Fibroblast growth factor-23 and Alpha-Klotho concentrations in dogs with canine Leishmaniasis.

This study aimed to assess the concentrations of Fibroblast Growth Factor-23 (FGF-23) and α-Klotho in healthy dogs and dogs at different stages of Canine Leishmaniasis (CanL), and investigate the changes of these parameters in relation to renal function and calcium­phosphorus metabolism. A total of 74 dogs (22 healthy and 52 with CanL) of varying ages, sexes, and medium-sized breeds were included. Dogs with CanL were categorized into different stages (Stage I-IV) based on Leishvet recommendations. In addition to routine hematological parameters, plasma FGF-23, serum α-Klotho, urea, creatinine, phosphorus, calcium, parathormone, vitamin D concentrations, and urine protein/creatinine ratio were measured. Data from healthy dogs were compared to dogs with CanL overall and by stage. Dogs with CanL exhibited higher concentrations of FGF-23 (p < 0.05), α-Klotho, and parathormone (p < 0.001), as well as lower concentrations of vitamin D and calcium (p < 0.001). FGF-23 concentration was particularly elevated in Stage IV compared to other stages. However, no significant differences in α-Klotho levels were observed among the stages. FGF-23 levels showed a weak positive correlation with urea and creatinine concentrations and a moderate positive correlation with urine protein/creatinine ratio. This study demonstrated increased levels of FGF-23 and α-Klotho in dogs with CanL for the first time. The increase in FGF-23 levels was more prominent in advanced stages of the disease and correlated with higher urea and creatinine concentrations. These findings may serve as a basis for future diagnostic and therapeutic investigations, contributing to the understanding of the pathophysiology of kidney disease in CanL.

Leishmaniasis patients' pilgrimage to access health care in rural Bolivia: a qualitative study using human rights to health approach.

BACKGROUND: Leishmaniasis is a neglected tropical disease endemic in Bolivia that disproportionately affects people with little social and political capital. Although the treatment is provided free of charge by the Bolivian government, there is an under-utilization of treatments in relation to the estimated affected population. This study explores the experiences of patients with leishmaniasis and the challenges faced when searching for diagnosis and treatment in Bolivia using a human rights approach. METHODS: We conducted open-ended interviews with 14 participants diagnosed with leishmaniasis. The qualitative data were analysed using thematic analysis and were interpreted under a human rights approach to health care. RESULTS: Four themes emerged during data analysis: (1) the decision for seeking a cure takes time; (2) the severity of symptoms and disruption of functioning drives the search for Western medicine; (3) the therapeutic journey between Western and traditional medicine; and (4) accessibility barriers to receive adequate medical treatment. This study showed that access to health care limitations were the most important factors that prevented patients from receiving timely diagnosis and treatment. Cultural factors played a secondary role in their decision to seek medical care. CONCLUSIONS: Accessibility barriers resulted in a large pilgrimage between public health care and traditional medicinal treatments for patients with leishmaniasis. This pilgrimage and the related costs are important factors that determine the decision to seek health care. This study contributes to the understanding of the under-utilisation problems of medical services in leishmaniasis and other similar diseases in remote and poor populations.

Treating leishmaniasis in Amazonia: A review of ethnomedicinal concepts and pharmaco-chemical analysis of traditional treatments to inspire modern phytotherapies.

ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous and mucocutaneous leishmaniasis are neglected tropical diseases that occur in all intertropical regions of the world. Amazonian populations have developed an abundant knowledge of the disease and its remedies. Therefore, we undertook to review traditional antileishmanial plants in Amazonia and have developed new tools to analyze this somewhat dispersed information. MATERIAL AND METHODS: A literature review of traditional remedies for cutaneous/mucocutaneous leishmaniasis in the Amazon was conducted and the data obtained was used to calculate distribution indexes designed to highlight the most relevant uses in Amazonia. The cultural distribution index represents the distribution rate of a given taxon among different cultural groups and was calculated as the ratio of the number of groups using the taxon to the total number of groups cited. The geographical distribution index allowed us to quantify spatial distribution of a taxon's uses in Amazonia and was calculated geometrically by measuring the average distance between the points where uses have been reported and the barycenter of those points. The general distribution index was defined as an arithmetic combination of the previous two and provides information on both cultural and spatial criteria. RESULTS: 475 use reports, concerning 291 botanical species belonging to 83 families have been gathered depicted from 29 sources. Uses concern 34 cultural groups. While the use of some taxa appears to be Pan-Amazonian, some others are clearly restricted to small geographical regions. Particular attention has been paid to the recipes and beliefs surrounding treatments. Topical application of the remedies dominated the other means of administration and this deserves particular attention as the main treatments against Neotropical leishmaniasis are painful systemic injections. The data set was analyzed using the previously defined distribution indexes and the most relevant taxa were further discussed from a phytochemical and pharmacological point of view. CONCLUSIONS: The Amazonian biodiversity and cultural heritage host a fantastic amount of data whose systematic investigation should allow a better large-scale understanding of the dynamics of traditional therapies and the consequent discovery of therapeutic solutions for neglected diseases. Distribution indices are indeed powerful tools for emphasizing the most relevant treatments against a given disease and should be very useful in the meta-analysis of other regional pharmacopeia. This focus on renowned remedies that have not yet benefitted from extended laboratory studies, could stimulate future research on new treatments of natural origin for leishmaniasis.

Avaliação da capacidade leishmanicida de espécies vegetais do cerrado / Evaluation of the leishmanicidal activity of plant species of the Brazilian savanna

Para identificar as propriedades químicas de plantas do Cerrado, realizou-se um levantamentoetnobotânico que resultou na seleção de sete espécies vegetais de acordo com as indicações terapêuticaspara antibiótico, anti-inflamatório, analgésico, antiofídico e cicatrizante. Foram testados os extratoshidroalcoólicos das seguintes plantas quanto à sua atividade contra as formas promastigotas de Leishmaniaamazonensis: Terminalia fagifolia Mart. (Combretaceae), Vellozia squamata Pohl. (Velloziaceae),Vochysia haenkeana (Spreng.) Mart. (Vochysyaceae), Siparuna guianensis Aublet (Siparunaceae),Lafoensia pacari St. Hil. (Lythraceae), Galactia glauscecens Kunth. (Leguminosae) e Plathymeniareticulata Benth. (Mimosaceae). Feita a triagem para identificação da atividade leishmanicida,calculou-se a concentração inibitória do crescimento (IC50) em relação às culturas não tratadas com osextratos. Nas espécies L. pacari, G. glaucensces e P. reticulata, seus extratos demonstraram IC50 comvalores de 14,6 mug/mL, 46,0 mug/mL e 59,5 mug/mL, respectivamente, apresentando maior eficácia eminduzir a morte dos parasitos. T. fagifolia, V. squamata e V. haenkeana apresentaram IC50 com valoresde 446,1 mug/mL, 305,0 mug/mL e 85,1 mug/mL, respectivamente, demonstrando eficácia moderada.A prospecção fitoquímica evidenciou a presença de flavonoides, triterpenoides, esteroides e taninosque, segundo a literatura, são responsáveis pela atividade leishmanicida. Esses resultados indicam anecessidade de mais estudos para a avaliação da atividade em infecções in vivo e do fracionamento dassubstâncias em busca dos princípios ativos responsáveis pela ação leishmanicida...

