Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos

Detalhes bibliográficos
Ano de defesa: 2024
Autor(a) principal: André Tetzl Costa
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://hdl.handle.net/1843/74053
Resumo: Leishmaniases are a group of diseases that affect millions of individuals globally. They are caused by protozoa of the genus Leishmania, mainly transmitted through the bite of vector insects, sandflies. Dogs stand out as the main domestic reservoir of this parasite and can develop the visceral form of the disease. Canine Visceral Leishmaniasis (CVL) can present a wide variety of clinical manifestations, ranging from asymptomatic forms to severe clinical signs. Studies have shown that the clinical progression of CVL is associated with the degree of parasitism in various organs. However, there is still a gap in the scientific literature regarding the threshold of parasitism in dogs that could influence transmission to these vectors. Additionally, it is not known whether there are hematological, immunological, or biochemical biomarkers that may be related to the risk of canine infectivity to sandflies. In Brazil, the Visceral Leishmaniasis Control Program (VLCP) encompasses the diagnosis and treatment of infected humans, vector control, and diagnosis and euthanasia of seropositive dogs. However, the requirement to deliver seropositive dogs to public authorities has been the subject of discussion and protests by owners, who often initiate treatment for CVL, even though it does not eliminate the parasite from their bodies, maintaining the risk of infection to the vector insect. In the current context, the Ministry of Health (MoH) together with the Ministry of Agriculture, Livestock, and Supply (MoAL), authorized the use of a medication for the treatment of dogs with CVL in 2016, Milteforan™. With the expectation of an increase in the number of dogs undergoing CVL treatment in Brazil, it becomes essential to identify biomarkers in CVL that can predict infection by L. infantum to sandflies. The main objective of this research was to evaluate naturally infected dogs with Leishmania infantum, aiming to identify biomarkers associated with resistance or susceptibility, and the possible correlation with the infection of these dogs by sandflies. Additionally, the study included the establishment of a new staging system in CVL, as well as the analysis of various biomarkers in animals with different clinical scores. Forty-seven dogs naturally infected with L. infantum were evaluated, considering hematobiochemical, immunological, clinical, and parasitological aspects. Some biomarkers were identified that showed a positive correlation with the parasitic load observed in sandflies, including: (i) parasitic load in the skin; (ii) in lymph nodes; and (iii) in the spleen; as well as (iv) serum levels of globulin; and (v) alkaline phosphatase. Negative correlation biomarkers were also identified, such as: (i) erythrocyte values; (ii) lymphocytes; (iii) monocytes; and (iv) TCD8+ lymphocyte count. However, the positive correlation was stronger when the animals were categorized according to the severity of clinical signs. This correlation supports the clinical staging system developed in this study as a tool to indicate a high risk of dogs with more severe clinical worsening to infect sandflies with a high parasitic load of L. infantum. This method, being easy to execute and low cost, can be valuable in practical contexts, such as in epidemiological analyses including the development of monitoring and treatment prognosis strategies for canine disease and also contribute to studies related to immunoprotection through vaccines against CVL.
