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Novaes RLM, Almeida B, Cláudio VC, Costa-Neto SF, Couto ALG, Schmidt E, Bertocchi NA, Costa JO, Ferreira CF, de Oliveira AMR, Dos Santos MLM, Monteverde TSD, de Abreu EMN, Cunha ENP, Borges AR, Garcia JG, Barboza CM, Cocchi M, Batista HBCR, Moratelli R. Rabies virus circulation in a highly diverse bat assemblage from a high-risk area for zoonoses outbreaks in the Brazilian Amazon. Acta Trop 2024; 257:107309. [PMID: 38955321 DOI: 10.1016/j.actatropica.2024.107309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 06/12/2024] [Accepted: 06/29/2024] [Indexed: 07/04/2024]
Abstract
Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases.
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Affiliation(s)
| | - Brunna Almeida
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | - Vinícius C Cláudio
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | - Sócrates F Costa-Neto
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | - Ademar Luiz G Couto
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | - Ellen Schmidt
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | - Natasha A Bertocchi
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil
| | | | - Claudio F Ferreira
- Secretaria de Saúde Pública do Estado do Pará, Divisão de Vigilância em Saúde - Nível Central, 66093-677, Belém, PA, Brazil
| | - Adi Marcus R de Oliveira
- Secretaria de Saúde Pública do Estado do Pará, Divisão de Vigilância em Saúde - Nível Central, 66093-677, Belém, PA, Brazil
| | - Mara Lucia M Dos Santos
- Secretaria de Saúde Pública do Estado do Pará, Divisão de Vigilância em Saúde - Nível Central, 66093-677, Belém, PA, Brazil
| | - Thays Steffanny D Monteverde
- Secretaria de Saúde Pública do Estado do Pará, Divisão de Vigilância em Saúde - Nível Central, 66093-677, Belém, PA, Brazil
| | - Elke Maria N de Abreu
- Secretaria de Saúde Pública do Estado do Pará, Divisão de Vigilância em Saúde - Nível Central, 66093-677, Belém, PA, Brazil
| | - Erickson N P Cunha
- Secretaria de Saúde Pública do Estado do Pará, 8º Centro Regional de Saúde, 68800-000, Breves, PA, Brazil
| | - Ailton R Borges
- Secretaria de Saúde Pública do Estado do Pará, 8º Centro Regional de Saúde, 68800-000, Breves, PA, Brazil
| | - Jaíne G Garcia
- Instituto Pasteur de São Paulo, Setor de Virologia, 01311-000, São Paulo, SP, Brazil
| | - Camila M Barboza
- Instituto Pasteur de São Paulo, Setor de Virologia, 01311-000, São Paulo, SP, Brazil
| | - Micheli Cocchi
- Instituto Pasteur de São Paulo, Setor de Virologia, 01311-000, São Paulo, SP, Brazil
| | | | - Ricardo Moratelli
- Fundação Oswaldo Cruz, Fiocruz Mata Atlântica, 22713-560, Rio de Janeiro, RJ, Brazil.
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Depickère S, Villacís AG, Santillán-Guayasamín S, Callapa Rafael JE, Brenière SF, Revollo Zepita S. Rhodnius (Stål, 1859) (Hemiptera, Triatominae) genus in Bolivian Amazonia: a risk for human populations? PARASITES & VECTORS 2022; 15:307. [PMID: 36038947 PMCID: PMC9426019 DOI: 10.1186/s13071-022-05423-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Accepted: 07/15/2022] [Indexed: 11/26/2022]
Abstract
Background Chagas disease, one of the most important neglected tropical diseases in the countries of Latin America, is considered to be a particularly important public health concern in the Amazon region due to increases in the number of outbreaks of acute Chagas disease and increased local transmission in the last 20 years. However, relative to other countries, in Bolivia there is little information available on its transmission in the Amazon region. The aim of this study was to investigate the infestation of palm trees, the main habitat of Triatominae in the region, in several localities, to evaluate the danger they represent to inhabitants. Methods Triatominae were collected using live bait traps left overnight in six localities in Pando and Beni Departments, Bolivia. DNA extraction and sequencing were used to establish the Triatominae species (Cytb, 16S and 28S-D2 gene fragments), and the blood meal sources (Cytb fragment). Trypanosoma sp. infection was analyzed by sequencing gene fragments (GPX, GPI, HMCOAR, LAP, PDH and COII) or by mini-exon multiplex PCR. Results A total of 325 Rhodnius were captured (97.3% of nymphs) from the 1200 traps placed in 238 palm trees and 32 burrows/ground holes. Sequence analyses on DNA extracted from 114 insects and phylogeny analysis identified two triatomine species: Rhodnius stali (17%) and Rhodnius montenegrensis (equated to Rhodnius robustus II, 83%). These were found in palm trees of the genera Attalea (69%), Astrocaryum (13%), Copernicia (12%), Euterpe (2%) and Acrocomia (1%). The infection rate was around 30% (165 analyzed insects), with 90% of analyzed insects infected by Trypanosoma cruzi (only the TcI discrete typing unit was detected), 3% infected by Trypanosoma rangeli (first time found in Bolivian Triatominae) and 7% infected by mixed T. cruzi (TcI)-T. rangeli. Rhodnius specimens fed on Didelphidae, rodents, gecko and humans. Conclusions The results of this study highlight the epidemiological importance of Rhodnius in the Bolivian Amazon region. The huge geographical distribution of Rhodnius and their proximity to the human dwellings, high infection rate and frequent meals on the human population highlight a risk of transmission of Chagas disease in the region. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s13071-022-05423-3.
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de Arias AR, Monroy C, Guhl F, Sosa-Estani S, Santos WS, Abad-Franch F. Chagas disease control-surveillance in the Americas: the multinational initiatives and the practical impossibility of interrupting vector-borne Trypanosoma cruzi transmission. Mem Inst Oswaldo Cruz 2022; 117:e210130. [PMID: 35830010 PMCID: PMC9261920 DOI: 10.1590/0074-02760210130] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Accepted: 04/13/2021] [Indexed: 11/21/2022] Open
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.
