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1.
Rev Soc Bras Med Trop ; 54: e06102020, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33605380

RESUMO

INTRODUCTION: Visceral leishmaniasis has a broad worldwide distribution and constitutes a public health problem in the Northeast of Brazil. Located in this region is the state of Alagoas, where the disease is endemic in humans and where there has been a significant increase in the number of positive dogs. The objective of this study was to describe the temporal and spatial distribution of the cases of human VL in the state of Alagoas with the aim of identifying transmission risk areas in the period from 2007 to 2018. METHODS: The data available in the National Disease Notification System (SINAN-NET) were used. The Bayesian incidence rate and the Moran's global index were calculated using the Terra View 4.2.2 program, and the maps were created using QGIS2.18.0. RESULTS: From the 102 municipalities, 68.6% (n= 70) had at least one notified case of VL in the years of study. A total of 489 cases were registered, with an average of 40.7 cases per year and an incidence rate of 1.25/100,000 inhabitants. The highest number of confirmed cases (105) occurred in 2018. Male individuals and children between 1-4 years old were the most affected, and 64% of the cases were in rural areas. Spatial dependence was detected in all the intervals except for the first triennium, and clusters were formed in the west of the state. CONCLUSIONS: Alagoas presented an accentuated geographical expansion of VL, and it is necessary to prioritize areas and increase surveillance actions and epidemiological control.


Assuntos
Leishmaniose Visceral , Animais , Teorema de Bayes , Brasil/epidemiologia , Cidades , Cães , Incidência , Leishmaniose Visceral/epidemiologia , Análise Espacial
2.
Rev Bras Parasitol Vet ; 30(1): e018620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33533796

RESUMO

Visceral leishmaniasis is a widely distributed zoonosis and canine infection is an important indicator of risk for the occurrence of the disease in humans. The goal of this analysis was to study the spatial clustering of canine leishmaniasis (CL) in the municipality of Santa Luzia, state of Paraíba. For this, 749 samples of canine plasma were tested using three serological tests. The dog was considered positive if it reacted in two serological tests. The location of the residences was performed with a Global Positioning System receiver (GPS Garmin® eTrex 30), and used to perform georeferencing and spatial analysis. The prevalence of CL was 15.49% and it was observed that most cases of the urban area were concentrated in the Frei Damião neighborhood, on the outskirts of the city, where a high-risk cluster for the occurrence of the disease was formed (p = 0.02; RR = 2.48). No statistically significant cluster was observed in rural areas. CL is widely distributed in the municipality of Santa Luzia in a heterogeneous manner and with a tendency to urbanization. The areas identified with high prevalence and highest risk should be prioritized to maximize the efficiency of the Visceral Leishmaniasis Surveillance and Control Program and minimize the chance of new canine and human cases.


Assuntos
Doenças do Cão , Leishmaniose Visceral , Análise Espacial , Animais , Anticorpos Antiprotozoários/sangue , Brasil/epidemiologia , Cidades/epidemiologia , Clima Desértico , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária
3.
Artigo em Inglês | MEDLINE | ID: mdl-33533815

RESUMO

Visceral leishmaniasis (VL) is a neglected tropical disease caused by the Leishmania infantum parasite. The protozoan is able to infect several domestic and wild mammals. Since the first report on Leishmania spp. infection in horses in South America, leishmaniasis in equids has been highlighted in Brazil. A molecular epidemiological survey was carried out to verify the occurrence of Leishmania spp. DNA in horses and donkeys, in leishmaniases endemic areas in Sao Paulo State, Brazil. To this end, blood samples were obtained from 107 horses and 36 donkeys and subjected to DNA extraction followed by PCR targeting the ITS-1 region. Among the horses and donkeys, 1.87% (2/107) and 8.33% (3/36) were positive by PCR, respectively. The DNA sequencing of the ITS-1 amplification products confirmed L. infantum DNA in these animals. Our results suggest that horses and donkeys from non-VL and VL endemic areas of São Paulo State may be infected by the parasite.


