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1.
Vet Parasitol ; 277: 109015, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31874403

RESUMO

Canine leishmaniosis (CanL)-associated chronic kidney disease is a leading cause of morbidity and mortality in Mediterranean countries. Novel renal biomarkers, such as serum symmetric dimethylarginine (sSDMA), may be useful surrogates for the detection of renal functional impairment. The objectives of this study were to investigate sSDMA concentrations in dogs with CanL, with and without azotemia, and to establish any potential association with the prevalence and severity of proteinuria, with the prevalence of decreased urine specific gravity and with the LeishVet clinical stages of CanL. Serum samples from 68 dogs with CanL (50 nonazotemic and 18 azotemic) and 17 healthy dogs were retrospectively examined. Increased sSDMA was documented in 26 % of dogs with CanL without azotemia and in 83.3 % of dogs with azotemia. Serum SDMA was significantly higher in azotemic compared to nonazotemic dogs and was associated with the presence and severity of proteinuria, the decreased urine specific gravity and the advanced clinical stages of CanL. The results of the present study indicate that sSDMA may be a useful adjunct to serum creatinine and urine protein/creatinine ratio for the detection of CanL-associated nephropathy, but it is of limited value for distinguishing among the LeishVet clinical stages of CanL.


Assuntos
Arginina/análogos & derivados , Doenças do Cão/diagnóstico , Leishmaniose Visceral/complicações , Leishmaniose Visceral/diagnóstico , Insuficiência Renal Crônica/etiologia , Animais , Arginina/sangue , Azotemia/veterinária , Biomarcadores/sangue , Doenças do Cão/sangue , Cães , Leishmania infantum/fisiologia , Insuficiência Renal Crônica/sangue , Estudos Retrospectivos
2.
J Vector Borne Dis ; 56(2): 127-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31397388

RESUMO

Background & objectives: Cutaneous leishmaniasis (CL) is widespread in the tropical and subtropical regions of the world including, Tukey. Environmental determinants for the CL endemic areas in Turkey are relatively poorly understood. The aim of the present study was to develop a model based on ecological niche modeling (ENM) to predict the distribution of CL in endemic areas of Adana Province in Turkey. Methods: The environmental data from different sources were extracted and information on 1831 native CL cases, obtained from the Provincial Health Directorate of Adana were recorded. The location information obtained from the Ministry of Health database were used for modeling the current probability of CL occurrence and predicting its future distribution using ENM analyses. ArcGIS and MaxEnt models were used to explore the ecological conditions of the disease. Results: According to the MaxEnt model, the area under the curve (AUC) values for the current and projected future of CL were 0.868 and 0.867, respectively. The environmental variables, Bio1 (Annual mean temperature), Bio4 (Temperature seasonality) and DEM (Digital elevation model) were found to be associated with the presence of human cases of Leishmania infantum for both the time periods in the study area. Interpretation & conclusion: The AUC curves and risk map generated by the ENM model indicate that the future status of CL is likely to be stable in the northern part of Adana, but the southern part will be affected by climate changes (change of temperature) with a large number of patient-reporting. The results of the study could be used as a reference for CL and vector control studies. The ENM could be useful for researchers in vector control studies and better understanding of the epidemiology of vector-borne diseases in a specific area.


Assuntos
Ecossistema , Leishmania infantum/fisiologia , Leishmaniose Cutânea/epidemiologia , Modelos Biológicos , Animais , Área Sob a Curva , Humanos , Insetos Vetores/parasitologia , Phlebotomus/parasitologia , Temperatura Ambiente , Turquia/epidemiologia
3.
J Immunol Res ; 2019: 9124326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31183394

RESUMO

Vaccination is the most effective tool against infectious diseases. Subunit vaccines are safer compared to live-attenuated vaccines but are less immunogenic and need to be delivered with an adjuvant. Adjuvants are essential for enhancing vaccine potency by improving humoral and cell-mediated immune responses. Only a limited number of adjuvants are licensed for human vaccines, and their mode of action is still not clear. Leishmania eukaryotic initiation factor (LeIF) has been described having a dual role, as a natural adjuvant and as an antigen that possesses advantageous immunomodulatory properties. In this study, we assessed the adjuvant properties of recombinant Leishmania infantum eukaryotic initiation factor (LieIF) through in vitro and in vivo assays. LieIF was intraperitoneally administered in combination with the protein antigen ovalbumin (OVA), and the widely used alum was used as a reference adjuvant. Our in vitro studies using J774A.1 macrophages showed that LieIF induced stimulatory effects as demonstrated by the enhanced surface expression of CD80 and CD86 co-stimulatory molecules and the induced production of the immune mediators NO and MIP-1α. Additionally, LieIF co-administration with OVA in an in vivo murine model induced a proinflammatory environment as demonstrated by the elevated expression of TNF-α, IL-1ß, and NF-κB2 genes in peritoneal exudate cells (PEC). Furthermore, PEC derived from OVA-LieIF-immunized mice exhibited elevated expression of CD80 molecule and production of NO and MIP-1α in culture supernatants. Moreover, LieIF administration in the peritoneum of mice resulted in the recruitment of neutrophils and monocytes at 24 h post-injection. Also, we showed that this immunopotentiating effect of LieIF did not depend on the induction of uric acid danger signal. These findings suggest the potential use of LieIF as adjuvant in new vaccine formulations against different infectious diseases.


