Leishmaniasis

A faunistic study of phlebotomine sandflies was carried out on the mainland and on four islands in Greece between 1999 and 2004. Sandflies were collected in 18 areas, and the population structure was observed and recorded. A total of 10 species were identified; their distribution is presented here. Of these, the species Phlebotomus neglectus Tonnoir and P. perfiliewi Parrot (Diptera: Psychodidae), epidemiologically the most important vectors of leishmaniases and sandfly fever in Greece, were shown to be present in the main endemic foci of the country.

The expression of iNOS by macrophages in 33 dogs suffering from spontaneous leishmaniasis was analysed by immunohistochemistry in skin, liver and lymph nodes. A correlation study between the number of macrophages expressing iNOS and the number of macrophages containing leishmania amastigotes was carried out. Formalin-fixed paraffin-embedded tissue sections from the skin (28 cases), popliteal lymph nodes (8 cases) and liver (3 cases) of dogs of different age, sex and breed suffering from leishmaniasis were included in the study. Dogs were referred as positive for Leishmania spp by serology and the diagnosis was confirmed by demonstration of leishmania amastigotes within macrophages by histopathology. Tissue samples of skin (3 cases), popliteal lymph nodes (5 cases) and liver (3 cases) from dogs seronegative for leishmaniasis with no histopathological changes were included in the study as controls. The immunohistochemical study revealed that macrophages containing a high number of leishmania did not express iNOS. Correlation between the number of macrophages expressing iNOS and the number of macrophages containing leishmania amastigotes was assessed using the Spearman test. High expression of iNOS in macrophages was related with low number of leishmania amastigotes in macrophages in all cases (r = À0.47, p = 0.002). These results suggest that iNOS expression by macrophages plays an important role during the control of Leishmania infection in dogs. #

The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dosetitration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg −1 day −1 . In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg −1 day −1 ) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological

PURPOSE,PATIENTS,ANDMETHODS: Theclassic agent for cutaneous leishmaniasis is pentavalent antimony. However, there are no reports of the efficacy of antimony versus placebo or of the efficacy of any alternative therapy versus either antimony or placebo. In the present report, the oral antifungal agent ketoconazole (600 n&day for 28 days) was compared to a recommended regimen of intramuscular Pentostam (20 mg antimony/kg, with a maximum of 850 mg antimony/day, for 20 days) in a randomized study of the treatment of Panama&n cutaneous leishmaniasis due to L&IImauia bradiensis paname& A separate group of patients with this disease was administered placebo.

Reporter genes have proved to be an excellent tool for studying disease progression. Recently, the green fluorescent protein (GFP) ability to quantitatively monitor gene expression has been demonstrated in different organisms. This report describes the use of Leishmania tarentolae (L. tarentolae) expression system (LEXSY) for high and stable levels of GFP production in different Leishmania species including L. tarentolae, L. major and L. infantum. The DNA expression cassette (pLEXSY-EGFP) was integrated into the chromosomal ssu locus of Leishmania strains through homologous recombination. Fluorescent microscopic image showed that GFP transgenes can be abundantly and stably expressed in promastigote and amastigote stages of parasites. Furthermore, flow cytometry analysis indicated a clear quantitative distinction between wild type and transgenic Leishmania strains at both promastigote and amastigote forms. Our data showed that the footpad lesions with GFP-transfected L. major are progressive over time by using fluorescence small-animal imaging system. Consequently, the utilization of stable GFP-transfected Leishmania species will be appropriate for in vitro and in vivo screening of anti-leishmanial drugs and vaccine development as well as understanding the biology of the host-parasite interactions at the cellular level.

Systemic diseases can present with ocular manifestations to the emergency physician. Although most ocular findings serve to alert the physician to a possible ocular complication, many are different enough to aid the physician in making an obscure diagnosis. Knowledge of the characteristic ophthalmologic manifestations of systemic disease can aid the physician in diagnosing a particular disorder, limit the progression of more common diseases, and prevent further visual loss or blindness in patients with serious ophthalmologic complications.

Anti-native DNA antibodies can be detected by indirect immunofluorescence assay with Crithidia luciliae, displaying an annular image due to a kinetoplast containing double stranded DNA. Other structures such as membrane, flagellum and basal corpuscle can be stained as well, showing what is called atypical fluorescent images. As C. luciliae belongs to the Trypanosomatidae family, which include the human pathogens Trypanosoma cruzi and Leishmania spp., it was considered that these atypical images could be caused by cross-reactions. Serological studies for Chagas' disease were performed in 105 serum samples displaying atypical images. Sixty four percent of the samples from non endemic and 78.3% from endemic areas for Chagas' disease showed fluorescence in both, membrane and flagellum (joint image). Fifty samples from normal blood donors and 57 samples from patients with conective tissue diseases were tested with C. luciliae. None of them presented the joint image except for two...

