Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil.

BACKGROUND: In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES: This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS: In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS: The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION: Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Different inoculum of Leishmania braziliensis concentrations influence immunopathogenesis and clinical evolution in the ear dermis hamster model of cutaneous leishmaniasis.

The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.

CXCL10 immunomodulatory effect against infection caused by an antimony refractory isolate of Leishmania braziliensis in mice.

Leishmania braziliensis is the main causative agent of American tegumentary leishmaniasis in Brazil. Current treatment includes different drugs that have important side effects and identification of cases of parasite resistance to treatment support the search for new therapeutic strategies. Recent findings have indicated that CXCL10, a chemokine that recruits and activates Th1 cells, NK cells, macrophages, dendritic cells and B lymphocytes, is a potential alternative to treat Leishmania infection. Here, we tested CXCL10 immunotherapy against experimental infection caused by an antimony-resistant isolate of Leishmania braziliensis. Following infection, mice were treated with CXCL10 for 7 days after onset of lesions. We demonstrate that mice treated with CXCL10 controlled lesion progression and parasite burden more efficiently comparing to controls. An increased IFN-γ, IL-10, TGF-ß and low IL-4 production combined with a distinct inflammatory infiltrate composed by activated macrophages, lymphocytes and granulomas was observed in the CXCL10-treated group comparing to controls. However, CXCL10 and Glucantime combined therapy did not improve CXCL10-induced protective effect. Our findings reinforce the potential of CXCL10 immunotherapy as an alternative treatment against infection caused by L. braziliensis resistant to conventional chemotherapy.

Physical Activity at Different Life Stages and Its Consequence on the Initial Immunization and Inflammatory Response Against COVID-19.

BACKGROUND: To evaluate the influence of previous physical activity (PA) during childhood, adolescence, and current PA practice on the production of antibodies and inflammatory response between the first and second doses of the COVID-19 vaccine. METHODS: Fifty-nine men and 56 women were evaluated before the first vaccine, and 12 weeks later, blood samples were taken to quantify production of anti-severe acute respiratory syndrome coronavirus-2 immunoglobulin G antibodies and cytokines. Previous PA during childhood and adolescence was self-referred, and current PA was assessed using the International Physical Activity Questionnaire. RESULTS: A positive and significant association was observed only between PA practice during adolescence and an increase in antibody production in adulthood (ß = 2012.077, 95% confidence interval, 257.7953-3766.358, P = .025). Individuals who practiced PA during adolescence showed higher production of antibodies between the first and second vaccine dose compared to nonpractitioners (P = .025) and those that accumulated ≥150 minutes per week of current moderate-vigorous PA (MVPA), and presented higher antibody production in relation to who did <150 minutes per week of MVPA (P = .046). Individuals that were practitioners during childhood produced higher G-CSF (P = .047), and those that accumulated ≥150 minutes per week of current MVPA demonstrated lower IP-10 levels (P = .033). However, PA practitioners during adolescence presented higher G-CSF (P = .025), IL-17 (P = .038), IL-1RA (P = .005), IL-1ß (P = .020), and IL-2 (P = .026) levels. CONCLUSION: Our results suggest that adults that accumulated at least 150 minutes of MVPA per week or practiced PA during adolescence developed an improved immune and inflammatory response against COVID-19 vaccination.

Characterisation of an area of coexistent visceral and cutaneous leishmaniasis transmission in the State of Piauí, Brazil

BACKGROUND In Brazil, transmission of visceral and cutaneous leishmaniasis has expanded geographically over the last decades, with both clinical forms occurring simultaneously in the same area. OBJECTIVES This study characterised the clinical, spatial, and temporal distribution, and performed entomological surveillance and natural infection analysis of a leishmaniasis-endemic area. METHODS In order to characterise the risk of leishmaniasis transmission in Altos, Piauí, we described the clinical and socio-demographic variables and the spatial and temporal distribution of cases of American visceral leishmaniasis (AVL) and American cutaneous leishmaniasis (ACL) cases and identified potential phlebotomine vectors. FINDINGS The urban area concentrated almost 54% of ACL and 86.8% of AVL cases. The temporal and spatial distribution of AVL and ACL cases in Altos show a reduction in the number of risk areas, but the presence of permanent disease transmission foci is observed especially in the urban area. 3,808 phlebotomine specimens were captured, with Lutzomyia longipalpis as the most frequent species (98.45%). Of the 35 females assessed for natural infection, one specimen of Lu. longipalpis tested positive for the presence of Leishmania infantum and Leishmania braziliensis DNA. MAIN CONCLUSION Our results indicate the presence of risk areas for ACL and AVL in the municipality of Altos and highlight the importance of entomological surveillance to further understand a possible role of Lu. longipalpis in ACL transmission.