Assuntos
Adjuvantes Imunológicos , Fatores de Iniciação em Eucariotos/imunologia , Inflamação/imunologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/imunologia , Macrófagos/imunologia , Proteínas de Protozoários/imunologia , Animais , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Fatores de Iniciação em Eucariotos/genética , Feminino , Humanos , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos , Ovalbumina/imunologia , Proteínas de Protozoários/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
PLoS Negl Trop Dis ; 13(4): e0007313, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30995227

RESUMO

Leishmaniasis is a zoonotic disease of worldwide relevance. Visceral leishmaniasis is endemic in Brazil, where it is caused by Leishmania infantum with Lutzomyia longipalpis being the most important invertebrate vector. Non-human primates are susceptible to L. infantum infection. However, little is known about the role of these species as reservoirs. The aim of this study was to evaluate the transmissibility potential of visceral leishmaniasis by non-human primates through xenodiagnosis using the phlebotomine Lu. longipalpis as well as to identify phlebotomine species prevalent in the area where the primates were kept in captivity, and assess infection by Leishmania in captured phlebotomine specimens. Fifty two non-human primates kept in captivity in an endemic area for leishmaniasis were subjected to xenodiagnosis. All primates were serologically tested for detection of anti-Leishmania antibodies. Additionally, an anti-Lu. longipalpis saliva ELISA was performed. Sand flies fed on all animals were tested by qPCR to identify and quantify L. infantum promastigotes. Eight of the 52 non-human primates were positive by xenodiagnosis, including three Pan troglodytes, three Leontopithecus rosalia, one Sapajus apella, and one Miopithecus talapoin, with estimated numbers of promastigotes ranging from 5.67 to 1,181.93 per µg of DNA. Positive animals had higher levels of IgG anti-Lu. longipalpis saliva when compared to negative animals, prior to xenodiagnosis. Captive non-human primates are capable of infecting Lu. longipalpis with L. infantum. Our findings also demonstrate the relevance of non-human primates as sentinels to zoonotic diseases. Several phlebotomine species, including Lu. longipalpis, have been identified in the area where the primates were maintained, but only one pool of Lutzomyia lenti was infected with L. infantum. This study has implications for public health strategies and conservation medicine.


Assuntos
Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/transmissão , Leishmaniose Visceral/veterinária , Primatas/parasitologia , Psychodidae/parasitologia , Animais , Animais de Zoológico , Brasil , Reservatórios de Doenças/veterinária , Feminino , Leishmania infantum/fisiologia
5.
Parasit Vectors ; 12(1): 110, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30871639

RESUMO

BACKGROUND: In Brazil, members of the sand fly species complex Lutzomyia longipalpis transmit Leishmania infantum, a protist parasite that causes visceral leishmaniasis. Male Lu. longipalpis produce a sex pheromone that is attractive to both females and males. During a cluster randomised trial, to determine the combined effect of synthetic sex-aggregation pheromone and insecticide on Le. infantum transmission Lu. longipalpis had been continuously exposed to insecticide for 30 months. The objective of this study was to determine the effect of continuous exposure to the insecticides used in the trial on the susceptibility of Lu. longipalpis population. METHODS: During the trial the sand flies had been exposed to either lambda-cyhalothrin [pheromone + residual insecticide spray (PI)], deltamethrin [dog collars (DC)] or no insecticide [control (C)], for 30 months (November 2012 to April 2015). The insecticide treatment regime was kept in place for an additional 12 months (May 2015-April 2016) during this susceptibility study. Sand flies collected from the field were exposed to WHO insecticide-impregnated papers cyhalothrin (0.05%), deltamethrin (0.5%) and control (silicone oil) in a modified WHO insecticide exposure trial to determine their susceptibility. RESULTS: We collected 788 Lu. longipalpis using CDC-light traps in 31 municipalities across the three trial arms. Probit analysis showed that the knockdown times (KDTs) of Lu. longipalpis collected from the lambda-cyhalothrin exposed PI-arm [KDT50: 31.1 min, confidence interval (CI): 29.6-32.6 and KDT90: 44.2 min, CI: 42.1-46.7] were longer than the KDTs from the non-insecticide-treated C-arm (KDT50: 26.3 min, CI: 25.1-27.6 and KDT90: 38.2, CI: 36.5-40.2) (no-overlapping 95% CIs). KDTs of Lu. longipalpis collected from the deltamethrin exposed DC-arm had similar values (KDT50: 13.7 min, CI: 10.1-16.2 and KDT90: 26.7 min, CI: 21.8-30.6) to those for the C-arm (KDT50: 13.5 min; CI: 12.2-14.8 and KDT90: 23.2 min, CI: 21.4-25.4) (overlapping CIs). The wild-caught unexposed Lu. longipalpis (C-arm), took approximately twice as long to knock down as laboratory-colonised specimens for both insecticides. CONCLUSIONS: Our study reveals slight changes in KDT, in sand flies after prolonged exposure to lambda-cyhalothrin in the presence of pheromone. These changes are not considered to have reached the reference levels indicative of resistance in sand flies suggesting that pheromone and insecticide treatment at the level indicated in this study do not constitute a significant risk of increased insecticide resistance. Prolonged exposure to deltamethrin in dog collars did not result in changes to KDT.