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spelling 2024-08-14T18:12:14Z2025-09-08T23:12:13Z2024-08-14T18:12:14Z2024-02-28https://hdl.handle.net/1843/74053Leishmaniases are a group of diseases that affect millions of individuals globally. They are caused by protozoa of the genus Leishmania, mainly transmitted through the bite of vector insects, sandflies. Dogs stand out as the main domestic reservoir of this parasite and can develop the visceral form of the disease. Canine Visceral Leishmaniasis (CVL) can present a wide variety of clinical manifestations, ranging from asymptomatic forms to severe clinical signs. Studies have shown that the clinical progression of CVL is associated with the degree of parasitism in various organs. However, there is still a gap in the scientific literature regarding the threshold of parasitism in dogs that could influence transmission to these vectors. Additionally, it is not known whether there are hematological, immunological, or biochemical biomarkers that may be related to the risk of canine infectivity to sandflies. In Brazil, the Visceral Leishmaniasis Control Program (VLCP) encompasses the diagnosis and treatment of infected humans, vector control, and diagnosis and euthanasia of seropositive dogs. However, the requirement to deliver seropositive dogs to public authorities has been the subject of discussion and protests by owners, who often initiate treatment for CVL, even though it does not eliminate the parasite from their bodies, maintaining the risk of infection to the vector insect. In the current context, the Ministry of Health (MoH) together with the Ministry of Agriculture, Livestock, and Supply (MoAL), authorized the use of a medication for the treatment of dogs with CVL in 2016, Milteforan™. With the expectation of an increase in the number of dogs undergoing CVL treatment in Brazil, it becomes essential to identify biomarkers in CVL that can predict infection by L. infantum to sandflies. The main objective of this research was to evaluate naturally infected dogs with Leishmania infantum, aiming to identify biomarkers associated with resistance or susceptibility, and the possible correlation with the infection of these dogs by sandflies. Additionally, the study included the establishment of a new staging system in CVL, as well as the analysis of various biomarkers in animals with different clinical scores. Forty-seven dogs naturally infected with L. infantum were evaluated, considering hematobiochemical, immunological, clinical, and parasitological aspects. Some biomarkers were identified that showed a positive correlation with the parasitic load observed in sandflies, including: (i) parasitic load in the skin; (ii) in lymph nodes; and (iii) in the spleen; as well as (iv) serum levels of globulin; and (v) alkaline phosphatase. Negative correlation biomarkers were also identified, such as: (i) erythrocyte values; (ii) lymphocytes; (iii) monocytes; and (iv) TCD8+ lymphocyte count. However, the positive correlation was stronger when the animals were categorized according to the severity of clinical signs. This correlation supports the clinical staging system developed in this study as a tool to indicate a high risk of dogs with more severe clinical worsening to infect sandflies with a high parasitic load of L. infantum. This method, being easy to execute and low cost, can be valuable in practical contexts, such as in epidemiological analyses including the development of monitoring and treatment prognosis strategies for canine disease and also contribute to studies related to immunoprotection through vaccines against CVL.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOutra AgênciaporUniversidade Federal de Minas Geraishttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessLeishmaniose visceral caninaLeishmania infantumcãobiomarcadoresresposta imuneqPCRXenodiagnósticoParasitologiaCãesLeishmaniose VisceralXenodiagnósticoReação em Cadeia da PolimeraseAvaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAndré Tetzl Costareponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGhttp://lattes.cnpq.br/6952163464581419Rodolfo Cordeiro Giunchettihttp://lattes.cnpq.br/8652593678886647Edelberto Santos DiasMaykelin Fuentes ZaldivarWendel Coura VitalNelder de Figueiredo GontijoRodrigo Dian de Oliveira Aguiar SoaresAdriane Pimenta da Costa Val BicalhoAs leishmanioses são um grupo de doenças que afeta milhões de indivíduos globalmente. São causadas por protozoários do gênero Leishmania, transmitidos principalmente pela picada de insetos vetores, os flebotomíneos. O cão se destaca como reservatório doméstico desse parasito e pode desenvolver a forma visceral da doença. A