Chemokines in host-parasite interactions in leishmaniasis.

Crucial to the defense against leishmaniasis is the ability of the host to mount a cell-mediated immune response capable of controlling and/or eliminating the parasite. Cell recruitment to the site of infection is essential to the development of the host cellular immune response. The process is controlled by chemokines, which are chemotactic cytokines produced by leukocytes and tissue cells.

Ocorrência de triatomíneos no Estado do Ceará, Brasil / Occurrence of triatomines in the state of Ceará, Brazil

Esta revisão integrativa tem como objetivo analisar as publicações científicas nos últimos doze anos sobre triatomíneos encontrados no Estado do Ceará. Para tal, nos bancos de dados da Biblioteca Virtual em Saúde (BVS) foi realizada uma busca com associação dos descritores "Doença de Chagas", "Triatomíneos" e "Brasil". Após aplicação dos critérios de inclusão, exclusão e da análise dos seus conteúdos, oito artigos realizados no Estado do Ceará foram selecionados para a análise do estudo. Algumas espécies de triatomíneos encontradas no Nordeste são de extrema importância epidemiológica para o homem, pois estão associadas com domicílios humanos. As espécies mais predominantes com maior importância epidemiológica, com distribuição ampla no Ceará e presente no ambiente peridoméstico foram: Triatoma brasiliensis, Triatoma pseudomaculata, Panstrogylus megistus, Panstrogylus lutzi e Rhodnius nasutus. Várias espécies de triatomíneos tem a capacidade de transmitir Trypanosoma cruzi e de se adaptar com o ambiente peridoméstico e doméstico tornando o homem mais suscetível a infecção, sendo assim necessário estratégias de vigilância e controle do vetor.

Ocorrência de triatomíneos no Estado do Ceará, Brasil / Occurrence of triatomines in the state of Ceará, Brazil

Esta revisão integrativa tem como objetivo analisar as publicações científicas nos últimos doze anos sobre triatomíneos encontrados no Estado do Ceará. Para tal, nos bancos de dados da Biblioteca Virtual em Saúde (BVS) foi realizada uma busca com associação dos descritores "Doença de Chagas", "Triatomíneos" e "Brasil". Após aplicação dos critérios de inclusão, exclusão e da análise dos seus conteúdos, oito artigos realizados no Estado do Ceará foram selecionados para a análise do estudo. Algumas espécies de triatomíneos encontradas no Nordeste são de extrema importância epidemiológica para o homem, pois estão associadas com domicílios humanos. As espécies mais predominantes com maior importância epidemiológica, com distribuição ampla no Ceará e presente no ambiente peridoméstico foram: Triatoma brasiliensis, Triatoma pseudomaculata, Panstrogylus megistus, Panstrogylus lutzi e Rhodnius nasutus. Várias espécies de triatomíneos tem a capacidade de transmitir Trypanosoma cruzi e de se adaptar com o ambiente peridoméstico e doméstico tornando o homem mais suscetível a infecção, sendo assim necessário estratégias de vigilância e controle do vetor. (AU)

This integrative review aims to analyze the scientific publications in the last twelve years on triatomines found at Ceará State. For this, a search was performed in the Biblioteca Virtual em Saúde (BVS) databases with association of the descriptors "Chagas Disease", "Triatomines" and "Brazil". After applying the inclusion, exclusion criteria and analysis of their content, eight articles were selected for the analysis and discussion. Some species of triatomines found in the Northeast region are of extreme epidemiological importance since they are associated with human households. The most prevalent species with epidemiological importance due to their large distribution in Ceará and presence in the peridomestic environment are: Triatoma brasiliensis, Triatoma pseudomaculata, Panstrogylus megistus, Panstrogylus lutzi and Rhodnius nasutus. Several species of triatomines have the capacity to transmit T. cruzi and the ability to adapt to the peridomestic and domestic environment turning humans more susceptible to infection, thus requiring surveillance and vector control strategies. (AU)