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Affiliation(s)
| | - Carlota Monroy
- Universidad de San Carlos, Laboratorio de Entomología y Parasitología Aplicadas, Ciudad de Guatemala, Guatemala
| | - Felipe Guhl
- Universidad de los Andes, Facultad de Ciencias, Centro de Investigaciones en Microbiología y Parasitología Tropical, Bogotá, Colombia
| | - Sergio Sosa-Estani
- Drugs for Neglected Diseases initiative Latin America, Rio de Janeiro, RJ, Brasil.,Centro de Investigaciones en Epidemiología y Salud Pública, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
| | - Walter Souza Santos
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Instituto Evandro Chagas, Laboratório de Epidemiologia das Leishmanioses, Ananindeua, PA, Brasil
| | - Fernando Abad-Franch
- Universidade de Brasília, Faculdade de Medicina, Núcleo de Medicina Tropical, Brasília, DF, Brasil
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Lázari Cacini G, de Oliveira J, Belintani T, Dos Santos Souza É, Olaia N, Pinto MC, da Rosa JA. Immature instars of three species of Rhodnius Stål, 1859 (Hemiptera, Reduviidae, Triatominae): morphology, morphometry, and taxonomic implications. Parasit Vectors 2022; 15:91. [PMID: 35303937 PMCID: PMC8932165 DOI: 10.1186/s13071-022-05200-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Accepted: 02/12/2022] [Indexed: 12/02/2022] Open
Abstract
Background Among the 18 genera of the Triatominae subfamily, three stand out for their diversity and epidemiological importance: Triatoma, Panstrongylus, and Rhodnius. Rhodnius includes 21 species that can transmit Trypanosoma cruzi (the etiological agent of Chagas disease, also known as American trypanosomiasis) and Trypanosoma rangeli. The Rhodnius prolixus complex comprises seven species, including Rhodnius marabaensis, Rhodnius prolixus, and Rhodnius robustus, which occur in the northern region of Brazil. Since both adults and immatures can carry T. cruzi, in this study the five nymphal instars of the three species mentioned were dorsally characterized. Methods Using microscopy, morphometrics, and geometric morphometrics, the present work measures and describes the morphological characters of the five nymphal instars of R. marabaensis, R. prolixus, and R. robustus. Results The study enabled the characterization of all five nymphal instars, as well as the distinction between the three species in each of their instars. Conclusions The morphological, morphometrics of the head, thorax, and abdomen and geometric morphometrics studies of the head enabled the specific distinction of these three species in all five instars. Graphical Abstract ![]()
Supplementary Information The online version contains supplementary material available at 10.1186/s13071-022-05200-2.
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Affiliation(s)
- Gustavo Lázari Cacini
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (Unesp), Rodovia Araraquara-Jaú km 1, Araraquara, SP, 14801-902, Brazil.
| | - Jader de Oliveira
- Departamento de Epidemiologia, Faculdade de Saúde Pública, Laboratório de Entomologia em Saúde Pública, Universidade de São Paulo, Av. Dr. Arnaldo 715, São Paulo, SP, Brazil
| | - Tiago Belintani
- Instituto de Biologia, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil
| | - Éder Dos Santos Souza
- Departamento de Entomologia, Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Amazonas, Brazil
| | - Nicoly Olaia
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (Unesp), Rodovia Araraquara-Jaú km 1, Araraquara, SP, 14801-902, Brazil
| | - Mara Cristina Pinto
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (Unesp), Rodovia Araraquara-Jaú km 1, Araraquara, SP, 14801-902, Brazil
| | - João Aristeu da Rosa
- Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista (Unesp), Rodovia Araraquara-Jaú km 1, Araraquara, SP, 14801-902, Brazil
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Saraiva RM, Mediano MFF, Mendes FSNS, Sperandio da Silva GM, Veloso HH, Sangenis LHC, Silva PSD, Mazzoli-Rocha F, Sousa AS, Holanda MT, Hasslocher-Moreno AM. Chagas heart disease: An overview of diagnosis, manifestations, treatment, and care. World J Cardiol 2021; 13:654-675. [PMID: 35070110 PMCID: PMC8716970 DOI: 10.4330/wjc.v13.i12.654] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 08/11/2021] [Accepted: 11/28/2021] [Indexed: 02/06/2023] Open
Abstract
Chagas heart disease (CHD) affects approximately 30% of patients chronically infected with the protozoa Trypanosoma cruzi. CHD is classified into four stages of increasing severity according to electrocardiographic, echocardiographic, and clinical criteria. CHD presents with a myriad of clinical manifestations, but its main complications are sudden cardiac death, heart failure, and stroke. Importantly, CHD has a higher incidence of sudden cardiac death and stroke than most other cardiopathies, and patients with CHD complicated by heart failure have a higher mortality than patients with heart failure caused by other etiologies. Among patients with CHD, approximately 90% of deaths can be attributed to complications of Chagas disease. Sudden cardiac death is the most common cause of death (55%–60%), followed by heart failure (25%–30%) and stroke (10%–15%). The high morbimortality and the unique characteristics of CHD demand an individualized approach according to the stage of the disease and associated complications the patient presents with. Therefore, the management of CHD is challenging, and in this review, we present the most updated available data to help clinicians and cardiologists in the care of these patients. We describe the clinical manifestations, diagnosis and classification criteria, risk stratification, and approach to the different clinical aspects of CHD using diagnostic tools and pharmacological and non-pharmacological treatments.
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Affiliation(s)
- Roberto M Saraiva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Mauro Felippe F Mediano
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Fernanda SNS Mendes
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | | | - Henrique H Veloso
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Luiz Henrique C Sangenis
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Paula Simplício da Silva
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Flavia Mazzoli-Rocha
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Andréa S Sousa
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Marcelo T Holanda
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
| | - Alejandro M Hasslocher-Moreno
- Evandro Chagas National Institute of Infectious Diseases, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, RJ, Brazil
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Nunes da Costa EAP, Victória C, Fortaleza CMCB. Predictors of development of cardiac and digestive disorders among patients with indeterminate chronic Chagas Disease. PLoS Negl Trop Dis 2021; 15:e0009680. [PMID: 34388146 PMCID: PMC8386853 DOI: 10.1371/journal.pntd.0009680] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 08/25/2021] [Accepted: 07/26/2021] [Indexed: 11/18/2022] Open
Abstract
American trypanosomiasis (Chagas disease, CD) affects circa 7 million persons worldwide. While of those persons present the asymptomatic, indeterminate chronic form (ICF), many will eventually progress to cardiac or digestive disorders. We studied a nonconcurrent (retrospective) cohort of patients attending an outpatient CD clinic in Southeastern Brazil, who were admitted while presenting the ICF in the period from 1998 through 2018 and followed until 2019. The outcomes of interest were the progression to cardiac or digestive CD forms. We were also interested in analyzing the impact of Benznidazole therapy on the progression of the disease. Extensive review of medical charts and laboratory files was conducted, collecting data up to year 2019. Demographics (upon inclusion), body mass index, comorbidities (including the Charlson index) and use of Benznidazole were recorded. The outcomes were defined by abnormalities in those test that could not be attributed to other causes. Statistical analysis included univariate and multivariable Cox regression models. Among 379 subjects included in the study, 87 (22.9%) and 100 (26.4%) progressed to cardiac and digestive forms, respectively. In the final multivariable model, cardiac disorders were positively associated with previous coronary syndrome (Hazzard Ratio [HR], 2.42; 95% Confidence Interval [CI], 1.53-3.81) and negatively associated with Benznidazole therapy (HR, 0.26; 95%CI, 0.11-0.60). On the other hand, female gender was the only independent predictor of progression to digestive forms (HR, 1.56; 95%CI, 1.03-2.38). Our results point to the impact of comorbidities on progression do cardiac CD, with possible benefit of the use of Benznidazole.
