Matrix metalloproteinases -2 and -9 expression in dogs with visceral leishmaniasis: A systematic review.

The matrix metalloproteinases (MMPs) are engaged in the degradation and remodeling of the extracellular matrix and vessels, allowing the progression of pathological processes. Recent studies pointed that MMP -2 and -9 are promising visceral leishmaniasis biomarkers. Thus, the present studystudy aimed to review published scientific literature related to MMP-2 and -9 activity on canine visceral leishmaniasis (CVL). The review followed the PRISMA method, searching for articles in ScienceDirect, PubMed, Scopus, Lilacs, Medline and Google Scholar from inception until 20 March 2022 by employing the following terms: "dog", "matrix metalloproteinases" and "Visceral Leishmaniasis" or "Kala Azar". The selected articles were read in full and only those consistent with the eligibility criteria were included in the review. Of 238 articles from the initial search, only five were deemed eligible, which were conducted between 2010 and 2018. All studies were performed in Brazil. It was observed that there was a higher expression of proMMP-2 in cerebrospinal (CS) fluid and serum and active MMP-2 in different skin areas, mainly in high parasite load areas. As for MMP-9, the pro and active forms were both expressed in CS fluid, serum and different skin areas. The MMP-2 can be considered a biomarker of bad prognostic as it plays an inflammatory role with a greater release in the initial phase of the disease, where MMP-9 is perceived in the chronic phase of CVL. Future research on the subject with greater methodological rigor and bigger sample sizes are mandatory to clarify the role of MMPs on disease progression.

Distribuição espacial e frequência da leishmaniose visceral canina no nordeste brasileiro: uma revisão sistemática / Spatial distribution and frequency of canine visceral leishmaniasis in northeastern Brazil: a systematic review

Introdução:o Brasil está entre os sete países responsáveis por mais de 90% dos casos de leishmaniose visceral humana (LVH), sendo a região Nordeste a mais endêmica. ALV também afeta cães, que apresentam sintomas debilitantes e podem ser fatais. Os cães são os principais os pedeiros desse parasita. No entanto,há carência de dados epidemiológicos sobre leishmaniose visceral canina (LVC) no Brasil, principalmente na região nordeste. Objetivo:realizar uma revisão sistemática para demonstrar a frequência e a distribuição espacial da LVC nos estados do nordeste do Brasil. Métodos:as seguintes bases de dados foram utilizadas para busca eletrônica: Google Scholar, Lilacs, Scopus, Pubmed, Scielo, Web of Science, Cochrane, OpenGrey e OpenThesis. Os descritores de busca foram: leishmaniose visceral canina, nordeste do Brasil, Alagoas, Bahia, Ceará, Maranhão, Paraíba, Pernambuco, Piauí, Rio Grande do Norte e Sergipe. Resultados:a análise dos 73 artigos selecionados demonstrou uma frequência de LVC de 4,1% no Nordeste do Brasil, entre 1973 a 2022. O estado da Bahia apresentou a frequência (43,9%) e o Piauí a menor (1,9%). Conclusão:os dados demonstram, pela primeira vez, o caráter endêmico da LVC em toda a região nordeste e o caráter propício de disseminação de LVC nessa região. Esses dados também destacam a necessidade de ações governamentais e aprofundamento das pesquisas por parte da comunidade científica

Seroprevalence of anti-Toxoplasma gondii antibodies in dogs from rural area of Nossa Senhora da Glória, Sergipe, Brazil / Soroprevalência de anticorpos anti-Toxoplasma gondii em cães de área rural de Nossa Senhora da Glória, Sergipe, Brasil

Toxoplasma gondii is a protozoan parasite with worldwide distribution. Dogs are considered sentinel animals, useful for the detection of environmental infections and outbreaks of disease through serological surveys. Considering this, we aimed to assess the seroprevalence of toxoplasmosis in dogs from rural areas of the hinterland of the state of Sergipe, Northeastern Brazil. A total of 77 blood samples were collected from dogs and analyzed by the Indirect Hemagglutination test for the detection of anti-T. gondii antibodies Samples were considered positive when titers greater than or equal to 1:16 were observed. In addition, an epidemiological questionnaire designed to identify characteristics of the animal was performed to owners regarding sex, breed, age, sterilization, access to areas outside the house, environmental hygiene, contact with other animals and dog food. A total of 49.3% of dogs (n = 38) were positive for anti-T. gondii antibodies, most with high titers (44.7%). A higher relative frequency of seropositivity was observed in male dogs, not sterilized, mixed breed, which were fed exclusively on homemade food and had access to the street and contact with other animals. Taken together, our data reinforce the importance of developing health education actions within the scope of public health aimed at preventing this zoonosis.

