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1.
mBio ; : e0099524, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38832792

RESUMO

Leishmania (L.) infantum is one of the main causative agents of animal and human leishmaniasis across many endemic areas in South America, Europe, North Africa, and Asia. Despite its clinical significance, little is known about the genetic diversity of L. infantum circulating in a given endemic area. Here, we investigate this important open question by applying a comparative genomics approach to seven L. infantum isolates from different hosts and Italian regions, including the northern part of the country (Emilia-Romagna, RER), Sicily, and Sardinia, as an initial attempt to explore the breadth of parasite genetic heterogeneity in Italy. Additionally, microsatellite analysis was carried out to compare the isolates from RER with other 70 L. infantum strains from the same region as well as 65 strains belonging to the L. donovani complex from other countries. We revealed important karyotypic instability and identified strain-specific changes in gene dosage, which affected important virulence factors such as amastins and surface antigen-like proteins. Single nucleotide polymorphism-based clustering analysis of these genomes together with over 80 publicly available L. infantum and L. donovani genomes placed the Italian isolates into three geographically distinct clusters within the Mediterranean basin and uncovered three isolates clustering with putative L. infantum/L. donovani hybrids isolated in Cyprus. As judged by microsatellite profiling, these hybrid isolates are representative of a sub-population of parasites circulating in northern Italy that preferentially infect humans but not dogs. Our results place Italy at the crossroads of L. infantum infection in the Mediterranean and call attention to the public health risk represented by the introduction of non-European Leishmania species.IMPORTANCEThis study closes important knowledge gaps with respect to Leishmania (L.) infantum genetic heterogeneity in a given endemic country, as exemplified here for Italy, and reveals genetic hybridization as a main cause for re-emerging human leishmaniasis in northern Italy. The observed high diversity of Leishmania parasites on the Italian peninsula suggests different geographical origins, with genomic adaptation to various ecologies affecting both pathogenicity and transmission potential. This is documented by the discovery of a putative L. infantum/L. donovani hybrid strain, which has been shown to preferentially infect humans but not dogs. Our results provide important information to health authorities, which need to consider the public health risk represented by the introduction of new Leishmania species into EU countries due to population displacement or travel from countries where exotic/allochthonous parasite species are endemic.

2.
Front Pharmacol ; 15: 1403203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873424

RESUMO

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite's N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite's changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

3.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 36(2): 215-218, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38857969

RESUMO

This case report summarizes the experience from diagnosis and treatment of a patient with repeated high fever, hepatosplenomegaly and pancytopenia. Following exclusion of bacterial, viral, fungal infections and hematological diseases, metagenomic next-generation sequencing of the patient's peripheral blood revealed Leishmania infantum infection, and rK39 rapid diagnostic test showed positive for anti-Leishmania antibody, while microscopic examination of bone marrow smears identified Leishmania amastigotes. Therefore, the case was definitively diagnosed as visceral leishmaniasis, and given anti-infective treatment with sodium antimony gluconate and hormone, hepatoprotection, elevation of white blood cell counts and personalized nursing. Then, the case was cured and discharged from hospital. Metagenomic next-generation sequencing is of great value in etiological detection of fever patients with unknown causes, which deserves widespread clinical applications.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Leishmaniose Visceral , Humanos , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Masculino , Metagenômica/métodos , Adulto , Pessoa de Meia-Idade
4.
Artigo em Inglês | MEDLINE | ID: mdl-38842679

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a neglected tropical disease that mostly affects the working class and impoverished segments of society, having a significant negative effect on the economic development of the affected nation. While anti-leishmanial medications lower mortality among VL patients, patients may still die or require more time to recover while receiving treatment. In this regard, there are limited studies in Ethiopia. This study aims to determine the time to recovery and its associated predictors among adult VL patients at Metema Hospital, Metema, Ethiopia. METHODS: A hospital-based cross-sectional study was employed and the data were collected from patient's charts from September 2017 to September 2021. Data were entered and analysed using EpiData version 3.1, Stata version 14.2 and R version 3.4.0 statistical software. Kaplan-Meier survival curves and logrank tests were used to compare the survival time. The Cox proportional hazards model assumption and model fitness were checked and used to identify statistical association predictors in VL patients. RESULTS: The Cox proportional hazards model was fitted. The overall medium recovery time was 7 d (minimum 4, maximum 14). The variables of nasal bleeding (adjusted hazard ratio [aHR] 0.44 [95% confidence interval {CI} 0.19 to 0.89]), no comorbidity (aHR 2.29 [95% CI 1.27 to 4.11]), relapse of VL (aHR 0.33 [95% CI 0.15 to 0.75]), low parasite load (aHR 2.58 [95% CI 1.48 to 4.51]) and ambulatory (aHR 3.26 [95% CI 2.45 to 6.53]) were significantly associated with time to recovery in VL patients. CONCLUSIONS: Patients with comorbidities, nasal bleeding, relapse of VL, bedridden and high parasite load should be treated and monitored carefully to recover quickly from their illness.

