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1.
BMC Infect Dis ; 20(1): 867, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213392

RESUMO

BACKGROUND: Micronutrients are minerals and vitamins and they are essential for normal physiological activities. The objectives of the study were to describe the progress and determinants of micronutrient levels and to assess the effects of micronutrients in the treatment outcome of kalazar. METHODS: A prospective cohort study design was used. The data were collected using patient interviews, measuring anthropometric indicators, and collecting laboratory samples. The blood samples were collected at five different periods during the leishmaniasis treatments: before starting anti-leishmaniasis treatments, in the first week, in the second week, in the third week, and in the 4th week of anti-leishmaniasis treatments. Descriptive statistics were used to describe the profile of patients and to compare the treatment success rate. The generalized estimating equation was used to identify the determinants of serum micronutrients. RESULTS: The mean age of the patients were 32.88 years [SD (standard deviation) ±15.95]. Male constitute 62.3% of the patients and problematic alcohol use was present in 11.5% of the patients. The serum zinc level of visceral leishmaniasis patients was affected by alcohol (B - 2.7 [95% CI: - 4.01 - -1.5]), DDS (B 9.75 [95% CI: 7.71-11.79]), family size (B -1.63 [95% CI: - 2.68 - -0.58]), HIV (B -2.95 [95% CI: - 4.97 - -0.92]), and sex (B - 1.28 [95% CI: - 2.5 - -0.07]). The serum iron level of visceral leishmaniasis patients was affected by alcohol (B 7.6 [95% CI: 5.86-9.35]), family size (B -5.14 [95% CI: - 7.01 - -3.28]), malaria (B -12.69 [95% CI: - 14.53 - -10.87]), Hookworm (- 4.48 [- 6.82 - -2.14]), chronic diseases (B -7.44 [95% CI: - 9.75 - -5.13]), and HIV (B -5.51 [95% CI: - 8.23 - -2.78]). The serum selenium level of visceral leishmaniasis patient was affected by HIV (B -18.1 [95% CI: - 20.63 - -15.58]) and family size (B -11.36 [95% CI: - 13.02 - -9.7]). The iodine level of visceral leishmaniasis patient was affected by HIV (B -38.02 [95% CI: - 41.98 - -34.06]), DDS (B 25 .84 [95% CI: 22.57-29.1]), smoking (B -12.34 [95% CI: - 15.98 - -8.7]), chronic illness (B -5.14 [95% CI: - 7.82 - -2.46]), and regular physical exercise (B 5.82 [95% CI: 0.39-11.26]). The serum vitamin D level of visceral leishmaniasis patient was affected by HIV (B -9.43 [95% CI: - 10.92 - -7.94]), DDS (B 16.24 [95% CI: 14.89-17.58]), malaria (B -0.61 [95% CI: - 3.37 - -3.37]), and family size (B -1.15 [95% CI: - 2.03 - -0.28]). The serum vitamin A level of visceral leishmaniasis patient was affected by residence (B 0.81 [95% CI: 0.08-1.54]), BMI (B 1.52 [95% CI: 0.42-2.6]), DDS (B 1.62 [95% CI: 0.36-2.88]), family size (B -5.03 [95% CI: - 5.83 - -4.22]), HIV (B -2.89 [95% CI: - 4.44 - -1.34]),MUAC (B 0.86 [95% CI: 0.52-1.21]), and age (B 0.09 [95% CI: 0.07-0.12]). CONCLUSION: The micronutrient levels of visceral leishmaniasis patients were significantly lower. The anti-leishmaniasis treatment did not increase the serum micronutrient level of the patients.


Assuntos
Antiprotozoários/uso terapêutico , Leishmaniose Visceral/tratamento farmacológico , Micronutrientes/sangue , Adulto , Consumo de Bebidas Alcoólicas , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Entrevistas como Assunto , Leishmaniose Visceral/complicações , Leishmaniose Visceral/patologia , Malária/complicações , Malária/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Selênio/sangue , Zinco/sangue
2.
Am J Trop Med Hyg ; 103(5): 1938-1941, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32815498

RESUMO

Interleukin-10 (IL-10) and interleukin-27 (IL-27) both exert counterregulatory immunodeactivation in visceral Leishmania donovani infection. We studied experimental L. donovani infection in the livers of IL-10-/- and IL-27Rα-/- mice and observed that in IL-27Rα-/-, but not IL-10-/- mice, interferon-gamma (IFN-γ) and tumor necrosis factor (TNF) were required for heightened granulomatous inflammation and accelerated control of intracellular parasite replication. This difference in mechanism, along with residual IL-10 activity in IL-27Rα-/- mice, suggested targeting IL-27 in addition to IL-10 in a macrophage-activating, anti-counterregulatory cytokine treatment strategy. In C57BL/6 wild-type mice with established liver infection, a single injection of anti-IL-27 p28 or anti-IL-10R monoclonal antibody enhanced granuloma assembly, enabled macrophage activation, and induced comparable parasite killing (49-56%). However, anti-IL-27 p28 plus anti-IL-10R combination treatment did not increase leishmanicidal effects. These results suggest that IL-27 and IL-10 may operate in a linked deactivating mechanism and that in this intracellular infection, either IL-27 or IL-10 is a suitable immunotherapeutic target.