Assuntos
Equidae/sangue , Cavalos/sangue , Leishmania infantum/genética , Leishmaniose Visceral/diagnóstico , Animais , Brasil , DNA , Leishmaniose Visceral/veterinária , Reação em Cadeia da Polimerase
4.
BMC Infect Dis ; 21(1): 124, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509123

RESUMO

BACKGROUND: Kidney involvement of visceral Leishmaniasis is previously reported, but knowledge is limited. Hypergammaglobulinemia is common in visceral leishmaniasis patients. Whether hypergammaglobulinemia after leishmaniasis depletion can cause kidney injury is not well reported yet. CASE PRESENTATION: We reported a patient who recovered from visceral Leishmaniasis but showed persistent hypergammaglobulinemia and elevated urinary protein. Kidney biopsy showed glomerular hypertrophy with mild segmental mesangial proliferation without tubulointerstitial involvement in light microscopy. No immune complex deposit was found in the mesangial area by neither immunofluorescent staining nor electronic microscope. Increased lysosomes were observed in proximal tubules by electronic microscope. Valsartan was administered to decrease urinary protein, and no immune-suppressive therapy was added. The urinary protein and serum IgG level gradually dropped, and serum creatinine level remained stable during three- month follow up. CONCLUSIONS: Hypergammaglobulinemia is unlikely to cause renal structural or functional damage in the short term. Angiotensin blockade significantly reduced urine protein, with a minor effect on IgG elimination.


Assuntos
Hipergamaglobulinemia/etiologia , Leishmaniose Visceral/complicações , Proteinúria/etiologia , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Humanos , Hipergamaglobulinemia/tratamento farmacológico , Hipergamaglobulinemia/patologia , Rim/patologia , Masculino , Proteinúria/tratamento farmacológico , Proteinúria/patologia , Resultado do Tratamento , Valsartana/uso terapêutico
5.
Sci Total Environ ; 764: 144275, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385656

RESUMO

Visceral leishmaniasis (VL) is a neglected disease caused by trypanosomatid protozoa in the genus Leishmania, which is transmitted by phlebotomine sandflies. Although this vector-borne disease has been eliminated in several regions of China during the last century, the reported human VL cases have rebounded in Western and Central China in recent decades. However, understanding of the spatial epidemiology of the disease remains vague, as the spatial risk factors driving the spatial heterogeneity of VL. In this study, we analyzed the spatiotemporal patterns of annual human VL cases in Western and Central China from 2007 to 2017. Based on the related spatial maps, the boosted regression tree (BRT) model was adopted to explore the relationships between VL and spatial correlates as well as predicting both the existing and potential infection risk zones of VL in Western and Central China. The mined links reveal that elevation, minimum temperature, relative humidity, and annual accumulated precipitation make great contributions to the spatial heterogeneity of VL. The maps show that Xinjiang Uygur Autonomous Region, Gansu, western Inner Mongolia Autonomous Region, and Sichuan are predicted to fall in the highest infection risk zones of VL. Approximately 61.60 million resident populations lived in the high-risk regions of VL in Western and Central China. Our results provide a better understanding of how spatial risk factors driving VL spread as well as identifying the potential endemic risk region of VL, thereby enhancing the biosurveillance capacity of public health authorities.


Assuntos
Leishmaniose Visceral , Doenças Negligenciadas , Psychodidae , Animais , China/epidemiologia , Humanos , Leishmaniose Visceral/epidemiologia , Fatores de Risco
6.
Parasit Vectors ; 14(1): 36, 2021 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-33422141