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Affiliation(s)
| | - Cassiano Victória
- Department of Zoonosis, Faculty of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), City of Botucatu, Brazil
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Santos WS, Gurgel-Gonçalves R, Garcez LM, Abad-Franch F. Deforestation effects on Attalea palms and their resident Rhodnius, vectors of Chagas disease, in eastern Amazonia. PLoS One 2021; 16:e0252071. [PMID: 34015050 PMCID: PMC8136634 DOI: 10.1371/journal.pone.0252071] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 05/07/2021] [Indexed: 01/05/2023] Open
Abstract
Attalea palms provide primary habitat to Rhodnius spp., vectors of Trypanosoma cruzi. Flying from palms, these blood-sucking bugs often invade houses and can infect people directly or via food contamination. Chagas disease (CD) risk may therefore increase when Attalea palms thrive near houses. For example, Attalea dominate many deforested landscapes of eastern Amazonia, where acute-CD outbreaks are disturbingly frequent. Despite this possible link between deforestation and CD risk, the population-level responses of Amazonian Attalea and their resident Rhodnius to anthropogenic landscape disturbance remain largely uncharted. We studied adult Attalea palms in old-growth forest (OGF), young secondary forest (YSF), and cattle pasture (CP) in two localities of eastern Amazonia. We recorded 1856 Attalea along 10 transects (153.6 ha), and detected infestation by Rhodnius spp. in 18 of 280 systematically-sampled palms (33 bugs caught). Distance-sampling models suggest that, relative to OGF, adult Attalea density declined by 70-80% in CP and then recovered in YSF. Site-occupancy models estimate a strong positive effect of deforestation on palm-infestation odds (βCP-infestation = 4.82±1.14 SE), with a moderate decline in recovering YSF (βYSF-infestation = 2.66±1.10 SE). Similarly, N-mixture models suggest that, relative to OGF, mean vector density sharply increased in CP palms (βCP-density = 3.20±0.62 SE) and then tapered in YSF (βYSF-density = 1.61±0.76 SE). Together, these results indicate that disturbed landscapes may support between ~2.5 (YSF) and ~5.1 (CP) times more Attalea-dwelling Rhodnius spp. per unit area than OGF. We provide evidence that deforestation may favor palm-dwelling CD vectors in eastern Amazonia. Importantly, our landscape-disturbance effect estimates explicitly take account of (i) imperfect palm and bug detection and (ii) the uncertainties about infestation and vector density arising from sparse bug data. These results suggest that incorporating landscape-disturbance metrics into the spatial stratification of transmission risk could help enhance CD surveillance and prevention in Amazonia.
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Affiliation(s)
- Walter Souza Santos
- Laboratório de Epidemiologia das Leishmanioses, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Ananindeua, Pará, Brazil
- Programa de Pós-graduação em Biologia Parasitária na Amazônia, Universidade do Estado do Pará, Belém, Pará, Brazil
| | - Rodrigo Gurgel-Gonçalves
- Núcleo de Medicina Tropical, Faculdade de Medicina, Universidade de Brasília, Brasília, Distrito Federal, Brazil
- Laboratório de Parasitologia Médica e Biologia de Vetores, Faculdade de Medicina, Universidade de Brasília, Brasília, Distrito Federal, Brazil
| | - Lourdes Maria Garcez
- Laboratório de Epidemiologia das Leishmanioses, Instituto Evandro Chagas, Secretaria de Vigilância em Saúde, Ministério da Saúde, Ananindeua, Pará, Brazil
- Programa de Pós-graduação em Biologia Parasitária na Amazônia, Universidade do Estado do Pará, Belém, Pará, Brazil
- Departamento de Patologia, Universidade do Estado do Pará, Belém, Pará, Brazil
| | - Fernando Abad-Franch
- Programa de Pós-graduação em Biologia Parasitária na Amazônia, Universidade do Estado do Pará, Belém, Pará, Brazil
- Núcleo de Medicina Tropical, Faculdade de Medicina, Universidade de Brasília, Brasília, Distrito Federal, Brazil
- Grupo Triatomíneos, Instituto René Rachou–Fiocruz, Belo Horizonte, Minas Gerais, Brazil
- * E-mail:
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Athie TS, Nascimento GC, Labis da Costa MJ, Sales Silva JD, Reis EA, Martin AP, Godman B, Dias Godói IP. Consumer willingness to pay for a hypothetical Chagas disease vaccine in Brazil: a cross-sectional study and the implications. J Comp Eff Res 2021; 10:659-672. [PMID: 33851872 DOI: 10.2217/cer-2020-0241] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Aim: Chagas disease is a serious public health problem, endemic in 21 countries in Latin America. A future vaccine can contribute to decreasing the number of cases and its complications. Methods: A cross-sectional study was conducted with residents of the northern region of Brazil, on the willingness to pay for a hypothetical vaccine against Chagas disease (effective protection of 80%). Results: We interviewed 619 individuals and seven were excluded from the analysis and the value of willingness to pay was US$23.77 (100.00 BRL). Conclusion: The Northern region of Brazil is one of the largest markets for this vaccine, due to its epidemiological relevance, so economic studies with this vaccine will be important to assist in the assessment of technologies.