Vesicular systems are novel means of delivering drug in controlled manner to enhance bioavailability and get therapeutic effect over a longer period of time. Niosomes are such hydrated vesicular systems containing nonionic surfactants along with cholesterol or other lipids delivering drug to targeted site which are non toxic, requiring less production cost, stable over a longer period of time in different conditions, so overcomes drawbacks of liposome. Present review describes history, all factors affecting niosome formulation, manufacturing conditions, characterization, stability, administration routes and also their comparison with liposome. This review also gives relevant information regarding various applications of niosomes in gene delivery, vaccine delivery, anticancer drug delivery, etc.

The author updates available data on leishmaniasis and phlebotomine sandflies in Cameroon. After describing the natural environment, we present all the cases of the cutaneous and visceral leishmaniases recorded so far in this country. He refers also to the first biochemical characterisation of Leishmania major MON-26 in Cameroon. The data of a leishmanin skin test survey conducted in the Mokolo cutaneous leishmaniasis focus are presented as well as a repertoire of the phlebotomine sandfly species identified in the country. The implications and shortcomings of these available data are discussed and recommendations are drawn for further research.

The leishmanicidal drug, meglumine antimoniate (MA), has been synthesized by the reaction of antimony oxyhydrated and N-methyl glucamine. Infrared and solid state NMR 13 C analysis of MA and the ligand strongly suggests that antimony binds to N-methyl glucamine through the oxygen of C-3 carbon. Potentiometric titration indicated that, between pH 4.5 and 7.5, MA exists in the zwitterionic form.

Protozoan parasites Leishmania alternate between a flagellated promastigote form and an amastigote form. In their mammalian hosts, Leishmania survive and multiply in macrophages. Both forms can be internalized by these host cells at different stages of the infectious process and eventually establish themselves within parasitophorous vacuoles exhibiting phagolysosomal properties. To determine whether the biogenesis of these organelles differs according to the parasitic stage used to initiate infection, we compared their formation kinetics after phagocytosis of either metacyclic promastigotes or amastigotes of L. amazonensis or of L. major by mouse bone-marrow-derived macrophages pre-exposed or not to IFN-γ. After 10 minutes of contact, an accumulation of F-actin was observed around the promastigotes and amatigotes undergoing phagocytosis or those that had already been internalized. This accumulation was transient and rapidly disappeared at later times. At 30 minutes, most of the prom...

Infections caused by protozoa of the genus Leishmania are a major worldwide health problem, with high endemicity in developing countries. The incidence of the disease has increased since the emergence of AIDS. In the absence of a vaccine, there is an urgent need for effective drugs to replace/supplement those in current use. The plant kingdom is undoubtedly valuable as a source of new medicinal agents. The present work constitutes a review of the literature on plant extracts and chemically defined molecules of natural origin showing antileishmanial activity. The review refers to 101 plants, their families, and geographical distribution, the parts utilized, the type of extract and the organism tested. It also includes 288 compounds isolated from higher plants and microorganisms, classified into appropriate chemical groups. Some aspects of recent antileishmanial-activity-directed research on natural products are discussed.

Leishmaniasis diagnosis in regions where multiple species exist should identify each species directly in the clinical sample without parasite culturing. The sensitivity of two PCR approaches which amplify part of the ssu rRNA gene and the ribosomal internal transcribed spacer (ITS), respectively, was determined using human and dog blood seeded with Leishmania promastigotes. ssu-rDNA-PCR was more sensitive than ITS1-PCR, however species identification was not possible by the former approach. When a nested ITS1-PCR was used its sensitivity equaled the ssu-rDNA-PCR. Digestion of ITS1 amplicon with the restriction enzyme HaeIII distinguished all medically relevant Leishmania species. ITS1-PCR was used to diagnose 162 local and imported suspected cases of leishmaniasis in Israel, the Palestinian Authority and Germany. 113 cases (69.7%) were positive by PCR and species identification was possible in 110 samples. Leishmania DNA was also amplified and identified at the species level from archived non-stained and Giemsa stained microscope slides.

