Showing papers on "Leishmania infantum published in 2005"
TL;DR: A number of tools have been developed for the control of the canine reservoir of L. infantum, including several canine vaccine candidates, in particular an FML Leishmania enriched fraction showing good clinical protection, and a number of insecticide-based preparations for dog protection against sand fly bites.
463 citations
TL;DR: Parasitology and serology tests that were performed in 30 wild canines showed 10% these animals were infected by Leishmania infantum, and anti-leishmanial antibodies were detected in some of the seropositive dogs with specific clinical signs.
261 citations
TL;DR: ELISAs based on soluble promastigotes or amastigote antigens seem to be most suited for the serological diagnosis of canine Leishmania infections in both symptomatic and asymptomatic dogs.
Abstract: Enzyme-linked immunosorbent assays (ELISAs) based on soluble antigens derived from promastigote or amastigote-like stages of Leishmania infantum and on the recombinant rK39 antigen, each in combination with different conjugates [anti-immunoglobulin G1 [IgG1], anti-IgG2, anti-IgG(γ), and anti-IgG heavy plus light chains], were compared to an immunofluorescent-antibody test (IFAT) and two commercially available rapid test systems (DiaMed-Vet-IT Leish and ID-PaGIA canine leishmaniasis antibody test) for the detection of specific anti-Leishmania antibodies in symptomatic and asymptomatic dogs with proven L. infantum infections. ELISAs based on soluble promastigote and amastigote antigens had very high sensitivities in symptomatic (n = 30; 100%) and asymptomatic dogs (n = 17; 94.1 to 100%), except when combined with the anti-IgG1 conjugate (41.2 to 82.4%). Specificities were high for all combinations (n = 50; 96 to 100%). The rK39 ELISA detected fewer asymptomatic cases (sensitivities, 52.9 to 64.7%) but was highly specific (96 to 100%). The IFAT was 90% sensitive in symptomatic dogs but was significantly less sensitive in asymptomatic cases (29.4%). However, it had an excellent specificity (100%). Test performances of the rapid tests based on the rK39 antigen were comparable to the ELISAs based on the same antigen. ELISAs based on soluble promastigote or amastigote antigens seem to be most suited for the serological diagnosis of canine Leishmania infections in both symptomatic and asymptomatic dogs. IFAT and the rK39 ELISA lack sensitivity in asymptomatic cases but are highly specific. Rapid tests like the rK39 dipstick test or the ID-PaGIA are helpful for confirming clinically suspected cases because of their high specificities in symptomatic animals.
201 citations
TL;DR: It is suggested that the vectorial capacity of R. sanguineus for L. chagasi should be evaluated further, opening new perspectives in the epidemiology of ZVL.
176 citations
TL;DR: The view that a LiESAp vaccine might be useful in a promising vaccination approach against natural L. infantum infection is supported, as increased levels of total anti-leishmanial antibodies were exclusively detected in infected dogs from group 1.
151 citations
TL;DR: It is proposed that the combination of DNA and recombinant protein vaccination using CPs could be instrumental to control (VL) in dogs.
137 citations
TL;DR: The ITS sequence analysis presented here supports the need for revision of the taxonomy of the L. donovani complex and identifies three main lineages of strains in East Africa: two quite distantly related groups of strains from Sudan/Ethiopia, and a third group including all strains from Kenya, which is more closely related to part of the Indian strains than to any of the Sudanese/ Ethiopian groups.
130 citations
TL;DR: It is concluded that vaccination with MML is not effective to prevent leishmaniasis infection and disease progression in dogs under field conditions.
126 citations
TL;DR: The results highlight for the first time the role of MRPA in antimony resistance in the amastigote stage of the parasite and suggest a strategy for reversing resistance.
