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1.
Rev Bras Parasitol Vet ; 34(1): e016524, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39907366

RESUMO

In this study, an evaluation was made of three treatments against feline leishmaniosis (FeL) and their impacts on the transmission of Leishmania infantum to its vector, Lutzomyia longipalpis. A cat with clinical signs of FeL was examined and L. infantum diagnosed. Subsequently, the cat was subjected to xenodiagnosis and L. infantum detected in the vectors. The cat was then treated with three different drugs and the clinical improvement and parasite transmissibility to the vector were evaluated. Promastigotes were observed in 21/52 female sandflies (40.38%) in a xenodiagnosis prior to the treatments. Clinical signs persisted after the first treatment with marbofloxacin, and the cat remained positive in serological, molecular, and parasitological tests. Therefore, the cat was treated with miltefosine but remained sick and tested positive. A second xenodiagnosis was performed a month after treatment with miltefosine, and promastigotes were observed in 5/9 females (55.55%). Lastly, the cat was treated with allopurinol, which led to good clinical improvement, but it remained positive, and a final xenodiagnosis revealed Leishmania in 2/29 (6.89%) females. The results showed that only treatment with allopurinol produced a good clinical response, but none of the treatments succeeded in eliminating L. infantum infection or preventing transmission to the vector.


Assuntos
Doenças do Gato , Leishmania infantum , Leishmaniose Visceral , Psychodidae , Animais , Gatos , Leishmania infantum/isolamento & purificação , Psychodidae/parasitologia , Doenças do Gato/diagnóstico , Doenças do Gato/parasitologia , Doenças do Gato/tratamento farmacológico , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/tratamento farmacológico , Feminino , Antiprotozoários/uso terapêutico , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Insetos Vetores/parasitologia , Fluoroquinolonas
2.
Infect Dis Poverty ; 14(1): 4, 2025 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-39885606

RESUMO

BACKGROUND: Human visceral leishmaniasis (VL) is a systemic disease with high case-fatality rates and a widespread distribution. Continuous evaluation of the risk factors for VL is essential to ensure the effective implementation of prevention and control measures. The present study reviews the factors associated with VL in the Americas. METHODS: This systematic review updates a previous 2013 report by including cross-sectional, cohort and case-control studies published between July 2011 and April 2024. Associations between VL and risk factors were analyzed using random-effects meta-analysis, subgroup analysis, and meta-regression models. Studies were classified according to level of evidence using the GRADE approach and the evolution in the quality of investigations was assessed. RESULTS: Forty-six studies were included in the review and 21 variables were evaluated in the meta-analyses. Combination of all study types revealed that men had greater chances of VL than women, but the association was strong and significant only in case-control studies. Although higher chances of VL in children and in households with dogs or chickens/other fowl were identified in case-control studies, an inverse association was observed in cross-sectional and cohort studies. Higher chances of VL were associated with poor economic/living conditions, individuals living in domiciles with backyards or with seropositive dogs, and individuals with prior contact with infected household members/relatives/neighbors. The level of evidence for associations of VL with sex and age was classified as moderate whilst that for all other associations was either low or very low. The methodological quality of recent studies showed a positive progression but shortcomings were still evident regarding selection criteria and methods of data analysis. CONCLUSION: While there is a higher incidence of symptomatic VL among men and children, the likelihood of infection is similar between the groups. There is insufficient evidence to support the claim that the presence of dogs or fowl at the domicile increases the chances of VL. However, socioeconomic and living conditions, as well as previous occurrence of human and canine VL, are influential factors. Future research should be conducted with greater statistical power and using molecular diagnostic techniques, preferably involving cohort studies in diverse Latin American countries.


Assuntos
Leishmaniose Visceral , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária , Humanos , Fatores de Risco , Animais , América/epidemiologia , Cães , Masculino , Feminino , Estudos Transversais , Estudos de Casos e Controles
3.
Rev Bras Parasitol Vet ; 34(1): e014824, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39813458

RESUMO

This study evaluated dynamics of antibodies in dogs treated for canine visceral leishmaniasis (CVL). Twenty-one dogs naturally infected by Leishmania spp. were grouped based on the treatment protocol: G1 (n=4) received allopurinol; G2 (n=10) allopurinol with miltefosine; and G3 (n=7) allopurinol, miltefosine and Leish-Tec® vaccine. The dogs were monitored monthly for a period of one year. To verify serum antibody titers, an indirect immunofluorescence reaction was performed. We found that dogs from G1 and G2 had lower clinical scores and antibody titers, when compared to the parameters evaluated in pre-treatment; however, clinical relapses were observed in three animals. In G3, clinical scores were lower than pre-treatment; however, they presented relatively stable antibody titers and no clinical relapse was observed. All animals submitted to the evaluated treatment protocols showed relative improvement in clinical signs. Furthermore, the immune response of animals must be considered, given the challenges of parasitic loads in infections. Therefore, it is necessary to complement the methods of clinical and therapeutic monitoring of dogs with CVL in order to establish the risk of transmissibility of the agent in infected and treated dogs.