Toxoplasma gondii é um protozoário com distribuição mundial. Os cães são considerados animais sentinela, úteis para a detecção de infecções ambientais e surtos da doença por meio de levantamentos sorológicos. Portanto, o presente estudo teve como objetivo determinar a soroprevalência da toxoplasmose em cães da zona rural da região rural do Alto Sertão Sergipano, Brasil. Um total de 77 amostras de sangue de cães foram coletadas no município de Nossa Senhora da Glória, Sergipe e submetidas ao teste de Hemaglutinação Indireta para detecção de anticorpos anti-T. gondii, considerando títulos maiores ou iguais a 1:16 como positivos. Além disso, foi aplicado um questionário epidemiológico aos proprietários solicitando informações sobre sexo, raça, idade, esterilização, acesso às ruas, limpeza do ambiente, contato com outros animais e ração, além de dados do proprietário, como renda familiar e nível de educação. 49,3% dos cães (38/77) apresentaram anticorpos anti-T. gondii, a maioria com títulos elevados (44,7%). Foi observado maior frequência relativa de soropositividade em cães macho, não esterilizados, sem raça definida, que se alimentam exclusivamente de comida caseira e tem acesso a rua e contato com outros animais. Os dados obtidos reforçam a importância do desenvolvimento de ações de educação em saúde no âmbito da saúde pública voltadas à prevenção dessa zoonose.

Anti-parasite therapy drives changes in human visceral leishmaniasis-associated inflammatory balance.

Visceral leishmaniasis (VL) remains a major public health problem worldwide. Cytokine balance is thought to play a critical role in the development of this disease. Here, we perform a prospective exploratory study addressing whether simultaneous assessment of circulating levels of different lipid mediators and cytokines could highlight specific pathways involved with VL pathogenesis. VL patients displayed substantial increases in serum levels of Prostaglandin F2α (PGF2α), Leukotriene B4 (LTB4), Resolvin D1 (RvD1), IL-1ß, IL-6, IL-8, IL-10, IL-12p70 and TNF-α compared with uninfected endemic control group, while exhibiting decreased levels of TGF-ß1. Hierarchical cluster analysis of the prospective changes in the expression level of theses parameters upon anti-Leishmania treatment initiation revealed that the inflammatory profile observed in active disease gradually changed over time and was generally reversed at day 30 of therapy. Furthermore, not only the individual concentrations of most of the inflammatory biomarkers changed upon treatment, but the correlations between those and several biochemical parameters used to characterize VL disease activity were also modified over time. These results demonstrate that an inflammatory imbalance hallmarks active VL disease and open perspective for manipulation of these pathways in future studies examining a potential host-directed therapy against VL.

Molecular signatures of neutrophil extracellular traps in human visceral leishmaniasis.

BACKGROUND: Infections with parasites of the Leishmania donovani complex result in clinical outcomes that range from asymptomatic infection to severe and fatal visceral leishmaniasis (VL). Neutrophils are major players of the immune response against Leishmania, but their contribution to distinct states of infection is unknown. Gene expression data suggest the activation of the NETosis pathway during human visceral leishmaniasis. Thus, we conducted an exploratory study to evaluate NET-related molecules in retrospective sera from VL patients, asymptomatic individuals and uninfected endemic controls. RESULTS: We demonstrate that VL patients and asymptomatic individuals exhibit differential regulation of molecules associated with neutrophil extracellular traps (NET). These differences were observed at the transcriptional level of genes encoding NET-associated proteins; in quantifications of cell free DNA and metalloproteinase 9; and in enzymatic activity of DNAse and elastase. Moreover, multivariate analysis resulted in class-specific signatures, and ROC curves demonstrate the ability of these molecules in discriminating asymptomatic infection from uninfected controls. CONCLUSION: Molecules that are associated with NETs are differentially regulated between distinct states of infection with L. infantum, suggesting that NETs might have distinct roles depending on the clinical status of infection. Although unlikely to be exclusive for VL, these signatures can be useful to better characterize asymptomatic infections in endemic regions of this disease.