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Affiliation(s)
- Thannuse Silva Athie
- Institute of Health & Biological Studies - Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
| | - Gesiane Cavalcante Nascimento
- Institute of Health & Biological Studies - Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
| | - Maria José Labis da Costa
- Institute of Health & Biological Studies - Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
| | - Juliana de Sales Silva
- Institute of Studies in Agricultural & Regional Development - Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
| | - Edna Afonso Reis
- Department of Statistics, Exact Sciences Institute, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.,Researcher of the Group (CNPq) for Epidemiological, Economic & Pharmacological Studies of Arboviruses (EEPIFARBO), Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
| | - Antony Paul Martin
- Faculty of Health & Life Sciences, Brownlow Hill, Liverpool, L69 3BX, UK.,QC Medica, York, North Yorkshire, YO23 2BD, UK
| | - Brian Godman
- Department of Pharmacoepidemiology, Institute of Pharmacy & Biomedical Sciences, 161 Cathedral Street, Glasgow G4 0RE, UK.,Division of Clinical Pharmacology, Karolinska Institute, Karolinska University Hospital, Stockholm SE-141 86, Sweden.,Department of Public Health & Pharmacy Management, School of Pharmacy, Sefako Health Sciences University, Pretoria, South Africa
| | - Isabella Piassi Dias Godói
- Institute of Health & Biological Studies - Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil.,Researcher of the Group (CNPq) for Epidemiological, Economic & Pharmacological Studies of Arboviruses (EEPIFARBO), Universidade Federal do Sul e Sudeste do Pará, Avenida dos Ipês, s/n, Cidade Universitária, Cidade Jardim, Marabá, Pará, Brazil
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Mule SN, Costa-Martins AG, Rosa-Fernandes L, de Oliveira GS, Rodrigues CMF, Quina D, Rosein GE, Teixeira MMG, Palmisano G. PhyloQuant approach provides insights into Trypanosoma cruzi evolution using a systems-wide mass spectrometry-based quantitative protein profile. Commun Biol 2021; 4:324. [PMID: 33707618 PMCID: PMC7952728 DOI: 10.1038/s42003-021-01762-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 01/24/2021] [Indexed: 01/31/2023] Open
Abstract
The etiological agent of Chagas disease, Trypanosoma cruzi, is a complex of seven genetic subdivisions termed discrete typing units (DTUs), TcI-TcVI and Tcbat. The relevance of T. cruzi genetic diversity to the variable clinical course of the disease, virulence, pathogenicity, drug resistance, transmission cycles and ecological distribution requires understanding the parasite origin and population structure. In this study, we introduce the PhyloQuant approach to infer the evolutionary relationships between organisms based on differential mass spectrometry-based quantitative features. In particular, large scale quantitative bottom-up proteomics features (MS1, iBAQ and LFQ) were analyzed using maximum parsimony, showing a correlation between T. cruzi DTUs and closely related trypanosomes' protein expression and sequence-based clustering. Character mapping enabled the identification of synapomorphies, herein the proteins and their respective expression profiles that differentiate T. cruzi DTUs and trypanosome species. The distance matrices based on phylogenetics and PhyloQuant clustering showed statistically significant correlation highlighting the complementarity between the two strategies. Moreover, PhyloQuant allows the identification of differentially regulated and strain/DTU/species-specific proteins, and has potential application in the identification of specific biomarkers and candidate therapeutic targets.
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Affiliation(s)
- Simon Ngao Mule
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Livia Rosa-Fernandes
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | | | - Carla Monadeli F Rodrigues
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Daniel Quina
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
| | - Graziella E Rosein
- Department of Biochemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil
| | | | - Giuseppe Palmisano
- Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
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10
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Zuma AA, de Souza W. Chagas Disease Chemotherapy: What Do We Know So Far? Curr Pharm Des 2021; 27:3963-3995. [PMID: 33593251 DOI: 10.2174/1381612827666210216152654] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 01/13/2021] [Indexed: 11/22/2022]
Abstract
Chagas disease is a Neglected Tropical Disease (NTD), and although endemic in Latin America, affects around 6-7 million people infected worldwide. The treatment of Chagas disease is based on benznidazole and nifurtimox, which are the only available drugs. However, they are not effective during the chronic phase and cause several side effects. Furthermore, BZ promotes cure in 80% of the patients in the acute phase, but the cure rate drops to 20% in adults in the chronic phase of the disease. In this review, we present several studies published in the last six years, which describes the antiparasitic potential of distinct drugs, from the synthesis of new compounds aiming to target the parasite, as well as the repositioning and the combination of drugs. We highlight several compounds for having shown results that are equivalent or superior to BZ, which means that they should be further studied, either in vitro or in vivo. Furthermore, we stand out the differences in the effects of BZ on the same strain of T. cruzi, which might be related to methodological differences such as parasite and cell ratios, host cell type and the time of adding the drug. In addition, we discuss the wide variety of strains and also the cell types used as a host cell, which makes it difficult to compare the trypanocidal effect of the compounds.
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Affiliation(s)
- Aline Araujo Zuma
- Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, 373, Centro de Ciências da Saúde, Cidade Universitária, Ilha do Fundão, 21491-590, Rio de Janeiro, RJ. Brazil
| | - Wanderley de Souza
- Laboratorio de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro. Av. Carlos Chagas Filho, 373, Centro de Ciências da Saúde, Cidade Universitária, Ilha do Fundão, 21491-590, Rio de Janeiro, RJ. Brazil
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11
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Duarte-Silva E, Maes M, Macedo D, Savino W, Peixoto CA. Shared neuroimmune and oxidative pathways underpinning Chagas disease and major depressive disorder. Transl Psychiatry 2020; 10:419. [PMID: 33268766 PMCID: PMC7710744 DOI: 10.1038/s41398-020-01105-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 10/24/2020] [Accepted: 11/10/2020] [Indexed: 12/12/2022] Open
Abstract
The cellular and molecular basis to understand the relationship between Chagas disease (CD), a infection caused by Trypanosoma cruzi, and depression, a common psychiatric comorbidity in CD patients, is largely unknown. Clinical studies show an association between CD and depression and preclinical evidence suggests that depressive-like behaviors in T. cruzi infected mice are due, at least partially, to immune dysregulation. However, mechanistic studies regarding this issue are still lacking. Herein, we present and discuss the state of art of data on CD and depression, and revise the mechanisms that may explain the development of depression in CD. We also discuss how the knowledge generated by current and future data may contribute to the discovery of new mechanisms underlying depressive symptoms associated with CD and, hence, to the identification of new therapeutic targets, which ultimately may change the way we see and treat CD and its psychiatric comorbidities.
