Cutaneous Leishmaniasis Research Papers - Academia.edu (original) (raw)

Leishmania major and an uncharacterized species have been reported from human patients in a cutaneous leishmaniasis (CL) outbreak area in Ghana. Reports from the area indicate the presence of anthropophilic Sergentomyia species that were... more

Leishmania major and an uncharacterized species have been reported from human patients in a cutaneous leishmaniasis (CL) outbreak area in Ghana. Reports from the area indicate the presence of anthropophilic Sergentomyia species that were found with Leishmania DNA. In this study, we analyzed the Leishmania DNA positive sand fly pools by PCR-RFLP and ITS1 gene sequencing. The trypanosome was determined using the SSU rRNA gene sequence. We observed DNA of L. major, L. tropica and Trypanosoma species to be associated with the sand fly infections. This study provides the first detection of L. tropica DNA and Trypanosoma species as well as the confirmation of L. major DNA within Sergentomyia sand flies in Ghana and suggests that S. ingrami and S. hamoni are possible vectors of CL in the study area. The detection of L. tropica DNA in this CL focus is a novel finding in Ghana as well as West Africa. In addition, the unexpected infection of Trypanosoma DNA within S. africana africana indicat...

Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this major cell surface glycoconjugate. Epitope mapping of four MAbs, designated... more

Monoclonal antibodies (MAbs) were generated against Leishmania major promastigote lipophosphoglycan (LPG) to use as tools in defining functional epitopes of this major cell surface glycoconjugate. Epitope mapping of four MAbs, designated 4A2-A2, 2Gll-A3, 5E6-D10 and 5E10-F2, revealed that the phosphorylated oligosaccharide repeat unit PO4-6[Gal(/31-3)]Gal(/3 1-4)Man ot 1-, P3, is a highly immunogenic epitope which has previously been demonstrated, by chemical analyses, to be a repeat unit specific to L. major. Two antibodies, 4A2-A2 and 5E10-F2, also recognised the repeat unit PO4-6[Ara(/31-2)Gal(/31-3)]Gal(/31-4)Manc~l-, P4a, with less affinity than P3, while 2Gll-A3 recognised P4a with greater affinity than for P3. The L. major metacyclic-specific antibody 3F12 only recognised repeat units terminating with arabinose residues. In particular, 3F12 recognised P4a, which is upregulated in metacyclic LPG compared to the procyclic form of the molecule. The oligosaccharides P3, P4a and P5a are specific to L. major LPG. The epitopes of 4A2-A2, 2G1 l-A3, 5E6-D10 and 5E10-F2 were found on the cell surface and in the flagellar pocket of both procyclic and metacyclic V121 promastigotes, but were only detected at very low levels on amastigotes. The repeat unit P3 is able to inhibit attachment of procyclic promastigotes to the midgut of the sandfly vector, but neither Fab fragments of the four antibodies nor purified P3 could inhibit attachment of metacyclic promastigotes to the macrophage cell line J774. It was also shown that human sera from patients with cutaneous leishmaniasis recognised purified P3. The data suggests that while P3 is an immunogen in the natural course of infection of the human host, P3 plays no role in attachment and internalisation of promastigotes into the macrophages of the mammalian host.

Herpes simplex virus type1 VP22 (HSV-1 VP22) Green fluorescent protein (GFP) a b s t r a c t An intercellular spreading strategy using herpes simplex virus type 1 (HSV-1) VP22 protein is employed to enhance DNA vaccine potency of... more

Herpes simplex virus type1 VP22 (HSV-1 VP22) Green fluorescent protein (GFP) a b s t r a c t An intercellular spreading strategy using herpes simplex virus type 1 (HSV-1) VP22 protein is employed to enhance DNA vaccine potency of Leishmania major amastin antigen in BALB/c mice model. We evaluated the immunogenicity and protective efficacy of plasmid DNA vaccines encoding amastin-enhanced green fluorescent protein (EGFP) and VP22-amastin-EGFP. Optimal cell-mediated immune responses were observed in BALB/c mice immunized with VP22-amastin-EGFP as assessed by cytokine gene expression analysis using real time RT-PCR. Vaccination with the VP22-amastin-EGFP fusion construct elicited significantly higher IFN-gamma response upon antigen stimulation of splenocytes from immunized mice compared to amastin as a sole antigen. Mice immunized by VP22-amastin-EGFP showed partial protection following infectious challenge with L. major, as measured by parasite load in spleens. These results suggest that the development of DNA vaccines encoding VP22 fused to a target Leishmania antigen would be a promising strategy to improve immunogenicity and DNA vaccine potency.

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... more

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.