Epidemiological aspects and spatial distribution of human and canine visceral leishmaniasis in an endemic area in northeastern Brazil.

Visceral leishmaniasis (VL) is a systemic disease endemic in tropical countries and transmitted through sand flies. In particular, Canis familiaris (or domesticated dogs) are believed to be a major urban reservoir for the parasite causing the disease Leishmania. The average number of human VL cases was 58 per year in the state of Sergipe. The city of Aracaju, capital of Sergipe in Northeastern Brazil, had 159 cases of VL in humans. Correlatively, the percentage of serologically positive dogs for leishmaniasis increased from 4.73% in 2008 to 12.69% in 2014. Thus, these studies aimed to delineate the spatial distribution and epidemiological aspects of human and canine VL as mutually supportive for increased incidence. The number of human cases of VL and the frequency of canine positive serology for VL both increased between 2008 and 2014. Spatial distribution analyses mapped areas of the city with the highest concentration of human and canine VL cases. The neighbourhoods that showed the highest disease frequency were located on the outskirts of the city and in urbanised areas or subjected to development. Exponential increase in VL-positive dogs further suggests that the disease is expanding in urban areas, where it can serve as a reservoir for transmission of dogs to humans via the sand fly vector.

Differential protein abundance in promastigotes of nitric oxide-sensitive and resistant Leishmania chagasi strains.

PURPOSE: Leishmania chagasi is the causative agent of zoonotic visceral leishmaniasis in Brazil. Domestic and stray dogs are the main reservoirs. The life cycle of the parasite involves two stages. Promastigotes are extracellular and develop within the sand fly gut. Amastigotes survive inside the harsh environment of the phagolysosome of mammalian host phagocytes, which display the nitric oxide defense mechanism. Surprisingly, we were able to isolate promastigotes that are also resistant to NO. This finding may be explained by the preadaptative hypothesis. An insight into the proteome of NO-sensitive and resistant promastigotes is presented herein. EXPERIMENTAL DESIGN: Total protein extracts were prepared from promastigote cultures of an NO-sensitive and a resistant strain at early-logarithmic, mid-logarithmic and stationary phase. A population enriched in metacyclic promastigotes was also isolated by Percoll gradient centrifugation. In vitro infectivity of both strains was compared. Differential protein abundance was analyzed by 2DE-MALDI-TOF/TOF. The most striking results were tested at the mRNA level by qRT-PCR. Three biological replicates were performed in all cases. RESULTS: NO-resistant L. chagasi promastigotes are more infective than NO-sensitive ones. Among the differentially abundant spots, 40 proteins could be successfully identified in the sensitive strain and 38 in resistant promastigotes. CONCLUSIONS AND CLINICAL RELEVANCE: The increase of G6PD and the decrease of ARG and GPX transcripts and proteins contribute to NO resistance in L. chagasi promastigotes. These proteins may be studied as potential drug targets and/or vaccine candidates in the future.

Acaricidal properties of vetiver essential oil from Chrysopogon zizanioides (Poaceae) against the tick species Amblyomma cajennense and Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

Ticks are arthropods widely distributed in tropical and subtropical regions, which can transmit infectious agents also responsible for zoonoses. Excessive use of conventional acaricides has resulted in the onset of drug resistance by these parasites, thus the need to use alternative methods for their control. This study evaluated the acaricidal activities of Chrysopogon zizanioides (vetiver) essential oils containing different zizanoic and khuzimol (high and low acidity) acid concentrations on Amblyomma cajennense and Rhipicephalus microplus (Acari: Ixodidae). To this aims, toxicity tests of different concentrations of examined essential oils were conducted on adult females and larval stages. Results showed that the essential oils of C. zizanioides with high and low acidity reduced oviposition of females, eggs hatch and larval survival, being more effective than some commercial products widely used to control these ectoparasites. These results indicate that the C. zizanoides essential oils are promising candidates as acaricidal agents and represent also an add value to vetiver oil with high acidity, which is commercially undervalued in the cosmetic industry.