Assuntos
Interleucina-10/metabolismo , Interleucinas/metabolismo , Leishmania donovani/imunologia , Leishmaniose Visceral/tratamento farmacológico , Animais , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/patologia , Fígado/imunologia , Fígado/parasitologia , Fígado/patologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL
3.
Am J Trop Med Hyg ; 103(4): 1490-1492, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32720633

RESUMO

Human visceral leishmaniasis (HVL) is a parasitic disease infecting children in the Mediterranean region. Here, we portray a case of a 2-year-old child with an epidemiological description of the situation surrounding the case. The patient was suffering from recurrent fever, weakness, and abdominal discomfort associated with loss of appetite. Routine blood investigations showed pancytopenia, whereas examination revealed hepatomegaly. A diagnosis of HVL was made by demonstrating amastigotes in a Giemsa-stained smear from a bone marrow aspirate followed by genotyping by PCR and sequencing. In conclusion, early detection of VL infection followed by appropriate treatment protocols is essential to saving the patient.


Assuntos
Medula Óssea/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral , Animais , Gluconato de Antimônio e Sódio/uso terapêutico , Antiprotozoários/uso terapêutico , Pré-Escolar , Reservatórios de Doenças , Cães/parasitologia , Diagnóstico Precoce , Feminino , Humanos , Insetos Vetores , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologia , Oriente Médio/epidemiologia , Phlebotomus/parasitologia
4.
BMC Infect Dis ; 20(1): 401, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503461

RESUMO

BACKGROUND: Visceral leishmaniasis is an important but neglected disease that is spreading and is highly lethal when left untreated. This study sought to measure the Leishmania infantum seroprevalence in dogs, the coverage of its control activities (identification of the canine reservoir by serological survey, dog culling and insecticide spraying) and to evaluate its relationship with the occurrence of the disease in humans in the municipalities of Araçatuba and Birigui, state of São Paulo, Brazil. METHODS: Information from 2006 to 2015 was georeferenced for each municipality and modeling was performed for the two municipalities together. To do this, latent Gaussian Bayesian models with the incorporation of a spatio-temporal structure and Poisson distribution were used. The Besag-York-Mollie models were applied for random spatial effects, as also were autoregressive models of order 1 for random temporal effects. The modeling was performed using the INLA (Integrated Nested Laplace Approximations) deterministic approach, considering both the numbers of cases as well as the coverage paired year by year and lagged at one and two years. RESULTS: Control activity coverage was observed to be generally low. The behavior of the temporal tendency in the human disease presented distinct patterns in the two municipalities, however, in both the tendency was to decline. The canine serological survey presented as a protective factor only in the two-year lag model. CONCLUSIONS: The canine serological coverage, even at low intensity, carried out jointly with the culling of the positive dogs, suggested a decreasing effect on the occurrence of the disease in humans, whose effects would be seen two years after it was carried out.


Assuntos
Formigas/parasitologia , Doenças do Cão/diagnóstico , Doenças do Cão/patologia , Leishmaniose Visceral/patologia , Animais , Teorema de Bayes , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Cães , Humanos , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/epidemiologia , Distribuição de Poisson , Fatores de Risco , Estudos Soroepidemiológicos
5.
PLoS Pathog ; 16(6): e1008291, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32479529

RESUMO

The protozoan parasite Leishmania donovani (L. donovani) causes visceral leishmaniasis, a chronic infection which is fatal when untreated. Herein, we investigated whether in addition to altering transcription, L. donovani modulates host mRNA translation to establish a successful infection. Polysome-profiling revealed that one third of protein-coding mRNAs expressed in primary mouse macrophages are differentially translated upon infection with L. donovani promastigotes or amastigotes. Gene ontology analysis identified key biological processes enriched for translationally regulated mRNAs and were predicted to be either activated (e.g. chromatin remodeling and RNA metabolism) or inhibited (e.g. intracellular trafficking and antigen presentation) upon infection. Mechanistic in silico and biochemical analyses showed selective activation mTOR- and eIF4A-dependent mRNA translation, including transcripts encoding central regulators of mRNA turnover and inflammation (i.e. PABPC1, EIF2AK2, and TGF-ß). L. donovani survival within macrophages was favored under mTOR inhibition but was dampened by pharmacological blockade of eIF4A. Overall, this study uncovers a vast yet selective reprogramming of the host cell translational landscape early during L. donovani infection, and suggests that some of these changes are involved in host defense mechanisms while others are part of parasite-driven survival strategies. Further in vitro and in vivo investigation will shed light on the contribution of mTOR- and eIF4A-dependent translational programs to the outcome of visceral leishmaniasis.