The purpose of this international, multicentric, and non-comparative field trial was to obtain complementary data on long-term clinical and parasitological follow-up of dogs treated with marbofloxacin for canine leishmaniosis (CanL). Seventy-four dogs with clinical signs of CanL and without severe renal failure were recruited in France, Spain and Italy, and 61 of them were part of the analysis. Each dog was treated with palatable tablets of marbofloxacin at 2 mg/kg once a day for 28 days. A clinical and parasitological follow-up was performed regularly up to 12 months. Efficacy was demonstrated in 42 dogs (68.9%), within 51 days (mean value), 10 of them (23.8%) being clinically cured after 3 months. A decrease of 61% in the sum of clinical scores was observed after 3 months. Haemato-biochemical parameters improved in general, supporting the observed clinical efficacy. Relapse was observed in 20/38 dogs (52.6%) approximately 5.5 months after treatment completion. The blood parasite load generally developed in conformity with the clinical outcome, even if exceptions were not rare. Lymph nodes remained positive by culture or PCR for a long time, even in dogs for which a good clinical response was observed. Despite the incomplete parasite clearance, as is also the case with other anti-leishmanial drugs, these results nevertheless confirm the relevance of marbofloxacin as a CanL treatment.

As leishmanioses representam um grande problema em saúde pública, sendo responsáveis por cerca de 60 mil óbitos e milhares de novos casos anualmente em todo o planeta, apresentando-se sob as formas mucocutânea, cutânea e visceral, sendo esta última, muitas vezes fatal. No Brasil são endêmicas nas regiões Norte, Nordeste, Centro-Oeste e Sudeste, infectando diversos mamíferos, incluindo o gato doméstico, a partir picada da fêmea de mosquitos do gênero Lutzomyia, os quais apresentam grande adaptação ao meio urbano. Elucidar a epidemiologia da doença tem sido o objetivo de várias pesquisas, já que a mesma tem comportamentos variados, conforme características da área e população. Apesar de serem susceptíveis e ter contato direto com humanos, o papel dos felinos na epidemiologia das leishmanioses ainda não foi esclarecido, pois esses animais podem ser assintomáticos ou ter a doença associada às doenças que causam imunossupressão, além de apresentarem uma resistência natural. A forma cutânea é a mais relatada em felinos, que podem apresentar também, uveíte, linfoadenopatia local ou generalizada êmese, diarréia, desidratação, estomatite e anorexia. O diagnóstico pode ser clínico, parasitológico, imunológico e molecular. O tratamento é descrito em poucos casos, com relatos clínicos que variam de completo sucesso até eutanásia. Apesar da existência de alguns estudos pesquisando a soroprevalência da infecção em populações de felinos residentes em áreas endêmicas, não está claro ainda se as baixas prevalências da infecção e da doença, em gatos provenientes de áreas endêmicas, são devidas as falhas na detecção de anticorpos ou ao fato dos gatos apresentarem resistência natural à leishmaniose.

Les leishmanioses, cutanée et viscérale, représentent les maladies vectorielles les plus fréquentes en Tunisie. Leur confirmation biologique est nécessaire avant l'administration des traitements contraignants, coûteux et toxiques qui leurs sont réservés. Une évaluation rétrospective de l'apport des cultures de leishmanies sur milieu NNN dans le diagnostic des leishmanioses a été réalisée sur les données de 375 cultures ayant intéressé 214 cas de LC (leishmaniose cutanée) et 125 de LV (leishmaniose viscérale) recrutés consécutivement à l'institut Pasteur de Tunis entre 1995 et 2007. La sensibilité globale au cours de la LC a été de 68,2 % ; elle était significativement supérieure avec les prélèvements de LC zoonotique (78,8 %) par rapport à ceux de LC sporadique (54,9 %) ; p < 0,001. Cette différence s'explique par la pousse plus aisée sur le milieu NNN de Leishmania (L.) major, agent de la première forme nosogéographique comparativement à L. infantum, particulièrement son zymodème MON-24, agent de la seconde. Au cours de la LV, la sensibilité des couches leucocytaires était non différente de celle des moelles osseuses (MO) (58,2 % versus 70,8 %, p = 0,1) témoignant de l'intérêt des prélèvements sanguins qui permettent d'éviter la traumatisante ponction de MO. Aussi bien au cours de la LC que la LV, le classique examen direct s'est révélé le plus sensible, respectivement 89,7 et 93,4 % ( p < 0,001 et p < 0,001). Cependant, la pratique systématique de la culture, en parallèle avec l'incontournable examen direct, est recommandée. En effet, en plus de redresser certains diagnostics, 22 cas dans notre série, la culture permet l'isolement et l'identification isoenzymatique de la souche parasitaire impliquée, ce qui permet de disposer des données épidémiologiques indispensables à la compréhension des cycles parasitaires et la mise en place des mesures de contrôle appropriées. Comme toutes les cultures, celles des leishmanies sont également confrontées au problème de contamination, dont le taux a été dans notre étude de 5,9 %. Conformément aux prévisions, la contamination a concerné davantage les prélèvements cutanés, soumis à la surinfection, 8,4 % que ceux de sang ou de MO (2,5 % ; p = 0,015). # 2008 Elsevier Masson SAS. Tous droits réservés.