Leishmaniose Visceral Canina (LVC) pode apresentar uma ampla variedade de manifestações clínicas, que vão desde formas assintomáticas até sinais clínicos graves. Estudos têm demonstrado que a evolução clínica da LVC está associada ao grau de parasitismo em órgãos diversos. Entretanto, ainda há uma lacuna na literatura científica em relação ao limiar de parasitismo no cão que poderia influenciar na transmissão a estes vetores. Além disso, não se sabe se existem biomarcadores hematológicos, imunológicos ou bioquímicos que possam correlacionar à de infectividade do cão aos flebotomíneos. No Brasil, o Programa de Controle da Leishmaniose Visceral (PCLV) abrange o diagnóstico e tratamento de humanos infectados, controle do vetor e diagnóstico e eutanásia de cães sororreagentes. Entretanto, a obrigatoriedade da entrega de cães soropositivos aos órgãos públicos tem sido alvo de discussão e protestos pelos tutores, que muitas vezes iniciam o tratamento da LVC, ainda que não elimine o parasito de seu organismo, mantendo risco de infecção ao inseto vetor. Diante do atual contexto, o Ministério da Saúde (MS) em conjunto com o Ministério da Agricultura, Pecuária e Abastecimento (MAPA) autorizou o uso de um medicamento para o tratamento de cães com LVC em 2016, o Milteforan™. Com base na expectativa de aumento no número de cães submetidos ao tratamento da LVC no Brasil, torna-se imprescindível identificar biomarcadores na LVC que possam predizer a infecção por L. infantum aos flebotomíneos. O objetivo principal desta pesquisa foi avaliar cães naturalmente infectados com Leishmania infantum, visando identificar biomarcadores associados à resistência ou susceptibilidade, e a possível correlação com a infecção desses cães pelos flebotomíneos. Adicionalmente, o estudo abrangeu o estabelecimento de um novo sistema de estadiamento na LVC, bem como a análise de diversos biomarcadores nos animais com escores clínicos diferentes. Foram avaliados 47 cães naturalmente infectados com L. infantum, sob os aspectos hemato-bioquímicos, imunológicos, clínicos e parasitológicos. Foram identificados alguns biomarcadores que apresentaram correlação positiva com a carga parasitária observada nos flebotomíneos, entre eles: (i) a carga parasitária na pele; (ii) nos linfonodos; e (iii) no baço; além dos (iv) níveis séricos de globulina; e (v) fosfatase alcalina. Também foram identificados biomarcadores com correlação negativa, como: (i) os valores de eritrócitos; (ii) linfócitos; (iii) monócitos; e a (iv) contagem de linfócitos TCD8+. No entanto, a correlação positiva foi mais forte quando os animais foram categorizados conforme a gravidade dos sinais clínicos. Essa correlação corrobora o sistema de estadiamento clínico desenvolvido neste estudo como ferramenta para indicar alto risco dos cães com maior agravamento clínico em infectarem flebotomíneos com alta carga parasitária de L. infantum. Esse método, por ser de fácil execução e baixo custo, pode ser valioso em contextos práticos, como em análises epidemiológicas incluindo o desenvolvimento de estratégias de monitoramento e prognóstico do tratamento da doença canina e também contribuir para estudos relacionados à imunoproteção por meio de vacinas contra a LVC.https://orcid.org/0000-0002-1621-8085BrasilICB - INSTITUTO DE CIÊNCIAS BIOLOGICASPrograma de Pós-Graduação em ParasitologiaUFMGORIGINALTese André Tetzl Costa_PDF-A.pdfapplication/pdf2139212https://repositorio.ufmg.br//bitstreams/e76799c1-d719-4264-bee8-76d03b2832e8/downloadab1556ee4ab6fcb8f7fab257741482deMD51trueAnonymousREADCC-LICENSElicense_rdfapplication/octet-stream811https://repositorio.ufmg.br//bitstreams/87049f7f-76d6-457f-8a18-f24ccb38a167/downloadcfd6801dba008cb6adbd9838b81582abMD52falseAnonymousREADLICENSElicense.txttext/plain2118https://repositorio.ufmg.br//bitstreams/d3f3ea1d-580d-477e-bf31-1e0b4b98b407/downloadcda590c95a0b51b4d15f60c9642ca272MD53falseAnonymousREAD1843/740532025-09-08 20:12:13.092http://creativecommons.org/licenses/by-nc-nd/3.0/pt/Acesso Abertoopen.accessoai:repositorio.ufmg.br:1843/74053https://repositorio.ufmg.br/Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2025-09-08T23:12:13Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)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
dc.title.none.fl_str_mv Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
title Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
spellingShingle Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
André Tetzl Costa
Parasitologia
Cães
Leishmaniose Visceral
Xenodiagnóstico
Reação em Cadeia da Polimerase
Leishmaniose visceral canina
Leishmania infantum
cão
biomarcadores
resposta imune
qPCR
Xenodiagnóstico