This paper reports attempts to develop a sensitive and inexpensive procedure for rapid diagnosis of cutaneous leishmaniasis at the species level using skin scrapings from patients. The presence of 3 species (Leishmania major, L. tropica... more

This paper reports attempts to develop a sensitive and inexpensive procedure for rapid diagnosis of cutaneous leishmaniasis at the species level using skin scrapings from patients. The presence of 3 species (Leishmania major, L. tropica and L. infantum) in Israel and the West Bank demonstrates the need for a species-specific detection method in this region. The primer pair Uni2 liLmj4 was developed on the basis of an L. major minicircle sequence but it also amplified other 'Old World' species of Leiskmania. Due to species-specific differences in the size of minicircles, these primers can be used in the polymerase chain reaction to answer diagnostic and epidemiological questions.

objective Information on Leishmania species diversity in western Brazilian Amazon and the clinical picture of human cutaneous leishmaniasis it causes is scarce. We describe clinical findings, diagnostic procedures and identification of... more

objective Information on Leishmania species diversity in western Brazilian Amazon and the clinical picture of human cutaneous leishmaniasis it causes is scarce. We describe clinical findings, diagnostic procedures and identification of Leishmania species in patients from that region.

a b s t r a c t PCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed... more

a b s t r a c t PCR has proved useful for rapid diagnosis and typing of Leishmania. Lack of specificity to discriminate between species and/or sensitivity to detect from clinical samples has always been an issue. Previously developed primers either require PCR-RFLP analysis for Leishmania aethiopica discrimination or lack sensitivity to detect L. aethiopica from clinical samples. Here we report the development and validation of L. aethiopica specific PCR primers (V5F/V10R) based on cysteine protease B (cpb), a multicopy and polymorphic gene of Leishmania. V5F/V10R primers differentiate L. aethiopica from Leishmania tropica, Leishmania major, Leishmania donovani and Leishmania infantum by direct PCR. In addition, they are sensitive enough to detect L. aethiopica from biopsy samples. The primers can be very useful for epidemiological studies, species typing and diagnosis of L. aethiopica directly from clinical samples. Implementation of these primers in routine L. aethiopica diagnosis can improve detection rate, save time, money and labor required for culturing Leishmania.

The sand fly Phlebotomus papatasi transmits Leishmania major, which causes cutaneous leishmaniasis, in vast regions of the Old World. In addition to blood, the sand flies feed on plants. In a study of this diet, we observed that one night... more

The sand fly Phlebotomus papatasi transmits Leishmania major, which causes cutaneous leishmaniasis, in vast regions of the Old World. In addition to blood, the sand flies feed on plants. In a study of this diet, we observed that one night of feeding on branches of Solanum jasminoides, Ricinus communis, or Bougainvillea glabra drastically shortened the life span of the sand flies. Flowering B. glabra attracted P. papatasi in the field. Nevertheless, in the region endemic for L. major in yards abounding with vector sand flies, the number of P. papatasi trapped near hedges of B. glabra was eight times less (62 versus 502 flies trapped) than in the control sites. The results imply that B. glabra affords local protection against sand fly bites and decreases the risk of leishmaniasis. We suggest that this and other ornamental plants that are harmful to sand flies can be used as a tool for this purpose.

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... more

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.

We present a model for the dynamics of transmission of American Cutaneous Leishmaniasis (ACL) that includes a population of incidental hosts for parasites (that is, they act only as sinks of infection), along with species that are... more

We present a model for the dynamics of transmission of American Cutaneous Leishmaniasis (ACL) that includes a population of incidental hosts for parasites (that is, they act only as sinks of infection), along with species that are reservoir hosts (that is, both source and sink of infection). Although, there is evidence that suggests the existence of incidental hosts for Leishmania parasites, there are no mathematical models developed to account for this. Based on this model we obtained expressions that allow computing the threshold conditions for the persistence of the infection using three different approaches. The three expressions agree in the parameters involved in the computation of the threshold, and also in the parameters that are excluded from it, which are those related to the transmission in incidental hosts. We also suggest alternatives for future development in the modelling of the dynamics of transmission of ACL, according to the needs of a more realistic, precise, or g...

Methods: All patients were hospitalised. Cutaneous lesions were biopsied and cultured for species identification. Individual information was collected by a physician or a nurse, using on a standardised, anonymous chart. Data were... more

Methods: All patients were hospitalised. Cutaneous lesions were biopsied and cultured for species identification. Individual information was collected by a physician or a nurse, using on a standardised, anonymous chart. Data were processed with EpiInfo 6.04 and SAS TM .

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... more

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.

Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS) during transmission from the sandfly vector (ambient temperature,... more

Protozoan parasites of genus Leishmania are the causative agents of leishmaniasis. These digenetic microorganisms undergo a marked environmental temperature shift (TS) during transmission from the sandfly vector (ambient temperature, 25-26uC) to the mammalian host (37uC). We have observed that this TS induces a rapid and dramatic increase in protein release from Leishmania mexicana (cutaneous leishmaniasis) within 4 h. Proteomic identification of the TS-induced secreted proteins revealed 72 proteins, the majority of which lack a signal peptide and are thus thought to be secreted via nonconventional mechanisms. Interestingly, this protein release is accompanied by alterations in parasite morphology including an augmentation in the budding of exovesicles from its surface. Here we show that the exoproteome of L. mexicana upon TS induces cleavage and activation of the host protein tyrosine phosphatases, specifically SHP-1 and PTP1-B, in a murine bone-marrow-derived macrophage cell line. Furthermore, translocation of prominent inflammatory transcription factors, namely NF-kB and AP-1 is altered. The exoproteome also caused inhibition of nitric oxide production, a crucial leishmanicidal function of the macrophage. Overall, our results provide strong evidence that within early moments of interaction with the mammalian host, L. mexicana rapidly releases proteins and exovesicles that modulate signalling and function of the macrophage. These modulations can result in attenuation of the inflammatory response and deactivation of the macrophage aiding the parasite in the establishment of infection. Citation: Hassani K, Antoniak E, Jardim A, Olivier M (2011) Temperature-Induced Protein Secretion by Leishmania mexicana Modulates Macrophage Signalling and Function. PLoS ONE 6(5): e18724.

Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both... more

Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. ( J Am Acad Dermatol 2009;60:897-925.) Learning objectives: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.

Two new natural triterpenes, lantaninilic acid and lantoic acid, along with the known triterpenes lantadene A, and oleanolic, ursolic, betulinic, lantanolic, and camaric acid, were obtained from the aerial parts of Lantana camara through... more

Two new natural triterpenes, lantaninilic acid and lantoic acid, along with the known triterpenes lantadene A, and oleanolic, ursolic, betulinic, lantanolic, and camaric acid, were obtained from the aerial parts of Lantana camara through bioassay-guided isolation, monitoring the in vitro antileishmanial activity against promastigotes of Leishmania major. Oleanolic acid (3), ursolic acid (4), lantadene A (5), and lantanilic acid (7) showed significant leishmanicidal activities with IC 50 values of 53. 0, 12.4, 20.4, and 21.3 mm, respectively. The IC 50 value of ursolic acid (4; 12.4 mm) was found to be comparable with that of the standard drugs, pentamidine (IC 50 15.0 mm) and amphotericin B (IC 50 0.31 mm). The in vitro activities of L. camara and its constituents against promastigotes of Leishmania major are reported here for the first time.

Dermatoscopy, also known as dermoscopy, epiluminescence microscopy, or surface microscopy, is a noninvasive technique allowing rapid and magnified (310) in vivo observation of the skin with the visualization of morphologic features often... more

Dermatoscopy, also known as dermoscopy, epiluminescence microscopy, or surface microscopy, is a noninvasive technique allowing rapid and magnified (310) in vivo observation of the skin with the visualization of morphologic features often imperceptible to the naked eye. Videodermatoscopy (VD) represents the evolution of dermatoscopy and is performed with a video camera equipped with lenses providing higher magnification (310 to 31000). Over the past few years, both dermatoscopy and VD have been demonstrated to be useful in a wide variety of cutaneous disorders, including ectoparasitic infestations, cutaneous/mucosal infections, hair and nail abnormalities, psoriasis, and other dermatologic as well as cosmetologic conditions. Depending on the skin disorder, both dermatoscopy and VD may be useful for differential diagnosis, prognostic evaluation, and monitoring response to treatment. Nowadays, it represents an important and relatively simple aid in daily clinical practice. ( J Am Acad Dermatol 2011;64:1135-46.)

Leishmaniosis is a zoonosis caused by protozoa of the genus Leishmania. American cutaneous leishmaniosis (ACL) is mainly caused by the species L. amazonensis and L. braziliensis, and American visceral leishmaniosis (AVL) is caused by L.... more

Leishmaniosis is a zoonosis caused by protozoa of the genus Leishmania. American cutaneous leishmaniosis (ACL) is mainly caused by the species L. amazonensis and L. braziliensis, and American visceral leishmaniosis (AVL) is caused by L. infantum chagasi. In addition to their proven roles as reservoirs of AVL, dogs are also suspected by researchers to be reservoirs of ACL due to reports of this infection in domestic environments and of infected dogs in endemic areas. The aim of this study was to detect Leishmania sp. infection in dogs from Vila Operária, Buerarema, Bahia, using parasitological tests, indirect immunofluorescent assay (IFA) and polymerase chain reaction (PCR). Furthermore, this study also aimed to identify risk factors associated with illness in dogs in this locality by conducting an epidemiological survey. For this purpose, 292 dogs were clinically evaluated for the presence of skin lesions, and the dogs that showed these changes were submitted to scarification injury to enable preparation of slides for microscopic study of amastigotes. Subsequently, the dogs underwent blood sampling for serological (IFA) and molecular (PCR) tests. Additionally, the owners of the dogs answered an epidemiological questionnaire to facilitate the identification of risk factors for exposure of dogs to pathogens of ACL. Of the 292 dogs studied, 13 (4.5%) had lesions suggestive of ACL, but with a negative parasitological examination and 147 (50.3%) were seropositive according to the IFA. Of the 273 dogs studied using PCR test, 10 (3.66%) were positive for L. braziliensis, and all samples were negative for L. infantum chagasi. Wastelands in the peridomicile and the presence of light in the household were risk factors associated with ACL. The results show that Vila Operária has asymptomatic dogs with ACL and that the detection sensitivity of the IFA was higher than that of PCR for the infected dogs.

Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both... more

Protozoan infections are very common among tropical countries and have an important impact on public health. Leishmaniasis is the most widely disseminated protozoan infection in the world, while the trypanosomiases are widespread in both Africa and South America. Amebiasis, a less common protozoal infection, is a cause of significant morbidity in some regions. Toxoplasmosis and pneumocystosis (formerly thought to be caused by a protozoan) are worldwide parasitic infections with a very high incidence in immunocompromised patients but are not restricted to them. In the past, most protozoan infections were restricted to specific geographic areas and natural reservoirs. There are cases in which people from other regions may have come in contact with these pathogens. A common situation involves an accidental contamination of a traveler, tourist, soldier, or worker that has contact with a reservoir that contains the infection. Protozoan infections can be transmitted by arthropods, such as sandflies in the case of leishmaniasis or bugs in the case of trypanosomiases. Vertebrates also serve as vectors as in the case of toxoplasmosis and its transmission by domestic cats. The recognition of the clinical symptoms and the dermatologic findings of these diseases, and a knowledge of the geographic distribution of the pathogen, can be critical in making the diagnosis of a protozoan infection. ( J Am Acad Dermatol 2009;60:897-925.) Learning objectives: After completing this learning activity, participants should be able to recognize the significance of protozoan infections worldwide, identify the dermatologic manifestations of protozoan infections, and select the best treatment for the patient with a protozoan infection.