Objetivo: Medir practicas, actitudes y conocimientos sobre uta en una población de alta prevalencia. Material y Método: Estudio observacional, descriptivo enfoque cuantitativo, realizado en el Centro Poblado Hierba Buena. Muestra obtenida de 975 hab. Nivel de confianza 95%, proporción esperada de 68% mediante EPIDAT 3.1, muestreo aleatorio estratificado. Durante análisis utilizamos SPSS versión 17,5 y Excel 2013. Resultados: conocimiento malo (67,87%) sobre la Uta; no reconocen herida de uta 84,34%; no reconoce agente etiológico 69,08%; se curan con hierbas 71,08%; no saben sobre la trasmisión 81,93% y el 99,20% no reconocen al principal reservorio. Las actitudes 98,39% están dispuestos a participar de medidas educativas y el 86,35% asistiría al puesto ante herida sospechosa. En prácticas solo el 6,46% utilizan mosquitero. Ninguno de ellos realiza otra práctica preventiva. Conclusión: Conocimientos y prácticas sobre Uta son malos; mientras que las actitudes son buenas en pobladores de Hierba Buena.

Leishmaniasis is a protozoan disease caused by the genus Leishmania transmitted by female phlebotomine sand flies. Surveillance of the prevalence of Leishmania and responsive vector species in endemic and surrounding areas is important for predicting the risk and expansion of the disease. Molecular biological methods are now widely applied to epidemiological studies of infectious diseases including leishmaniasis. These techniques are used to detect natural infections of sand fly vectors with Leishmania protozoa and are becoming powerful tools due to their sensitivity and specificity. Recently, genetic analyses OPEN ACCESS Int. J. Environ. Res. Public Health 2010, 7 815

Background: Leishmaniasis is a complex devastating disease that is widespread across the globe with 400 million people in 90 countries at a risk of acquiring leishmaniasis. It is caused by intracellular parasites belonging to genus Leishmania. Objective: The therapeutic use of commonly available drugs like Pentostam, Glucantime, Amphotericin B, Paramomycin, and Miltefosine have has been declined due to their low efficacy , drug resistance and high toxicity. Therefore, a continuous effort is needed in order to find out less toxic and more successful drugs in future for the handling of leishmaniasis. Results: Quinazoline derivatives are reported to have promising antileishmanial activities. A number of quinazoline derivatives were synthesized in the past three decades, by means of various synthetic pathways due to their ease of synthesis and favorable physicochemical properties. Conclusion: This review focuses on various synthetic procedures, chemical characteristics and antileishmanial activities of various quinazoline derivatives with respect to antileishma-nial drug discovery.

Leishmaniasis, a group of tropical diseases caused by protozoan parasites of genus Leishmania, is a major health problem worldwide that affects millions of people especially in the developing nations. Generic pentavalent antimonials have been the mainstay for therapy in the endemic regions due to efficacy and cost effectiveness, but the growing incidence of their resistance has seriously hampered their use. In many cases the drugs employed for the treatment are toxic, marginally effective, given by injection and, compromised by the development of resistance. Therefore, the development of new mechanism based safe, effective and affordable chemotherapeutic agents to fight leishmaniasis would be an urgent priority research. The recent researches focused on natural products have shown a wise way to get a true and potentially rich source of drug candidates against leishmaniasis, where alkaloids have been found more effective. The present review briefly illustrates an account on current status of leishmaniasis, life cycle of parasites and biology, synergy of the disease with HIV, therapeutic options available to cure this disease and, highlights why natural products especially alkaloids as folk medicines are so important? Additionally, the outlines for the leishmanicidal activities of various alkaloids including indole, quinoline, isoquinoline, pyrimidine-β-carboline, steroidal and diterpene alkaloids from various plants as well as alkaloids from marine sources have been provided with their mechanistic studies.

Diseases caused by insect borne trypanosomatid parasites are significant, yet remain a neglected public health problem. Leishmania, a unicellular protozoan parasite is the causative organism of Leishmaniasis and is transmitted by female phlebotamine sandflies affecting millions of people worldwide. In the wake of resistance to pentavalent antimonial drugs, new therapeutic alternatives are desirable. The plant kingdom has in the past provided several affordable compounds and this review aims to provide an overview of the current status of available leishmanicidal plant derived compounds that are effective singly or in combination with conventional anti-leishmanial drugs, yet are non toxic to mammalian host cells. Furthermore, delineation of the contributory biochemical mechanisms involved in mediating their effect would help develop new chemotherapeutic approaches.