Assuntos
Fator de Iniciação 4A em Eucariotos/metabolismo , Leishmania donovani/metabolismo , Leishmaniose Visceral , Macrófagos , Biossíntese de Proteínas , RNA/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Leishmaniose Visceral/metabolismo , Leishmaniose Visceral/patologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Macrófagos/patologia , Camundongos
6.
PLoS Negl Trop Dis ; 14(5): e0008319, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32413028

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a vector-borne disease that is deadly if left untreated. Understanding which factors have prognostic value may help to focus clinical management and reduce case fatality. However, information about prognostic factors is scattered and conflicting. We conducted a systematic review and meta-analysis to identify prognostic factors for mortality among VL patients in East Africa. METHODOLOGY/PRINCIPAL FINDINGS: The review protocol was registered in PROSPERO (CRD42016043112). We included studies published in English after 1970 describing VL patients treated in East African health facilities. To be included, studies had to report on associations between clinical or laboratory factors and mortality during admission or during VL treatment, with a minimal study size of ten patients. Conference abstracts and evaluations of genetic or immunological prognostic factors were excluded. We searched for studies in MEDLINE and four other databases in December 2018. To assess the risk of bias in observational studies and clinical trials, we used the Quality in Prognostic Studies (QUIPS) tool. We included 48 studies in the systematic review, describing 150,072 VL patients of whom 7,847 (5.2%) died. Twelve prognostic factors were evaluated in five or more studies and these results were submitted to meta-analysis producing one pooled crude odds ratio (OR) per prognostic factor. The following factors were strongly (OR>3) and significantly (P-value<0.05) associated with mortality: jaundice (OR = 8.27), HIV (OR = 4.60), tuberculosis (OR = 4.06), age >45 years (OR = 3.69), oedema (OR = 3.52), bleeding (OR = 3.37), and haemoglobin ≤6.5 g/dl (OR = 3.26). Factors significantly and moderately (OR between one and three) associated with death were severe malnutrition, long duration of illness, young age (<5 years), and large spleen size. CONCLUSIONS/SIGNIFICANCE: These prognostic factors can be identified by health professionals in resource-constrained settings. They should be considered as "core" prognostic factors in future studies that aim at improving the prognosis of VL patients.


Assuntos
Regras de Decisão Clínica , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/mortalidade , Adolescente , Adulto , África Oriental , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
7.
Rev Soc Bras Med Trop ; 53: e20190446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32130324

RESUMO

INTRODUCTION: Visceral leishmaniasis (VL) represents a public health concern in several areas of the world. In the American continent, VL transmission is typically zoonotic, but humans with active VL caused by Leishmania infantum are able to infect sandflies. Thus, individuals with cutaneous parasitic infections may act as reservoirs and allow interhuman transmission. Additionally, the skin may be responsible for reactivation of the disease after therapy. This study's objective was to evaluate cutaneous parasitism in humans with VL in an American endemic area. METHODS: A cross-sectional hospital-based study was conducted in northeast Brazil from October 2016 to April 2017. Biopsies of healthy skin for histopathology and immunohistochemistry were performed prior to treatment in all study patients. RESULTS: Twenty-two patients between the ages of five months to 78 years were included in the study. Seven patients (31.8%) tested positive for HIV. Only one patient had cutaneous parasitism, as confirmed by immunohistochemistry prior to treatment. Parasitism was not detected after treatment. CONCLUSIONS: Cutaneous parasitism in the healthy skin of humans with visceral leishmaniasis, although unusual, may be a source of infection for phlebotomine sandflies.


Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Pele/parasitologia , Adolescente , Adulto , Idoso , Biópsia , Criança , Pré-Escolar , Estudos Transversais , Escolaridade , Doenças Endêmicas , Feminino , Humanos , Imuno-Histoquímica , Lactente , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Pele/patologia , Adulto Jovem
8.
PLoS Pathog ; 16(3): e1008435, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32210480