5.
Cureus ; 16(5): e60153, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38864073

RESUMO

It is known that there are several clinical forms that diseases can take when presented in patients living with HIV, especially those in the AIDS phase. Here, we present a case that demonstrates the peculiar capacity of diseases to assume the most varied forms, highlighting the limited research on neglected infectious parasitic diseases. This study aimed to underscore the ability of these diseases to mimic other pathologies, emphasizing the importance of infectious diseases as differential diagnoses in the most diverse clinical entities, as is the case of visceral leishmaniasis.

6.
Front Cell Infect Microbiol ; 14: 1414493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881737

RESUMO

Visceral leishmaniasis is a potentially devastating neglected tropical disease caused by the protozoan parasites Leishmania donovani and L. infantum (chagasi). These parasites reside in tissue macrophages and survive by deploying a number of mechanisms aimed at subverting the host immune response. CD4+ T cells play an important role in controlling Leishmania parasites by providing help in the form of pro-inflammatory cytokines to activate microbiocidal pathways in infected macrophages. However, because these cytokines can also cause tissue damage if over-produced, regulatory immune responses develop, and the balance between pro-inflammatory and regulatory CD4+ T cells responses determines the outcomes of infection. Past studies have identified important roles for pro-inflammatory cytokines such as IFNγ and TNF, as well as regulatory co-inhibitory receptors and the potent anti-inflammatory cytokine IL-10. More recently, other immunoregulatory molecules have been identified that play important roles in CD4+ T cell responses during VL. In this review, we will discuss recent findings about two of these molecules; the NK cell granule protein Nkg7 and the anti-inflammatory cytokine TGFß, and describe how they impact CD4+ T cell functions and immune responses during visceral leishmaniasis.


Assuntos
Linfócitos T CD4-Positivos , Leishmania donovani , Leishmaniose Visceral , Fator de Crescimento Transformador beta , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Humanos , Linfócitos T CD4-Positivos/imunologia , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/imunologia , Leishmania donovani/imunologia , Animais , Macrófagos/imunologia , Leishmania infantum/imunologia , Citocinas/metabolismo
7.
Parasite Immunol ; 46(5): e13036, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720445

RESUMO

Apolipoprotein E (ApoE) has been associated with several diseases including Parkinson's disease, Alzheimer's and multiple sclerosis. ApoE also has documented immunomodulatory functions. We investigated gene expression in circulating monocytes and in bone marrows of patients with visceral leishmaniasis (VL) living in an endemic area in Bihar, India, and contrasted these with control healthy subjects or other diagnostic bone marrows from individuals in the same region. Samples from VL patients were obtained prior to initiating treatment. Our study revealed significant upregulated expression of the apoE transcript in patients with VL. Furthermore, the levels of ApoE protein were elevated in serum samples of subjects with VL compared with healthy endemic controls. These observations may provide clues regarding the complex interactions between lipid metabolism and immunoregulation of infectious and inflammatory diseases.


Assuntos
Apolipoproteínas E , Leishmaniose Visceral , Monócitos , Regulação para Cima , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Apolipoproteínas E/genética , Medula Óssea , Índia/epidemiologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/sangue , Leishmaniose Visceral/parasitologia , Monócitos/imunologia
8.
J Infect Dis ; 229(6): 1909-1912, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38713583

RESUMO

In an area endemic with Indian visceral leishmaniasis (VL), we performed direct xenodiagnosis to evaluate the transmission of Leishmania donovani from patients with VL-human immunodeficiency virus (HIV) coinfection to the vector sandflies, Phlebotomus argentipes. Fourteen patients with confirmed VL-HIV coinfection, with a median parasitemia of 42 205 parasite genome/mL of blood, were exposed to 732 laboratory-reared pathogen-free female P argentipes sandflies on their lower arms and legs. Microscopy revealed that 16.66% (122/732) of blood-fed flies were xenodiagnosis positive. Notably, 93% (13/14) of the VL-HIV group infected the flies, as confirmed by quantitative polymerase chain reaction and/or microscopy, and were 3 times more infectious than those who had VL without HIV.