In order to identify chemical properties of plants of the Brazilian savanna (Cerrado) an ethnobotanicalsurvey was performed. Seven plant species were selected according to their indications for antibiotic,anti-inflammatory, analgesic, anti-ophidian and healing properties. The following hydroalcoholic extracts of these plants were tested for activity against promastigotes of Leishmania amazonensis:Terminalia fagifolia Mart. (Combretaceae), Vellozia squamata Pohl. (Velloziaceae), Vochysiahaenkeana (Spreng.) Mart. (Vochysyaceae), Siparuna guianensis Aublet (Siparunaceae), Lafoensiapacari St. Hil. (Lythraceae), Galactia glauscecens Kunth. (Leguminosae) and Plathymeniareticulata Benth. (Mimosaceae). The growth inhibitory concentration (IC50) of these extracts wascalculated in relation to untreated cultures. Higher efficacy in inducing the death of parasites wasdemonstrated with extracts of L. pacari, G. glaucensces and P. reticulata, which showed IC50 valuesof 14.6 mg/mL, 46.0 mg/mL and 59.5 mg/mL, respectively. Moderate effectiveness was shown withT. fagifolia, V. squamata and V. haenkeana extracts, with values of 446.1, mg/mL 305.0 mg/mL and85.1 mg/mL respectively. Phytochemical studies showed the presence of flavonoids, triterpenoids,steroids and tannins that, according to the literature, are responsible for the leishmanicidal activity.These results indicate the need for future studies to evaluate the activity of these extracts againstinfections in vivo, as well as the fractionation of substances, in search of the active componentsresponsible for the leishmanicidal action...

Drug discovery for the treatment of leishmaniasis, African sleeping sickness and Chagas disease.

The trypanosomatid protozoa Leishmania, Trypanosoma brucei and Trypanosoma cruzi are the caustive agents of the human diseases respectively, leishmaniasis, African sleeping sickness and Chagas disease. Among the 17 'neglected tropical diseases' highlighted by WHO, progress towards the treatment of these diseases has improved in recent decades, as a result of increased awareness, the emergence of public-private research partnerships and advances in drug-discovery technologies and techniques. Despite this, the current therapies for these diseases have serious shortcomings and, as such, the need to develop novel drugs, improve diagnosis and control the spread of disease is of paramount importance. Future Medicinal Chemistry invited leading experts in the field to share their thoughts and opinions on the changing face of drug discovery in the pursuit of treatments for trypanosomatid-based diseases.

Leishmania parasite detection and quantification using PCR-ELISA.

This protocol describes an improved and optimized PCR-ELISA method for detection and quantification of Leishmania parasites in host tissues. Unlike other DNA-based assays, this method uses digoxigenin- and biotin-labeled primers. This eliminates the need for a separate step of hybridization of the PCR product with labeled probes. The PCR product is detected using sandwich ELISA with antidigoxigenin-detecting antibodies. Primers are complementary to the kinetoplast minicircle conserved region of parasite DNA, allowing the detection of several Leishmania species. For measurement of a wide range of parasite concentrations, +/-25 cycles were optimal. The sensitivity of this technique is 0.3 fg of parasite DNA per reaction in 40-cycle PCR-ELISA, corresponding to 0.004 parasites. DNA preparation by a standard TRI reagent procedure takes about 4 h. When DNA is prepared, a single person can test a large number of samples (at least 150) in a maximum of 7 h. This method might also be suitable for detecting and quantifying other pathogens, especially for detecting small differences in pathogen numbers.

Leishmaniasis laríngea. Presentación de un caso clínico / Laryngeal leishmaniasis. Presentation of a clinical case

La leishmaniasis aislada de laringe es una forma muy poco frecuente de leishmaniasis mucosa, hasta tal punto que su presentación en la clínica habitual es excepcional. En nuestro medio y en todo el área mediterránea, se asocia fundamentalmente con la infección por Leishmania donovani infantum. Presentamos un caso de leishmaniasis laríngea diagnosticado en nuestro hospital. Se trata de un paciente sin antecedentes de viajes al extranjero ni infección por el virus de la inmunodeficiencia humana (VIH). El único antecedente relevante es la toma crónica de esteroides inhalados como consecuencia del asma bronquial que padecía. El diagnóstico se realizó por observación directa del protozoo en la biopsia de la mucosa laríngea. El tratamiento empleado ha sido la anfotericina B y la evolución clínica ha sido satisfactoria (AU)