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Affiliation(s)
- Eduardo Duarte-Silva
- Laboratory of Ultrastructure. Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, Brazil.
- Postgraduate Program in Biosciences and Biotechnology for Health (PPGBBS), Aggeu Magalhães Institute, Oswaldo Cruz Foundation, Recife, Brazil.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Recife, Brazil.
| | - Michael Maes
- Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Danielle Macedo
- Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil
- Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Brazil
- National Institute of Science and Technology on Translational Medicine (INCT-TM, CNPq), Ribeirão Preto, Brazil
| | - Wilson Savino
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
- Rio de Janeiro Research Network on Neuroinflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Christina Alves Peixoto
- Laboratory of Ultrastructure. Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, Brazil.
- National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
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12
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Domingues CS, Cardoso FDO, Hardoim DDJ, Pelajo-Machado M, Bertho AL, Calabrese KDS. Host Genetics Background Influence in the Intragastric Trypanosoma cruzi Infection. Front Immunol 2020; 11:566476. [PMID: 33329529 PMCID: PMC7732431 DOI: 10.3389/fimmu.2020.566476] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 10/23/2020] [Indexed: 01/21/2023] Open
Abstract
Background Considering the complexity of the factors involved in the immunopathology of Chagas disease, which influence the Chagas' disease pathogenesis, anti-T. cruzi immune response, and chemotherapy outcome, further studies are needed to improve our understanding about these relationships. On this way, in this article we analyzed the host genetic influence on hematological, histopathological and immunological aspects after T. cruzi infection. Methods BALB/c and A mice were intragastrically infected with T. cruzi SC2005 strain, isolated from a patient of an outbreak of Chagas disease. Parameters such as parasite load, survival rates, cytokines production, macrophages, T and B cell frequencies, and histopathology analysis were carried out. Results BALB/c mice presented higher parasitemia and mortality rates than A mice. Both mouse lineages exhibited hematological alterations suggestive of microcytic hypochromic anemia and histopathological alterations in stomach, heart and liver. The increase of CD8+ T cells, in heart, liver and blood, and the increase of CD19+ B cells, in liver, associated with a high level of proinflammatory cytokines (IL-6, TNF-α, IFN-γ), confer a resistance profile to the host. Although BALB/c animals exhibited the same findings observed in A mice, the response to infection occurred later, after a considerable parasitemia increase. By developing an early response to the infection, A mice were found to be less susceptible to T. cruzi SC2005 infection. Conclusions Host genetics background shaping the response to infection. The early development of a cytotoxic cellular response profile with the production of proinflammatory cytokines is important to lead a less severe manifestation of Chagas disease.
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Affiliation(s)
- Carolina Salles Domingues
- Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Flávia de Oliveira Cardoso
- Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Daiana de Jesus Hardoim
- Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Marcelo Pelajo-Machado
- Laboratório de Patologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Alvaro Luiz Bertho
- Laboratório de Imunoparasitologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
- Plataforma de Citometria de Fluxo, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
| | - Kátia da Silva Calabrese
- Laboratório de Imunomodulação e Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
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13
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Oral Trypanosoma cruzi Transmission Resulting in Advanced Chagasic Cardiomyopathy in an 11-Month-Old Male. Case Rep Infect Dis 2020; 2020:8828950. [PMID: 33123392 PMCID: PMC7586178 DOI: 10.1155/2020/8828950] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 09/09/2020] [Accepted: 10/03/2020] [Indexed: 12/02/2022] Open
Abstract
Our case report describes the youngest clinical acute Chagas disease case and their unusual disease presentation of cardiac failure. In parts of the Brazilian Amazon, cultural practices include weaning infants from breastmilk to solid foods with açaí consumption serving as an intermediary. This practice could place infants at an increased risk of oral Trypanosoma cruzi infection and severe Chagasic cardiac disease.
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14
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Sampaio GHF, Silva ANBD, Brito CRDN, Honorato NRM, Oliveira LMD, Câmara ACJD, Galvão LMDC. Epidemiological profile of acute Chagas disease in individuals infected by oral transmission in northern Brazil. Rev Soc Bras Med Trop 2020; 53:e20200088. [PMID: 32935781 PMCID: PMC7491568 DOI: 10.1590/0037-8682-0088-2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 06/24/2020] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION: Oral infection by Trypanosoma cruzi is currently the most important route of transmission of acute Chagas disease (ACD) in the North region of Brazil, and the reported outbreaks are usually related to ingestion of contaminated food, especially unprocessed açaí pulp. METHODS A retrospective cohort study was performed to analyze the epidemiological profile of individuals with suspected cases of ACD in the municipality of Breves, located in the state of Pará, Brazil. Therefore, notifications of suspected cases of ACD were collected from the Municipal Health Department of Breves from January 2007 to December 2017. RESULTS A total of 265 individuals were registered, and the majority were male (54.7%; 145/265). Age ranged from nine months to 79 years, with a greater number of notifications for individuals aged between 1 and 39 years (71.3%; 189/265). Most of them had a low level of education (74.3%, 197/265), were living in rural and urban areas (58.9%; 156/265 and 37.7%; 100/265, respectively). Infection occurred mainly in the domestic environment (96.2%; 255/265) through oral transmission (98.1%; 260/265). There were a greater number of notifications in November, December and January. CONCLUSIONS These data showed that oral transmission of T. cruzi has become increasingly high in the study region, and health education programs need to be implemented as strategies to ensure good manufacturing practices of unprocessed food.