Assuntos
Coinfecção , Infecções por HIV , Leishmania donovani , Leishmaniose Visceral , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/complicações , Animais , Humanos , Índia/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Feminino , Adulto , Coinfecção/virologia , Coinfecção/epidemiologia , Coinfecção/parasitologia , Leishmania donovani/isolamento & purificação , Masculino , Phlebotomus/parasitologia , Phlebotomus/virologia , Doenças Endêmicas , Pessoa de Meia-Idade , Adulto Jovem , Xenodiagnóstico , Insetos Vetores/parasitologia , Insetos Vetores/virologia , Adolescente
9.
Cureus ; 16(4): e58237, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38745796

RESUMO

Visceral leishmaniasis (VL) is a parasitic vector-borne disease endemic in Armenia. Its complications include hemophagocytic lymphohistiocytosis (HLH), which is a potentially fatal syndrome if misdiagnosed or left untreated. Higher clinical caution is required for the prompt diagnosis of HLH since the clinical findings associated with systemic inflammation overlap with those of many other pathological conditions, such as sepsis or Kawasaki disease. This study aims to provide an overview of the most common presentations that should prompt consideration of HLH. We described a case series of three pediatric patients with VL who developed HLH during antiparasitic treatment and received total doses of 40 mg/kg of liposomal amphotericin B for complete elimination of the pathogen.

10.
Infect Drug Resist ; 17: 2009-2014, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800583

RESUMO

Background: Visceral leishmaniasis (VL), also known as kala-azar, is caused by an intracellular parasite transmitted to humans by the bite of a sand fly, and with the source of the infection mainly being dogs. The main features of the disease are irregular fever, weight loss, hepatosplenomegaly and anaemia. Diagnosis relies mainly on bone marrow aspiration tests to find Leishman-Donovan(LD) bodies. And we report the case without febrile symptoms and hepatitis C virus antibody was probably false positive. Case Presentation: The case was a 74-year-old male residing in Yangquan City, Shanxi Province, a VL endemic area. He presented with generalised malaise, hepatosplenomegaly and scarring pigmentation on the skin as a result of scratching. Laboratory tests showed pancytopenia, positive hepatitis C virus antibody (HCV-Ab), positive direct anti-human globulin test (DAT), positive anti-cardiolipin antibody IgG, IgM (+), and increased immunoglobulin IgG. Symptomatic treatments such as hepatoprotection and blood transfusion were given, but the patient's symptoms still persisted and his spleen and liver further enlarged. Further repeat tests were performed and found to be negative for hepatitis C virus antibodies and antigens. The patient was eventually found to be infected with Leishmania protozoa by rk39 rapid diagnostic test and metagenomic next-generation sequencing(mNGS). And the patient quickly relieved after one course of treatment with sodium stibogluconate. Conclusion: Patients with VL may cause abnormalities in the immune system, leading to false positives for various antibodies without clear febrile symptoms, resulting in misdiagnosis or delayed diagnosis. It is important to consider VL in cases where there is a significant hepatosplenomegaly with a relevant epidemiological history. If the diagnosis cannot be confirmed through bone marrow aspiration and the patient is not suitable for splenic aspiration, the rk39 test can be used for initial exclusion and further verified through mNGS.

11.
Microorganisms ; 12(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38792746

RESUMO

Diagnosing canine visceral leishmaniasis (CVL) in Brazil faces challenges due to the limitations regarding the sensitivity and specificity of the current diagnostic protocol. Therefore, it is urgent to map new antigens or enhance the existing ones for future diagnostic techniques. Immunoinformatic tools are promising in the identification of new potential epitopes or antigen candidates. In this study, we evaluated peptides selected by epitope prediction for CVL serodiagnosis in ELISA assays. Ten B-cell epitopes were immunogenic in silico, but two peptides (peptides No. 45 and No. 48) showed the best performance in vitro. The selected peptides, both individually and in combination, were highly diagnostically accurate, with sensitivities ranging from 86.4% to 100% and with a specificity of approximately 90%. We observed that the combination of peptides showed better performance when compared to peptide alone, by detecting all asymptomatic dogs, showing lower cross-reactivity in sera from dogs with other canine infections, and did not detect vaccinated animals. Moreover, our data indicate the potential use of immunoinformatic tools associated with ELISA assays for the selection and evaluation of potential new targets, such as peptides, applied to the diagnosis of CVL.