Isolated laryngeal leishmaniasis is a very uncommon form of leishmaniasis mucous membrane, up to such a point that its presentation in the usual clinical practice is rare. In both our setting and in the entire mediterranean area, it is fundamentally associated to Leishmania donovani infantum infection. We present a case of laryngeal leishmaniasis diagnosed in our hospital. This patient had no background of having travelled abroad or of HIV infection. The only relevant background is chronic administration of inhaled steroids due to his bronchial asthma. Diagnosis was by direct observation of the protozoan in the biopsy of the laryngeal mucous membrane. Treatment has been B-amphotericin with satisfactory clinical evolution (AU)

Manifestaciones orales de patologías tropicales / Oral manifestations of tropical diseases

El presente trabajo expone las características clínias e histopatológicas de las pricnipales patologías tropicales (micóticas, parasitarias y virales) que presentan manifestaciones bucales, poniendo énfasis en la paracoccidioidomicosis, histoplasmosis, critpcocosis, dengue, leishmaniasis e infección micótica (AU)

Fever in the returning traveler, part one: A methodological approach to initial evaluation.

The advent of modern commercial air travel ensures that a returning traveler could present to any emergency department or private physician's office in the United States bearing any infection from the farthest corner of the earth. Exotic illnesses in the returned traveler are of concern to the physician because they often strike an otherwise young and healthy segment of the population and may carry significant morbidity and mortality if not recognized early. The infrequency with which these diseases are encountered demands a systematic approach to history, a physical exam, and the construction of a differential diagnosis. Information about the geographic distribution, routes of transmission, and incubation periods of the pathogens allows a clinician to reduce the differential to a manageable number of the likeliest etiologies. This article, to be presented in 2 parts to run over 2 issues of Wilderness & Environmental Medicine, proposes an algorithm for use by the physician faced with a febrile returned traveler. The clinical features of specific diseases and their incubation periods are presented to support the assumptions on which an algorithm-centered approach is based.

Recent developments in leishmaniasis.

PURPOSE OF REVIEW: The leishmaniases, caused by protozoan parasites of the genus Leishmania, are a significant health problem in many regions of the world. This review highlights the recent advances in the study of leishmaniasis related to parasite biology, disease pathogenesis, clinical evaluation and treatment, and prevention. RECENT FINDINGS: Genetic heterogeneity and clonal diversity is common among Leishmania strains. Gene knockout, overexpression, and re-introduction studies have identified a number of genes that play a role in parasite virulence. Surprisingly, the importance of the surface lipophosphoglycan in parasite virulence appears to differ among Leishmania spp. Studies in experimental animal models have further defined the roles of CD4 and CD8 T cells, IL-4, IL-10, and IL-12 in the control, maintenance, or progression of disease. The effect of Leishmania on dendritic cells and macrophage effector function has also been an important area of investigation. A number of new vaccine candidates have been identified through experimental animal studies. Clinical studies of leishmaniasis have focused on the host determinants of disease (most notably HIV co-infection), serological and DNA-based diagnostic assays, and treatment. Antimony-resistant cases of cutaneous and visceral leishmaniasis have become more common; liposomal amphotericin and oral miltefosine are promising alternative therapies. SUMMARY: Significant advances have been made in the areas of pathogenesis, host defence, and treatment of leishmaniasis. A number of new vaccine candidates and potential targets of drug therapy have been identified, but progress from preclinical studies to clinical trials has been slow. Translational research, built upon the solid foundation of existing and ongoing basic investigation, is a high priority.

29 casos de leishmaniasis tegumentaria diagnosticadas en la medicatura rural de Delicias Estado Táchira-Venezuela / 29 cases of cutaneous leishmaniasis diagnosticed in rural ambulatory of Delicias. Estado Táchira-Venezuela

Se trata de un estudio descriptivo en el cual quisimos determinar la incidencia de Leishmaniasis durante el año 84, y comprobar el Diagnóstico Clínico con Biopsia y frotis por aposición de una muestra representativa. Se analizaron los 29 casos de Leishmaniasis, de los cuales a 21 (72 por ciento ) se les realizó la Intradermoreacción de Montenegro, resultando positiva en un 48 por ciento , además se les realizó Biopsia a 8 de los casos, que representa el 28 por ciento las cuales todas reportaron ser positivas para Leishmaniasis