Assuntos
Resistência a Inseticidas/efeitos dos fármacos , Inseticidas/farmacologia , Leishmaniose Visceral/transmissão , Controle de Mosquitos , Mosquitos Vetores/efeitos dos fármacos , Psychodidae/efeitos dos fármacos , Animais , Feminino , Leishmania infantum/fisiologia , Leishmaniose Visceral/parasitologia , Masculino , Nitrilos/farmacologia , Piretrinas/farmacologia , Atrativos Sexuais/farmacologia , Fatores de Tempo
6.
Med Vet Entomol ; 33(2): 322-325, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30652325

RESUMO

Lutzomyia longipalpis (Diptera: Psychodidae) is the primary vector of Leishmania infantum (Kinetoplastida: Trypanosomatidae) in the Americas. Studies have been carried out to identify new alternatives for monitoring and controlling this sandfly species, particularly with the use of chemical baits. The attractiveness of odours emitted by foxes and alcohols found in some plants has already been demonstrated in laboratory tests with Lu. longipalpis. However, no studies have evaluated the responses of these insects to volatile organic compounds (VOCs) emitted by dogs. The present study was carried out to investigate the effects on Lu. longipalpis of individual and blends of VOCs identified in hair from dogs infected with L. infantum. Effects in male and female Lu. longipalpis were assessed using wind tunnel methodology. Individual compounds including octanal, nonanal, decanal and heptadecane showed capacity for activating and/or attracting male Lu. longipalpis. Only decanal and nonanal showed effects on females. The combination of octanal, decanal and heptadecane increased activation and attraction behaviour in male sandflies, as did the blend of octanal and decanal. These findings indicate that VOCs emitted by dogs may be an interesting source of new attractants of sandflies.


Assuntos
Quimiotaxia , Leishmania infantum/fisiologia , Psychodidae/fisiologia , Compostos Orgânicos Voláteis/metabolismo , Animais , Biomarcadores/metabolismo , Doenças do Cão/parasitologia , Cães , Feminino , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Masculino
8.
Front Immunol ; 9: 2558, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30519235

RESUMO

Metacyclic Leishmania promastigotes are transmitted by sand flies that inject parasites and saliva into the host's skin. Previous studies have demonstrated that DNA plasmids encoding Lutzomyia longipalpis salivary proteins LJM17 and LJL143, when used to immunize dogs, resulted in a systemic and local Th1 cell-mediated immunity that interfered in parasite survival in vitro. Here we evaluated the ability of these same salivary antigens to induce anti-Leishmania immunity and to confer protection by immunizing dogs using a novel vaccination strategy more suitable for use in the field. The strategy consisted of a single dose of plasmid followed by two doses of recombinant Canarypoxvirus (rCanarypoxvirus) expressing L. longipalpis salivary proteins (LJM17 or LJL143). Thirty days after the final immunization, dogs were intradermally challenged with 107 Leishmania infantum promastigotes in the presence of L. longipalpis saliva. We followed the experimentally infected dogs for 10 months to characterize clinical, parasitological, and immunological parameters. Upon vaccination, all immunized dogs presented strong and specific humoral responses with increased serum concentrations of IFN-γ, TNF, IL-7, and IL-15. The serum of dogs immunized with LJM17 also exhibited high levels of IL-2, IL-6, and IL-18. L. infantum infection was established in all experimental groups as evidenced by the presence of anti-Leishmania IgG, and by parasite detection in the spleen and skin. Dogs immunized with LJM17-based vaccines presented higher circulating levels of IFN-γ, IL-2, IL-6, IL-7, IL-15, IL-18, TNF, CXCL10, and GM-CSF post-infection when compared with controls. Results demonstrated that relevant Leishmania-specific immune responses were induced following vaccination of dogs with L. longipalpis salivary antigen LJM17 administered in a single priming dose of plasmid DNA, followed by two booster doses of recombinant Canarypox vector. Importantly, a significant increase in pro-inflammatory cytokines and chemokines known to be relevant for protection against leishmaniasis was evidenced after challenging LJM17-vaccinated dogs as compared to controls. Although similar results were observed following immunization with LJL143, the pro-inflammatory response observed after immunization was attenuated following infection. Collectively, these data suggest that the LJM17-based vaccine induced an immune profile consistent with the expected protective immunity against canine leishmaniosis. These results clearly support the need for further evaluation of the LJM17 antigen, using a heterologous prime-boost vaccination strategy against canine visceral leishmaniosis (CVL).