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Affiliation(s)
- George Harisson Felinto Sampaio
- Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, Natal, RN, Brasil
| | - Andressa Noronha Barbosa da Silva
- Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Natal, RN, Brasil
| | - Carlos Ramon do Nascimento Brito
- Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Departamento de Análises Clínicas e Toxicológicas, Natal, RN, Brasil
| | - Nathan Ravi Medeiros Honorato
- Universidade Federal do Rio Grande do Norte, Centro de Biociências, Programa de Pós-Graduação em Biologia Parasitária, Natal, RN, Brasil
| | | | - Antônia Claudia Jácome da Câmara
- Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Departamento de Análises Clínicas e Toxicológicas, Natal, RN, Brasil.,Universidade Federal do Rio Grande do Norte, Centro de Biociências, Programa de Pós-Graduação em Biologia Parasitária, Natal, RN, Brasil
| | - Lúcia Maria da Cunha Galvão
- Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, Natal, RN, Brasil.,Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas, Natal, RN, Brasil.,Universidade Federal do Rio Grande do Norte, Centro de Ciências da Saúde, Departamento de Análises Clínicas e Toxicológicas, Natal, RN, Brasil
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15
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Hasslocher-Moreno AM, Salles Xavier S, Magalhães Saraiva R, Conde Sangenis LH, Teixeira de Holanda M, Horta Veloso H, Rodrigues da Costa A, de Souza Nogueira Sardinha Mendes F, Alvarenga Americano do Brasil PE, Sperandio da Silva GM, Felix Mediano MF, Silvestre de Sousa A. Progression Rate from the Indeterminate Form to the Cardiac Form in Patients with Chronic Chagas Disease: Twenty-Two-Year Follow-Up in a Brazilian Urban Cohort. Trop Med Infect Dis 2020; 5:tropicalmed5020076. [PMID: 32408570 PMCID: PMC7345528 DOI: 10.3390/tropicalmed5020076] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/08/2020] [Accepted: 05/09/2020] [Indexed: 11/30/2022] Open
Abstract
Most patients with chronic Chagas disease (CD) present the indeterminate form and are at risk to develop the cardiac form. However, the actual rate of progression to the cardiac form is still unknown. Methods: In total, 550 patients with the indeterminate CD form were followed by means of annual electrocardiogram at our outpatient clinic. The studied endpoint was progression to cardiac form defined by the appearance of electrocardiographic changes typical of CD. The progression rate was calculated as the cumulative progression rate and the incidence progression rate per 100 patient years. Results: Thirty-seven patients progressed to the CD cardiac form within a mean of 73 ± 48 months of follow-up, which resulted in a 6.9% cumulative progression rate and incidence rate of 1.48 cases/100 patient years. Patients who progressed were older (mean age 47.8 ± 12.2 years), had a higher prevalence of associated heart diseases (p < 0.0001), positive xenodiagnosis (p = 0.007), and were born in the most endemic Brazilian states (p = 0.018). Previous co-morbidities remained the only variable associated with CD progression after multivariate Cox proportional hazards regression analysis (p = 0.002). Conclusion: The progression rate to chronic CD cardiac form is low and inferior to rates previously reported in other studies.
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16
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Santos VRCD, Antunes D, Souza DDSMD, Moreira OC, Lima ICDA, Farias-de-Oliveira DA, Lobo JP, de Meis E, Coura JR, Savino W, Junqueira ACV, de Meis J. Human acute Chagas disease: changes in factor VII, activated protein C and hepatic enzymes from patients of oral outbreaks in Pará State (Brazilian Amazon). Mem Inst Oswaldo Cruz 2020; 115:e190364. [PMID: 32130371 PMCID: PMC7046146 DOI: 10.1590/0074-02760190364] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 01/22/2020] [Indexed: 11/22/2022] Open
Abstract
Oral transmission of Chagas disease has been increasing in Latin American
countries. The present study aimed to investigate changes in hepatic function,
coagulation factor levels and parasite load in human acute Chagas disease (ACD)
secondary to oral Trypanosoma cruzi transmission. Clinical and
epidemiological findings of 102 infected individuals attended in the State of
Pará from October 2013 to February 2016 were included. The most common symptoms
were fever (98%), asthenia (83.3%), face and limb edema (80.4%), headache
(74.5%) and myalgia (72.5%). The hepatic enzymes alanine aminotransferase (ALT)
and aspartate aminotransferase (AST) of 30 ACD patients were higher compared
with controls, and this increase was independent of the treatment with
benznidazole. Moreover, ACD individuals had higher plasma levels of activated
protein C and lower levels of factor VII of the coagulation cascade. Patients
with the highest parasite load had also the most increased transaminase levels.
Also, ALT and AST were associated moderately (r = 0.429) and strongly (r =
0.595) with parasite load respectively. In conclusion, the present study raises
the possibility that a disturbance in coagulation and hepatic function may be
linked to human ACD.
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Affiliation(s)
- Valéria Regina Cavalcante Dos Santos
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisas sobre o Timo, Rio de Janeiro, RJ, Brasil.,Secretaria de Saúde Pública do Estado do Pará, Belém, PA, Brasil
| | - Dina Antunes
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisas sobre o Timo, Rio de Janeiro, RJ, Brasil.,Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação, Rio de Janeiro, RJ, Brasil
| | | | - Otacilio Cruz Moreira
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro, RJ, Brasil
| | | | - Désio A Farias-de-Oliveira
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisas sobre o Timo, Rio de Janeiro, RJ, Brasil.,Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação, Rio de Janeiro, RJ, Brasil
| | - João Pedro Lobo
- Secretaria de Saúde Pública do Estado do Pará, Belém, PA, Brasil
| | | | - José Rodrigues Coura
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Doenças Parasitárias, Rio de Janeiro, RJ, Brasil
| | - Wilson Savino
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisas sobre o Timo, Rio de Janeiro, RJ, Brasil.,Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação, Rio de Janeiro, RJ, Brasil
| | | | - Juliana de Meis
- Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Pesquisas sobre o Timo, Rio de Janeiro, RJ, Brasil.,Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação, Rio de Janeiro, RJ, Brasil
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17
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Calvopina M, Segovia G, Cevallos W, Vicuña Y, Costales JA, Guevara A. Fatal acute Chagas disease by Trypanosoma cruzi DTU TcI, Ecuador. BMC Infect Dis 2020; 20:143. [PMID: 32059706 PMCID: PMC7023793 DOI: 10.1186/s12879-020-4851-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 02/06/2020] [Indexed: 11/28/2022] Open
Abstract
Background Chagas disease is caused by the haemoflagellate protozoan Trypanosoma cruzi. Currently, T. cruzi recognizes seven discrete typing units (DTUs): TcI to TcVI and Tcbat. The genetic diversity of T. cruzi is suspected to influence the clinical outcome. Acute clinical manifestations, which include myocarditis and meningoencephalitis, are sometimes fatal; occur most frequently in children and in immunocompromised individuals. Acute disease is often overlooked, leading to a poor prognosis. Case presentation A 38-year-old man from a subtropical area of the Andes mountains of Ecuador was hospitalized after 3 weeks of evolution with high fever, chills, an enlarged liver, spleen, and lymph nodes, as well as facial edema. ECG changes were also observed. T. cruzi was identified in blood smears, culture and amplification of DNA by PCR. Tests for anti-T. cruzi IgG and IgM and HIV were negative. Molecular typing by restriction fragment length polymorphism (PCR-RFLP) determined the parasite to DTU TcI. In the absence of a timely anti-T. cruzi medication, the patient died. Conclusions This is a case of severe pathogenicity and the virulence of a DTU TcI strain in an adult patient. The severe acute Chagas disease was probably overlooked due to limited awareness and its low incidence. Our findings suggest that T. cruzi DTU TcI strains circulating in Ecuador are capable of causing fatal acute disease. Early diagnosis and prompt treatment is of paramount importance to avoid fatalities in acute infections.