Assuntos
Alopurinol , Anticorpos Antiprotozoários , Antiprotozoários , Doenças do Cão , Leishmaniose Visceral , Cães , Animais , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/diagnóstico , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Doenças do Cão/imunologia , Doenças do Cão/sangue , Anticorpos Antiprotozoários/sangue , Alopurinol/uso terapêutico , Antiprotozoários/uso terapêutico , Antiprotozoários/administração & dosagem , Fosforilcolina/uso terapêutico , Fosforilcolina/imunologia , Fosforilcolina/análogos & derivados , Fosforilcolina/administração & dosagem , Masculino , Feminino
4.
Parasit Vectors ; 18(1): 2, 2025 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-39773298

RESUMO

BACKGROUND: We standardized two recombinase polymerase amplification (RPA) assays coupled with lateral flow (LF) strips for the detection of Leishmania braziliensis and Leishmania infantum kinetoplast DNA (kDNA). METHODS: The RPA-LF assays were tested at different temperatures and reaction times, using DNA from cultured L. braziliensis and L. infantum. The L. infantum RPA-LF was also tested using clinical samples (bone marrow and skin) from infected and uninfected dogs. RESULTS: The detection limits (analytical sensitivity) of the assays were 0.04 pg/µl and 0.04 ng/µl for L. braziliensis and L. infantum kDNA, respectively. Using clinical samples, the L. infantum RPA-LF successfully detected the parasite kDNA in bone marrow (21/30; 70.0%) and skin samples (23/30, 76.6%) from naturally infected dogs. We found an almost perfect agreement (kappa = 0.807) between RPA-LF for L. infantum and our reference quantitative real-time polymerase chain reaction (qPCR), considering clinical samples with a quantification cycle (Cq) < 30, whereas the agreement with samples with a Cq > 30 (lower parasite loads) was moderate (kappa = 0.440). CONCLUSIONS: The RPA-LF assays developed here may be promising diagnostic tools for point-of-care diagnosis of L. infantum and L. braziliensis infection in dogs, particularly in remote rural areas lacking laboratory infrastructure.


Assuntos
DNA de Cinetoplasto , Doenças do Cão , Leishmania braziliensis , Leishmania infantum , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Sensibilidade e Especificidade , Animais , Cães , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Leishmania braziliensis/genética , Leishmania braziliensis/isolamento & purificação , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/veterinária , Técnicas de Diagnóstico Molecular/métodos , DNA de Cinetoplasto/genética , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/veterinária , Leishmaniose Cutânea/parasitologia , DNA de Protozoário/genética , Pele/parasitologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/veterinária
5.
PLoS One ; 20(1): e0313167, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39787198

RESUMO

In Brazil, Visceral Leishmaniases is caused by Leishmania infantum, and domestic dogs are the main reservoirs in its urban transmission cycle. As an alternative to euthanizing dogs, miltefosine has been used to treat canine visceral leishmaniasis since 2016. In this study, we have assessed the efficacy of miltefosine for treating canine visceral leishmaniasis in a new endemic area through follow-up of naturally infected dogs was evaluated. The clinical, parasitological, and histopathological characteristics of 21 dogs naturally infected with L. infantum were assessed at three time points: on the day before initiating miltefosine treatment (T0), immediately after treatment completion (T1), and 6 months after treatment completion (T2). Three dogs were treated exclusively with miltefosine, while eighteen received combination therapy with miltefosine with other treatments such as allopurinol, domperidone and immunotherapy. Skin biopsies were obtained from the abdomen to assess inflammatory responses and to quantify parasite loads using qPCR. The parasites were isolated using aspirates acquired from popliteal lymph nodes. Molecular and parasitological analyses confirmed the presence of L. infantum in all dogs, validating the effectiveness of skin and lymph node samples for diagnosis. The clinical conditions of the infected animals were improved and the skin parasite load decreased after treatment, even when distinct combination therapies were performed. The histopathological assessment revealed a miltefosine-induced reduction in the inflammatory response and a decrease in amastigotes number. Furthermore, a positive correlation was established between the reduction in parasite load and the enhancement of clinical scoring, as well as a reduction in the skin inflammatory response. Our findings suggest that miltefosine-based combination therapies reduce skin parasite load and improve clinical outcomes, while the dogs treated with miltefosine alone showed increased parasitic load and worsened clinical staging at T2. Considering this data belonging to a recent transmission area, treatment strategy suggests effective in controlling canine visceral leishmaniasis.