This paper reviews the current knowledge of leishmaniasis epidemiology in Venezuela, Colombia, Ecuador, Peru, and Bolivia. In all 5 countries leishmaniasis is endemic in both the Andean highlands and the Amazon basin. The sandfly vectors belong to subgenera Helcocyrtomyia, Nyssomiya, Lutzomyia, and Psychodopygus, and the Verrucarum group. Most human infections are caused by Leishmania in the Viannia subgenus. Human Leishmania infections cause cutaneous lesions, with a minority of L. ( Viannia) infections leading to mucocutaneous leishmaniasis. Visceral leishmaniasis and diffuse cutaneous leishmaniasis are both rare. In each country a significant proportion of Leishmania transmission is in or around houses, often close to coffee or cacao plantations. Reservoir hosts for domestic transmission cycles are uncertain. The paper first addresses the burden of disease caused by leishmaniasis, focusing on both incidence rates and on the variability in symptoms. Such information should provide a rational basis for prioritizing control resources, and for selecting therapy regimes. Secondly, we describe the variation in transmission ecology, outlining those variables which might affect the prevention strategies. Finally, we look at the current control strategies and review the recent studies on control. Resumo Este trabalho revisa o conhecimento atual sobre a epidemiologia da leishmaniose na Venezuela, Colômbia, Equador, Peru e Bolívia, países nos quais a doença é endêmica, tanto nos Andes quanto na Amazônia. Os vetores flebótomos pertencem a vários subgêneros e ao grupo Verrucarum. A maioria dos casos de infecção humana é causada pelos parasitas Leishmania do subgênero Viannia. As infecções humanas por Leishmania provocam lesões cutâneas, com uma minoria de infecções por L. ( Viannia) levando à leishmaniose mucocutânea. Tanto a leishmaniose visceral quanto a leishmaniose cutânea difusa são raras. Em cada país, parte significativa da transmissão de Leishmania ocorre no intra ou peridomicílio, muitas vezes próximo à lavoura de café ou cacau. Não se sabe ao certo quais são os hospedeiros reservatórios para os ciclos de transmissão doméstica. Discute-se a carga da doença provocada pela leishmaniose na região, chamando atenção para os coeficientes de incidência e para a variabilidade dos sintomas. Tal informação fornecerá uma base racional, visando priorizar os recursos voltados para o controle da doença e selecionar esquemas terapêuticos. Os autores também descrevem a variação na ecologia da transmissão, delineando as variáveis que poderiam afetar a definição de estratégias preventivas. Palavras-chave Leishmaniose; Ecossistema Andino; Doenças Endêmicas; Controle de Vetores DAVIES, C. R. et al. 926 Cad. Saúde Pública, Rio de Janeiro, 16(4):925-950, out-dez, 2000

Introduction: The present study was designed to assess the occurrence of co-infection or cross-reaction in the serological techniques used for detecting the anti-Leishmania spp., -Babesia canis vogeli and -Ehrlichia canis antibodies in urban dogs from an area endemic to these parasites. Methods: The serum samples from dogs were tested for the Babesia canis vogeli strain Belo Horizonte antigen and Ehrlichia canis strain São Paulo by immunofl uorescence antibody test (IFAT) and by anti-Leishmania immunoglobulin G (IgG) antibody detection to assess Leishmania infection. We used the following four commercial kits for canine visceral leishmaniasis: ELISA, IFAT, Dual Path Platform (DPP) (Bio Manguinhos®/FIOCRUZ/MS) and a rK39 RDT (Kalazar Detect Canine Rapid Test; Inbios). Results: Of 96 serum samples submitted to serological assays, 4 (4.2%) were positive for Leishmania as determined by ELISA; 12 (12.5%), by IFAT; 14 (14.6%) by rK39 RDT; and 20 (20.8%), by DPP. Antibodies against Ehrlichia and Babesia were detected in 23/96 (23.9%) and 30/96 (31.2%) samples, respectively. No signifi cant association was identifi ed between the results of tests for detecting Babesia or Ehrlichia and those for detecting Leishmania (p-value>0.05). Conclusions: In the present study, we demonstrated co-infection with Ehrlichia or Babesia and Leishmania in dogs from Minas Gerais (Brazil); we also found that the serological tests that were used did not cross-react.