Abstract: Antimonial compounds are the mainstay for the treatment of infections with the protozoan parasite Leishmania. We present our studies on Leishmania infantum amastigote parasites selected for resistance to potassium antimonyl tartrate [Sb(III)]. Inside macrophages, the Sb(III)-selected cells are cross-resistant to sodium stibogluconate (Pentostam), the main drug used against Leishmania. Putative alterations in the level of expression of more than 40 genes were compared between susceptible and resistant axenic amastigotes using customized DNA microarrays. The expression of three genes coding for the ABC transporter MRPA (PGPA), S-adenosylhomocysteine hydrolase, and folylpolyglutamate synthase was found to be consistently increased. The levels of cysteine were found to be increased in the mutant. Transfection of the MRPA gene was shown to confer sodium stibogluconate resistance in intracellular parasites. This MRPA-mediated resistance could be reverted by using the glutathione biosynthesis-specific inhibitor buthionine sulfoximine. These results highlight for the first time the role of MRPA in antimony resistance in the amastigote stage of the parasite and suggest a strategy for reversing resistance.
123 citations
TL;DR: This is the first report of maternal transmission of a North American isolate of L. infantum from an experimentally infected dog and DNA was detectable by PCR in liver, bone marrow, and heart from all 3 puppies and in the spleen, lymph node, kidney, and placenta in 2 puppies.
Abstract: Leishmania infantum, an etiologic agent of zoonotic visceral leishmaniasis, is widespread among foxhounds in the United States. Although sand flies are widely distributed throughout the United States, epidemiological data do not support a major role for sand flies in the transmission of L. infantum in foxhounds in this country. Congenital transmission of human visceral leishmaniasis is reported in humans and might also occur in dogs. We have previously isolated L. infantum from Virginia foxhounds and used this isolate (LIVT-1) to experimentally infect beagles. Four female beagles, chronically infected with LIVT-1, were bred to a male beagle chronically infected with L. infantum chagasi. One beagle was able to maintain her pregnancy, and 4 puppies were delivered by cesarean section. One puppy was malformed and autolytic at delivery, and tissues were not collected or analyzed. The remaining puppies were killed at the time of cesarean section, and selected tissues were collected for parasite culture and PCR. Promastigotes were not cultured from tissues in any of the puppies. Leishmania sp. DNA was detectable by PCR in liver, bone marrow, and heart from all 3 puppies and in the spleen, lymph node, kidney, and placenta in 2 puppies. Placental tissue from the dam was PCR negative. This is the first report of maternal transmission of a North American isolate of L. infantum from an experimentally infected dog.
122 citations
TL;DR: The present work describes the cytokine expression in peripheral blood mononuclear cells (PBMC) obtained from asymptomatic dogs experimentally infected with L. infantum that present a cellular protective immune response and In vitro stimulation of PBMC with soluble leishmanial antigen (SLA) promoted the expression of IL-2, IFN-gamma, TNF-alpha, IL-18, Il-4, IL -6 and IL-10 mRNA.
TL;DR: The majority of these transcripts contain a conserved 450 nt cis-acting 3'UTR element shown previously to regulate stage-specific gene expression at the level of translation, which suggests that several amastin homologs may be regulated by a similar mechanism of translational control inside the macrophage.
TL;DR: The study showed that atisine-type C20-diterpenoid alkaloids exhibited promising anti-leishmanial properties with strong molecular selectivity, which might have implications for other intracellular pathogens- or phylogenetically related parasites, such as Trypanosoma spp.
TL;DR: In vivo evaluation in the BALB/C mouse model demonstrated that >90% reduction of liver amastigote burdens was obtained 1 week after a single subcutaneous dose at 0.2-0.4 mg/kg was administered.
Abstract: The methanolic extract from the leaves of the Vietnamese medicinal plant Maesa balansae showed potent in vitro and in vivo activity against the tropical protozoal parasite Leishmania infantum. Bioa...
TL;DR: The relevant epitopes of K9, K26, and K39 antigens were joined by PCR strategy to produce the chimeric recombinant protein, which was found highly expressed in Escherichia coli and efficiently purified by affinity chromatography.