RESUMO

A striking feature of human visceral leishmaniasis (VL) is chronic inflammation in the spleen and liver, and VL patients present increased production levels of multiple inflammatory mediators, which contribute to tissue damage and disease severity. Here, we combined an experimental model with the transcriptional profile of human VL to demonstrate that the TLR4-IFN-ß pathway regulates the chronic inflammatory process and is associated with the asymptomatic form of the disease. Tlr4-deficient mice harbored fewer parasites in their spleen and liver than wild-type mice. TLR4 deficiency enhanced the Th1 immune response against the parasite, which was correlated with an increased activation of dendritic cells (DCs). Gene expression analyses demonstrated that IRF1 and IFN-ß were expressed downstream of TLR4 after infection. Accordingly, IRF1- and IFNAR-deficient mice harbored fewer parasites in the target organs than wild-type mice due to having an increased Th1 immune response. However, the absence of TLR4 or IFNAR increased the serum transaminase levels in infected mice, indicating the presence of liver damage in these animals. In addition, IFN-ß limits IFN-γ production by acting directly on Th1 cells. Using RNA sequencing analysis of human samples, we demonstrated that the transcriptional signature for the TLR4 and type I IFN (IFN-I) pathways was positively modulated in asymptomatic subjects compared with VL patients and thus provide direct evidence demonstrating that the TLR4-IFN-I pathway is related to the nondevelopment of the disease. In conclusion, our results demonstrate that the TLR4-IRF1 pathway culminates in IFN-ß production as a mechanism for dampening the chronic inflammatory process and preventing immunopathology development.


Assuntos
Fator Regulador 1 de Interferon/imunologia , Interferon beta/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Células Th1/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Fator Regulador 1 de Interferon/genética , Interferon beta/genética , Leishmaniose Visceral/genética , Leishmaniose Visceral/patologia , Camundongos , Camundongos Knockout , Células Th1/patologia , Receptor 4 Toll-Like/genética
9.
Sci Rep ; 10(1): 4689, 2020 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-32170135

RESUMO

Visceral leishmaniasis is an infectious parasitic disease caused by the protozoan parasites Leishmania donovani and Leishmania infantum. The drugs currently used to treat visceral leishmaniasis suffer from toxicity and the emergence of parasite resistance, and so a better solution would be the development of an effective subunit vaccine; however, no approved vaccine currently exists. The comparative testing of a large number of vaccine candidates requires a quantitative and reproducible experimental murine infection model, but the parameters that influence infection pathology have not been systematically determined. To address this, we have established an infection model using a transgenic luciferase-expressing L. donovani parasite and longitudinally quantified the infections using in vivo bioluminescent imaging within individual mice. We examined the effects of varying the infection route, the site of adjuvant formulation administration, and standardised the parasite preparation and dose. We observed that the increase in parasite load within the liver during the first few weeks of infection was directly proportional to the parasite number in the initial inoculum. Finally, we show that immunity can be induced in pre-exposed animals that have resolved an initial infection. This murine infection model provides a platform for systematic subunit vaccine testing against visceral leishmaniasis.


Assuntos
Modelos Animais de Doenças , Leishmania donovani/imunologia , Vacinas contra Leishmaniose/imunologia , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/parasitologia , Camundongos Transgênicos , Animais , Progressão da Doença , Vacinas contra Leishmaniose/administração & dosagem , Leishmaniose Visceral/patologia , Leishmaniose Visceral/prevenção & controle , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Camundongos Knockout
10.
Rev Bras Parasitol Vet ; 29(1): e016319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32049143

RESUMO

Leishmania infantum is a trypanosomatid that causes parasitic dermatopathy in dogs. Trypanosoma caninum is another trypanosomatid, which infects the skin of dogs, although cutaneous abnormalities are absent. This study aimed to investigate the occurrence of T. caninum infection and its associated cutaneous and histological changes and compare it with the occurrence of L. infantum infection in dogs. The study included 150 dogs, of which T. caninum infection was identified in 3 (2%) and L. infantum infection in 15 (10%) of them, with no association (p>0.05) of these infections with the breed, gender, age, or cutaneous abnormalities. The cutaneous abnormalities were based on 1 (4.8%) and 12 (57.1%) dogs infected by T. caninum and L. infantum, respectively. The dermatohistopathological abnormalities in the dogs infected with T. caninum included mild perivascular lymphohistioplasmacytic infiltrates in the clinically asymptomatic ones, while in those with dermatological abnormalities, acanthosis, epidermal orthokeratotic hyperkeratosis, melanomacrophages, and co-infection with Microsporum sp. and Trichophyton sp. were observed. InL. infantum infected, the histopathological findings included chronic granulomatous inflammatory infiltrates and structures compatible with amastigotes. Despite the low frequency of T. caninum infection, our findings suggest that this trypanosomatid, unlike L. infantum, does not cause any macroscopic skin abnormalities.