We report here the first known cases of natural infection of hedgehogs with Leishmania major. Cutaneous leishmaniasis is an important public health problem in the area of M'sila, a semi-arid province in Algeria's northern Sahara, where... more

We report here the first known cases of natural infection of hedgehogs with Leishmania major. Cutaneous leishmaniasis is an important public health problem in the area of M'sila, a semi-arid province in Algeria's northern Sahara, where two species of hedgehog live, Atelerix algirus and Paraechinus aethiopicus. The aim of this research was to survey Leishmania infection in these hedgehogs and evaluate whether they were reservoir hosts of Leishmania in an endemic zoonotic focus of leishmaniasis. Serological and molecular methods were used to determine the presence of Leishmania in 24 hedgehogs caught directly by hand and identified at species level as 19 A. algirus and 5 P. aethiopicus. Specific anti-Leishmania antibodies were detected in 29.2% of individuals by Western blot and in 26.3% by ELISA. The real-time PCR performed in spleen, ear and blood samples detected Leishmania spp. DNA in 12.5% of the individuals, one A. algirus and two P. aethiopicus. Three skin and two spleen samples of these animals were found to be parasitized and were identified by molecular test as L. major. Considering our results, it is suggested that hedgehogs have a potential epidemiological role as reservoir hosts of L. major.

Parasitic zoonotic diseases are prevalent throughout India at varying rates. First reports of zoonotic parasites and new emerging diseases have been recorded in both the human and animal populations in recent decades. The prevalence of... more

Parasitic zoonotic diseases are prevalent throughout India at varying rates. First reports of zoonotic parasites and new emerging diseases have been recorded in both the human and animal populations in recent decades. The prevalence of zoonotic parasites is likely to be an underestimate, owing to the lack of proper surveillance and the shortage of information about the existence of asymptomatic animal carriers. Emergence of diseases such as human echinococcosis/hydatidosis, neurocysticercosis, cryptosporidiosis and toxoplasmosis in those with acquired immune deficiency syndrome, together with the re-emergence of cutaneous leishmaniosis, poses a serious threat in India and the prevention and control of these parasitic zoonoses, and others, is a great challenge.

In this study, we aimed to evaluate the validity of the conventional enzyme-linked immunosorbent assay (ELISA) and the Western blotting test for the diagnosis of anthroponotic cutaneous leishmaniasis (ACL) using serum samples obtained... more

In this study, we aimed to evaluate the validity of the conventional enzyme-linked immunosorbent assay (ELISA) and the Western blotting test for the diagnosis of anthroponotic cutaneous leishmaniasis (ACL) using serum samples obtained from 51 patients with parasitologically proven nontreated CL (NonT-CL patients) and 62 patients under treatment for CL (UT-CL patients). Additionally, 29 serum samples obtained from patients with parasitologically and serologically proven visceral leishmaniasis (VL) were also used as positive controls, and serum samples from 43 blood donors were used as negative controls. All sera were diluted to the same dilution (1/100). Leishmania infantum MON-1 was used as the antigen in the conventional ELISA. The sera of 27 (93.1%) of 29 VL patients were seropositive by ELISA, while the sera of 40 (78.4%) of 51 NonT-CL patients and 43 (69.3%) of 62 UT-CL patients were seropositive by the conventional ELISA. The absorbance values of the CL patients' sera were significantly lower than the absorbance values of the VL patients' sera. Bands between 15 and 118 kDa were detected in two groups of CL patients. Among all bands, the 63-kDa band was found to be more sensitive (88.5%). When we evaluated the Western blotting results for the presence of at least one of the diagnostic antigenic bands, the sensitivity was calculated to be 99.1%. By using serological tests, a measurable antibody response was detected in most of the CL patients in Sanliurfa, Turkey. It is also noted that this response can be changed according to the sizes, types, and numbers of lesions that the patient has. The Western blot test was found to be more sensitive and valid than the conventional ELISA for the serodiagnosis of ACL. In some instances, when it is very difficult to demonstrate the presence of parasites in the smears, immunodiagnosis can be a valuable alternative for the diagnosis of ACL.

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is... more

Th1-type cellular immune responses play a critical role in protection against infection with Leishmania parasites, whereas activation of Th2-type cells results in progressive disease. Cutaneous leishmaniasis caused by Leishmania major is often a self-healing disease; however, persistent nonhealing forms are also known. In the present study, we have described cell-mediated immune responses in nonhealing patients by measuring T-cell proliferation, cytokine production, and phenotypic characterization of these cells. The responses were compared with those of patients with active lesions, patients who had recovered from infection, and healthy controls. Peripheral blood mononuclear cells from patients with active lesions and recovered donors proliferated vigorously and produced Th1-type cytokine when stimulated with L. major antigens, whereas in nonhealing patients the proliferative responses were significantly lower and showed a Th2-type response to Leishmania antigens. Interleukin-10 (IL-10) production was not a feature of L. major stimulation. Flow cytometric analysis revealed that L. major antigen induced proliferation of the CD4-positive population and that these cells were the major source of gamma interferon and IL-4. These results show a distinct dichotomy in the cytokine response to L. major infection.