Leishmaniasis remains a public health problem worldwide, affecting approximately 12 million people in 88 countries; 50 000 die of it each year. The disease is caused by Leishmania, obligate intracellular vector-borne parasites. In spite of its huge health impact on the populations in vast areas, leishmaniasis is one of the most neglected diseases. No safe and effective vaccine currently exists against any form of human leishmaniasis. The spectrum and efficacy of available antileishmanial drugs are also limited. First part of this review discusses the approaches used for the vaccination against leishmaniasis that are based on the pathogen and includes virulent or attenuated parasites, parasites of related nonpathogenic species, whole killed parasites, parasites' subunits, DNA vaccines, and vaccines based on the saliva or saliva components of transmitting phlebotomine vector. Second part describes parasite detection and quantification using microscopy assays, cell cultures, immunodetection, and DNA-based methods, and shows a progress in the development and application of these techniques. In the third part, first-line and alternative drugs used to treat leishmaniasis are characterized, and pre-clinical research of a range of natural and synthetic compounds studied for the leishmanicidal activity is described. The review also suggests that the application of novel strategies based on advances in genetics, genomics, advanced delivery systems, and high throughput screenings for leishmanicidal compounds would lead to improvement of prevention and treatment of this disease.

Leishmaniasis remains a major public health problem worldwide and is classified as Category I by the TDR/WHO, mainly due to the absence of control. Many experimental models like rodents, dogs and monkeys have been developed, each with specific features, in order to characterize the immune response to Leishmania species, but none reproduces the pathology observed in human disease. Conflicting data may arise in part because different parasite strains or species are being examined, different tissue targets (mice footpad, ear, or base of tail) are being infected, and different numbers ("low" 1x10 2 and "high" 1x10 6 ) of metacyclic promastigotes have been inoculated. Recently, new approaches have been proposed to provide more meaningful data regarding the host response and pathogenesis that parallels human disease. The use of sand fly saliva and low numbers of parasites in experimental infections has led to mimic natural transmission and find new molecules and immune mechanisms which should be considered when designing vaccines and control strategies. Moreover, the use of wild rodents as experimental models has been proposed as a good alternative for studying the host-pathogen relationships and for testing candidate vaccines. To date, using natural reservoirs to study Leishmania infection has been challenging because immunologic reagents for use in wild rodents are lacking. This review discusses the principal immunological findings against Leishmania infection in different animal models highlighting the importance of using experimental conditions similar to natural transmission and reservoir species as experimental models to study the immunopathology of the disease.

Leishmaniasis is a deadly vector-borne disease that causes significant morbidity and mortality in Africa, Asia, Latin America and Mediterranean regions. The causative agent of leishmaniasis is transmitted from man to man by a tiny insect called sandfly. Approximately, 600 species of sandflies are known but only 10% of these act as disease vectors. Further, only 30 species of these are important from public health point. Fauna of Indian sub-zone is represented by 46 species, of these, 11 belong to Phlebotomine species and 35 to Sergentomyia species. Phlebotomus argentipes is the proven vector of kala-azar or visceral leishmaniasis in India. This review gives an insight into the insect vectors of human leishmaniasis, their geographical distribution, recent taxonomic classification, habitat, and different control measures including indoor residual spraying (IRS), insecticide-treated bednets (ITNs), environmental management, biological control, and emerging resistance to DDT. Role of satellite remote sensing for early prediction of the disease by identifying the sandflygenic conditions cannot be undermined. The article also underlines the importance of synthetic pheromones which can be used in near future for the control of these vectors.

Leishmania infection continues to have a major impact on public health inducing significant morbidity and mortality mostly in the poorest populations. Drug resistance, toxicity and side effects associated with expensive chemotherapeutic treatments and difficult reservoir control emphasize the need for a safe and effective vaccine which is not available yet. Although, Leishmanization (LZ) was shown to be effective against cutaneous leishmaniasis, standardization and safety are the main problems of LZ. First generation killed parasites demonstrated limited efficacy in phase 3 trials and moreover well defined molecules have not reached to phase 3 yet. Limited efficacy in vaccines against leishmaniasis is partly due to lack of an appropriate adjuvant. Hence, the use of particulate delivery systems as carriers for antigen and/or immunostimulatory adjuvants for effective delivery to the antigen-presenting cells (APCs) is a valuable strategy to enhance vaccine efficacies. Particle-based delivery systems such as emulsions, liposomes, virosomes, and polymeric microspheres have the potential for successfully delivering antigens, which can then be further improved via incorporation of additional antigenic or immustimulatory adjuvant components in or onto the particle carrier system. In this review, we have attempted to provide a list of particulate vaccine delivery systems involved in the production of candidate leishmaniasis vaccines and introduced some potentially useful vaccine delivery systems for leishmaniasis in future experiments. In conclusion, combination vaccines (adjuvant systems) composed of candidate antigens and more importantly well-developed particulate delivery systems, such as lipid-based particles containing immunostimulatory adjuvants, have a chance to succeed as antileishmanial vaccines.