Assuntos
Antiprotozoários , Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Fosforilcolina , Animais , Cães , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico , Fosforilcolina/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/parasitologia , Doenças do Cão/patologia , Antiprotozoários/uso terapêutico , Antiprotozoários/farmacologia , Masculino , Feminino , Alopurinol/uso terapêutico , Brasil , Carga Parasitária , Seguimentos
6.
Acta Parasitol ; 70(1): 16, 2025 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-39777570

RESUMO

INTRODUCTION: Ensuring accuracy in the diagnosis of leishmaniasis is crucial due to the myriad of potential differential diagnoses. Given the inherent limitations of serological techniques, real-time polymerase chain reaction (qPCR) emerges as a superior alternative. Furthermore, parasitological methods, conventionally regarded as the gold standard owing to their high specificity, encounter challenges concerning sensitivity and invasiveness for patients. In this context, the present study aims to assess, via meta-analysis, the performance of qPCR in diagnosing visceral and cutaneous leishmaniasis. METHOD: This meta-analysis encompassed studies published between January 2011 and December 2022, sourced from six databases (PubMed, LILACS, Scopus, Scielo, EMBASE, and Web of Science), utilizing the keywords "qPCR," "molecular diagnosis," and "leishmaniasis." Epidemiological studies focusing on the efficacy of qPCR for leishmaniasis diagnosis were included. Data such as study demographics, geographic locations, sampling techniques, and the number of positive qPCR results were aggregated and analyzed to derive overall positivity rates, sensitivity, and specificity values associated with qPCR. Heterogeneity analysis was conducted on the data to select appropriate models, and the collective efficacy data of qPCR were illustrated in forest plots. RESULTS: Fifty-four studies met all inclusion criteria. The positivity rates for human visceral and cutaneous leishmaniasis were 27.07% (95% CI: 17.81-36.33%) and 60.40% (95% CI: 30.23-90.57%), respectively. In cases of visceral leishmaniasis in dogs, cats, and wild animals, the positivity rates were 26.55% (95% CI: 21.40-31.70%), 0.92% (95% CI: 0.09-1.75%), and 28.98% (95% CI: 21.86-35.10%), respectively. Analysis of the selected studies revealed high overall sensitivity and specificity values achieved with qPCR, at 91.08% (95% CI: 81.77-100.39%) and 98.08% (95% CI: 97.13-99.03%), respectively. CONCLUSION: This study indicates that qPCR is a highly sensitive and specific tool, adequately suitable for the diagnosis of human visceral and cutaneous leishmaniasis, as well as visceral leishmaniasis in animals.


Assuntos
Leishmania , Leishmaniose Cutânea , Leishmaniose Visceral , Reação em Cadeia da Polimerase em Tempo Real , Animais , Gatos , Cães , Humanos , Leishmaniose Cutânea/diagnóstico , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Sensibilidade e Especificidade , Leishmania/genética , Leishmania/isolamento & purificação
7.
Parasitol Res ; 123(11): 372, 2024 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-39514097

RESUMO

Canine visceral leishmaniasis (CVL) is a parasitic disease caused by the protozoan Leishmania infantum. Neurological infection occurs due to the parasite's ability to cross the blood-brain barrier. It is known that dogs can remain infected with a subclinical infection for life, potentially acting as reservoirs for L. infantum when bitten by sandflies. In this context, the objective of this study was to evaluate the occurrence of Leishmania spp. in the brains of dogs from the metropolitan region of Rio Grande do Sul, Brazil, without a history of neurological disease but residing in an endemic area for L. infantum. A total of 200 samples, from 2022 to 2023, were evaluated using conventional Polymerase Chain Reaction (PCR) with the primers Leishmini-F GGKAGGGGCGTTCTGC and Leishmini-R STATWTTACACCAACCCC, aiming to amplify a product of 120 base pairs for Leishmania spp. To identify the species, a multiplex PCR was used, differentiating L. braziliensis (127 bp), L. amazonensis (100 bp), and L. infantum (60 bp), with the molecular target being the conserved region of the kinetoplast DNA (kDNA) minicircle, specific to Leishmania spp. Of the 200 samples evaluated, 26.5% (53/200) tested positive in the conventional PCR reaction for Leishmania spp., with the PCR multiplex the only species detected was Leishmania infantum. The average age of the positive animals was 5.08 years, with 47.2% being females and 52.8% being males; among these, mixed-breed dogs were the most predominant, representing 43.4% of the total. Clinical signs varied: hepatomegaly in two dogs, pronounced neutrophilic hepatitis in one, splenomegaly in one with lymphoid hyperplasia, and glomerulonephritis and nephritis in two animals. Mild anemia and thrombocytopenia were found in eight, with pale mucous membranes in three, and diffuse alveolar edema in one case. Notable pathological findings included suspected distemper in one animal and lymphoplasmacytic meningitis in another. Histopathological findings revealed alveolar edema and acute renal failure. A third dog exhibited bilateral hydrocephalus and diffuse edema in the brain. Additional changes, such as mild inflammatory infiltrate and slight vacuolar degeneration, were observed in 11.3% of the analyzed brains. There was no clinical suspicion of leishmaniasis in any of the studied cases. Therefore, the detection of L. infantum DNA in the brains of dogs suggests that animals with subclinical infection may play a crucial role in the spread of leishmaniasis, and infection by Leishmania spp. should be considered as a differential diagnosis for neurological disease in endemic areas for the protozoan.