We have determined the specificity of the classes of anti-leishmanial antibodies which are detectable in serum from patients with active cutaneous leishmaniasis. On immunoblots, differences exist in the patterns of antigen recognition by... more

We have determined the specificity of the classes of anti-leishmanial antibodies which are detectable in serum from patients with active cutaneous leishmaniasis. On immunoblots, differences exist in the patterns of antigen recognition by IgG, IgM, IgA and IgE antibodies present in localized cutaneous leishmaniasis (LCL) and diffuse cutaneous leishmaniasis (DCL) patient serum. Each class of antibody showed differing patterns of banding to the various molecular species of parasite antigens. There was significant variation in the specificities of the IgG antibody reactivities between individual patients. The patterns of IgM binding were generally homogeneous and restricted to antigens with M(r) greater than 40 kDa. The only class of anti-Leishmania antibodies which showed shared patterns of common antigen recognition by all of the patients studied were IgA antibodies. The reactivities of IgE antibodies encompassed two antigens of M(r) 36 and 46-48 kDa which were not recognized by any of the other isotypes. Such antibody class associated reactivity may be useful in the design of serodiagnostic assays for the detection of Leishmania infection or other infectious agents.

Cutaneous leishmaniasis is endemic in Salta, the northwestern province of Argentina. We describe an outbreak involving five recreational hunters whose exposure was limited to several hours in a residual patch of primary forest. All... more

Cutaneous leishmaniasis is endemic in Salta, the northwestern province of Argentina. We describe an outbreak involving five recreational hunters whose exposure was limited to several hours in a residual patch of primary forest. All patients presented with typical cutaneous lesions after a mean incubation period of 59 days (range 15-78), and one developed simultaneous mucosal involvement. Polymerase chain reaction analysis of lesions confirmed Leishmania (V.) braziliensis as the etiologic agent in three cases. All patients were cured with anti-Leishmania treatment. Entomologic surveys in the transmission area revealed a predominance of Lutzomyia neivai. This outbreak report confirms a microfocal transmission pattern of tegumentary leishmaniasis in the Americas and based on a well-determined exposure, allows the determination of incubation times for leishmaniasis caused by Leishmania braziliensis.

The current study was aimed to investigate the epidemiological status cutaneous leishmaniasis, in endemic regions of district Malakand KP province of Pakistan. The prospective study was conducted during July 2020 to December 2020 in... more

The current study was aimed to investigate the epidemiological status cutaneous leishmaniasis, in endemic regions of district Malakand KP province of Pakistan. The prospective study was conducted during July 2020 to December 2020 in different villages of district Malakand KP province. A total of 278 CL active lesions samples were collected by applying cotton on the lesion site with 100% of ethanol and then punctured via disposable blood lancet. The blood or tinged fluid was then poured on the slide. Microscopy on Giesma stained slides were done of all collected lesion samples. The data were analyzed by using Chi square tests, SPSS version 23.0. A major portion (54%; n=151) of age group 1-15 years were more effected with CL. The highest prevalence 54% was found in males followed by females 46%. The statistical analysis revealed a significant association (p value = 0.02) between the various age groups and gender with 5% significance level. No association between the lesion and gender was observed. The mean age was found to be 18.63±15.91 years. It is concluded that CL infection is health threatening issue for local population of District Malakand. Current study could be helpful for health authorities to take instant action against this negligible disease. Additionally, the healthcare department should arrange sessions and awareness campaigns for locals.

In the district of Paracambi, State of Rio de Janeiro an epidemiological survey for American tegumentary leishmaniasis in canine population was carried out in endemic localities. A total of 179 dogs was registered and 138 (77.1%) examined... more

In the district of Paracambi, State of Rio de Janeiro an epidemiological survey for American tegumentary leishmaniasis in canine population was carried out in endemic localities. A total of 179 dogs was registered and 138 (77.1%) examined for their clinical aspects, development of delayed hypersensitivity (DHS) with Imunoleish® antigen and serological responses by indirect immunofluorescent reaction and enzyme-linked immunosorbent assay. In 9 (6.5%) dogs with active cutaneous lesions or suspect scars, 66.7% were caused by Leishmania sp; 44.4% produced infection in hamsters and showed growth in culture media, which was considered to be compatible with the species of Leishmania braziliensis complex. The molecular characterization (isoenzyme and KDNA restriction profiles) defined two strains with similar profiles for L. (Viannia) braziliensis. The prevalence of canine infection estimated by the cutaneous test, IFR and ELISA was 10.1%, 16.7% and 27.8%, respectively. The presence of clinical / sub-clinical form of ATL in canine population associated with human infections suggested that the dog can act as source of infection as well as for dissemination of the disease.