Current and future ecological niche of Leishmaniasis (Kinetoplastida: Trypanosomatidae) in the Neotropical region. The leishmaniasis is a complex disease system, caused by the protozoan parasite Leishmania and transmitted to humans by the vector Lutzomyia spp. Since it is listed as a neglected disease according to the World Health Organization, the aim of this study was to determine the current and future niche of cutaneous and visceral leishmaniasis in the Neotropical region. We built the ecological niche model (ENM) of cutaneous (N= 2 910 occurrences) and visceral (N= 851 occurrences) leishmaniasis using MaxEnt algorithm. Nine bioclimatic variables (BIO1, BIO4, BIO5, BIO6, BIO7, BIO12, BIO13, BIO14, BIO15 (downloaded from the Worldclim) and disease occurrences data were used for the construction of ENM for three periods (current, 2050 and 2070) and four climate change scenarios (RCP 2.6, 4.5, 6.0 y 8.5). We analyzed the number of pixels occupied, identity niche, modified niche (stable, loss, and gain) and seasonality. Our analyses indicated the expansion for cutaneous leishmaniasis (CL), a comparison for visceral leishmaniasis (VL). We rejected the null hypothesis of niche identity between CL and VL with Hellinger’s index = 0.91 (0.92-0.98) and Schoener’s Index = 0.67 (0.85-1.00) but with an overlap niche of 56.3 %. The differences between the two leishmaniasis types were detected in relation to RCP scenarios and niche shifts (area gained / loss). Seasonality was more impor- tant for CL. We provided a current picture of CL and VL distributions and the predicted distributional changes associated to different climate change scenarios for the Neotropical region. We can anticipate that increasing range is likely although it will depend locally on the future trends in weather seasonality. Rev. Biol. Trop. 64 (3): 1237-1245. Epub 2016 September 01.

This paper reviews our exploration of the dynamics of the Leishmania genome and its contribution to epidemiology and diagnosis. We used as a model Peruvian populations of L. (Viannia) braziliensis and L. (V.) peruviana, 2 species very close phylogenetically, but phenotypically very different in biotope and pathology. We initially focused on karyotype analysis. Our data showed that chromosomes were subject to a fast rate of evolution, and were sensitive indicators of genetic drift. Therefore, molecular karyotyping appeared an adequate tool for monitoring (i) emergence of close species, (ii) ecogeographical differentiation at the intraspecific level, and (iii) strain ‘fingerprinting’. Chromosome size variation was mostly due to the number of tandemly repeated genes (rDNA, mini-exon, gp63, and cysteine proteinase genes), and could involve the deletion of unique genes (L. (V.) braziliensis-specific gp63 families). Considering the importance of these genes in parasitism, their rearrangement might have functional implications: adaptation to different environments and pleomorphic pathogenicity. Our knowledge of genome structure and dynamics was used to develop new polymerase chain reaction (PCR) techniques. Amplification of gp63 genes followed by cleavage with restriction enzymes and study of restriction fragment length polymorphism (gp63 PCR-RFLP) allowed the discrimination of all species tested, even directly in biopsies with 95% sensitivity (compared with PCR amplification of kinetoplast deoxyribonucleic acid). At the intra-specific level, RFLP was also observed and corresponded to mutations in major immunogen domains of gp63. These seem to be under strong selection pressure, and the technique should facilitate addressing how the host's immune pressure may modulate parasite population structure. Altogether, gp63 PCR-RFLP represents a significant operational improvement over the other techniques for molecular epidemiology and diagnosis: it combines sensitivity, discriminatory power and prognostic value.

Leishmaniasis is caused by protozoan parasites of the genus Leishmania and causes a wide spectrum of clinical manifestations ranging from self-healing cutaneous lesions to the fatal visceral form. The use of pentavalent antimony, the mainstay of therapy of Leishmaniasis is now limited by its toxicity and alarming increase in unresponsiveness, especially in the Indian subcontinent. Furthermore, other anti-leishmanial drugs are unaffordable in many affected countries and as vaccination based approaches have not yet proved to be effective, chemotherapy remains the only alternative, emphasizing the need for identifying novel drug targets. In this review, we have described the different host immune signaling pathways that could be considered as potential drug targets for Leishmania chemotherapy.