RESUMO

BACKGROUND: Zoonotic visceral leishmaniasis by Leishmania infantum is a first-order pathology in canine veterinary clinics in endemic areas. Moreover, canine infections are considered the main reservoir for human disease; despite their importance in the control of the disease within a One Health approach, no scientometric study has been published. Aims of the study included analyzing the impact of canine leishmaniasis (CanL) on the scientific literature, drugs or combinations used, trends in the period from 2000 to 2020 and efficacy criteria employed. METHODS: A Web of Science (WOS)-based analysis of publications on CanL and chemotherapy of the disease in the period 2000-2020 was carried out using a stepwise methodology. Data were analyzed by year, geographical origin, chemical groups, drugs and combinations, and efficacy criteria. RESULTS: Reports on CanL (n = 3324) represented < 16% of all publications on leishmaniasis (n = 20,968), and of these around 18% (n = 596) were related to chemotherapy. Publication records on CanL followed the distribution of the infection by L. infantum in endemic areas although Mediterranean countries were overrepresented in the reports on chemotherapy of CanL. Publications on the main antileishmanial drugs used in clinical practice showed a sustained tendency in the period analyzed. Pentavalent antimonials (SbV), alone or in combination with allopurinol, represented > 50% of all publications on chemotherapy of CanL despite the availability of more recently marketed drugs. CONCLUSIONS: Chemotherapy of CanL still relies on SbV and combinations and to a lesser extent on miltefosine (MIL). Reports on chemotherapy are scarce and mostly publicly funded, and the variability of experimental conditions hampers the direct comparison of the efficacy of drugs, combinations and schedules. The vast majority of reports on efficacy do not include any information on supportive therapy; this reduces the actual value of the studies if intended for the practical management of the disease. Complete reports on the chemotherapy (etiological + symptomatic) would add value to the trials performed.


Assuntos
Antiprotozoários/uso terapêutico , Doenças do Cão/tratamento farmacológico , Tratamento Farmacológico/métodos , Leishmaniose/tratamento farmacológico , Alopurinol/uso terapêutico , Anfotericina B/uso terapêutico , Animais , Doenças do Cão/epidemiologia , Cães , Combinação de Medicamentos , Humanos , Leishmania infantum , Leishmaniose/epidemiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/terapia , Fosforilcolina/análogos & derivados , Publicações
7.
Exp Parasitol ; 221: 108059, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33338468

RESUMO

Treatment for visceral leishmaniasis (VL) is hindered mainly by the toxicity and/or high cost of therapeutic drugs. In addition, parasite resistance has been registered. Thus, there is an urgent need for the identification of novel, effective and low-cost antileishmanial agents. Since drug discovery is a long and expensive process, drug repositioning for treatment of leishmaniasis should be considered. In the present study, Ivermectin (IVE), a broad-spectrum drug used for treatment of parasitic diseases, was evaluated in vitro and in vivo against Leishmania infantum species. Results in vitro showed that IVE presented 50% Leishmania and macrophage inhibitory concentrations (IC50 and CC50, respectively) of 3.64 ± 0.48 µM and 427.50 ± 17.60 µM, respectively, with a selectivity index (SI) of 117.45; whereas Amphotericin B (AmpB), which was used as control, showed IC50 and CC50 values of 0.12 ± 0.05 µM and 1.06 ± 0.23 µM, respectively, with a corresponding SI of 8.90. Treatment with IVE effectively reduced the infection percentage and parasite burden in infected and treated macrophages and displayed a prophylactic activity by inhibiting macrophage infection with pre-treated parasites. Furthermore, preliminary studies suggested that IVE targets the parasite's mitochondria. Activity of IVE in its free format or incorporated into Pluronic® F127-based polymeric micelles (IVE/Mic) was also evaluated in vivo as a treating drug for L. infantum-infected BALB/c mice. Miltefosine was used as a control. Results showed that Miltefosine, IVE and IVE/Mic-treated animals presented significant reductions in the parasite load in their spleens, livers, bone marrows and draining lymph nodes, as well as development of an antileishmanial Th1-type immune response one and 15 days after treatment. Notably, IVE/Mic showed a better parasitological and immunological response in comparison to other alternative treatments. In conclusion, results suggest that IVE/Mic could be considered in future studies as a therapeutic alternative to treat VL.


Assuntos
Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Ivermectina/farmacologia , Ivermectina/uso terapêutico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/farmacologia , Animais , Antiprotozoários/toxicidade , Eritrócitos/efeitos dos fármacos , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Concentração Inibidora 50 , Ivermectina/toxicidade , Macrófagos Peritoneais/efeitos dos fármacos , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos BALB C , Espécies Reativas de Oxigênio/metabolismo , Baço/parasitologia
8.
PLoS Negl Trop Dis ; 14(12): e0008947, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33338041

RESUMO

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be considered for further studies in human leishmaniases. Further clinical trials are needed to confirm these findings, to determine if there are relapses after treatment and if dogs remain infective to sandflies, to define the ideal therapeutic dosage and duration of treatment with artesunate.