Assuntos
Encéfalo , DNA de Protozoário , Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Reação em Cadeia da Polimerase , Animais , Cães , Brasil/epidemiologia , Leishmania infantum/genética , Leishmania infantum/isolamento & purificação , Doenças do Cão/parasitologia , Doenças do Cão/epidemiologia , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/diagnóstico , Encéfalo/parasitologia , DNA de Protozoário/genética , Reação em Cadeia da Polimerase/veterinária , Doenças Endêmicas/veterinária , Feminino , Masculino
8.
Parasit Vectors ; 17(1): 468, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39548568

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a zoonotic disease caused by Leishmania infantum and transmitted by the sand fly Lutzomyia longipalpis. Dogs are the major domestic reservoir of L. infantum. To prevent the spread of the disease, dog collars impregnated with 4% deltamethrin have been effectively used in VL endemic areas. However, this approach may contribute to the emergence of insecticide resistance in sand flies. Therefore, it is important to characterize the susceptibility of different populations of Lu. longipalpis to deltamethrin in areas where insecticide-impregnated dog collars are used. METHODS: Six field sand fly populations from Brazil were exposed to deltamethrin in CDC bottle bioassays at the diagnostic doses (DD) of 21.9 µg/bottle and 30 µg/bottle. For the dose-response (DR) experiments, doses of 1, 3, 5, 7, 9 and 11 µg/bottle of deltamethrin were used to impregnate bottles; control group bottles were impregnated with acetone only. Each bottle contained an average of 20 sand flies, both male and female, and they were exposed to either deltamethrin or acetone for 60 min. RESULTS: Based on the DD of 21.9 µg/bottle, three populations were susceptible to deltamethrin. In contrast, two populations collected from the states of Ceará and Minas Gerais exhibited mortality rates of 94.9% and 95.7%, indicating possible resistance, and one population from the state of Ceará showed resistance, with a mortality rate of 87.1%. At the DD of 30 µg/bottle, two populations from the states of Ceará and Piauí showed possible resistance, while the other four populations were susceptible. The resistance ratio (RR50) ranged from 2.27 to 0.54, and RR95 ranged from 4.18 to 0.33, indicating a low resistance intensity. CONCLUSIONS: This study established a DD for Lu. longipalpis using the CDC bottle bioassay. We found that Lu. longipalpis populations in three Brazilian states where insecticide-impregnated dog collars were used for VL control were susceptible to deltamethrin. However, one population in Ceará State was classified as resistant to deltamethrin. These results contribute to the current knowledge on sand fly resistance and surveillance, and highlight the need for a better understanding of the resistance mechanisms of Lu. longipalpis in areas where insecticide-impregnated dog collars have been widely used.


Assuntos
Resistência a Inseticidas , Inseticidas , Leishmaniose Visceral , Nitrilas , Psychodidae , Piretrinas , Animais , Piretrinas/farmacologia , Psychodidae/efeitos dos fármacos , Psychodidae/parasitologia , Nitrilas/farmacologia , Inseticidas/farmacologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/transmissão , Cães , Feminino , Brasil , Masculino , Doenças do Cão/prevenção & controle , Doenças do Cão/parasitologia , Doenças do Cão/transmissão , Leishmania infantum/efeitos dos fármacos , Controle de Insetos/métodos , Insetos Vetores/efeitos dos fármacos , Insetos Vetores/parasitologia
9.
Rev Saude Publica ; 58: 49, 2024.
Artigo em Português, Inglês | MEDLINE | ID: mdl-39607212

RESUMO

Lutzomyia longipalpis (Lutz & Neiva, 1912) constitutes the most epidemiologically relevant vector of visceral leishmaniasis (VL) in the New World. On October 25, 2023, the Macapá Center for Strategic Information in Health Surveillance registered a case of VL in the Km9 neighborhood, in Macapá. This study aimed to describe the Phlebotominae species in this area to assist the confirmation of the autochthony of the case. In total, 12 specimens were collected, of which five belonged to the Lutzomyia longipalpis species, confirming the presence of the VL agent vector and the possible autochthony of the transmission.


Lutzomyia longipalpis (Lutz & Neiva, 1912) é o vetor do agente da leishmaniose visceral (LV) no Novo Mundo de maior relevância epidemiológica. Em 25 de outubro de 2023, o Centro de Informações Estratégicas em Vigilância em Saúde de Macapá detectou um caso de LV no bairro Km9 desse município. O objetivo deste estudo foi identificar as espécies de flebotomíneos nessa área a fim de auxiliar na confirmação da autoctonia do caso. Foram coletados 12 espécimes, desses, cinco foram de Lu. longipalpis, confirmando assim a presença do vetor do agente da LV e a possível autoctonia da transmissão.