12.
Microorganisms ; 12(5)2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38792771

RESUMO

We studied some fibrotic aspects of chronic interstitial pneumonitis in the lungs of dogs infected with Leishmania infantum. The lungs of eleven naturally infected dogs, twelve experimentally infected with two distinct strains of L. infantum (BH401 and BH46), and six uninfected (controls) dogs, were analyzed by histological, parasitological, and immunohistochemical studies. Conventional histology (HE), collagen deposition (Gomori's silver staining for reticulin collagen fibers), and immunohistochemistry for myofibroblast characterization were carried out based on the cellular expression of alpha-smooth muscle actin, vimentin, cytokeratin, E-cadherin, snail antigen homologue 1 (SNAI1) (Snail), and the cytokine expression of transforming growth factor-beta (TGF-ß). Parasitological screening was carried out using conventional polymerase chain reaction (PCR) and the immunohistochemical reaction of streptavidin-peroxidase for visualizing Leishmania amastigotes. Dogs naturally infected with L. infantum and experimentally infected with L. infantum BH401 strains showed intense interstitial pneumonitis characterized by thickening of the alveolar septa as a consequence of an intense diffuse and focal (plaques) chronic exudate of mononuclear cells associated with fibrogenesis. The expression of alpha-actin, vimentin, and TGF-ß was higher in the lung interstitium of all infected dogs than in the other two groups (BH46 strain and controls). Moreover, in both the naturally and experimentally infected dog (BH401 strain) groups, the expression of Snail was moderate to intense in contrast to the other groups. Based on these immunohistochemical results, we concluded that mesenchymal cells are active in promoting changes in the extracellular matrix in the lungs of dogs naturally and experimentally infected with L. infantum, but it depends on the virulence of the parasite.

13.
Pathogens ; 13(5)2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38787223

RESUMO

Canine visceral leishmaniasis (CVL), caused by the protozoan Leishmania infantum, affects several organs, including the skin. Dogs are considered the major domestic reservoir animals for leishmaniasis, and through their highly parasitized skin, they can serve as a source of infection for sandfly vectors. Therefore, studies of the skin parasite-host relationship can contribute to the understanding of the infectious dissemination processes of parasites in the dermis and help to identify targets for diagnosis and treatment. Thus, the aim of this study was to evaluate the association of anatomical vascular differences and Leishmania-induced vascular morphological changes with clinical signs and parasite load by analyzing the ear and abdominal skin from dogs naturally infected with L. infantum. Paired samples of ear and abdominal skin from L. infantum-positive dogs (n = 26) were submitted for histological and immunohistochemistry analyses. The ear skin samples showed a more intense and more diffusely distributed granulomatous inflammatory reaction, a higher number and larger diameter of blood vessels, increased parasite load, higher expression of VEGF+ (vascular endothelial growth factor) and MAC 387+ (calprotectin) recently infiltrating cells, and more intense collagen disruption compared to the abdominal skin samples. Intracellular amastigotes were observed in blood vessels and inside endothelial cells and were diffusely distributed throughout the dermis in the ear skin samples. The NOS2/MAC387+ cell ratio was lower in the ear skin samples than in those of the abdomen, suggesting that in the ear dermis, the inflammatory infiltrate was less capable of producing NO and thereby control the parasite load. Together, these findings indicate how parasites and immune cells are distributed in the skin and suggest an important role for dermal vascularization in cellular influx and thereby in parasite dissemination through the skin of naturally infected dogs.

