group (n=47). The primary endpoint was sustained negative results by PCR at end of treatment and on each visit up to four months of follow-up. This study is registered with ClinicalTrials.gov, NCT03587766, and EudraCT, 2016-004905-15.
    Findings: Between Oct 16, 2017, and Aug 7, 2018, we enrolled 45 patients (n=15 for each group), of whom 43 completed the study. Eight (19%) of 43 fexinidazole-treated patients reached the primary endpoint, compared with six (13%) of 46 in the historical control group. Mean parasite load decreased sharply following treatment but rebounded beginning 10 weeks after treatment. Five participants had seven grade 3 adverse events: carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole.
    Interpretation: The fexinidazole regimens in this study had an acceptable safety profile but did not prove effective against T cruzi infection. Development of fexinidazole monotherapy for treating T cruzi infection has been stopped.
    Funding: The Drugs for Neglected Diseases initiative.
    MeSH term(s) Adult ; Humans ; Adolescent ; Young Adult ; Middle Aged ; Treatment Outcome ; Chagas Disease/drug therapy ; Trypanosoma cruzi ; Nifurtimox/adverse effects ; Double-Blind Method ; Nitroimidazoles
    Chemical Substances fexinidazole (306ERL82IR) ; Nifurtimox (M84I3K7C2O) ; Nitroimidazoles
    Language English
    Publishing date 2024-01-11
    Publishing country United States
    Document type Randomized Controlled Trial ; Multicenter Study ; Clinical Trial, Phase II ; Journal Article
    ZDB-ID 2061641-7
    ISSN 1474-4457 ; 1473-3099
    ISSN (online) 1474-4457
    ISSN 1473-3099
    DOI 10.1016/S1473-3099(23)00651-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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