Abstract: Wild canids and domestic dogs are the main reservoir of zoonotic visceral leishmaniasis (VL) caused by Leishmania infantum (syn.: Leishmania chagasi). Serological diagnosis of VL is therefore important in both human and dog leishmaniasis from a clinical and epidemiological point of view. Routine diagnosis of VL is traditionally carried out by immunofluorescent antibody test (IFAT), which is laborious and difficult to standardize and to interpret. In the last decade, however, several specific antigens of Leishmania infantum have been characterized, allowing the development of a recombinant-based immunoassay. Among them, the whole open reading frame encoding K9 antigen, the gene fragment encoding the repetitive sequence of K26, and the 3′-terminal gene fragment of the kinesin-related protein (K39sub) were previously evaluated as diagnostic markers for canine leishmaniasis and proved to be independent in their antibody reactivity. Since sensitivity of serological test is usually higher in multiple-epitope format, in this study the relevant epitopes of K9, K26, and K39 antigens were joined by PCR strategy to produce the chimeric recombinant protein. The resulting mosaic antigen was found highly expressed in Escherichia coli and efficiently purified by affinity chromatography. Antigenic properties of this recombinant antigen were evaluated by indirect enzyme-linked immunosorbent assay (ELISA) using a panel of human and dog sera previously characterized by parasitological and/or serological techniques. Chimeric ELISA showed 99% specificity in both human (n = 180) and canine (n = 343) control groups, while sensitivity was higher in canine VL (96%, n = 213) than in human VL (82%, n = 185). Accordingly, concordance between IFAT and canine chimeric ELISA (k = 0.95, 95% confidence interval = 0.93 to 0.98) was higher than between IFAT and human chimeric ELISA (k = 0.81, 95% confidence interval = 0.76 to 0.87). Results suggest the potential use of this new antigen for routine serodiagnosis of VL in both human and canine hosts.
TL;DR: From the present study, quinoline 5 is the most promising compound against both cutaneous and visceral leishmaniasis.
Abstract: We report in this study the in vivo efficacy of nine 2-substituted quinolines on the Leishmania amazonensis cutaneous infection murine model and on the Leishmania infantum and Leishmania donovani visceral infection murine models. In the case of the L. amazonensis model, quinolines were administered orally at 25 mg/kg twice daily for 15 days. Quinolines 1, 2, 3, and 7 reduced by 80 to 90% the parasite burdens in the lesion, whereas N-methylglucamine antimoniate (Glucantime), administered by subcutaneous injections at 100 mg [28 mg Sb(V)] per kg of body weight daily, reduced the parasite burdens by 98%. In visceral leishmaniasis due to L. infantum, mice treated orally at 25 mg/kg daily for 10 days with quinolines 1, 4, 5, and 6 showed a significant reduction of parasite burdens in the liver and spleen. These quinolines were significantly more effective than meglumine antimoniate to reduce the parasite burden in both the liver and spleen. Also, the oral in vivo activity of three quinolines (quinolines 4, 5, and 2-n-propylquinoline) were determined against L. donovani (LV 9) at 12.5 and 25 mg/kg for 10 days. Their activity was compared with that of miltefosine at 7.5 mg/kg. Miltefosine, 2-n-propylquinoline, and quinoline 5 at 12.5 mg/kg significantly reduced the parasite burdens in the liver by 72, 66, and 61%, respectively. From the present study, quinoline 5 is the most promising compound against both cutaneous and visceral leishmaniasis. The double antileishmanial and antiviral activities of these compounds suggest that this series could be a potential treatment for coinfection of Leishmania-human immunodeficiency virus.
TL;DR: Comparable levels of protection were found for mice boosted with either LACK-WR or Lack-MVA, supporting the use of an attenuated vaccinia virus-based vaccine against human visceral leishmaniasis.
Abstract: This study reports the efficacy of a heterologous prime-boost vaccination using DNA and vaccinia viruses (Western Reserve [WR] virus and modified [attenuated] vaccinia virus Ankara [MVA]) expressing the LACK antigen (Leishmania homologue of receptors for activated C kinase) and an intradermal murine infection model employing Leishmania infantum. At 1 month postinfection, vaccinated mice showed high levels of protection in the draining lymph node (240-fold reduction in parasite burden) coupled with significant levels of gamma interferon (20 to 200 ng/ml) and tumor necrosis factor alpha/lymphotoxin (8 to 134 pg/ml). Significant but lower levels of protection (6- to 30-fold) were observed in the spleen and liver. Comparable levels of protection were found for mice boosted with either LACK-WR or LACK-MVA, supporting the use of an attenuated vaccinia virus-based vaccine against human visceral leishmaniasis.