Assuntos
Insetos Vetores , Leishmaniose Visceral , Psychodidae , Psychodidae/classificação , Animais , Insetos Vetores/classificação , Leishmaniose Visceral/transmissão , Brasil , Feminino , Masculino , Humanos
10.
BMC Pediatr ; 24(1): 726, 2024 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-39533219

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a zoonotic disease caused by protozoa of the genus Leishmania and is transmitted by sandflies of the genus Lutzomyia. Children under 15 years are disproportionately affected. In pediatric patients, the clinical and laboratory features of VL often overlap with those of other infectious and hematology-oncology diseases, making differential diagnosis challenging. Rapid and accurate identification of VL is critical for effective treatment. This study aimed to evaluate the epidemiological, clinical, and laboratory characteristics of pediatric patients initially suspected of having VL and to compare their final diagnoses upon discharge from a referral hospital. METHODS: We retrospectively analyzed medical records of children with suspected VL, admitted between July 2014 and June 2019. RESULTS: Infectious diseases were confirmed in 61% of cases (86 patients), with VL confirmed in 55 cases. Hematology-oncology diseases were the second most common diagnosis, affecting 22.7% of patients (32 cases). Comparisons between the VL-confirmed group and those with other diagnoses revealed no significant age difference (p = 0.690). However, female sex, spleen size, and leukopenia were identified as significant predictors of VL. CONCLUSIONS: Female sex, spleen size, and leukopenia were key predictors for differentiating VL from other pediatric diseases in a referral center in the Northeast Region of Brazil.


Assuntos
Leishmaniose Visceral , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Criança , Diagnóstico Diferencial , Pré-Escolar , Lactente , Adolescente , Brasil/epidemiologia , Hospitais Pediátricos , Leucopenia/diagnóstico , Leucopenia/epidemiologia , Leucopenia/etiologia , Fatores Sexuais , Encaminhamento e Consulta
11.
Antimicrob Agents Chemother ; 68(11): e0083124, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39382276

RESUMO

Leishmaniasis is a parasitic neglected tropical disease, affecting 12 million people. Available treatments present several limitations, with an increasing number of resistance cases. In the search for new chemotherapies, the natural product dehydrodieugenol B was used as a scaffold for the synthesis of a series of derivatives, resulting in the discovery of the promising analog [4-(4-(5-allyl-3-methoxy-2-((4-methoxybenzyl)oxy)phenoxy)-3-methoxybenzyl)morpholine, 1]. In this work, we investigated the effect of compound 1 on cell signaling in Leishmania (L.) infantum, culminating in cell death, as well as its immunomodulatory effect in the host cell. Additionally, we performed a pharmacokinetic profile study in an animal model. After treatment, compound 1 induced the alkalinization of acidocalcisomes and concomitant Ca2+ release in the parasite. These events may induce depolarization of the mitochondrial potential, with successive collapse of the bioenergetic system, leading to a reduction of ATP and reactive oxygen species (ROS) levels. The analysis of total proteins and protein profile by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) demonstrated that compound 1 also altered the parasite proteins after treatment. Transmission electron microscopy studies revealed ultrastructural damage to mitochondria; together, these data suggest that compound 1 may promote autophagic cell death. Additionally, compound 1 also induced an immunomodulatory effect in host cells, with a reduction of Th1 and Th2 cytokine response, characterizing an anti-inflammatory compound. The obtained pharmacokinetic profile in rats enhances the potential of the compound, with a mean plasma half-life (T1/2) of 21 h. These data reinforce the potential of compound 1 as a new lead for future efficacy studies.


Assuntos
Antiprotozoários , Leishmania infantum , Leishmaniose Visceral , Espécies Reativas de Oxigênio , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Animais , Leishmania infantum/efeitos dos fármacos , Antiprotozoários/farmacologia , Antiprotozoários/farmacocinética , Antiprotozoários/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Eugenol/farmacologia , Eugenol/farmacocinética , Eugenol/análogos & derivados , Eugenol/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Humanos , Ratos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Feminino
12.
Parasite Immunol ; 46(10): e13063, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39360782

RESUMO

Interleukin 27 (IL-27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL-27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL-27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL-21, anti-L. infantum antibodies and parasite loads. We performed functional assays followed by IL-27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD-1, CTLA-4, phospho-Stat-1/3, T-bet, GATA3 and nitric oxide production (NO). Both IL-27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL-21 (r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti-L. infantum IgG antibodies (r = 0.38, p < 0.040) and parasite load (r = 0.47, p < 0.009). IL-27 and IL-21 participate of immune responses in CanL. IL-27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD-1, CTLA-4, T-bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL-27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.