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Affiliation(s)
- Manuel Calvopina
- OneHealth Research Group, Carrera de Medicina, Facultad de Ciencias de la Salud, Universidad de Las Américas (UDLA), Calle Jose Queri s/n entre Av. Granados y Av. Eloy Alfaro, PO BOX 17-17-9788, Quito, Ecuador.
| | - Gabriela Segovia
- Instituto de Biomedicina, Carrera de Medicina, Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
| | - William Cevallos
- Instituto de Biomedicina, Carrera de Medicina, Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
| | - Yosselin Vicuña
- Instituto de Biomedicina, Carrera de Medicina, Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
| | - Jaime A Costales
- Centro de Investigación para la Salud en América Latina (CISeAL), Escuela de Ciencias Biológicas, Pontificia Universidad Católica del Ecuador, Quito, Ecuador
| | - Angel Guevara
- Instituto de Biomedicina, Carrera de Medicina, Facultad de Ciencias Médicas, Universidad Central del Ecuador, Quito, Ecuador
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18
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Jansen AM, Xavier SCDC, Roque ALR. Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment. Front Cell Infect Microbiol 2020; 10:10. [PMID: 32117794 PMCID: PMC7016096 DOI: 10.3389/fcimb.2020.00010] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 01/10/2020] [Indexed: 12/13/2022] Open
Abstract
Trypanosomatids are ancient parasitic eukaryotes that still maintain prokaryotic characteristics. Trypanosoma cruzi, a primarily wild mammal parasite, infected humans already long before European colonization of the Americas. T. cruzi heterogeneity remains an unsolved question, and until now, it has still not been possible to associate T. cruzi genotypes with any biological or epidemiological feature. One of the first biochemical attempts to cluster the T. cruzi subpopulations recognized three main subpopulations (zymodemes) that have been associated with the transmission cycles in the wild (Z1; Z3) and in the domestic environment (Z2). The description of wild mammal species harboring Z2 two decades later challenged this assemblage attempt. Currently, the genotypes of T. cruzi are assembled in seven discrete typing units (DTUs). The biology of T. cruzi still shows novelties such as the description of epimastigotes multiplying and differentiating to metacyclic trypomastigotes in the lumen of the scent glands of Didelphis spp. and the capacity of the true meiosis in parallel to clonal reproduction. The study of the transmission cycle among wild animals has broken paradigms and raised new questions: (i) the interaction of the T. cruzi DTUs with each of its mammalian host species displays peculiarities; (ii) the impact of mixed genotypes and species on the transmissibility of one or another species or on pathogenesis is still unknown; (iii) independent T. cruzi transmission cycles may occur in the same forest fragment; (iv) the capacity to act as a reservoir depends on the peculiarities of the host species and the parasite genotype; and (v) faunistic composition is a defining trait of the T. cruzi transmission cycle profile. The development of models of environmental variables that determine the spatial distribution of the elements that make up T. cruzi transmission by spatial analysis, followed by map algebra and networking, are the next steps toward interpreting and dealing with the new profile of Chagas disease with its many peculiarities. There is no way to solve this neglected disease once and for all if not through a multidisciplinary look that takes into account all kinds of human and animal activities in parallel to environmental variations.
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Affiliation(s)
- Ana Maria Jansen
- Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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19
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Fujita DM, Nascimento MS, de Andrade Júnior HF. The oral transmission of chagas disease in Brazil: New food supplies and travel experience. Acta Trop 2019; 197:105038. [PMID: 31136731 DOI: 10.1016/j.actatropica.2019.05.029] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Revised: 04/30/2019] [Accepted: 05/23/2019] [Indexed: 11/26/2022]
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20
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Epidemiology of concurrent Chagas disease and ischemic stroke in a population attending a multicenter quaternary rehabilitation network in Brazil. Neurol Sci 2019; 40:2595-2601. [PMID: 31363936 DOI: 10.1007/s10072-019-04018-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 07/19/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND AND PURPOSE Chagas disease and ischemic stroke (IS) have a close but poorly understood correlation. In endemic settings, continued transmission over time has resulted in increasing prevalence of both asymptomatic infection and cardiomyopathy with increasing age. Latin America has made substantial progress towards Chagas disease control. Although several epidemiological studies have been conducted, information regarding epidemiology and distribution of IS in Chagas disease is still lacking. METHODS We retrospectively studied the electronic medical record data of all patients with both IS and Chagas disease admitted at SARAH Hospitals across Brazil from 2009 to 2013 to make epidemiological quantifications and statistical inferences. RESULTS A total of 279 patients with Chagas disease and IS were analyzed from 7729 IS-related admissions, indicating a median prevalence of 3.6% of Chagas disease in IS patients in our cohort. Mean age was 60 years, with female predominance (65%). Most of the cases were from Bahia (61%), followed by Minas Gerais (19%) and Goiás (9.7%). Low-income cities, with decreased access to healthcare, showed the highest number of cases. Distribution of vascular risk factors and outcome after stroke differed among the units. According to current guidelines, secondary prevention was inadequate in 60% of patients. CONCLUSIONS Chagas disease was common in IS patients; prevalence of concurrent Chagas disease and IS was high in some regions of the country. However, the infection frequency seems to be reduced in the last few years. Public health issues for improving the treatment of Chagas disease and IS are urgently needed.