Assuntos
Proteínas de Insetos/imunologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/imunologia , Proteínas e Peptídeos Salivares/imunologia , Vacinas de DNA/imunologia , Animais , Vírus da Varíola dos Canários/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Vetores Genéticos , Humanos , Imunidade Humoral , Imunização , Mediadores da Inflamação/metabolismo , Proteínas de Insetos/genética , Psychodidae/imunologia , Proteínas Recombinantes/genética , Proteínas e Peptídeos Salivares/genética
9.
PLoS One ; 13(12): e0208613, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532255

RESUMO

To reduce morbidity and mortality caused by visceral leishmaniasis (VL), the Brazilian Visceral Leishmaniasis Control and Surveillance Program promotes the diagnosis and treatment of cases, vector control, euthanasia of seropositive dogs, and health education. Nevertheless, the effectiveness of these measures is questionable as they lead to little reduction in the transmission of the disease. Thus, the effectiveness of strategies such as insecticide-impregnated collars, spot-on insecticides, and immunization of dogs should be assessed. Herein, we evaluated the effectiveness of deltamethrin-impregnated collars on reducing the incidence of Leishmania infantum infection in dogs living in an endemic area of VL. An intervention study was conducted and a total 5,850 dogs were analyzed in baseline. Of these 3,742 seronegative dogs were divided into two groups: collared and uncollared (control). Dogs were followed for 12 months and three interventions were performed. The Cox regression model was used to evaluate the effectiveness of the collar. All analyzes were performed by Intention-to-treat and per-protocol. By intention-to-treat, the incidence rates of L. infantum infection were 7.5 and 7.9 in the collar group, and 6.5 and 13.2 per 1,000 dogs-months in the control group after 6 and 12 months, respectively. In the per-protocol analysis, the incidence rates in the control group were similar to those observed in the intention-to-treat analysis. In the collar group, the incidence rate was 5.1/1,000 dogs-months after 6 and 12 months. The effectiveness by intention-to-treat after adjustment by the multivariate Cox model was 48%. In the analysis per-protocol, the effectiveness increased to 63%. Although collar use was effective when it was evaluated by intention-to-treat, higher effectiveness was found in the per-protocol analysis after one year of follow-up. The data emphasize the importance of the uninterrupted use of deltamethrin-impregnated collars to increase protection against canine VL.


Assuntos
Doenças do Cão/epidemiologia , Inseticidas/química , Leishmaniose Visceral/epidemiologia , Nitrilos/química , Piretrinas/química , Animais , Brasil/epidemiologia , Doenças do Cão/patologia , Cães , Feminino , Incidência , Inseticidas/toxicidade , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/fisiologia , Leishmaniose Visceral/patologia , Masculino , Nitrilos/toxicidade , Controle de Pragas , Modelos de Riscos Proporcionais , Piretrinas/toxicidade , Sifonápteros/efeitos dos fármacos , Sifonápteros/parasitologia , Carrapatos/efeitos dos fármacos , Carrapatos/parasitologia
10.
BMC Vet Res ; 14(1): 378, 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509251

RESUMO

BACKGROUND: Leishmania parasites cause visceral leishmaniasis (VL), an important infectious disease that is endemic to large parts of the world and often leads to epidemics. Sand flies are the primary transmission vector for the parasite in endemic regions. We hypothesized that sheep might serve as an overlooked reservoir for Leishmania transmission to humans due to the asymptomatic nature of infection in many species. As a preliminary test of this hypothesis, the aim of the present study was to investigate sheep in an area of China that is endemic for the desert sub-type of zoonotic VL and establish if they are potential carriers of Leishmania. RESULTS: Sheep tissue samples were collected from abattoirs in VL endemic areas of Jiashi County, China during the non-transmission season. rK39 immunochromatographic tests were performed to detect the presence of the parasite in blood samples. In addition, DNA was extracted from the blood, and used for detection of the Leishmania-specific internal transcribed spacer-1 (ITS-1) genomic region using a nested polymerase chain reaction (PCR) approach. PCR products were further analyzed to identify restriction fragment-length polymorphism patterns and representative sequences of each pattern were selected for phylogenetic analysis. The rK-39 and nested PCR data indicated positive detection rates for Leishmania in sheep of 26.32 and 54.39%, respectively. The phylogenetic analysis revealed that all of the samples belonged to the species L. infantum and were closely related to strains isolated from human infections in the same area. CONCLUSIONS: Sheep could be a potential host for Leishmania in VL endemic areas in China and may be an overlooked reservoir of human VL transmission in this region. To further confirm livestock as a potential host, further verification is required using a sand fly biting experiment.