Assuntos
Doenças do Cão , Interleucina-27 , Leishmania infantum , Leishmaniose Visceral , Carga Parasitária , Animais , Cães , Doenças do Cão/imunologia , Doenças do Cão/parasitologia , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/parasitologia , Interleucina-27/metabolismo , Imunidade Adaptativa , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Masculino , Baço/imunologia , Baço/parasitologia , Interleucinas/metabolismo , Interleucinas/imunologia , Feminino , Citocinas/metabolismo , Leucócitos/imunologia , Leucócitos/parasitologia
13.
Acta Trop ; 260: 107441, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39481509

RESUMO

Visceral leishmaniasis (VL) poses a serious health threat, particularly when untreated, necessitating accurate diagnosis. While the gold-standard method involves identifying amastigotes in bone marrow aspirate (BMA), this procedure is invasive and occasionally contraindicated. Additionally, when VL is associated with HIV infection the serologies accuracies could be affected. This study aims to evaluate and compare diagnostic methods for VL in patients with and without HIV coinfection. We enrolled prospectively 127 consecutive adult VL patients, 48 (37.8%) of whom had HIV coinfection, in Brazil's Midwestern region, where VL is endemic. Parasitological examination served as the reference standard for accuracy analysis, with index tests including immunofluorescent antibody test (IFAT), immunochromatographic test with rK39 protein (rK39-ICT), and blood polymerase chain reaction (PCR). Specificity assessment involved 430 healthy blood donors from the same endemic area. Ninety-two patients had parasitologically confirmed VL. Among HIV-uninfected patients, rK39-ICT exhibited sensitivity comparable to PCR (93.6%; 95% CI: 83.6-100 vs. 97.8%; 95% CI: 93.6-99.2, respectively) and superior to IFAT (71.1%; 95% CI: 57.9-84.3). However, in HIV-infected patients, rK39-ICT sensitivity was notably lower than PCR (40.0%; 95% CI: 22.5-57.5 vs. 97.4%; 95% CI: 92.5-98.9) and similar to IFAT (67.5%; 95% CI: 52.9-82.0). Combining two serological tests in parallel identified 82.1% of parasitologically confirmed VL cases, with a negative likelihood ratio significantly lower than either test alone. No test achieved a specificity of 90%, and there were no significant differences in specificity observed among the index tests. The positivity rate of parasitological examination in the 127 VL patients was higher in HIV-infected compared to HIV-uninfected patients, 91.3% (95% CI: 83.2-99.4) versus 67.6% (95% CI: 56.9-78.3), respectively. These findings underscore the necessity of accounting for HIV infection when choosing VL diagnostic methods. Although rK39-ICT provides reliable results in HIV-uninfected patients, BMA examination remains crucial for accurate diagnosis in individuals with HIV/AIDS. In cases where bone marrow aspiration is contraindicated, employing IFAT and rK39-ICT in parallel could be considered, as the occurrence of both positive results is uncommon in healthy individuals from endemic areas.


Assuntos
Infecções por HIV , Leishmaniose Visceral , Reação em Cadeia da Polimerase , Sensibilidade e Especificidade , Humanos , Leishmaniose Visceral/diagnóstico , Adulto , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Masculino , Feminino , Brasil/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Reação em Cadeia da Polimerase/métodos , Adulto Jovem , Testes Diagnósticos de Rotina/métodos , Cromatografia de Afinidade/métodos , Coinfecção/diagnóstico , Coinfecção/virologia , Adolescente , Antígenos de Protozoários/sangue
14.
Molecules ; 29(19)2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39407583

RESUMO

Visceral leishmaniasis (VL), caused by protozoa of the genus Leishmania, remains a significant public health concern due to its potentially lethal nature if untreated. Current chemotherapy options are limited by severe toxicity and drug resistance. Derivatives of 1,2,4-oxadiazole have emerged as promising drug candidates due to their broad biological activity. This study investigated the effects of novel 1,2,4-oxadiazole derivatives (Ox1-Ox7) on Leishmania infantum, the etiological agent of VL. In silico predictions using SwissADME suggest that these compounds have high oral absorption and good bioavailability. Among them, Ox1 showed the most promise, with higher selectivity against promastigotes and lower cytotoxicity towards L929 fibroblasts and J774.G8 macrophages. Ox1 exhibited selectivity indices of 18.7 and 61.7 against L. infantum promastigotes and amastigotes, respectively, compared to peritoneal macrophages. Ultrastructural analyses revealed severe morphological damage in both parasite forms, leading to cell death. Additionally, Ox1 decreased the mitochondrial membrane potential in promastigotes, as shown by flow cytometry. Molecular docking and dynamic simulations indicated a strong affinity of Ox1 for the L. infantum CYP51 enzyme. Overall, Ox1 is a promising and effective compound against L. infantum.