Ocorrência de triatomíneos no Estado do Ceará, Brasil / Occurrence of triatomines in the state of Ceará, Brazil

Esta revisão integrativa tem como objetivo analisar as publicações científicas nos últimos doze anos sobre triatomíneos encontrados no Estado do Ceará. Para tal, nos bancos de dados da Biblioteca Virtual em Saúde (BVS) foi realizada uma busca com associação dos descritores “Doença de Chagas”, “Triatomíneos” e “Brasil”. Após aplicação dos critérios de inclusão, exclusão e da análise dos seus conteúdos, oito artigos realizados no Estado do Ceará foram selecionados para a análise do estudo. Algumas espécies de triatomíneos encontradas no Nordeste são de extrema importância epidemiológica para o homem, pois estão associadas com domicílios humanos. As espécies mais predominantes com maior importância epidemiológica, com distribuição ampla no Ceará e presente no ambiente peridoméstico foram: Triatoma brasiliensis, Triatoma pseudomaculata, Panstrogylus megistus, Panstrogylus lutzi e Rhodnius nasutus. Várias espécies de triatomíneos tem a capacidade de transmitir Trypanosoma cruzi e de se adaptar com o ambiente peridoméstico e doméstico tornando o homem mais suscetível a infecção, sendo assim necessário estratégias de vigilância e controle do vetor.

This integrative review aims to analyze the scientific publications in the last twelve years on triatomines found at Ceará State. For this, a search was performed in the Biblioteca Virtual em Saúde (BVS) databases with association of the descriptors “Chagas Disease”, “Triatomines” and “Brazil”. After applying the inclusion, exclusion criteria and analysis of their content, eight articles were selected for the analysis and discussion. Some species of triatomines found in the Northeast region are of extreme epidemiological importance since they are associated with human households. The most prevalent species with epidemiological importance due to their large distribution in Ceará and presence in the peridomestic environment are: Triatoma brasiliensis, Triatoma pseudomaculata, Panstrogylus megistus, Panstrogylus lutzi and Rhodnius nasutus. Several species of triatomines have the capacity to transmit T. cruzi and the ability to adapt to the peridomestic and domestic environment turning humans more susceptible to infection, thus requiring surveillance and vector control strategies.

Leishmania braziliensis isolates differing at the genome level display distinctive features in BALB/c mice.

Leishmania braziliensis is the species responsible for the majority of cases of human cutaneous leishmaniasis in Brazil. In the present study, L. braziliensis isolates from two different geographic areas in Brazil were studied by RAPD, using arbitrary primers. We also evaluated other biological features of these two isolates. We compared (a) the clinical features they initiate or not once delivered subcutaneously as stationary-phase promastigotes in the footpad of BALB/c mice; (b) the parasite load in both the footpad and the draining lymph node; (c) the cytokines present in the supernatant of cultures of the cell suspensions from the draining lymph nodes; and (d) the cell types present at the site of parasite delivery. The results show that the L. braziliensis strain from Ceará (H3227) is genotypically different from the L. braziliensis strain from Bahia (BA788). H3227-parasitized mice developed detectable lesions, whereas BA788-parasitized mice did not. Fifteen days post parasite inoculation there was an increase in the numbers of macrophages and lymphocytes in the footpads, whatever the parasite inoculum. Parasite load at the inoculation site--namely the footpad--did not differ significantly; in draining lymph nodes, however, it increased over the period under study. Early after parasite inoculation, the cells recovered from the draining lymph nodes of BA788-parasitized mice produced higher levels of IFN-gamma, a feature coupled to a higher number of NK cells. Later, after the parasite inoculation, there was an increased content of IL-12p70 and IL-10 in the supernatant of cells recovered from the lymph nodes of H3227-parasitized mice. This comparative analysis points out that L. braziliensis isolates differing in their genomic profiles do establish different parasitic processes in BALB/c mice.

Distinct cellular migration induced by Leishmania infantum chagasi and saliva from Lutzomyia longipalpis in a hemorrhagic pool model.