Assuntos
Doenças do Cão/patologia , Leishmania infantum/genética , Leishmaniose Visceral/veterinária , Trypanosoma/genética , Tripanossomíase/veterinária , Animais , Brasil/epidemiologia , Coinfecção , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Cães , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/patologia , Reação em Cadeia da Polimerase , Prevalência , Tripanossomíase/epidemiologia , Tripanossomíase/patologia
11.
PLoS Negl Trop Dis ; 14(1): e0008020, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31961866

RESUMO

Myeloid-related protein 14 (MRP14) belongs to the S100 calcium-binding protein family and is expressed in neutrophils and inflammatory macrophages. Increase in the number of MRP14+ cells or serum level of MRP14 is associated with various diseases such as autoimmune diseases and infectious diseases, suggesting the involvement of the molecule in pathogenesis of those diseases. In this study, to examine the pathological involvement of MRP14 during cutaneous and visceral leishmaniasis, wild-type (WT) and MRP14 knockout (MRP14KO) mice were infected with Leishmania major and L. donovani. Increase in the number of MRP14+ cells at the infection sites in wild-type mice was commonly found in the skin during L. major infection as well as the spleen and liver during L. donovani infection. In contrast, the influence of MRP14 to the pathology seemed different between the two infections. MRP14 depletion exacerbated the lesion development and ulcer formation in L. major infection. On the other hand, the depletion improved anemia and splenomegaly but not hepatomegaly at 24 weeks of L. donovani infection. These results suggest that, distinct from its protective role in CL, MRP14 is involved in exacerbation of some symptoms during VL.


Assuntos
Anemia/metabolismo , Anemia/patologia , Calgranulina B/metabolismo , Leishmaniose Visceral/metabolismo , Leishmaniose Visceral/patologia , Esplenomegalia/metabolismo , Esplenomegalia/patologia , Anemia/genética , Anemia/parasitologia , Animais , Calgranulina B/genética , Feminino , Humanos , Leishmania donovani/fisiologia , Leishmania major/fisiologia , Leishmaniose Visceral/genética , Leishmaniose Visceral/parasitologia , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Baço/metabolismo , Baço/parasitologia , Baço/patologia , Esplenomegalia/genética , Esplenomegalia/parasitologia
12.
J Infect Public Health ; 13(4): 538-543, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31718991

RESUMO

BACKGROUND: The timely identification of visceral leishmaniasis (VL) patients with a higher risk of death is essential for meeting the target of reducing case-fatality rates in the Americas. This study aimed to identify factors associated with death from VL in the State of Piaui, Brazil. METHODS: Case-control study evaluating the following putative risk factors for death from VL: gender and age of the patient, local of residence, signs, and symptoms, laboratory data, comorbidities and days of evolution of the disease. The associations between risk factors and death were expressed as odds ratios and their respective 95% confidence intervals. RESULTS: In the period analyzed a total of 2525 VL patients were admitted to the hospital, corresponding to 9,3% of all VL admissions in Brazil. Among them, 177 patients died (case-fatality rate of 7.0%). In the multivariate analysis the following variables showed a statistically significant association with death: ≥60 years, vomiting, edema, diarrhea, platelets<50.000/mm³, jaundice, splenomegaly, and pneumonia. CONCLUSIONS: The identified factors associated to death from VL can be easily assessed at the time of or up to 48h after admission and may be used to inform clinical decisions, improving the clinical and laboratory monitoring of patients.


Assuntos
Mortalidade Hospitalar , Leishmaniose Visceral/mortalidade , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Leishmaniose Visceral/complicações , Leishmaniose Visceral/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Adulto Jovem
13.
J Infect Public Health ; 13(2): 306-308, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31416795

RESUMO

Visceral leishmaniasis (VL) is an endemic infection in different regions of Italy and Europe caused by protozoan parasites of the genus Leishmania, transmitted to humans through sandflies bites. Reactivation after Solid Organ Transplantation was reported and could be a risk of organ rejection. A 48 years old woman was admitted to our hospital, complaining about low-grade fever, loss of weight and new onset pancytopenia in a known cirrhosis due to active HBV/HDV co-infection. Clinical, microbiological and anatomo-pathological elements were pivotal to define the diagnosis of VL and started an appropriate anti-infective treatment. After that she underwent liver transplantation and a therapy for VL was set. No signs of reactivation were reported in the 14 months of follow-up.


Assuntos
Coinfecção/complicações , Hepatite B/complicações , Hepatite D/complicações , Leishmania/isolamento & purificação , Leishmaniose Visceral/diagnóstico , Anfotericina B/uso terapêutico , Antiprotozoários/uso terapêutico , Biópsia , Medula Óssea/patologia , Coinfecção/parasitologia , Feminino , Hepatite B/parasitologia , Hepatite D/parasitologia , Humanos , Itália , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologia , Transplante de Fígado , Pessoa de Meia-Idade , Pancitopenia/complicações , Resultado do Tratamento
14.
Rev. bras. parasitol. vet ; 29(1): e016319, 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1058011