Assuntos
Leishmania infantum/classificação , Leishmania infantum/fisiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Animais , China/epidemiologia , DNA Espaçador Ribossômico/genética , Especificidade de Hospedeiro , Humanos , Leishmania infantum/genética , Filogenia , Ovinos
11.
J Vector Ecol ; 43(2): 321-327, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30408299

RESUMO

An entomological study was conducted in a Leishmania infantum focus, including the identification of the sand fly species, the detection and the characterization of Leishmania DNA in female sand flies, and blood meal origins in engorged sand flies. A total of 643 sand flies (31% female, 69% male) was identified based on their morphological features or molecular markers. Ten different species were identified, with Phlebotomus perniciosus, the confirmed vector of L. infantum, being the most abundant (56%), P. papatasi in 25% of sand flies, the unique vector species of L. major, and P. longicuspis in 7% of cases, the suspected second vector of L. infantum. Moreover, the infection rate was 3.4% in P. perniciousus, P. papatasi, P. longicuspis, and Sergentomya minuta. Also, L. infantum was identified in five unfed P. perniciosus and two P. longicuspis. Our results suggest the vector role of P. perniciosus and P. longicuspis in the transmission cycle of L. infantum. The DNA of four mammalian species (human, rabbit, horse, and cow) was identified in the blood meals of sand flies, suggesting that these species are potential reservoirs of leishmaniasis, though it is not yet fully elucidated (especially for MON-24 and MON-80). We suggest the existence of different transmission cycles of L. infantum involving different species of sand flies and hosts.


Assuntos
Reservatórios de Doenças/parasitologia , Insetos Vetores/classificação , Leishmania infantum/fisiologia , Leishmaniose Visceral/transmissão , Psychodidae/classificação , Animais , Bovinos , Feminino , Cavalos , Especificidade de Hospedeiro , Humanos , Insetos Vetores/parasitologia , Leishmaniose Visceral/parasitologia , Masculino , Phlebotomus/classificação , Phlebotomus/parasitologia , Psychodidae/parasitologia , Coelhos
12.
Res Vet Sci ; 121: 94-103, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30366124

RESUMO

Leishmaniosis caused by Leishmania infantum is a widespread zoonotic disease that can be transmitted to animals and humans by their vectors, blood-sucking phlebotomine sand flies. To prevent canine leishmaniosis across the whole Mediterranean region, vector control is essential. Because of phlebotomine breeding sites are diverse, environmental larval controls have limited practical value. Control methods of adults are being evaluated, such as selective baits based on sugar feeding of males and females or Attractive Toxic Sugar Baits (ATSB), and the indoor use of Long-Lasting-Insecticidal Nets (LLINs) treated with permethrin to prevent sand fly bites complementing the Indoor Residual Spraying (IRS) approach suggested by WHO. Although several strategies exist, the best control measure to prevent canine Leishmania infantum is to treat dogs using biocidal topical formulations based on legal insecticides (PTs18) or repellents (PTs19) (as collars, spot-ons and/or sprays) during the period when the vectors are active. This means we need to really know the biology and life cycle of the sand fly vector. According to available data, by mapping ambient temperatures we can already predict high risk areas where vector densities will be higher. In ongoing research, new candidates are emerging to fight against sand flies including natural plant extracts with low impacts on the environment and host animal. Other options in the future could be systemic insecticides to help reduce sand fly populations in high density areas. In parallel, health authorities and professionals involved in animal and public health (veterinarians, physicians, entomologists and epidemiologists) must work together in a One Health approach to minimize Leishmania infection. Veterinarians play a crucial role in liaising between key stake holders and dog owners to ensure the latter act responsibly in using repellents as a preventive measure against sand fly bites.


Assuntos
Doenças do Cão/prevenção & controle , Controle de Insetos , Repelentes de Insetos , Insetos Vetores , Inseticidas , Leishmaniose/veterinária , Psychodidae , Animais , Doenças do Cão/parasitologia , Cães , Feminino , Controle de Insetos/métodos , Leishmania infantum/fisiologia , Leishmaniose/parasitologia , Leishmaniose/prevenção & controle , Traços de História de Vida , Masculino , Psychodidae/fisiologia
13.
J Integr Med ; 16(6): 404-410, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30195443

RESUMO

OBJECTIVE: In the present study, we evaluated the effects of the aqueous extract of Physalis angulata root (AEPa) on Leishmania infantum proliferation, morphology, and the driving mechanism in leishmanicidal activity and modulatory action on macrophages. METHODS: L. infantum promastigotes were treated with 50 and 100 µg/mL AEPa for 72 h and then antipromastigote assay was performed by counts in a Newbauer chamber, morphological changes were analyzed by transmission electron microscopy and the mechanism of the leishmanicidal activity was detected. In addition, macrophages were infected with L. infantum and were used to evaluate anti-amastigote activity of AEPa and effects of AEPa on cytokine secretion after 72-hour treatment. RESULTS: Treatment with AEPa reduced the numbers of L. infantum promastigotes (50% inhibitory concentration (IC50) = 65.9 µg/mL; selectivity index (SI) = 22.1) and amastigotes (IC50 = 37.9 µg/mL; SI = 38.5) compared with the untreated control. Amphotericin B reduced 100% of the promastigote numbers after 72 h of treatment (IC50 = 0.2 µg/mL). AEPa induced several morphological changes and increased the production of reactive oxygen species and apoptotic death in promastigotes after treating for 72 h. AEPa (100 µg/mL) promoted tumor necrosis factor-α secretion in macrophages infected with L. infantum after 72 h of treatment, but did not induce an increase in this cytokine in noninfected macrophages. In addition, AEPa showed no cytotoxic effect on J774-A1 cells (50% cytotoxic concentration >1000 µg/mL). CONCLUSION: AEPa presented antileishmanial activity against the promastigotes and amastigotes of L. infantum without macrophage cytotoxicity; these results show that natural products such as P. angulata have leishmanicidal potential and in the future may be an alternative treatment for leishmaniasis.