Annales de dermatologie et de vénéréologie (2009) 136, 815-820 LETTRES À LA RÉDACTION Leishmaniose cutanée multifocale à Leishmania infantum sous traitement par adalimumab Multifocal cutaneous leishmaniasis due to Leishmania infantum... more

Annales de dermatologie et de vénéréologie (2009) 136, 815-820 LETTRES À LA RÉDACTION Leishmaniose cutanée multifocale à Leishmania infantum sous traitement par adalimumab Multifocal cutaneous leishmaniasis due to Leishmania infantum under adalimumab therapy Les nouvelles biothérapies sont à l'origine d'un risque infectieux accru, en particulier pour la tuberculose. Nous rapportons le cas d'une femme de 51 ans, originaire d'Algérie, qui consultait en juin 2008 pour des lésions cutanées ulcérobourgeonnantes. La malade était suivie en rhumatologie pour une spondylarthrite ankylosante à forme axiale et périphérique, HLAB27 positive, diagnostiquée en 2004 et non contrôlée par une association de méthotrexate (15 mg/semaine) et d'antiinflammatoires non stéroïdiens. Un traitement par anticorps monoclonaux anti-TNF␣ (adalimumab, Humira ® ) était instauré en juin 2006 à la posologie de 40 mg toutes les deux semaines, en association avec du méthotrexate par voie orale jusqu'en juin 2007, puis poursuivi en monothérapie. Une lésion cutanée douloureuse du genou droit apparaissait en février 2008, six mois après le retour d'un voyage en Kabylie. Dans l'hypothèse d'un abcès infectieux bactérien, un traitement antibiotique par amoxicilline + acide clavulanique était débuté, puis remplacé par une synergistine et enfin par des fluoroquinolones et du métronidazole, toujours sans aucune efficacité.

Cutaneous leishmaniasis (CL) in Iran could be considered as an emerging disease that is rapidly increasing and expanding its traditional geographical range to new foci. Sixteen registered emerging epidemics have occurred since 1998 in... more

Cutaneous leishmaniasis (CL) in Iran could be considered as an emerging disease that is rapidly increasing and expanding its traditional geographical range to new foci. Sixteen registered emerging epidemics have occurred since 1998 in different provinces. Various risk factors, including agricultural development, earthquake, movement to endemic areas, construction of buildings near colonies of rodents, sleeping outside, cross-border movements, and poor sanitation, play crucial roles in the expansion of the disease. The mentioned risk factors can lead to the gradual or sudden emergence of new CL epidemics, and long-lasting endemic foci can also erupt into epidemics. This paper reviews the emerging epidemics published between 1998 and 2019 in Iran with particular emphasis on the operational aspects of control and related risk factors caused by anthroponotic CL (ACL) and zoonotic CL (ZCL). The competent surveillance system should be extended to all high-risk areas to facilitate controlling the emerging epidemics of ACL and ZCL in the affected areas.

Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral... more

Recently, there has been a renewed interest in the development of new drugs for the treatment of leishmaniasis. This has spurred the need for pharmacodynamic markers to monitor and compare therapies specifically for visceral leishmaniasis, in which the primary recrudescence of parasites is a particularly long-term event that remains difficult to predict. We performed a systematic review of studies evaluating biomarkers in human patients with visceral, cutaneous, and post-kala-azar dermal leishmaniasis, which yielded a total of 170 studies in which 53 potential pharmacodynamic biomarkers were identified. In conclusion, the large majority of these biomarkers constituted universal indirect markers of activation and subsequent waning of cellular immunity and therefore lacked specificity. Macrophage-related markers demonstrate favorable sensitivity and times to normalcy, but more evidence is required to establish a link between these markers and clinical outcome. Most promising are the markers directly related to the parasite burden, but future effort should be focused on optimization of molecular or antigenic targets to increase the sensitivity of these markers. In general, future research should focus on the longitudinal evaluation of the pharmacodynamic biomarkers during treatment, with an emphasis on the correlation of studied biomarkers and clinical parameters.

Our laboratory is characterizing Leishmania stabilates and isolates from active leishmaniasis cases. Smears and cultures from aspirates made on different dates from a single lesion on the bridge of the nose of an 18 years old Kenyan male... more

Our laboratory is characterizing Leishmania stabilates and isolates from active leishmaniasis cases. Smears and cultures from aspirates made on different dates from a single lesion on the bridge of the nose of an 18 years old Kenyan male from Nyandarua District contained Leishmaniu. The isolates, NLB-271 and NLB-271-IA, were characterized by cellulose acetate electrophoresis (CAE) using 20 enzyme systems and by Southern analysis using 2 deoxyribonucleic acid (DNA) probes (pDK10 and pDK20) from a Dakar strain of L. major (MHOMISNiOOiDKl) and a third probe, ~7-059 from L. infuntum strain ITMAP-263. Digestion of the two Leishmania DNAs with endonucleases Hind111 and PstI, followed by hybridization with rhe 3 probes, revealed DNA fragment banding patterns indistinguishable from those of the L. donovani species complex. The CAE isoenzyme profiles of these 2 Kenyan isolates were indistinguishable from those of Kenyan L. donovani strains we designated as zymodeme 26. Excluding post-kala-azar dermal leishmaniasis, this constitutes the first human case of cutaneous leishmaniasis caused by L. donovani s.1. in Kenya. Previously, cutaneous leishmaniasis cases in Kenya have been due to L. aethiopica, L. major and L. tropica only.