RESUMO

Abstract Leishmania infantum is a trypanosomatid that causes parasitic dermatopathy in dogs. Trypanosoma caninum is another trypanosomatid, which infects the skin of dogs, although cutaneous abnormalities are absent. This study aimed to investigate the occurrence of T. caninum infection and its associated cutaneous and histological changes and compare it with the occurrence of L. infantum infection in dogs. The study included 150 dogs, of which T. caninum infection was identified in 3 (2%) and L. infantum infection in 15 (10%) of them, with no association (p>0.05) of these infections with the breed, gender, age, or cutaneous abnormalities. The cutaneous abnormalities were based on 1 (4.8%) and 12 (57.1%) dogs infected by T. caninum and L. infantum, respectively. The dermatohistopathological abnormalities in the dogs infected with T. caninum included mild perivascular lymphohistioplasmacytic infiltrates in the clinically asymptomatic ones, while in those with dermatological abnormalities, acanthosis, epidermal orthokeratotic hyperkeratosis, melanomacrophages, and co-infection with Microsporum sp. and Trichophyton sp. were observed. InL. infantum infected, the histopathological findings included chronic granulomatous inflammatory infiltrates and structures compatible with amastigotes. Despite the low frequency of T. caninum infection, our findings suggest that this trypanosomatid, unlike L. infantum, does not cause any macroscopic skin abnormalities.


Resumo Leishmania infantum é um tripanosomatídeo que causa dermatopatia parasitária em cães. Trypanosoma caninum é outro tripanosomatídeo, que infecta a pele de cães, embora anormalidades cutâneas sejam ausentes. Este estudo teve como objetivo investigar a ocorrência da infecção por T. caninum e suas alterações cutâneas e histológicas associadas e compará-las com a ocorrência da infecção por L. infantum em cães. O estudo incluiu 150 cães, dos quais a infecção por T. caninum foi identificada em 3 (2%) e a infecção por L. infantum em 15 (10%) deles, sem associação (p>0,05) dessas infecções com a raça, sexo, idade ou anormalidades cutâneas. As alterações cutâneas foram observadas em 1 (4,8%) e 12 (57,1%) cães infectados por T. caninum e L. infantum, respectivamente. As anormalidades dermato-histopatológicas nos cães infectados por T. caninum incluíram infiltrados linfo-histioplasmocitários perivasculares leves nos clinicamente assintomáticos, enquanto naqueles com anormalidades dermatológicas, foram observados acantose, hiperqueratose ortoqueratótica epidermal e melanomacrófagos e co-infecção por Microsporum sp. e Trichophyton sp. Nos cães infectados por L. infantum, os achados histopatológicos incluíram infiltrados inflamatórios granulomatosos crônicos e estruturas compatíveis com amastigotas. A despeito da baixa frequência da infecção por T. caninum, nossos achados sugerem que esse tripanosomatídeo, diferentemente de L. infantum, não causa anormalidades macroscópicas na pele.


Assuntos
Animais , Cães , Trypanosoma/genética , Tripanossomíase/veterinária , Leishmania infantum/genética , Doenças do Cão/patologia , Leishmaniose Visceral/veterinária , Tripanossomíase/patologia , Tripanossomíase/epidemiologia , Brasil/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , DNA de Protozoário/genética , Doenças do Cão/epidemiologia , Coinfecção , Leishmaniose Visceral/patologia , Leishmaniose Visceral/epidemiologia
15.
PLoS One ; 14(12): e0226336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31841533

RESUMO

INTRODUCTION: In southern European countries, multicentric lymphoma and leishmaniosis are the main differential diagnoses in dogs presented with generalized lymphadenomegaly. The cytological examination is in some cases inconclusive and polymerase chain reaction (PCR) for antigen receptor rearrangement (PARR) has become a common method to confirm or rule out a lymphoproliferative neoplasia. According to the literature, leishmaniosis may lead to clonal arrangements and therefore to a false diagnosis of lymphoma, but this assumption is made from a single leishmania infected dog. Therefore, the objective of this study was to prospectively evaluate results from PARR in dogs with lymphadenomegaly due to clinical leishmaniosis at the moment of diagnosis. MATERIALS AND METHODS: 31 dogs with a diagnosis of leishmaniosis based on the LeishVet guidelines were included in the study. Samples from enlarged lymph nodes were taken for cytological examination, clonality testing and Leishmania infantum PCR. RESULTS: All 31 dogs had medium to high positive antibody titers against Leishmania spp. and 30/31 had a positive Leishmania PCR from the lymph node. A polyclonal arrangement for B cells (immunoglobulin heavy chain gene) and T cells (T-cell receptor gamma chain gene) antigen receptors was found in 28/31 dogs. Two out of 31 dogs showed a monoclonal arrangement for Ig with high (1:2) and low (1:7) polyclonal background respectively; and one of the 31 dogs showed a monoclonal arrangement for T cell receptor with low (1:3) polyclonal background. CONCLUSION: Infections with Leishmania infantum resulted in clonal rearrangement, and therefore in a possible false diagnosis of lymphoma, in 3 out of 31 dogs (9.7%). Although, PARR is a useful method to differentiate lymphoma from reactive lymphoid hyperplasia in dogs with leishmaniosis, mono-/biclonal results should be interpreted carefully, especially in the presence of any degree of polyclonal background, and together with other clinicopathological findings.