Assuntos
Alopurinol/uso terapêutico , Antiprotozoários/uso terapêutico , Artesunato/uso terapêutico , Doenças do Cão/tratamento farmacológico , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Antimoniato de Meglumina/uso terapêutico , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Masculino , Carga Parasitária/veterinária , Parasitemia/tratamento farmacológico , Zoonoses
9.
Washington, D.C.; PAHO; 2020-12-23.
em Inglês | PAHO-IRIS | ID: phr-53166

RESUMO

In the Region of the Americas, the leishmaniases are a group of diseases caused by various species of Leishmania, which cause a set of clinical syndromes in infected humans that can involve the skin, mucosa, and visceral organs. The spectrum of clinical disease is varied and depends on the interaction of several factors related to the parasite, the vector, and the host. Cutaneous leishmaniasis is the form most frequently reported in the Region and nearly 90% of cases present single or multiple localized lesions. Other cutaneous clinical forms, such as disseminated and diffuse cutaneous leishmaniasis, are more difficult to treat and relapses are common. The mucosal form is serious because it can cause disfigurement and severe disability if not diagnosed and treated early on. Visceral leishmaniasis is the most severe form, as it can cause death in up to 90% of untreated people. In the Americas, clinical differences can be frequently found between endemic countries, mainly in the cutaneous form. Furthermore, many other diseases can be confused clinically with the different presentations of leishmaniasis and this is one of the greatest challenges for diagnosticians of the disease, who must also be aware of epidemiological reports and the patient’s clinical history. This Interactive Atlas of Leishmaniasis in the Americas: Clinical Aspects and Differential Diagnosis is a joint effort of the Pan American Health Organization, experts on this subject, and other collaborators, with support from the Federico Lleras Acosta University Hospital Dermatology Center of Colombia and the health ministries of the countries of the Region. This is an important and innovative publication that takes a practical approach to the subject, allowing professionals to interactively search for and study photographs and illustrations that reflect their daily work in the health services. The atlas discusses the main concepts and knowledge about leishmaniasis in the Americas, illustrating the clinical situation of these diseases in 10 endemic countries, through 1,029 photographs and illustrations that can be viewed on smartphones, tablets, and desktop or laptop computers. We believe the material will be valuable for all students and professionals at all levels of health care, including those in other continents, when treating patients infected in the Americas.


Assuntos
Leishmaniose , Dermatopatias , Doenças Transmissíveis , América , Leishmaniose Mucocutânea , Leishmaniose Cutânea , Leishmaniose Visceral
10.
Informe de Leishmanioses;9OPAS/CDE/VT/20-0041.
Monografia em Português | PAHO-IRIS | ID: phr-53091

RESUMO

Nas Américas, as leishmanioses são um problema de saúde pública por sua magnitude e distribuição geográfica e por produzir formas clínicas que podem causar morte, invalidez e mutilação. Nos últimos anos, a Organização Pan-Americana da Saúde (OPAS) - de acordo com o mandato conferido na Iniciativa da OPAS para a eliminação de doenças: política para aplicar um enfoque integrado e sustentável às doenças transmissíveis na Região das América (Resolução CD57/7, aprovada pelo Conselho Diretivo da OPAS em 2019) e de acordo com o roteiro para doenças tropicais negligenciadas 2021-2030 (publicado pela Organização Mundial da Saúde em 2020) - tem apoiado a países endêmicos, com os quais tem desenvolvido iniciativas conjuntas em prol do fortalecimento das ações de vigilância e controle, com o objetivo de reduzir as formas graves da doença, por meio do acesso ao diagnóstico precoce, ao tratamento adequado de casos e redução do contato entre pessoas e vetores. A organização dos serviços, o fortalecimento do conhecimento e da capacidade técnica dos profissionais em diagnóstico e tratamento, bem como o fortalecimento das capacidades entomológicas e do sistema de vigilância para disponibilizar informação atualizada, são medidas que vem sendo implementadas e impulsionadas nas Américas. Este informe apresenta a situação epidemiológica da leishmaniose na Região, por meio de uma análise detalhada dos dados correspondentes a 2019, reportados ao Sistema de Informação Regional de Leishmaniose nas Américas (SisLeish), bem como infográficos dos países endêmicos.