14.
Parasite Immunol ; 46(5): e13037, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38720446

RESUMO

The treatment for visceral leishmaniasis (VL) causes toxicity in patients, entails high cost and/or leads to the emergence of resistant strains. No human vaccine exists, and diagnosis presents problems related to the sensitivity or specificity of the tests. Here, we tested two phage clones, B1 and D11, which were shown to be protective against Leishmania infantum infection in a murine model as immunotherapeutics to treat mice infected with this parasite species. The phages were used alone or with amphotericin B (AmpB), while other mice received saline, AmpB, a wild-type phage (WTP) or WTP/AmpB. Results showed that the B1/AmpB and D11/AmpB combinations induced polarised Th1-type cellular and humoral responses, which were primed by high levels of parasite-specific IFN-γ, IL-12, TNF-α, nitrite and IgG2a antibodies, which reflected in significant reductions in the parasite load in distinct organs of the animals when analyses were performed 1 and 30 days after the treatments. Reduced organic toxicity was also found in these animals, as compared with the controls. In conclusion, preliminary data suggest the potential of the B1/AmpB and D11/AmpB combinations as immunotherapeutics against L. infantum infection.


Assuntos
Anfotericina B , Anticorpos Antiprotozoários , Imunoterapia , Leishmania infantum , Leishmaniose Visceral , Camundongos Endogâmicos BALB C , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/tratamento farmacológico , Animais , Anfotericina B/uso terapêutico , Anfotericina B/administração & dosagem , Anticorpos Antiprotozoários/sangue , Leishmania infantum/imunologia , Leishmania infantum/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Feminino , Antiprotozoários/uso terapêutico , Antiprotozoários/administração & dosagem , Imunoglobulina G/sangue , Carga Parasitária , Modelos Animais de Doenças , Técnicas de Visualização da Superfície Celular , Citocinas/metabolismo , Células Th1/imunologia
15.
mBio ; 15(5): e0085924, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38639536

RESUMO

Visceral leishmaniasis is a deadly infectious disease and is one of the world's major neglected health problems. Because the symptoms of infection are similar to other endemic diseases, accurate diagnosis is crucial for appropriate treatment. Definitive diagnosis using splenic or bone marrow aspirates is highly invasive, and so, serological assays are preferred, including the direct agglutination test (DAT) or rK39 strip test. These tests, however, are either difficult to perform in the field (DAT) or lack specificity in some endemic regions (rK39), making the development of new tests a research priority. The availability of Leishmania spp. genomes presents an opportunity to identify new diagnostic targets. Here, we use genome data and a mammalian protein expression system to create a panel of 93 proteins consisting of the extracellular ectodomains of the Leishmania donovani cell surface and secreted proteins. We use these panel and sera from murine experimental infection models and natural human and canine infections to identify new candidates for serological diagnosis. We observed a concordance between the most immunoreactive antigens in different host species and transmission settings. The antigen encoded by the LdBPK_323600.1 gene can diagnose Leishmania infections with high sensitivity and specificity in patient cohorts from different endemic regions including Bangladesh and Ethiopia. In longitudinal sampling of treated patients, we observed reductions in immunoreactivity to LdBPK_323600.1 suggesting it could be used to diagnose treatment success. In summary, we have identified new antigens that could contribute to improved serological diagnostic tests to help control the impact of this deadly tropical infectious disease. IMPORTANCE: Visceral leishmaniasis is fatal if left untreated with patients often displaying mild and non-specific symptoms during the early stages of infection making accurate diagnosis important. Current methods for diagnosis require highly trained medical staff to perform highly invasive biopsies of the liver or bone marrow which pose risks to the patient. Less invasive molecular tests are available but can suffer from regional variations in their ability to accurately diagnose an infection. To identify new diagnostic markers of visceral leishmaniasis, we produced and tested a panel of 93 proteins identified from the genome of the parasite responsible for this disease. We found that the pattern of host antibody reactivity to these proteins was broadly consistent across naturally acquired infections in both human patients and dogs, as well as experimental rodent infections. We identified a new protein called LdBPK_323600.1 that could accurately diagnose visceral leishmaniasis infections in humans.