Assuntos
Evolução Clonal , Doenças do Cão/imunologia , Leishmania infantum/imunologia , Leishmaniose Visceral/diagnóstico , Linfonodos/metabolismo , Linfadenopatia/diagnóstico , Animais , Evolução Clonal/genética , Evolução Clonal/imunologia , Diagnóstico Diferencial , Doenças do Cão/diagnóstico , Doenças do Cão/genética , Doenças do Cão/patologia , Cães , Feminino , Rearranjo Gênico do Linfócito B , Rearranjo Gênico do Linfócito T , Testes Genéticos/métodos , Testes Genéticos/veterinária , Leishmania infantum/genética , Leishmaniose Visceral/genética , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Linfonodos/imunologia , Linfadenopatia/genética , Linfadenopatia/imunologia , Linfadenopatia/parasitologia , Linfoma/diagnóstico , Linfoma/genética , Linfoma/veterinária , Masculino , Reação em Cadeia da Polimerase/métodos , Reação em Cadeia da Polimerase/veterinária , Estudos Prospectivos , Esplenomegalia/diagnóstico , Esplenomegalia/veterinária
16.
Int J Exp Pathol ; 100(4): 222-233, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31696580

RESUMO

The objectives of this work were to study some pathological aspects of kidneys obtained from dogs naturally infected with Leishmania infantum and from dogs experimentally infected with two different strains of L infantum with special emphasis on fibrotic process. Seventy eight specimens of paraffin-embedded kidney fragments were collected as follows: (a) CNI group composed by 62 kidney samples of adult mongrel dogs, naturally infected with L infantum; (b) BH401 group composed by five kidney samples of adult Beagles experimentally infected with L infantum strain MCAN BR/2002/BH401; (c) BH400 group composed by eleven kidney samples of adult Beagles experimentally infected with L infantum strain MCAN/BR/2000/BH400, at the same dose and same route of the previous group, denominated group BH400; Control group (CC) composed by four kidney samples of adult Beagles. All animals revealed glomerular and interstitial fibropoiesis associated with different types of glomerulonephritis and chronic interstitial nephritis. Fibrosis was markedly more intense in the BH401 group, followed by animals in the CNI group. Markers for myofibroblasts (mesenchymal markers) such as alpha-actin (α-SMA), vimentin and the cytokine transforming growth factor beta (TGF-ß) were done by immunohistochemistry. BH401 group showed higher expression of all these markers than others. Intracellular amastigotes forms of Leishmania was mainly found in BH401. These results could be indicating that the MCAN/BR/2002/BH401 strain is a good choice for the study of renal LVC experimental model.


Assuntos
Doenças do Cão/patologia , Rim/patologia , Leishmania infantum , Leishmaniose Visceral/patologia , Leishmaniose Visceral/veterinária , Actinas , Animais , Cães , Fibrose , Imuno-Histoquímica , Rim/metabolismo , Rim/parasitologia , Leishmania infantum/genética , Fator de Crescimento Transformador beta , Vimentina
18.
Parasit Vectors ; 12(1): 487, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619264

RESUMO

BACKGROUND: The liver plays a central role in the development of canine visceral leishmaniasis. Studies of natural infection in animals and humans indicate a direct relationship between resolution of infection and the formation and maturation of granulomas in the liver. However, in contrast to other reports in the literature, the present study found no differences in the characteristics of hepatic granulomas that could be related to resistance or susceptibility to Leishmania. Here, we describe the hepatic alterations observed in dogs with differing clinical manifestations of visceral leishmaniasis in an endemic area in the state of Bahia, Brazil. METHODS: We examined 148 animals in an endemic area. The animals were clinically examined, and the infection was determined by ELISA, spleen aspirate culture and quantitative PCR. The animals were grouped into asymptomatic or symptomatic based on the number of signs of LV. The histological liver evaluation was performed in a blinded way. RESULTS: Our results indicated no association between the characteristics of granulomas and clinical presentation. We found an association between the intensity of this inflammatory response and parasite load in the animals' spleens. It is important to note that while hepatic alterations, such as portal and perivascular inflammation and the presence of larger amounts of granulomas, were linked with higher parasite loads, we found the inverse to be true with respect to intrasinusoidal lymphocytosis, the formation of intrasinusoidal inflammatory cell aggregates and Kupffer cell hypertrophy. CONCLUSIONS: Our findings suggest that the presence of mononuclear inflammatory cells inside the sinusoids is more important than that of organized granulomas in terms of the containment of parasitism by the host. We suggest that the presence of granulomas indicates the failure of a first line of defense mechanism in the control of parasite infection, which could be related to the presence of inflammatory cells and Kupffer cell hypertrophy inside the sinusoids. We further demonstrated that dogs with active Leishmania spp. infection present a higher frequency of inflammatory changes in the liver. In addition to being correlated with the severity of clinical manifestation, these hepatic alterations were also associated with changes in hematological and biochemical parameters.