We report on a German tourist returning from vacations in Southern Greece with cutaneous leishmaniasis (CL) presenting as multiple erythematosquamous lesions caused by Leishmania tropica (zymodeme MON-57). In spite of its endemicity, only... more

We report on a German tourist returning from vacations in Southern Greece with cutaneous leishmaniasis (CL) presenting as multiple erythematosquamous lesions caused by Leishmania tropica (zymodeme MON-57). In spite of its endemicity, only few data are available on the incidence and current distribution of CL in Greece, which may allow for an assessment of the risk for travelers.

The diseases originating from animals or associated with man and animals are remerging and have resulted in considerable morbidity and mortality. The present review highlights the re-emergence of emerging mainly zoonotic diseases like... more

The diseases originating from animals or associated with man and animals are remerging and have resulted in considerable morbidity and mortality. The present review highlights the re-emergence of emerging mainly zoonotic diseases like chikungunya, scrub typhus, and extension of spatial distribution of cutaneous leishmaniasis from western Rajasthan to Himachal Pradesh, Kerala, and Haryana states; West Nile virus to Assam, and non-endemic areas of Japanese encephalitis (JE) like Maharashtra and JE to Delhi; Crimean-Congo hemorrhagic fever making inroads in Ahmedabad; and reporting fifth parasite of human malaria with possibility of zoonosis have been highlighted, which necessitates further studies for prevention and control. Emphasis has been given on understanding the ecology of reservoir hosts of pathogen, micro niche of vector species, climatic, socioeconomic risk factors, etc. Development of facilities for diagnosis of virus from insects, reservoirs, and human beings (like BSL4, which has been established in NIV, Pune), awareness about symptoms of new emerging viral and other zoonotic diseases, differential diagnosis, risk factors (climatic, ecological, and socioeconomic) and mapping of disease-specific vulnerable areas, and mathematical modeling for projecting epidemiological scenario is needed for preparedness of public health institutes. It is high time to understand the ecological link of zoonotic or anthroponotic diseases for updated risk maps and epidemiological knowledge for effective preventive and control measures. The public health stakeholders in India as well as in Southeast Asia should emphasize on understanding the eco-epidemiology of the discussed zoonotic diseases for taking preventive actions.

Leishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen... more

Leishmania, affects millions of individuals worldwide, causing serious morbidity and mortality. This study directly determined the frequency of cells producing key immunoregulatory cytokines in response to the recombinant antigen Leishmania homolog of receptors for activated kinase C (LACK) and soluble leishmania antigen (SLA), and it determined relative contributions of these antigens to the overall cytokine profile in individuals infected for the first time with Leishmania braziliensis. All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry). The following were determined. (i) The Th1-type response previously seen in patients with cutaneous leishmaniasis is due to gamma interferon (IFN-␥) production by several different sources, listed in order of contribution: CD4 ؉ T lymphocytes, CD4 ؊ , CD8 ؊ lymphocytes, and CD8 ؉ T lymphocytes. (ii)

Leishmaniasis is one of the most important infectious diseases in the world. There are wide differences in the clinical features of Leishmaniasis. Cutaneous leishmaniasis is self-healing while visceral leishmaniasis is fatal. Efforts have... more

Leishmaniasis is one of the most important infectious diseases in the world. There are wide differences in the clinical features of Leishmaniasis. Cutaneous leishmaniasis is self-healing while visceral leishmaniasis is fatal. Efforts have been made since more than a century ago to control and treat the disease, but appropriate vaccines, drugs and pesticides have not yet been prepared. While in these conditions, alternative medicines and herbal medicines were approved by WHO and other reliable worldwide references, Rubia tinctorum has been used traditionally in medicine throughout history. The purpose of this study was to examine the effect of Rubia tinctorum extract on cutaneous leishmaniasis in BALB/c Mice.Rubia tinctorum extracts with 40, 60 and 80% concentrations were prepared. Then, the BALB/c mice were infected with leishmania (L) major [MRHO/IR/75/ER]. Soon after the ulcer started to appear in the early stage, one dose of the herbal medicine with 40, 60 and 80% concentration on honey base was used to treat the ulcer and dosing continued till the death of the mice of negative control group occurred. The mean weight of the mice that received 40% concentration of Rubia. tinctorum extract showed a statistically significant difference compared to the mean weight of the mice receiving 60% concentration of Rubia. tinctorum extract (P=0.001), but showed no statistically significant difference compared to the mean weight of the mice receiving 80% concentration of Rubia. tinctorum extract (P>0.05)The mean weight of the mice that received 40, 60 and 80% concentrations of Rubia tinctorum extracts showed a statistically significant difference compared to the mean weight of the mice in control group (P=0.000).The mean of lesion size of the mice that received 40, 60 and 80% R. tinctorum extracts showed no statistically significant difference compared to the mean of the lesion size of the mice in control group (P>0.05). When the mice infected with Rural Cutaneous Leishmaniasis {Leishmania (L) major [MRHO/IR/75/ER]} were not treated, they develop Visceral Leishmaniasis. When the weight decreased and lesion size of the Cutaneous Leishmaniasis widened, the animal would die. As a whole, in the all of the time,the mice that received 40, 60 and 80% Rubia tinctorum extract their lesion were wet, without secondary infection and without necrosis.