Assuntos
Antiprotozoários , Leishmania infantum , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Oxidiazóis , Proteínas de Protozoários , Leishmania infantum/efeitos dos fármacos , Oxidiazóis/química , Oxidiazóis/farmacologia , Antiprotozoários/farmacologia , Antiprotozoários/química , Animais , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Camundongos , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Linhagem Celular , Potencial da Membrana Mitocondrial/efeitos dos fármacos
15.
Antimicrob Agents Chemother ; 68(11): e0075624, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39387580

RESUMO

Visceral leishmaniasis, caused by Leishmania infantum in New World countries, is the most serious and potentially fatal form of leishmaniasis, if left untreated. There are currently no effective prophylactic measures, and therapeutic options are limited. Therefore, we investigated whether the aromatase inhibitor letrozole (LET), which is already used to treat breast cancer, has an antileishmanial activity and/or immunomodulatory potential and therefore may be used to treat L. infantum infection. LET was active against L. infantum promastigote and amastigote life cycle stages in an in vitro infection model using human THP-1 cell-derived macrophages. In human peripheral blood leukocytes ex vivo, LET reduced the internalized forms of L. infantum by classical monocytes and activated neutrophils. Concomitantly, LET stimulated the production of IL-12/TNF-α and decreased the production of IL-10/TGF-ß by peripheral blood phagocytes, while in T and B cells, it promoted the production of TNF-α/IFN-γ and decreased that of IL-10. In a murine infection model, LET significantly reduced the parasite load in the liver after just 5 days and in the spleen after 15 days. During in vivo treatment with LET, the production of TNF-α/IFN-γ also increased. In addition, the proportion of developing granulomas decreased and that of mature granulomas increased in the liver, while there was no significant change in organ architecture in the spleen. Based on these data, repositioning of LET may be promising for the treatment of visceral leishmaniasis in humans.


Assuntos
Reposicionamento de Medicamentos , Interleucina-10 , Leishmania infantum , Leishmaniose Visceral , Letrozol , Fator de Necrose Tumoral alfa , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Animais , Leishmania infantum/efeitos dos fármacos , Humanos , Camundongos , Letrozol/uso terapêutico , Letrozol/farmacologia , Interleucina-10/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/parasitologia , Feminino , Células THP-1 , Camundongos Endogâmicos BALB C , Interferon gama , Interleucina-12/metabolismo , Monócitos/efeitos dos fármacos , Monócitos/parasitologia , Carga Parasitária , Baço/parasitologia , Baço/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo
16.
Rev Soc Bras Med Trop ; 57: e007122024, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39319954

RESUMO

BACKGROUND: Although canine visceral leishmaniasis (CVL) transmission primarily occurs through the bite of phlebotomine sand flies infected with Leishmania infantum, alternative routes may exist. METHODS: Thirty-four dogs diagnosed with CVL were sampled for parasitological investigation in tissues from the reproductive tract. RESULTS: Amastigotes of Leishmania sp. were present in 79% (27/34) of the reproductive system samples, with distinct infection rates depending on the tissue. CONCLUSIONS: Our data confirms that alternative routes, such as horizontal and vertical transmissions, should be considered in the epidemiological chain of CVL.


Assuntos
Doenças do Cão , Leishmaniose Visceral , Animais , Cães , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/transmissão , Doenças do Cão/parasitologia , Feminino , Masculino , Leishmania infantum/isolamento & purificação
17.
Vet Parasitol Reg Stud Reports ; 55: 101108, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39326963

RESUMO

Here we described a case of fatal canine visceral leishmaniasis (VL) in French Guiana, a non-endemic VL Amazonian area. The dog was a 2-year-old pug imported from Brazil to French Guiana. Initially seen for a pruriginous lesion on the muzzle which healed after treatment, the dog was in a deteriorated condition and had sublingual, foreleg and eye ulcers, one month later. A visceral leishmaniasis was suspected by the veterinarian. The dog was hospitalized awaiting results, which revealed the presence of L. infantum. However, the dog succumbed suddenly before the results were returned. Few imported and scarce autochthonous canine VL cases have been previously reported in French Guiana, raising the need for local epidemiological surveillance, considering the possibility of unusual transmission routes of the parasite.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Animais , Leishmaniose Visceral/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/tratamento farmacológico , Cães , Guiana Francesa , Doenças do Cão/parasitologia , Doenças do Cão/diagnóstico , Leishmania infantum/isolamento & purificação , Evolução Fatal , Brasil , Masculino , Doenças Transmissíveis Importadas/parasitologia , Doenças Transmissíveis Importadas/veterinária , Doenças Transmissíveis Importadas/diagnóstico
18.
Sci Rep ; 14(1): 21542, 2024 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-39278963

RESUMO

Visceral leishmaniasis (VL) is an urgent public health concern in Brazil. We evaluated the spatiotemporal distribution of VL to better understand the effects of economic activities related to agriculture, livestock, and deforestation on its incidence in the Brazilian Legal Amazon (BLA). The data on newly confirmed cases of VL in Brazilian municipalities from 2007 to 2020 were extracted from the Brazilian Notifiable Diseases Information System (SINAN) and analyzed. The data on agricultural production (planted area in hectares) and livestock (total number of cattle) were obtained from the Brazilian Institute of Geography and Statistics (IBGE), whereas deforestation data (in hectares) were obtained from the Amazon Deforestation Estimation Project (PRODES). SatScan and the local indicators of spatial association (LISA) were used to identify the spatial and temporal patterns of VL and its relationships with economic and environmental variables. The cumulative incidence rate was found to be 4.5 cases per 100,000 inhabitants. Based on the LISA results, areas with a high incidence of VL and deforestation were identified in the states of Roraima, Pará, and Maranhão. Strengthening deforestation monitoring programs and environmental enforcement actions can help implement public policies to control illegal deforestation and mitigate the socio-environmental vulnerability in the BLA. Therefore, areas identified in this study should be prioritized for controlling VL.