Assuntos
Antiprotozoários/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose/parasitologia , Physalis/química , Extratos Vegetais/farmacologia , Linhagem Celular , Humanos , Leishmania infantum/crescimento & desenvolvimento , Leishmania infantum/fisiologia , Leishmaniose/tratamento farmacológico , Leishmaniose/genética , Leishmaniose/metabolismo , Estágios do Ciclo de Vida/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/parasitologia , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
14.
Ticks Tick Borne Dis ; 9(6): 1421-1430, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30207274

RESUMO

The aim of this study was to evaluate aspects of the innate cellular and humoral immune response by evaluating hemocyte dynamics, phagocytosis, phenoloxidase (PO) activity and nitric oxide (NO) production in Rhipicephalus sanguineus sensu lato (s.l.) (Acari: Ixodidae) infected with Leishmania infantum and to assess the persistence of parasites at time 0 and 1, 2, 5, and 7 days post-infection (dpi). The total and differential count of the five types of hemocytes circulating in the hemolymph of R. sanguineus s.l. females showed the average total number of hemocytes in the group infected with L. infantum to be significantly higher (p < 0.05) on the 1st and 2nd dpi compared to the control group. The hemocyte differential count showed that the average number of plasmatocytes and granulocytes increased significantly on the 1st, 2nd, and 5th dpi with L. infantum compared to the control group (p < 0.001). Phagocytosis assays revealed that plasmatocytes and granulocytes were able to perform phagocytosis of latex beads and L. infantum on the 1st and 2nd dpi, respectively. NO production was significantly increased (p < 0.001) on the 1st, 2nd, and 5th dpi with L. infantum and PO activity increased significantly (p < 0.05) only on the 5th dpi. L. infantum DNA was significantly increased (p < 0.001) on the 5th and 7th dpi compared to time 0. Although there are no studies describing the response of R. sanguineus s.l. to an infection with L. infantum, these results suggest that R. sanguineus s.l. activates the cellular and humoral immune response after infection with L. infantum. Further studies are however, needed to assess the impact of such a response on fighting infection.


Assuntos
Imunidade Celular , Imunidade Humoral , Leishmania infantum/fisiologia , Rhipicephalus sanguineus/imunologia , Animais , Proteínas de Artrópodes/metabolismo , Hemócitos/parasitologia , Monofenol Mono-Oxigenase/metabolismo , Óxido Nítrico/metabolismo , Fagocitose , Rhipicephalus sanguineus/parasitologia
15.
Trends Parasitol ; 34(10): 881-890, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30131210

RESUMO

Visceral leishmaniasis (VL) is a life-threatening outcome of Leishmania infantum or Leishmania donovani infection. Dogs are the primary domestic reservoir of L. infantum parasites, and ownership of infected dogs increases the risk of human VL. Controlling infection within dog populations is regarded as critical to VL management in endemic countries, both preventing progression of canine disease and limiting parasite transmission to humans and dogs. Here we discuss various strategies that are used to diagnose canine visceral leishmaniasis (CVL) and the possibilities of adapting these for use within population screening and control programs. In addition, given the variable transmissibility of L. infantum to the sand fly vector, we outline some possibilities for the preferential identification of 'super-spreader' dogs among the overall infected population.


Assuntos
Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/prevenção & controle , Zoonoses/diagnóstico , Zoonoses/prevenção & controle , Animais , Doenças do Cão/diagnóstico , Doenças do Cão/prevenção & controle , Doenças do Cão/transmissão , Cães , Humanos , Leishmania infantum/fisiologia , Leishmaniose Visceral/transmissão , Psychodidae/parasitologia , Zoonoses/transmissão
16.
Infection ; 46(6): 801-809, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30097989

RESUMO

PURPOSE: Climate changes and immunosuppression are influencing the spread of leishmaniasis and re-emergence in Northern Italy, respectively. We evaluated the prevalence of subclinical leishmaniasis in patients from a Northern Italian region with chronic inflammatory rheumatism (CIRD) receiving biological drugs (BD) and correlated it to the area of residence. METHODS: DNA from PBMC of patients affected by CIRD treated with either BD for at least 5 years (Group A) or other immunosuppressive drugs (Group B) was investigated by a qPCR for Leishmania infantum kDNA and compared to healthy subjects (Group C). Variables such as sex and age, rural areas, dog ownership, type of BD administered and association between BD and steroids, were evaluated by statistical analysis. RESULTS: A higher proportion of L. infantum DNA positivity was found in Group A than in Group C (p < 0.05), while no parasite DNA was detected in Group B. In Group A, 18/50 patients (36%) had higher rates of parasite DNA (from 1 to 136 to 1.000.000 copies/ml) than Group C (from 1 to 10 copies/ml). 14/18 (77.7%) of positive patients from Group A lived in rural areas, but no statistical differences occurred in relation to dog ownership or BD type (p < 0.0003). CONCLUSIONS: We can speculate that exposure to rural areas appears to be a factor closely linked with the risk of developing Leishmania subclinical infection. A screening with molecular methods in patients with CIRD treated with BD living in these areas and monitoring Leishmania DNA during such therapies, would be mandatory to prevent delay in diagnosis should VL symptoms appear.