Assuntos
Anticorpos Antiprotozoários , Antígenos de Protozoários , Leishmania donovani , Leishmaniose Visceral , Proteínas de Protozoários , Testes Sorológicos , Leishmania donovani/genética , Leishmania donovani/imunologia , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Animais , Humanos , Camundongos , Cães , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Anticorpos Antiprotozoários/sangue , Anticorpos Antiprotozoários/imunologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Testes Sorológicos/métodos , Biomarcadores/sangue , Feminino , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Camundongos Endogâmicos BALB C , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Sensibilidade e Especificidade , Doenças do Cão/diagnóstico , Doenças do Cão/parasitologia
16.
Front Epidemiol ; 4: 1367387, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655403

RESUMO

Introduction: Visceral leishmaniasis (VL), a neglected tropical disease that causes substantial morbidity and mortality, is a serious health problem in Ethiopia. Infections are caused by Leishmania (L.) donovani parasites. Most individuals remain asymptomatic, but some develop VL, which is generally fatal if not treated. We identified the area of Metema-Humera in Northwest Ethiopia as a setting in which we could follow migrant workers when they arrived in an endemic area. The demographic characteristics of this population and factors associated with their risk of asymptomatic infection are poorly characterised. Methods: We divided our cohort into individuals who visited this area for the first time (first comers, FC) and those who had already been in this area (repeat comers, RC). We followed them from the beginning (Time 1, T1) to the end of the agricultural season (Time 2, T2), performing tests for sand fly bite exposure (anti-sand fly saliva antibody ELISA) and serology for Leishmania infection (rK39 rapid diagnostic test and the direct agglutination test) at each time point and collecting information on risk factors for infection. Results: Our results show that most migrant workers come from non-endemic areas, are male, young (median age of 20 years) and are farmers or students. At T1, >80% of them had been already exposed to sand fly bites, as shown by the presence of anti-saliva antibodies. However, due to seasonality of sand flies there was no difference in exposure between FC and RC, or between T1 and T2. The serology data showed that at T1, but not at T2, a significantly higher proportion of RC were asymptomatic. Furthermore, 28.6% of FC became asymptomatic between T1 and T2. Over the duration of this study, one FC and one RC developed VL. In multivariable logistic regression of asymptomatic infection at T1, only age and the number of visits to Metema/Humera were significantly associated with asymptomatic infection. Conclusion: A better understanding of the dynamics of parasite transmission and the risk factors associated with the development of asymptomatic infections and potentially VL will be essential for the development of new strategies to prevent leishmaniasis.

17.
Clin Infect Dis ; 78(Supplement_2): S175-S182, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38662705

RESUMO

BACKGROUND: Neglected tropical diseases are responsible for considerable morbidity and mortality in low-income populations. International efforts have reduced their global burden, but transmission is persistent and case-finding-based interventions rarely target asymptomatic individuals. METHODS: We develop a generic mathematical modeling framework for analyzing the dynamics of visceral leishmaniasis in the Indian sub-continent (VL), gambiense sleeping sickness (gHAT), and Chagas disease and use it to assess the possible contribution of asymptomatics who later develop disease (pre-symptomatics) and those who do not (non-symptomatics) to the maintenance of infection. Plausible interventions, including active screening, vector control, and reduced time to detection, are simulated for the three diseases. RESULTS: We found that the high asymptomatic contribution to transmission for Chagas and gHAT and the apparently high basic reproductive number of VL may undermine long-term control. However, the ability to treat some asymptomatics for Chagas and gHAT should make them more controllable, albeit over relatively long time periods due to the slow dynamics of these diseases. For VL, the toxicity of available therapeutics means the asymptomatic population cannot currently be treated, but combining treatment of symptomatics and vector control could yield a quick reduction in transmission. CONCLUSIONS: Despite the uncertainty in natural history, it appears there is already a relatively good toolbox of interventions to eliminate gHAT, and it is likely that Chagas will need improvements to diagnostics and their use to better target pre-symptomatics. The situation for VL is less clear, and model predictions could be improved by additional empirical data. However, interventions may have to improve to successfully eliminate this disease.


Assuntos
Infecções Assintomáticas , Doença de Chagas , Leishmaniose Visceral , Modelos Teóricos , Doenças Negligenciadas , Humanos , Doenças Negligenciadas/prevenção & controle , Doenças Negligenciadas/epidemiologia , Doença de Chagas/transmissão , Doença de Chagas/prevenção & controle , Doença de Chagas/epidemiologia , Doença de Chagas/tratamento farmacológico , Infecções Assintomáticas/epidemiologia , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/transmissão , Leishmaniose Visceral/tratamento farmacológico , Tripanossomíase Africana/prevenção & controle , Tripanossomíase Africana/epidemiologia , Tripanossomíase Africana/transmissão , Tripanossomíase Africana/tratamento farmacológico , Índia/epidemiologia , Animais
18.
Trop Med Infect Dis ; 9(4)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38668537