Assuntos
Leishmaniose , Leishmaniose Visceral , Leishmaniose Mucocutânea , Zoonoses , Doenças Negligenciadas , Doenças Transmissíveis , Vigilância , Monitoramento Epidemiológico , América
11.
Leishmaniases Report;9PAHO/CDE/VT/20-0041.
Monografia em Inglês | PAHO-IRIS | ID: phr-53090

RESUMO

In the Americas, leishmaniasis are a public health problem due to their magnitude and geographic distribution and because they produce clinical forms that can cause death, disability, and mutilation. In recent years, the Pan American Health Organization (PAHO)—in accordance with the mandate conferred in the PAHO initiative for disease elimination: policy for an Integrated Sustainable Approach to Communicable Diseases in the Americas (Resolution CD57/7, approved by the Directing Council of PAHO in 2019) and in line with the roadmap for neglected tropical diseases 2021-2030 (published by the World Health Organization in 2020)—has supported endemic countries, with which it has developed joint initiatives in favor of strengthening surveillance and control actions, with the goal of reducing severe forms of the disease, through access to early diagnosis, adequate treatment of cases and reduction of contact between people and vectors. The organization of services, the strengthening of knowledge and the technical capacity of professionals in diagnosis and treatment, as well as the strengthening of entomological capacities and the surveillance system to provide updated information, are measures that have been implemented and promoted in the Americas. This report presents the epidemiological situation of leishmaniasis in the Region, through a detailed analysis of the data corresponding to 2019, reported to the Regional Information System of Leishmaniasis in the Americas (SisLeish), as well as infographics of the endemic countries.


Assuntos
Leishmaniose , Leishmaniose Visceral , Leishmaniose Mucocutânea , Doenças Transmissíveis , Zoonoses , Monitoramento Epidemiológico , Doenças Negligenciadas , Vigilância , América
12.
Informe de Leishmaniasis;9OPS/CDE/VT/20-0041.
Monografia em Espanhol | PAHO-IRIS | ID: phr-53089

RESUMO

En las Américas, las leishmaniasis son un problema de salud pública debido a su magnitud y distribución geográfica y a que producen formas clínicas que pueden causar muerte, incapacidad y mutilaciones. En los últimos años, la Organización Panamericana de la Salud (OPS) —de conformidad con el mandato conferido en la Iniciativa de la OPS para la eliminación de enfermedades: política para aplicar un enfoque integrado y sostenible de las enfermedades transmisibles en la Región de las Américas (resolución CD57/7, aprobada por el Consejo Directivo de la OPS en el 2019) y en consonancia con la hoja de ruta para las enfermedades tropicales desatendidas 2021-2030 (publicada por la Organización Mundial de la Salud en el 2020)— ha prestado su apoyo a los países endémicos, con los que ha desplegado iniciativas conjuntas en favor del fortalecimiento de las acciones de vigilancia y control, con el objetivo de reducir las formas graves de la enfermedad, a través del acceso al diagnóstico temprano, el tratamiento adecuado de los casos y la reducción del contacto entre las personas y los vectores. La organización de los servicios, el fortalecimiento del conocimiento y la capacidad técnica de los profesionales en el diagnóstico y tratamiento, así como el fortalecimiento de las capacidades entomológicas y del sistema de vigilancia para facilitar información actualizada, son medidas que se han puesto en marcha e impulsado en las Américas. Este informe presenta la situación epidemiológica de las leishmaniasis en la Región, mediante un análisis detallado de los datos correspondientes al 2019, notificados al Sistema de Información Regional de las Leishmaniasis en la Américas (SisLeish), así como infografías de los países endémicos.


Assuntos
Leishmaniose , Doenças Transmissíveis , Doenças Negligenciadas , Zoonoses , Vigilância , Leishmaniose Mucocutânea , Leishmaniose Visceral , Monitoramento Epidemiológico , América
13.
PLoS Negl Trop Dis ; 14(12): e0008963, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382690