The complex cell mediated immune response in parasitic diseases can be evaluated in different body compartments. In the present work we describe the results of studies of peripheral blood lymphocytes and the cutaneous lesions in the three... more

The complex cell mediated immune response in parasitic diseases can be evaluated in different body compartments. In the present work we describe the results of studies of peripheral blood lymphocytes and the cutaneous lesions in the three clinical forms of tegumentary leishmaniasis. These clinical forms, that constitute a clinical, histological and immunological spectrum, are: localized cutaneous leishmaniasis (LCL), diffuse cutaneous (DCL9, and the intermediate forms that include mucous and verrocous leishmaniasis (MCL). The overall results suggest that the cytokine pattern of lymphocytes in the blood and lesions of LCL, the self-limiting form of the disease, is T-helper type 1. This leads to the cure of the lesions in these patients, either spontaneously or after appropriate therapy. The disseminated disease in DCL patients is resistant to chemotherapy, and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn-gamma production when the lymphocytes are specifically stimulated by leishmanial antigen. This is probably why these patients are unable to control the infection, and allows the cutaneous dissemination of the parasite. The intermediate MCL form is characterized by destructive lesions of the oral and nasopahryngeal mucosas, with a tendency to the chronicity of the infection. The cytokine pattern of MCL patients is a mixture of Type 1 and Type 2 responses. This may be responsible for the progression of the disease in these patients, as it is possible that when both types of cytokines are produced, the Type 2 responses can predominate over the Type 1 and the disease is maintained in a chronic, although activated, state. The examination of the cutaneous lesions demonstrated that the epidermis in the DCL lesions is deficient in ICAM-1 accessory signals and MHC-II expression by keratinocytes, and presents a variable number of Langerhans cells. In MCL lesions, the expression of ICAM-1 and MHC-II is elevated, and Langerhans cells are absent in the damaged epithelium. The epidermis of LCL lesions show ICAM-1 in patches and MHC uniformly expressed by keratinocytes. DCL lesions are characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T gamma delta cells, and an apparent defect in the expression of LFA-1 directional receptors. The cytokine patterns are Th1 and Th2, with the latter predominating. MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2 cytokine pattern. LCL granulomas are characterized by a normal CD4/CD8 ratio, a high memory/naive cell ratio, numerous groups of T gamma delta, a high expression of directional receptors, and Th1/Th0 cytokine patterns. We discuss the results in the context of the immunological effects, both in immunotherapy and immunoprophylasis, of the combined vaccine of BCG plus promastigotes of Leishmania. In immunotherapy we demonstrate that the combined vaccine simulates a Th1 response in LCL patients. As an immunoprophylactic vaccine in healthy individuals from an endemic area of leishmaniasis, it stimulates a Th1 response (positivity in the Montenegro cutaneous reactions, proliferative responses in vitro and production of IFN-gamma), with a low specific antibody response. This demonstrates that the combined vaccine is potentially useful both in the treatment of LCL patients, as well as being potentially protective applied as immunoprophylaxis in the control of leishmaniasis.

Two hundred twenty-six consecutive adult patients with cutaneous leishmaniasis in Colombia were treated with Glucantime and 81% were cured. The 19% who failed treatment had received a statistically significant lower total amount of... more

Two hundred twenty-six consecutive adult patients with cutaneous leishmaniasis in Colombia were treated with Glucantime and 81% were cured. The 19% who failed treatment had received a statistically significant lower total amount of antimony (354 mg/kg) than those who were cured (405 mg/kg) (P ‫ס‬ 0.002). Thirty-nine of the failures were re-treated with Glucantime and 59% were cured. This large experience on initial and re-treatment cure rates probably represents the values found in clinical practice. In this series, parasite resistance may have been induced by the relatively low initial dose of antimony administered to some patients.

Here we report the case of a patient with cutaneous leishmaniasis, who was referred to our clinic in Yazd, Iran. On examining the patient, who was a housekeeper, we found a small plaque in the palmoplantar region due to cutaneous... more

Here we report the case of a patient with cutaneous leishmaniasis, who was referred to our clinic in Yazd, Iran. On examining the patient, who was a housekeeper, we found a small plaque in the palmoplantar region due to cutaneous leishmaniasis. She had not any history from an identical case in this patient. After treatment, the lesions improved.

The Moroccan province of Al Haouz is an emerging focus of human cutaneous leishmaniasis caused by Leishmania tropica. In an entomological investigation of three communes in the province (Ourika, Stti Fatma and Rhmate), 3440 sandflies were... more

The Moroccan province of Al Haouz is an emerging focus of human cutaneous leishmaniasis caused by Leishmania tropica. In an entomological investigation of three communes in the province (Ourika, Stti Fatma and Rhmate), 3440 sandflies were collected on sticky traps in [2005][2006][2007]. Of the six Phlebotomus species caught, Phlebotomus papatasi (13.3% of the total collection), P. sergenti (12.8%) and P. perniciosus (12.8%) were predominant, followed by P. longicuspis (7.9%), P. ariasi (2.6%) and P. alexandri (1.1%). All the other sandflies were Sergentomyia fallax (24.2%), S. minuta (22.0%) or S. dreyfussi (3.4%). The distribution of these species among the many biotopes, at varying altitudes (667-1772 m), is discussed.