Assuntos
Antirreumáticos/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Leishmaniose Visceral/epidemiologia , Doenças Reumáticas/tratamento farmacológico , Adulto , Idoso , Infecções Assintomáticas/epidemiologia , Doença Crônica/tratamento farmacológico , Feminino , Geografia , Humanos , Itália/epidemiologia , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/fisiologia , Leishmaniose Visceral/parasitologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real
17.
PLoS Negl Trop Dis ; 12(7): e0006684, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30059494

RESUMO

In some transmission foci of Leishmania infantum in Brazil, Lutzomyia cruzi could be considered the main vector of this pathogen. In addition, L. cruzi is a permissive vector of L. amazonensis. Its geographical distribution seems to be restricted and limited to Cerrado and Pantanal biomes, which includes some areas in Brazil and Bolivia. Considering that predicting the distribution of the species involved in transmission cycles is an effective approach for assessing human disease risk, this study aims to predict the spatial distribution of L. cruzi using a multiscale ecological niche model based in both climate and habitat variables. Ecological niche modelling was used to identify areas in South America that are environmentally suitable for this particular vector species, but its presence is not recorded. Vector occurrence records were compiled from the literature, museum collections and Brazilian Health Departments. Bioclimatic variables, altitude, and land use and cover were used as predictors in five ecological niche model algorithms: BIOCLIM, generalised linear model (logistic regression), maximum entropy, random forests, and support vector machines. The vector occurs in areas where annual mean temperature values range from 21.76°C to 26.58°C, and annual total precipitation varies from 1005 mm and 2048 mm. Urban areas were most present around capture locations. The potential distribution area of L. cruzi according to the final ecological niche model spans Brazil and Bolivia in patches of suitable habitats inside a larger climatically favourable area. The bigger portion of this suitable area is located at Brazilian States of Mato Grosso do Sul and Mato Grosso. Our findings identified environmentally suitable areas for L. cruzi in regions without its known occurrence, so further field sampling of sand flies is recommended, especially in southern Goiás State, Mato Grosso do Sul (borders with Mato Grosso, São Paulo and Minas Gerais); and in Bolivian departments Santa Cruz and El Beni.


Assuntos
Insetos Vetores/fisiologia , Leishmania infantum/fisiologia , Leishmaniose Visceral/transmissão , Psychodidae/fisiologia , Distribuição Animal , Animais , Bolívia/epidemiologia , Brasil/epidemiologia , Clima , Ecossistema , Humanos , Insetos Vetores/parasitologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Modelos Lineares , Psychodidae/parasitologia
18.
PLoS Negl Trop Dis ; 12(7): e0006595, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29975697

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) caused by Leishmania infantum is an ongoing health problem in southern Europe, where dogs are considered the main reservoirs of the disease. Current data point to a northward spread of VL and canine leishmaniasis (CanL) in Italy, with new foci in northern regions previously regarded as non-endemic. METHODOLOGY/PRINCIPAL FINDINGS: Multilocus microsatellite typing (MLMT) was performed to investigate genetic diversity and population structure of L. infantum on 55 samples from infected humans, dogs and sand flies of the E-R region between 2013 and 2017. E-R samples were compared with 10 L. infantum samples from VL cases in other Italian regions (extra E-R) and with 52 strains within the L. donovani complex. Data displayed significant microsatellite polymorphisms with low allelic heterozygosity. Forty-one unique and eight repeated MLMT profiles were recognized among the L. infantum samples from E-R, and ten unique MLMT profiles were assigned to the extra E-R samples. Bayesian analysis assigned E-R samples to two distinct populations, with further sub-structuring within each of them; all CanL samples belonged to one population, genetically related to Mediterranean MON-1 strains, while all but one VL cases as well as the isolate from the sand fly Phlebotomus perfiliewi fell under the second population. Conversely, VL samples from other Italian regions proved to be genetically similar to strains circulating in dogs. CONCLUSIONS/SIGNIFICANCE: A peculiar epidemiological situation was observed in northeastern Italy, with the co-circulation of two distinct populations of L. infantum; one population mainly detected in dogs and the other population detected in humans and in a sand fly. While the classical cycle of CanL in Italy fits well into the data obtained for the first population, the population found in infected humans exhibits a different cycle, probably not involving a canine reservoir. This study can contribute to a better understanding of the population structure of L. infantum circulating in northeastern Italy, thus providing useful epidemiologic information for public health authorities.