RESUMO

Diagnosis of a first-time visceral leishmaniasis (VL) infection in Ethiopia is established by use of a rapid diagnostic test (RDT) detecting antibodies against rK39, direct agglutination test (DAT) and microscopy according to the national algorithm. The performance of individual tests and algorithm is variable and depends on several factors, one being HIV status. Limited data are available on the performance of tests in VL-HIV coinfected patients. Assessment of the performance of DAT (ITM-A), rK39 ELISA (Serion) and six RDT (Onsite Leishmania Ab CTK, Antigen ICT Xinjier, IT Leish Biorad, Kalazar Detect Inbios, rK39 IgG1 Coris, rk28 IgG1 Coris) for the diagnosis of VL was done on a panel of 91 stored serum and plasma samples of 'first-episode' suspected VL patients, with HIV coinfection (n = 51) and without (n = 40). A combined reference standard was used: either positive microscopy on tissue aspirates, or in case of negative microscopy, positive PCR results on the aspirate slide. Additionally, endemic healthy controls (n = 20), non-endemic controls (n = 10) and patients with confirmed malaria infection (n = 10) were tested for specificity evaluation. Sensitivities ranged from 69.2% for DAT (applied cut-off ≥ 1/3200) to 92.2% for the Onsite RDT, whereas specificities ranged from 20.0% for Kalazar Antigen ICT to 100% for IT Leish and rK39 IgG1. Sensitivities from all assays decreased upon stratification according to HIV status but was only significantly different for rK39 Serion ELISA (p-value 0.0084) and the Onsite RDT (p-value 0.0159). In conclusion, performance of commercially available assays for VL on samples from Northern-Ethiopian patients varied widely with a substantial decrease in sensitivity in the VL-HIV coinfected group. Clear guidelines on minimal performance criteria of individual tests and algorithms are needed, as well as which reference standard should be used to determine the performance.


Assuntos
Antígenos de Protozoários/imunologia , Infecções por HIV/complicações , Leishmania/imunologia , Leishmaniose Visceral/diagnóstico , Testes de Aglutinação , Testes Diagnósticos de Rotina , Ensaio de Imunoadsorção Enzimática , Etiópia/epidemiologia , Humanos , Leishmaniose Visceral/parasitologia , Padrões de Referência
14.
PLoS Pathog ; 16(12): e1009136, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33370418

RESUMO

The level of CD40 expression on dendritic cells (DCs) plays a decisive role in disease protection during Leishmania donovani (LD) infection. However, current understanding of the molecular regulation of CD40 expression remains elusive. Using molecular, cellular and functional approaches, we identified a role for Runx1 and Runx3 transcription factors in the regulation of CD40 expression in DCs. In response to lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFα) or antileishmanial drug sodium antimony gluconate (SAG), both Runx1 and Runx3 translocated to the nucleus, bound to the CD40 promoter and upregulated CD40 expression on DCs. These activities of Runx proteins were mediated by the upstream phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Notably, LD infection attenuated LPS- or TNFα-induced CD40 expression in DCs by inhibiting PI3K-Akt-Runx axis via protein tyrosine phosphatase SHP-1. In contrast, CD40 expression induced by SAG was unaffected by LD infection, as SAG by blocking LD-induced SHP-1 activation potentiated PI3K-Akt signaling to drive Runx-mediated CD40 upregulation. Adoptive transfer experiments further showed that Runx1 and Runx3 play a pivotal role in eliciting antileishmanial immune response of SAG-treated DCs in vivo by promoting CD40-mediated type-1 T cell responses. Importantly, antimony-resistant LD suppressed SAG-induced CD40 upregulation on DCs by blocking the PI3K-Akt-Runx pathway through sustained SHP-1 activation. These findings unveil an immunoregulatory role for Runx proteins during LD infection.


Assuntos
Antígenos CD40/imunologia , Subunidades alfa de Fatores de Ligação ao Core/imunologia , Células Dendríticas/imunologia , Regulação da Expressão Gênica/imunologia , Leishmaniose Visceral/imunologia , Animais , Antígenos CD40/biossíntese , Cricetinae , Humanos , Leishmania donovani/imunologia , Camundongos , Camundongos Endogâmicos BALB C
15.
Rev Soc Bras Med Trop ; 53: e20200680, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33331613