Recruitment of a specific cell population after Leishmania infection can influence the outcome of the disease. Cellular migration in response to Leishmania or vector saliva has been reported in air pouch model, however, cellular migration induced by Leishmania associated with host's blood and vector saliva in this model has not been described. Herein we investigated cellular migration into air pouch of hamster after stimulation with combination of L. chagasi and host's blood and Lutzomyia longipalpis saliva. Migration induced by saliva was 3-fold more than those induced by L. chagasi alone. Additionally, L. chagasi associated with blood and saliva induced significantly even more leukocytes into air pouch than Leishmania alone. L. chagasi recruited a diverse cell population; however, most of these cells seem to have not migrated to the inflammatory exudate, remaining in the pouch lining tissue. These results indicate that L. chagasi can reduce leukocyte accumulation to the initial site of infection, and when associated with vector saliva in the presence of blood components, increase the influx of more neutrophils than macrophages, suggesting that the parasite has developed a strategy to minimize the initial inflammatory response, allowing an unlimited progression within the host. This work reinforces the importance of studies on the salivary components of sand fly vectors of leishmaniasis in the transmission process and the establishment of the infection.

DISTINCT CELLULAR MIGRATION INDUCED BY Leishmania infantum chagasi AND SALIVA FROM Lutzomyia longipalpis IN A HEMORRHAGIC POOL MODEL / Migração celular distinta induzida por Leishmania infantum chagasi e saliva de Lutzomyia longipalpis em um modelo de pool hemorrágico

Recruitment of a specific cell population after Leishmania infection can influence the outcome of the disease. Cellular migration in response to Leishmania or vector saliva has been reported in air pouch model, however, cellular migration induced by Leishmania associated with host's blood and vector saliva in this model has not been described. Herein we investigated cellular migration into air pouch of hamster after stimulation with combination of L. chagasi and host's blood and Lutzomyia longipalpis saliva. Migration induced by saliva was 3-fold more than those induced by L. chagasi alone. Additionally, L. chagasi associated with blood and saliva induced significantly even more leukocytes into air pouch than Leishmania alone. L. chagasi recruited a diverse cell population; however, most of these cells seem to have not migrated to the inflammatory exudate, remaining in the pouch lining tissue. These results indicate that L. chagasi can reduce leukocyte accumulation to the initial site of infection, and when associated with vector saliva in the presence of blood components, increase the influx of more neutrophils than macrophages, suggesting that the parasite has developed a strategy to minimize the initial inflammatory response, allowing an unlimited progression within the host. This work reinforces the importance of studies on the salivary components of sand fly vectors of leishmaniasis in the transmission process and the establishment of the infection.

O recrutamento de uma população de células específicas após infecção por Leishmania pode influenciar o resultado da doença. A migração celular em resposta a Leishmania ou saliva do vetor tem sido reportada utilizando o modelo da bolsa de ar subcutânea, entretanto, a migração celular induzida por Leishmania associada com o sangue do hospedeiro e saliva do vetor neste modelo ainda não foi descrita. Neste trabalho foi investigada a migração celular no modelo da bolsa de ar subcutânea em hamster após a estimulação com a combinação de L. chagasi, sangue do hospedeiro e saliva de Lutzomyia longipalpis. A migração induzida por saliva foi três vezes maior do que a induzida por L. chagasi sozinha. Adicionalmente, L. chagasi associada com sangue e saliva induziu significativamente ainda mais leucócitos no exsudato inflamatório do que o estímulo com Leishmania sozinha. L. chagasi recrutou uma população de células distintas, no entanto, a maioria dessas células parece não ter migrado para o exsudato inflamatório, permanecendo no tecido da bolsa de ar. Estes resultados indicam que L. chagasi pode reduzir o acúmulo de leucócitos para o local inicial da infecção e que quando associada à saliva do vetor e na presença de componentes do sangue aumenta o influxo de mais neutrófilos do que macrófagos, sugerindo que o parasito desenvolveu uma estratégia para minimizar a resposta inflamatória inicial, permitindo uma progressão ilimitada dentro do hospedeiro. Este trabalho reforça a importância de mais estudos sobre os componentes da saliva dos vetores das leishmanioses no processo de transmissão e no estabelecimento da infecção.

Distinct Leishmania braziliensis isolates induce different paces of chemokine expression patterns.

Inflammatory events during Leishmania braziliensis infection in mice were investigated. Large lesions were directly correlated with the inflammatory reaction but not with parasite burden. Different L. braziliensis strains induce different paces of chemokine expression patterns, leading to diverse cell recruitment and differential inflammatory responses.