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Esper HR, Freitas VLTD, Assy JGPL, Shimoda EY, Berreta OCP, Lopes MH, França FOS. Fatal evolution of acute Chagas disease in a child from Northern Brazil: factors that determine poor prognosis. Rev Inst Med Trop Sao Paulo 2019; 61:e27. [PMID: 31066753 PMCID: PMC6502456 DOI: 10.1590/s1678-9946201961027] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 04/02/2019] [Indexed: 11/22/2022] Open
Abstract
Trypanosoma cruzi is the causative agent of Chagas disease. Nowadays, the transmission in Brazil occurs mainly by oral ingestion of contaminated food that has been associated with more severe clinical manifestations. We report a case of Acute Chagas disease caused by oral transmission in a child from Northern Brazil. In the hospital admission, physical examination showed tachycardia, hepatomegaly, bipalpebral edema and anasarca. Trypanosoma cruzi trypomastigotes were found in microscopy during blood cell count. Twenty-three days before hospitalization, the child had ingested the "bacaba palm fruit's wine". Even with the appropriate diagnosis and starting of treatment, she did not survive. Quantitative analysis of Trypanosoma cruzi DNA in a blood sample resulted in 54,053.42 parasite equivalents/mL and the DTU TcIV was identified. The outcome may have been determined by several factors, including the delay to seek a medical service beyond the high parasitemia, detected by qPCR. DTU TcIV could also have influenced the natural history of the disease.
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Affiliation(s)
- Helena Rangel Esper
- Hospital Municipal, Santarém, Pará, Brazil.,Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil
| | | | | | - Erika Yoshie Shimoda
- Universidade de São Paulo, Hospital das Clínicas, Laboratório de Investigação Médica em Imunologia (LIM 48), São Paulo, São Paulo, Brazil
| | - Olivia Campos Pinheiro Berreta
- Hospital Municipal, Santarém, Pará, Brazil.,Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil
| | - Marta Heloisa Lopes
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil.,Universidade de São Paulo, Hospital das Clínicas, Laboratório de Investigação Médica em Imunologia (LIM 48), São Paulo, São Paulo, Brazil
| | - Francisco Oscar Siqueira França
- Universidade de São Paulo, Faculdade de Medicina, São Paulo, São Paulo, Brazil.,Universidade de São Paulo, Hospital das Clínicas, Laboratório de Investigação Médica em Imunologia (LIM 48), São Paulo, São Paulo, Brazil
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Antunes D, Marins-Dos-Santos A, Ramos MT, Mascarenhas BAS, Moreira CJDC, Farias-de-Oliveira DA, Savino W, Monteiro RQ, de Meis J. Oral Route Driven Acute Trypanosoma cruzi Infection Unravels an IL-6 Dependent Hemostatic Derangement. Front Immunol 2019; 10:1073. [PMID: 31139194 PMCID: PMC6527737 DOI: 10.3389/fimmu.2019.01073] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2018] [Accepted: 04/26/2019] [Indexed: 01/19/2023] Open
Abstract
Oral transmission of Trypanosoma cruzi, the etiologic agent of Chagas disease, is presently the most important route of infection in Brazilian Amazon. Other South American countries have also reported outbreaks of acute Chagas disease associated with food consumption. A conspicuous feature of this route of transmission is presenting symptoms such as facial and lower limbs edema, in some cases bleeding manifestations and risk of thromboembolism are evident. Notwithstanding, studies that address this route of infection are largely lacking regarding its pathogenesis and, more specifically, the crosstalk between immune and hemostatic systems. Here, BALB/c mice were orally infected with metacyclic trypomastigotes of T. cruzi Tulahuén strain and used to evaluate the cytokine response, primary and secondary hemostasis during acute T. cruzi infection. When compared with control uninfected animals, orally infected mice presented higher pro-inflammatory cytokine (TNF-α, IFN-γ, and IL-6) serum levels. The highest concentrations were obtained concomitantly to the increase of parasitemia, between 14 and 28 days post-infection (dpi). Blood counts in the oral infected group revealed concomitant leukocytosis and thrombocytopenia, the latter resulting in increased bleeding at 21 dpi. Hematological changes paralleled with prolonged activated partial thromboplastin time, Factor VIII consumption and increased D-dimer levels, suggest that oral T. cruzi infection relies on disseminated intravascular coagulation. Remarkably, blockade of the IL-6 receptor blunted hematological abnormalities, revealing a critical role of IL-6 in the course of oral infection. These results unravel that acute T. cruzi oral infection results in significant alterations in the hemostatic system and indicates the relevance of the crosstalk between inflammation and hemostasis in this parasitic disease.
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Affiliation(s)
- Dina Antunes
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Alessandro Marins-Dos-Santos
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Mariana Tavares Ramos
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Barbara Angelica S Mascarenhas
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | | | - Désio Aurélio Farias-de-Oliveira
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Wilson Savino
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Robson Q Monteiro
- Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Juliana de Meis
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
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Smith K, Marcos LA. Pathogenesis of Chagas Disease: an Emphasis for Transplant Patient Populations. CURRENT TROPICAL MEDICINE REPORTS 2019. [DOI: 10.1007/s40475-019-0168-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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24
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Barreto de Albuquerque J, Silva Dos Santos D, Stein JV, de Meis J. Oral Versus Intragastric Inoculation: Similar Pathways of Trypanosoma cruzi Experimental Infection? From Target Tissues, Parasite Evasion, and Immune Response. Front Immunol 2018; 9:1734. [PMID: 30100907 PMCID: PMC6072848 DOI: 10.3389/fimmu.2018.01734] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/13/2018] [Indexed: 12/27/2022] Open
Abstract
Currently, oral infection is the most frequent transmission mechanism of Chagas disease in Brazil and others Latin American countries. This transmission pathway presents increased mortality rate in the first 2 weeks, which is higher than the calculated mortality after the biting of infected insect vectors. Thus, the oral route of Trypanosoma cruzi infection, and the consequences in the host must be taken into account when thinking on the mechanisms underlying the natural history of the disease. Distinct routes of parasite entry may differentially affect immune circuits, stimulating regional immune responses that impact on the overall profile of the host protective immunity. Experimental studies related to oral infection usually comprise inoculation in the mouth (oral infection, OI) or gavage (gastrointestinal infection, GI), being often considered as similar routes of infection. Hence, establishing a relationship between the inoculation site (OI or GI) with disease progression and the mounting of T. cruzi-specific regional immune responses is an important issue to be considered. Here, we provide a discussion on studies performed in OI and GI in experimental models of acute infections, including T. cruzi infection.
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Affiliation(s)
| | - Danielle Silva Dos Santos
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| | - Jens V Stein
- Theodor Kocher Institute, University of Bern, Bern, Switzerland
| | - Juliana de Meis
- Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.,National Institute of Science and Technology on Neuroimmunomodulation (INCT-NIM), Rio de Janeiro, Brazil
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