RESUMO

INTRODUCTION: The use of insecticide-impregnated dog collars is a potentially useful tool for the control of visceral leishmaniasis. The objective of the present study was to perform a cost-effectiveness analysis of a program based on insecticide-impregnated collars compared to traditional visceral leishmaniasis control strategies used in Brazil. METHODS: A cost-effectiveness analysis was performed from the perspective of the Unified Health System, using data from the Visceral Leishmaniasis Control Program implemented in the municipality of Montes Claros, Minas Gerais. The direct costs of the three control strategies, which were 1) canine infection screening + sacrifice, 2) residual chemical control of the vector, and 3) insecticide-impregnated dog collars (Scalibor®), were evaluated over the two-year study period. RESULTS: The total cost of the program in the area subjected to the traditional control strategies (strategies 1 and 2; control area) was R$ 1,551,699.80, and in the area subjected to all three control strategies (intervention area), it was R$ 1,898,190.16. The collar program was considered highly cost-effective at preventing canine visceral leishmaniasis (incremental cost-effectiveness ratio of approximately R$ 578 per avoided dog sacrifice). CONCLUSIONS: These results provide support for the decision by the Brazilian Ministry of Health in 2019 to provide insecticide-impregnated collars for the control of canine visceral leishmaniasis in a pilot project.


Assuntos
Doenças do Cão , Inseticidas , Leishmaniose Visceral , Piretrinas , Animais , Brasil , Análise Custo-Benefício , Doenças do Cão/prevenção & controle , Cães , Leishmaniose Visceral/prevenção & controle , Leishmaniose Visceral/veterinária , Nitrilos , Projetos Piloto
16.
Rev Soc Bras Med Trop ; 54: e20200208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338118

RESUMO

Post-kala-azar dermal leishmaniasis is a skin disorder occurring in 5-10% of visceral leishmaniasis patients after treatment with miltefosine,the first-line drug for this skin disorder. We reported a case of acute anterior uveitis,a rare adverse effect, experienced by a patient treated with miltefosine for post-kala-azar dermal leishmaniasis. This adverse effect developed after 15 days of miltefosine consumption, and the patient himself discontinued the treatment. The ophthalmic complication was completely resolved with antibiotics and steroid eye drops. After recovery from the ophthalmic complication, the patient was successfully treated with liposomal amphotericin B for the skin lesions.


Assuntos
Antiprotozoários , Leishmaniose Cutânea , Leishmaniose Visceral , Uveíte , Antiprotozoários/efeitos adversos , Humanos , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/tratamento farmacológico , Fosforilcolina/análogos & derivados , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico
17.
BMC Infect Dis ; 20(1): 946, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33308170

RESUMO

BACKGROUND: Direct agglutination test (DAT) as a simple, accurate and reliable method, has been widely used for serodiagnosis of visceral leishmaniasis (VL) during the last three decades. The present study is a systematic review and meta-analysis to evaluate the diagnostic accuracy of DAT for serodiagnosis of human VL. METHODS: Electronic databases, including MEDLINE (via PubMed), SCOPUS, Web of Science, SID and Mag Iran (two Persian scientific search engines) were searched from December 2004 to April 2019. We determined the pooled sensitivity and specificity rates of DAT for the diagnosis of human VL, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic (ROC) curves parameters across the eligible studies. RESULTS: Of the 2928 records identified in the mentioned electronic databases and after examining reference lists of articles, 24 articles met inclusion criteria and were enrolled in the systematic review and out of them 20 records qualified for meta-analysis. The pooled sensitivity and specificity rates of DAT was 96% [95% CI, 92-98] and 95% [CI95% 86-99], respectively. The likelihood ratio of a positive test (LR+) was found to be 21 [CI95%, 6.6-66.5] and the likelihood ratio of a negative test (LR-) was found to be 0.04 [(CI95%, 0.02-0.08]. The combined estimate of the diagnostic odds ratio for DAT was high [467 (CI95%, 114-1912]). We found that the summary receiver operating characteristic curve (SROC) is positioned near the upper left corner of the curve and the area under curve (AUC) was 0.98 (95% CI, 0.97 to 0.99). CONCLUSION: Referring to our analysis, we determined that DAT can be considered as a valuable tool for the serodiagnosis of human VL with high sensitivity and specificity. As DAT is a simple, accurate and efficient serological test, it can be recommended for serodiagnosis of human VL particularly in endemic areas.