Assuntos
Doenças do Cão/parasitologia , Leishmania infantum/isolamento & purificação , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/veterinária , Repetições de Microssatélites , Animais , Doenças do Cão/epidemiologia , Cães , Feminino , Variação Genética , Genótipo , Especificidade de Hospedeiro , Humanos , Itália/epidemiologia , Leishmania infantum/classificação , Leishmania infantum/genética , Leishmania infantum/fisiologia , Leishmaniose Visceral/epidemiologia , Masculino , Filogenia , Psychodidae/parasitologia
19.
Cell Immunol ; 331: 67-77, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29871740

RESUMO

Visceral leishmaniasis (VL) is a fatal disease when acute and untreated. The treatment against this disease is long and presents toxicity and/or high costs. Moreover, parasite resistance has been increasing. Therefore, alternative control measures to avoid the spread of disease should be considered. It is accepted that the development of the T helper (Th)1 immune response, based on the production of pro-inflammatory cytokines, is required for the control of parasites. Although recombinant protein-based vaccines have been tested against VL, they require supplementation with immune adjuvants. In addition, there is a scarcity of studies that comparatively evaluate the efficacy of the immunogens when administered by different delivery systems in mammalian hosts. In the present study, a Leishmania hypothetical protein, LiHyR, was cloned and evaluated by immunization as a plasmid deoxyribonucleic acid (DNA) vaccine or in a recombinant format plus saponin against Leishmania infantum infection. Results showed that both vaccination regimens induced a Th1 cell-based immunity, since high levels of interferon-gamma (IFN-γ), interleukin (IL)-2, IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-α) were found, and were associated with the low production of IL-4, IL-10, and anti-parasite immunoglobulin (IgG)1 isotype. In addition, significant reductions in the parasite load were found in the evaluated organs of the DNA LiHyR or rLiHyR/saponin-vaccinated animals. No significant difference was achieved between groups vaccinated with DNA or the recombinant protein. The antigen proved to be also immunogenic in human peripheral blood mononuclear cells (PBMCs) collected from healthy subjects and from untreated and treated VL patients. A higher IgG2 isotype was also found in sera samples of these subjects, thus demonstrating its possible use as a human vaccine. This study demonstrates the protective efficacy of a new Leishmania protein against VL, when it is administered as a DNA vaccine or a recombinant protein plus saponin, and points out its use as a human vaccine against disease.


Assuntos
Leishmania infantum/imunologia , Leishmaniose Visceral/imunologia , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/imunologia , Vacinas de DNA/imunologia , Adjuvantes Imunológicos/administração & dosagem , Sequência de Aminoácidos , Animais , Anticorpos Antiprotozoários/imunologia , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/fisiologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Camundongos Endogâmicos BALB C , Proteínas de Protozoários/genética , Proteínas Recombinantes/administração & dosagem , Homologia de Sequência de Aminoácidos , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Vacinação/métodos , Vacinas de DNA/administração & dosagem , Vacinas de DNA/genética
20.
PLoS Negl Trop Dis ; 12(5): e0006496, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29758031

RESUMO

BACKGROUND: Visceral leishmaniasis (VL) is a zoonosis of great importance. Limitations in current VL control measures compromise efficacy, indicating the need to implement new strategies. The aim of this study was to evaluate the effectiveness of the mass use of deltamethrin-impregnated collars in dogs as a public health measure to control and prevent canine visceral leishmaniasis (CVL). METHODOLOGY: An interventional study was implemented in two endemic areas in the district of Monte Gordo (Bahia-Brazil): an intervention area, in which VL seronegative dogs were collared, and a control area in which only conventional CVL control measures were applied. At baseline, seropositive dogs were removed and seronegative dogs were included. Dogs were then reevaluated every 7-8 months for almost two years. At each time point, dogs in the intervention area that remained seronegative received new collars and newly identified seronegative dogs were included and collared. The local zoonosis control authorities were notified of any dogs that tested seropositive in both areas, which were subsequently marked for euthanasia as mandated by the Brazilian Ministry of Health. PRINCIPAL FINDINGS: In the first serological survey, seroprevalence was similar in both areas. At the second evaluation, significant reductions in seroprevalence were seen in both areas, while seroprevalence in the intervention area reduced to 6.0% during the final evaluation versus an increase of 11.0% in the control area. This significant increase and the estimated relative risk (RR = 0.55) indicated protection against CVL in the intervention area. Although CVL incidence did not differ significantly between the areas, an increased tendency was observed in the control area, which could be due to low seroconversion rates throughout the study or a high loss to follow-up. CONCLUSIONS/SIGNIFICANCE: Although our evaluation of the effectiveness of deltamethrin-impregnated collars as a community-wide public health control measure was inconclusive, this measure likely provides protection over time. In endemic areas of Brazil, this strategy represents an operational challenge for local zoonosis control authorities, indicating the need for adjustments, including improved collar design.


Assuntos
Antiprotozoários/administração & dosagem , Doenças do Cão/prevenção & controle , Leishmaniose Visceral/veterinária , Nitrilos/administração & dosagem , Controle de Pragas/métodos , Piretrinas/administração & dosagem , Animais , Brasil/epidemiologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Cães , Leishmania infantum/efeitos dos fármacos , Leishmania infantum/fisiologia , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/prevenção & controle , Controle de Pragas/instrumentação
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