Assuntos
Doenças do Cão/patologia , Leishmania infantum/patogenicidade , Leishmaniose Visceral/veterinária , Fígado/patologia , Animais , Brasil , Doenças do Cão/parasitologia , Cães , Doenças Endêmicas/veterinária , Granuloma/parasitologia , Granuloma/patologia , Granuloma/veterinária , Leishmaniose Visceral/patologia , Fígado/parasitologia , Hepatopatias Parasitárias/parasitologia , Hepatopatias Parasitárias/patologia , Hepatopatias Parasitárias/veterinária , Baço/parasitologia
19.
Front Immunol ; 10: 2360, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31649671

RESUMO

Altered sialylation is generally maintained by a fine balance between sialidases and sialyltransferases, which plays an essential role during disease pathogenesis. TLR4 is a membrane-bound highly sialylated glycoprotein predominantly having α2,3-linked sialic acids. It is one of the most important client molecules in the anti-leishmanial innate immune arm. Here, we initiated a comprehensive study on the modulation of TLR4 sialylation in Leishmania donovani (L. d)-infected macrophages by a mammalian sialidase/neuraminidase-1 (Neu1) having substrate specificity toward α2,3-linked sialic acids. We observed reduced membrane-associated Neu1 with its decreased enzyme activity in infected macrophages. Moreover, we demonstrated reduced association of Neu1 with TLR4 leading to enhanced sialylation of TLR4 in these infected cells. Conversely, Neu1 over expression exhibited enhanced association of TLR4 with Neu1 leading to reduced sialylation which possibly linked to increased association of TLR4 with its downstream adaptor protein, MyD88. This, in turn, activated downstream MAP kinase signaling pathway, with enhanced nuclear translocation of NFκB that resulted in increased genetic and protein levels expression of Th1 cytokines and effector molecule nitric oxide secretion which ultimately leads to reduced parasite burden in macrophages. This was further validated by Neu1 silencing in infected macrophages which reversed such a situation. Such events strongly confirm the importance of Neu1 in modulation of TLR4 sialylation during parasite infection resulting in impairment of innate immune response. Furthermore, decreased membrane-bound Neu1 in infected macrophages could be attributed to its reduced tyrosine-phosphorylation as well as diminished association with cathepsin A. Both these phenomenon possibly play significant roles in inhibiting translocation of the sialidase from cytosol to membrane. Taken together, our study first time demonstrated impaired translocation of cytosolic Neu1 to the membrane of L. donovani-infected macrophages due to impaired phosphorylation of this enzyme. This novel finding establishes a link between enhanced α2,3-linked sialic acids on TLR4 and reduced membrane-bound Neu1 which plays a significant role for inhibiting downstream signaling to establish successful infection in the host cells.


Assuntos
Leishmania donovani/imunologia , Leishmaniose Visceral , Sistema de Sinalização das MAP Quinases/imunologia , Macrófagos , Neuraminidase/imunologia , Receptor 4 Toll-Like/imunologia , Animais , Leishmaniose Visceral/imunologia , Leishmaniose Visceral/patologia , Macrófagos/imunologia , Macrófagos/parasitologia , Macrófagos/patologia , Mesocricetus , Camundongos , Camundongos Endogâmicos BALB C , Ácidos Siálicos/imunologia
20.
J Comp Pathol ; 171: 6-11, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31540627

RESUMO

Canine visceral leishmaniosis (CVL) is an important zoonotic disease, which is endemic in Brazil and several other parts of the world. The disease may affect multiple organs, but lesions in the oral cavity are considered uncommon. Twenty-three cases of oral lesions compatible with CVL were diagnosed from 2015 to 2018 in the Federal District, Brazil. Six cases were confirmed to be CVL based on histopathology, immunohistochemistry and polymerase chain reaction amplification of Leishmania infantum kDNA. Most of the affected dogs were >9 years of age, of mixed breed and were classified as having stage C of the disease. The most important gross findings were ulcerated nodular lesions in the tongue, lip, gingiva and hard palate. Microscopically, there was lymphoplasmacytic to granulomatous inflammation that was diffuse, moderate to severe and associated with ulceration. CVL should be considered in the differential diagnosis of nodular and ulcerative oral lesions in dogs.


Assuntos
Doenças do Cão/patologia , Leishmaniose Visceral/veterinária , Boca/patologia , Animais , Cães , Leishmania infantum , Leishmaniose Visceral/patologia , Estudos Retrospectivos
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