TL;DR: The results indicate that lymph node and bone marrow cytology is a highly sensitive and specific method for the diagnosis of canine patent leishmaniasis, whereas its sensitivity is relatively low in asymptomatic infections.
Abstract: The sensitivity and specificity of lymph node and bone marrow smear microscopy for the diagnosis of Leishmania infantum-infected dogs was evaluated in 79 dogs with leishmaniasis (Group A), 52 asymptomatically infected dogs (Group B), and 44 healthy noninfected dogs (Group C). Light microscopy examination included 10 to 1,000 oil immersion fields, and the density of Leishmania amastigotes was scored by a 0 to +6 scale. Using polymerase chain reaction as the gold standard, the specificity of lymph node and bone marrow cytology was 100%, whereas sensitivity ranged from 7.8% to 92.6%, being significantly higher in Group A compared with Group B. The amastigote scores were also significantly higher in Group A compared with Group B. These results indicate that lymph node and bone marrow cytology is a highly sensitive and specific method for the diagnosis of canine patent leishmaniasis, whereas its sensitivity is relatively low in asymptomatic infections.
TL;DR: New in vitro insights into the wide-spectrum efficacy of PI are added and it is suggested that studying their action on amastigote forms of leishmania within macrophages in order to validate their potential contribution against opportunistic infections in treated seropositive patients is suggested.
TL;DR: It is reported that a cytosolic SIR2 homolog in Leishmania is determinant to parasite survival and an unrelated essential function for the life cycle of this unicellular pathogenic organism is revealed.
TL;DR: Monitoring parameters in dogs after immunisation and before experimental challenge can represent a useful and easy way to rapidly evaluate vaccine candidates against canine visceral leishmaniasis.
TL;DR: Data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.
Abstract: We have examined the efficacy of the administration in mice of a molecularly defined vaccine based on the Leishmania infantum acidic ribosomal protein P0 (rLiP0). Two different challenge models of murine cutaneous leishmaniasis were used: (i) subcutaneous inoculation of L. major parasites in susceptible BALB/c mice (a model widely used for vaccination analysis) and (ii) the intradermal inoculation of a low infective dose in resistant C57BL/6 mice (a model that more accurately reproduces the L. major infection in natural reservoirs and in human hosts). First, we demonstrated that C57BL/6 mice vaccinated with LiP0-DNA or rLiP0 protein plus CpG oligodeoxynucleotides (ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load. This protection was associated with production of gamma interferon (IFN-γ) in the dermal site. Secondly, we showed that immunization with rLiP0 plus CpG ODN is able to induce only partial protection in BALB/c, since these mice finally developed a progressive disease. Further, we demonstrated that LiP0 vaccination induces a Th1 immunological response in both strains of mice. In both cases, the antibodies against LiP0 were predominantly of the immunoglobulin G2a isotype, which was correlated with an rLiP0-stimulated production of IFN-γ in draining lymph nodes. Finally, we demonstrated that LiP0 vaccination does not prevent the Th2 response induced by L. major infection in BALB/c mice. Taken together, these data indicate that the BALB/c model of cutaneous leishmaniasis may undervalue the potential efficacy of some vaccines based on defined proteins, making C57BL/6 a suitable alternative model to test vaccine candidates.
TL;DR: Serological positivity to Leishmania sp.
TL;DR: Hepatic tissue samples were obtained from 26 dogs humanely destroyed because of naturally occurring leishmaniosis and histopathological patterns may, however, represent sequential stages of hepatic leishmania infection during the chronic course of the disease.
TL;DR: It is suggested that this previously unreported cutaneous presentation of canine leishmaniosis appears to be associated with specific immunocompetence and, consequently, with a favourable prognosis.