RESUMO

This study was carried out to identify the spatial distribution and characterize the clinical-epidemiological profile of Visceral Leishmaniasis (VL) in Maranhão state, Brazil, from 2009 to 2020. This descriptive ecological study collected sociodemographic and clinical data of VL cases from the Brazilian Notifiable Diseases Information System database. A spatial autocorrelation analysis (Moran statistics) was performed. From 2009 to 2020, 5699 cases of VL were reported, with incidence of 6.5 cases/100,000 and prevalence of 7.1 cases/100,000. The temporal analysis showed a significant growth in incidence from 2009 to 2018, followed by a significant decrease between 2019 and 2020. The Moran map shows hotspots of high values in the central-west and central-east regions, and hotspots of low values in the northern region of Maranhão. The profile of patients affected by VL comprises males (OR = 1.8; IC95% = 1.72-1.92), aged under 14 years, brown, and with incomplete elementary schooling. The main symptoms reported were fever, fatigue, and edema. The main diagnostic method was laboratory. The mortality rate was 6.8%, and co-infection with HIV was reported by 8.5% of patients. The results of this study indicated the increase in incidence and lethality, as well as the expansion, of leishmaniasis in the state of Maranhão.

19.
Trop Med Infect Dis ; 9(4)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38668552

RESUMO

The zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and dogs are reservoirs for this parasite. For the diagnosis of Leishmania at the species level in dogs in formalin-fixed, paraffin-embedded skin (FFPES) samples, colorimetric in situ hybridization (CISH) and quantitative real-time polymerase chain reaction (qPCR) are options, but their sensitivities are not well established. Therefore, the aim of this study was to determine the sensitivity of these two techniques in FFPES for the diagnosis of the L. infantum infection in dogs using culture as the reference standard. The FFPES of 48 dogs with cutaneous infection by L. infantum confirmed by culture and by multilocus enzyme electrophoresis were examined by CISH and qPCR using specific probes for L. infantum. The sensitivities of qPCR, CISH and their combination were, respectively, 77.0%, 58.0% and 83.3%. The sensitivities of qPCR in dogs with and without clinical signs were, respectively, 74.2% and 82.4%. The sensitivities of CISH in dogs with and without clinical signs were, respectively, 61.3% and 52.9%. The CISH and qPCR showed satisfactory sensitivities for the diagnosis of L. infantum in the FFPES of dogs, even in dogs without clinical signs, and their combination increases the sensitivity for this diagnosis.

20.
Iran J Parasitol ; 19(1): 28-37, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654944

RESUMO

Background: Black disease, also known as visceral leishmaniasis (VL), is a parasitic illness caused by various Leishmania species. The risk of morbidity and mortality increases with delayed diagnosis and treatment. Early VL diagnosis and fast appropriate treatment are critical issues in endemic areas. Methods: This study was a retrospective cross-sectional study to investigate the diagnostic and therapeutic course of patients admitted with the diagnosis of VL in the Children's Medical Center (CMC) Hospital, Tehran, Iran. All cases of VL in patients under the age of 18 hospitalized between the years 2012 to 2022 were enrolled. Results: Twenty-seven patients were enrolled with an average age of 28.13 months with the majority of females (51.8%). Common clinical signs were fever (96.2%) and splenomegaly (92.59%). However, lymphadenopathy was rare. The largest number of patients was from Tehran Province, followed by Ardabil, Khuzestan, Gilan, and Alborz provinces. The most common hematological abnormalities were anemia (85.1%) and thrombocytopenia (44.4%). In accordance with the treatment strategy, liposomal amphotericin B and amphotericin B deoxycholate were given to 11 and 5 patients, respectively. Eleven of them received glucantime. The average length of hospitalization for liposomal amphotericin B was 15.36 ± 12.49 days. In comparison with glucantime (18.38 ±10.26 days) and amphotericin B deoxycholate (20.20± 6.18 days), liposomal amphotericin B group hospitalization was shorter than others were. Conclusion: VL should be included in the differential diagnosis of any child who presents with fever, splenomegaly, and anemia. Concerning the treatment strategy in this study, liposomal amphotericin B had more efficiency and shorter hospitalization duration.

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