title_short Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
title_full Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
title_fullStr Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
title_full_unstemmed Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
title_sort Avaliação de biomarcadores preditivos da capacidade de cães com leishmaniose visceral atuarem como reservatório para transmissão do parasito aos flebotomíneos
author André Tetzl Costa
author_facet André Tetzl Costa
author_role author
dc.contributor.author.fl_str_mv André Tetzl Costa
dc.subject.por.fl_str_mv Parasitologia
Cães
Leishmaniose Visceral
Xenodiagnóstico
Reação em Cadeia da Polimerase
topic Parasitologia
Cães
Leishmaniose Visceral
Xenodiagnóstico
Reação em Cadeia da Polimerase
Leishmaniose visceral canina
Leishmania infantum
cão
biomarcadores
resposta imune
qPCR
Xenodiagnóstico
dc.subject.other.none.fl_str_mv Leishmaniose visceral canina
Leishmania infantum
cão
biomarcadores
resposta imune
qPCR
Xenodiagnóstico
description Leishmaniases are a group of diseases that affect millions of individuals globally. They are caused by protozoa of the genus Leishmania, mainly transmitted through the bite of vector insects, sandflies. Dogs stand out as the main domestic reservoir of this parasite and can develop the visceral form of the disease. Canine Visceral Leishmaniasis (CVL) can present a wide variety of clinical manifestations, ranging from asymptomatic forms to severe clinical signs. Studies have shown that the clinical progression of CVL is associated with the degree of parasitism in various organs. However, there is still a gap in the scientific literature regarding the threshold of parasitism in dogs that could influence transmission to these vectors. Additionally, it is not known whether there are hematological, immunological, or biochemical biomarkers that may be related to the risk of canine infectivity to sandflies. In Brazil, the Visceral Leishmaniasis Control Program (VLCP) encompasses the diagnosis and treatment of infected humans, vector control, and diagnosis and euthanasia of seropositive dogs. However, the requirement to deliver seropositive dogs to public authorities has been the subject of discussion and protests by owners, who often initiate treatment for CVL, even though it does not eliminate the parasite from their bodies, maintaining the risk of infection to the vector insect. In the current context, the Ministry of Health (MoH) together with the Ministry of Agriculture, Livestock, and Supply (MoAL), authorized the use of a medication for the treatment of dogs with CVL in 2016, Milteforan™. With the expectation of an increase in the number of dogs undergoing CVL treatment in Brazil, it becomes essential to identify biomarkers in CVL that can predict infection by L. infantum to sandflies. The main objective of this research was to evaluate naturally infected dogs with Leishmania infantum, aiming to identify biomarkers associated with resistance or susceptibility, and the possible correlation with the infection of these dogs by sandflies. Additionally, the study included the establishment of a new staging system in CVL, as well as the analysis of various biomarkers in animals with different clinical scores. Forty-seven dogs naturally infected with L. infantum were evaluated, considering hematobiochemical, immunological, clinical, and parasitological aspects. Some biomarkers were identified that showed a positive correlation with the parasitic load observed in sandflies, including: (i) parasitic load in the skin; (ii) in lymph nodes; and (iii) in the spleen; as well as (iv) serum levels of globulin; and (v) alkaline phosphatase. Negative correlation biomarkers were also identified, such as: (i) erythrocyte values; (ii) lymphocytes; (iii) monocytes; and (iv) TCD8+ lymphocyte count. However, the positive correlation was stronger when the animals were categorized according to the severity of clinical signs. This correlation supports the clinical staging system developed in this study as a tool to indicate a high risk of dogs with more severe clinical worsening to infect sandflies with a high parasitic load of L. infantum. This method, being easy to execute and low cost, can be valuable in practical contexts, such as in epidemiological analyses including the development of monitoring and treatment prognosis strategies for canine disease and also contribute to studies related to immunoprotection through vaccines against CVL.
publishDate 2024
dc.date.accessioned.fl_str_mv 2024-08-14T18:12:14Z
2025-09-08T23:12:13Z
dc.date.available.fl_str_mv 2024-08-14T18:12:14Z
dc.date.issued.fl_str_mv 2024-02-28
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