Assuntos
Agricultura , Conservação dos Recursos Naturais , Leishmaniose Visceral , Gado , Análise Espaço-Temporal , Brasil/epidemiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Animais , Gado/parasitologia , Humanos , Incidência , Bovinos
19.
Front Immunol ; 15: 1373498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39192975

RESUMO

Introduction: Visceral leishmaniasis (VL) is an important tropical and neglected disease and represents a serious global health problem. The initial interaction between the phagocytes and the parasite is crucial to determine the pathogen's capacity to initiate infection and it shapes the subsequent immune response that will develop. While type-1 T-cells induce IL-6, IL-1ß, TNF-α, and IL-12 production by monocytes/macrophages to fight the infection, type-2 T-cells are associated with a regulatory phenotype (IL-10 and TGF-ß) and successful infection establishment. Recently, our group demonstrated the role of an important Th1/Th17 T-cell population, the mucosal-associated invariant T (MAIT) cells, in VL. MAIT cells can respond to L. infantum by producing TNF-α and IFN-γ upon MR1-dependent activation. Objective and methods: Here, we describe the impact of the MR1-blockage on L. infantum internalization on the functional profile of circulating neutrophils and monocytes as well as the impact of the MR1-blockage on the soluble mediator signatures of in vitro whole blood cultures. Results: Overall, our data showed that VL patients presents higher percentage of activated neutrophils than asymptomatic and non-infected controls. In addition, MR1 blockade led to lower TNF-α and TGF-ß production by non-activated neutrophils from asymptomatic individuals. Moreover, TNF-α and IL-10 production by monocytes was higher in VL patients. In the analysis of soluble mediators produced in vitro, MR1-blockade induced a decrease of IFN-γ and an increase of IL-10, IL-27 and IL-33 in the cell cultures of AS group, a cytokine pattern associated with type 2 deleterious response. Discussion and conclusion: These data corroborate the hypothesis that MR1-restricted responses are associated to a protective role during Leishmania infection.


Assuntos
Citocinas , Leishmaniose Visceral , Monócitos , Leishmaniose Visceral/imunologia , Humanos , Citocinas/metabolismo , Adulto , Feminino , Masculino , Monócitos/imunologia , Monócitos/metabolismo , Leishmania infantum/imunologia , Neutrófilos/imunologia , Neutrófilos/metabolismo , Células T Invariantes Associadas à Mucosa/imunologia , Células T Invariantes Associadas à Mucosa/metabolismo , Pessoa de Meia-Idade , Adulto Jovem , Adolescente
20.
BMC Infect Dis ; 24(1): 854, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39174900

RESUMO

BACKGROUND: Coronavirus disease 2019 originated in China and swiftly spread worldwide, posing a significant threat to public health. Caused by SARS-CoV-2, it manifests as a flu-like illness that can escalate to Acute Respiratory Distress Syndrome, potentially resulting in fatalities. In countries where HIV/Leishmania infantum is endemic, the occurrence of concurrent SARS-CoV-2/HIV/Leishmania infantum infections is a reality, prompting inquiries into appropriate clinical management. CASE PRESENTATION: We present the case of a 48-year-old woman who was hospitalized for 36 days across three different hospitals in the state of Pernambuco, Brazil. She was diagnosed with SARS-CoV-2/HIV/L. infantum coinfection. The patient exhibited severe COVID-19 symptoms, including fever, productive cough, and dyspnea. Throughout her hospitalization, she experienced oxygen saturation levels of ≤ 93%, along with fluctuations in blood pressure, respiratory rate, and heart rate. Her blood tests revealed lymphopenia, leukopenia, and neutropenia, while laboratory results indicated abnormal levels of d-dimer, AST, ALT, lactate dehydrogenase, ferritin, and C-reactive protein. A computed tomography scan revealed 75% involvement of the lung parenchyma with patchy ground-glass opacities. CONCLUSION: Against all odds, the patient was discharged. The leukopenia associated with HIV/L. infantum may have played a decisive role. Further studies are necessary to better understand diagnostic strategies and clinical management measures for HIV/L. infantum coinfected patients who are susceptible to SARS-CoV-2 infection.


Assuntos
COVID-19 , Coinfecção , Infecções por HIV , Leishmania infantum , SARS-CoV-2 , Humanos , Feminino , COVID-19/complicações , Pessoa de Meia-Idade , Coinfecção/virologia , Coinfecção/parasitologia , Infecções por HIV/complicações , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Brasil
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