Abstract: Papular dermatitis due to Leishmania spp. infection was diagnosed in three boxers and two Rottweilers with Leishmania-specific cellular immunity. Diagnosis was based on histological and immunohistochemical examination of papules in four dogs and on cytological examination in one dog. Serum protein electrophoresis was within reference ranges and low antibody levels to Leishmania infantum were detected. Delayed-type hypersensitivity (DTH) reaction to leishmanin was evaluated before treatment in three dogs with positive results. After meglumine antimoniate therapy for 3 to 4 weeks and allopurinol treatment for 6 to 10 months, all dogs were clinically normal, had positive DTH reactions to leishmanin and reduced antibody titres. In conclusion, we suggest that this previously unreported cutaneous presentation of canine leishmaniosis appears to be associated with specific immunocompetence and, consequently, with a favourable prognosis.
TL;DR: From the results, it appears that Greece has a high background of canine leishmaniasis, which is likely to be a risk factor for the emergence of human MVL.
TL;DR: This work presents a meta-analysis of 124 cases of canine coronavirus found in Italy over a 25-year period from 1991 to 2002 that shows clear patterns of decline in the number of cases with age and disease severity.
Abstract: S. Vita1,∗, D. Santori1, I. Aguzzi2, E. Petrotta3 and A. Luciani1 1Dipartimento di Scienze Cliniche Veterinarie, Università degli Studi di Teramo, Viale Crispi 212, I-64100 Teramo, Italy; 2Dipartimento di Scienze Biomediche Comparate, Università degli Studi di Teramo, Viale Crispi 212, I-64100 Teramo, Italy; 3Centro Referenza Nazionale Leishmania, Istituto Zooprofilattico Sperimentale della Sicilia “A. Mirri”, Italy ∗Correspondence: E-mail: boari@unite.it
TL;DR: In veterinary practice, feline leish maniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.
Abstract: Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.
TL;DR: It is demonstrated that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets, and increased expression of the TH2-type cytokine IL-4 is associated with both severe clinical signs and a high parasite burden in the skin lesions.
Abstract: Skin lesions are a frequent manifestation of Leishmania infantum infections in Mediterranean countries. This study demonstrates by real-time reverse transcriptase-polymerase chain reaction the local cy- tokine response in skin biopsies from Leishmania-infected dogs (n 10). As controls, we investigated skin biopsies from healthy (n 10) and fleabite hypersensitive dogs (n 10). We established a quantitative PCR to determine the parasite burden in biopsies. The objective was to elucidate whether a correlation exists between parasite number, histologic response, and T helper-1 (TH1)/T helper-2 (TH2) cytokine expression in lesional skin of naturally infected dogs. In Leishmania-infected dogs, interleukin-4 (IL-4), tumor necrosis factor (TNF- ) and interferon- (IFN-) messenger RNA production was significantly higher than controls. Furthermore, dogs with a high Leishmania burden had a significantly higher IL-4 expression, whereas no difference was noted with regard to expression of other cytokines. By comparing the pattern of inflammation and cytokine expression, a clear trend became evident in that levels of IL-4, TNF-, and IFN- were elevated in biopsies with a periadnexal nodular pattern and in biopsies where the severity of the periadnexal infiltrate was equal to the perivascular to interstitial infiltrate. Expression of IL-4, IL-13, and TNF- was slightly increased in biopsies where plasma cells prevailed on lymphocytes, whereas expression of IFN- was moderately higher when lym- phocytes were predominating. In summary, the present study demonstrates that the local immune response in naturally occurring leishmaniasis includes TH1 as well as TH2 cytokine subsets. Furthermore, respective data suggest that increased expression of the TH2-type cytokine IL-4 is associated with both severe clinical signs and a high parasite burden in the skin lesions.
TL;DR: A valuation of the antifungal activity of these xanthanolides against Candida albicans, Candida glabrata and Aspergillus fumigatus and of their antileishmanial activity against Leishmania infantum and Leishmannia mexicana is presented.