The crude alkaloidal extract of Zanthoxylum chiloperone stem bark exhibited in vitro activity against various strains of Leishmania ssp. at 100 mg/ml. Two active major constituents were isolated and identified as canthin-6-one and 5-methoxycanthin-6one. The effect of these compounds was also tested in an in vivo assay using BALB/c mice infected with Leishmania amazonensis . The mice were treated for 5 weeks postinfection with these alkaloids by oral (14 days) or intralesional route (4 days) at 10 mg/kg daily. The reference drug, N -methylglucamine antimonate was administered by subcutaneous injections at 100 mg/kg for 10 days. Intralesional administration of canthin-6-one reduced the parasite burden but not significantly when it was compared with the untreated group, while the reference drug reduced by 91% the parasite loads in the lesion. #

Os Flebotomíneos ocupam a maioria das regiões compostas por vegetação, com exceção de regiões polares e oceânicas. Algumas espécies são vetores de uma doença endêmica, a leishmaniose cuja transmissão é influenciada por diversos padrões espaço-temporal que englobam chuvas, temperatura, o tipo de vegetação e etc., que podem ser ou não favoráveis à proliferação destes insetos. Dentro deste contexto, o estudo da distribuição geográfica desses insetos é de fundamental importância para se conhecer a localização das espécies de flebotomíneos na Amazônia legal. As bases iniciais deste trabalho foram às diversas publicações científicas sobre flebotomíneos entre as décadas de 70 e 2000, com indicação da localização geográfica. As informações coletadas foram dispostas em um banco de dados ACCESS ® , e posteriormente gerado mapas temáticos confeccionados através do programa ARCGIS 9.1 ® . Dos 767 municípios da Amazônia legal, em apenas 103 (13,43%) tiveram reportada a ocorrência de flebotomíneos do gênero Lutzomyia.

Phlebotominae sand flies are natural hosts of various microorganisms including etiological agents of diseases of medical and veterinary importance such as viruses, bacteria and protozoa. Parasites of the genus Leishmania is widely spread around the world and are pathogenic to man, wild and domestic animals with a variety of species and, in most cases, a specific vectors. In the Neotropical region nearly 530 species of sand flies are known and this current review updates the information on the vectors of leishmaniases in the Americas.

Parasitic protozoa belonging to the genus Leishmania are the cause of a spectrum of diseases in humans, as well as chronic long-term infections. These parasites exhibit a remarkable capacity to survive and proliferate within the phagolysosome compartment of host macrophages. Studies with defined Leishmania mutants in mouse models of infection have highlighted processes that are required for parasite survival in macrophages. Parasite mutants have been identified that (i) are poorly virulent when the insect (promastigote) stage is used to initiate infection, but retain wild-type virulence following transformation to the obligate intracellular amastigote stage, (ii) are highly attenuated when either promastigotes or amastigotes are used, and (iii) are unable to induce characteristic lesion granulomas, but can persist within macrophages in other tissues. From these analyses it can be concluded that promastigote stages of some species require the surface expression of lipophosphoglycan, ...

Background The WHO considers leishmaniasis as one of the six most important tropical diseases worldwide. It is caused by parasites of the genus Leishmania that are passed on to humans and animals by the phlebotomine sandfly. Despite all of the research, there is still a lack of understanding on the metabolism of the parasite and the progression of the disease. In this study, a mathematical model of disease progression was developed based on experimental data of clinical symptoms, immunological responses, and parasite load for Leishmania amazonensis in BALB/c mice. Results Four biologically significant variables were chosen to develop a differential equation model based on the GMA power-law formalism. Parameters were determined to minimize error in the model dynamics and time series experimental data. Subsequently, the model robustness was tested and the model predictions were verified by comparing them with experimental observations made in different experimental conditions. The mod...

Phlebotomine sand flies are medically important insects widespread throughout the world and responsible for the transmission of several diseases to humans and other animals including leishmaniasis and sand fly fever. In Sri Lanka, a total of 22 species of sand flies belonging to two genera, namely: Phlebotomus and Sergentomyia, have been recorded with 6 and 16 species, respectively. The current study reports a complete list of the species of sand flies reported from Sri Lanka with a review on global and local distribution, biology and bionomics of each species as per published literature up to June 2018.

Some novel 4-N-substituted terpenyl pyrimidines 5(aed) and 7(aeg) have been synthesized using novel synthetic methods. The compounds were screened for in vivo antileishmanial screening. When compared to 4-thiomethoxy substituted pyrimidine 2 4-N-substituted terpenyl pyrimidines 5(aed) and 7(aeg) were found inactive.