Assuntos
Testes de Aglutinação/métodos , Confiabilidade dos Dados , Leishmania donovani/imunologia , Leishmaniose Visceral/diagnóstico , Humanos , Leishmaniose Visceral/parasitologia , Razão de Chances , Curva ROC , Sensibilidade e Especificidade
18.
Medicine (Baltimore) ; 99(45): e22787, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157924

RESUMO

INTRODUCTION: Non-HIV-related visceral leishmaniasis (VL) is becoming increasingly prevalent in nontropical countries because of the increasing number of patients with chronic diseases and the development of immune-modulating drugs. PATIENT CONCERNS: Case 1 is a 60-year-old male patient of Senegalese origin presented with weight loss, lymphadenopathy, anemia, and elevated lactate dehydrogenases. Case 2 is a 46-year-old male patient of Algerian origin, with a negative HIV serology presented with cutaneous lesions. DIAGNOSIS: Patient 1: The diagnosis of stage IV lymphocytic lymphoma (LL) was confirmed by an inguinal nodal biopsy in 2013. Patient 2: The diagnosis of T-cell lymphoma was made in 2003. INTERVENTIONS: Patient 1 received 5 cycles of bendamustine and rituximab followed by a complete remission. Patient 2 was initially treated with >10 different treatments followed by 8 different chemotherapy regimens due to the disease progression. OUTCOMES: Patient 1: In 2017, after a follow-up of 4 years, the patient presented with fever, lymphadenopathy, splenomegaly, and pancytopenia in the setting of hemophagocytic syndrome. The initial diagnosis was a relapse of lymphoma and the patient was treated with ibrutinib. His status worsened, and Leishmania DNA was detected by polymerase chain reaction (PCR) on the blood and bone marrow aspirates. Ibrutinib was stopped. Amphotericin B treatment induced a complete clinical remission and clearance of Leishmania DNA from the blood.Patient 2: In 2017, after a follow-up of 14 years, the patient presented with fever, lymphadenopathy, hepatosplenomegaly, pancytopenia with hemophagocytic syndrome, and an increase in the tumor skin lesions. A skin biopsy was taken from the face and the patient. A careful reexamination of the skin biopsy revealed the presence of Leishmania bodies. He was treated with 40 mg/kg liposomal amphotericin B leading to a regression of the clinical symptoms and negativation of the blood PCR. CONCLUSIONS: This case study shows that VL may be a diagnostic challenge in patients with lymphoma. Reactivation or primary infection should be considered in the differential diagnosis. The purpose of this study is to remind clinicians to think of VL in patients with systemic symptoms that could be misdiagnosed as a progression of the underlying lymphoma.


Assuntos
Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Diagnóstico Diferencial , Progressão da Doença , Humanos , Leishmaniose Visceral/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/diagnóstico , Masculino , Pessoa de Meia-Idade , Indução de Remissão
19.
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
20.
Ann Parasitol ; 63(3): 295-302, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33128446

RESUMO

Visceral leishmaniosis is one of the most fatal old-world neglected disease with estimated 90 thousand worldwide cases emerge each year. In Iraq, the cutaneous and visceral form are endemic but available chemotherapies are either toxic with diverse side effects, expensive available drugs or parasite resistant is arising. Artemisinin (ART) is a semi-synthetic compound which proved its effectiveness against protozoan parasites, such as malaria and Leishmania. In this study, the efficacy of different concentrations of pure artemisinin was screened in vitro against promastigotes and axenic amastigotes by MTT assay after 24, 48 and 27 hours follow up. In addition, the infectivity ability and number was investigated of intra-cellular Leishman bodies in treated murine peritoneal macrophages after 24 and 48 hours ART treatment. The results verified ART efficacy against the promastigotes and axenic amastigotes viability with IC50 measured after 24, 48- and 72-hours treatment. Infectivity percentage of murine macrophages and parasite burden were significantly reduced in treated cells. These findings indicate the leishmanicidal activity of ART against the Iraqi isolate of L. donovani and further in vivo study is recommended for assigning ART as a natural anti visceral leishmaniosis compound.


Assuntos
Antiprotozoários , Artemisininas , Leishmania donovani , Leishmaniose Visceral , Animais , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Iraque , Leishmaniose Visceral/tratamento farmacológico , Macrófagos , Camundongos
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