Visceral leishmaniasis infection in a rheumatoid arthritis patient treated with adalimumab.
Explore the source record for details and available documents.
Adalimumab↗
Biomedical subjects
L Gradoni
Publications and source records attributed to L Gradoni.
Deltamethrin-impregnated collars for the control of canine leishmaniasis: evaluation of the protective effect and influence on the clinical outcome of Leishmania infection in kennelled stray dogs.
A 2-year field study on kennelled stray dogs living in a highly endemic area of leishmaniasis was designed to evaluate whether deltamethrin-impregnated collars (Scalibor) Protector Band) could confer protection against leishmaniasis in this peculiar setting, and to assess differences in clinical outcomes between collared and uncollared dogs. A cohort of 120 clinically healthy and Leishmania-seronegative dogs was enrolled, 50% of which were collared before the 2003 transmission season, and then re-collared before the subsequent season. Collared and uncollared animals were allowed to live with infected dogs in same groups within the kennel. Follow-up included serological (IFAT) assessment twice a year with parasitological Leishmania confirmation, and clinical evaluation performed every 3 months on seroconverted dogs from both groups. Collar losses during the two seasons were high (35%). About 50% of enrolled dogs were lost at follow-up because of death or they were moved to other locations. After the 2003 season, cross-sectional serological examinations tested positive in 5 out of 44 collared animals (11.4%) and in 14 out of 34 controls (41.2%), with 72.3% estimated protection (P<0.005). After the 2004 season, 7/31 seronegative collared dogs seroconverted (22.6%) compared with 7/17 seronegative controls (41.2%), with 45.1% protection (P=0.15). At the end of the study, the cumulative rate of protection was 50.8% (P=0.005). At the clinical evaluation of 21 seroconverted dogs from both groups, canine leishmaniasis signs were significantly more frequent (90% versus 36%, P=0.017) and rapidly progressive in uncollared than in collared dogs. Reasons for such partial clinical protection in collared dogs may be found in the vector anti-feeding effect of protector bands, resulting in a lower number of infectious bites and, probably, in the reduction of antigenic stimuli necessary to shift toward a non-protective immune response.
Animals↗
Pathological changes in the bone marrow of dogs with leishmaniosis.
Bone marrow aspiration smears from 15 dogs naturally infected with leishmania were evaluated. Three of the dogs showed no clinical signs, six had up to three clinical signs and six had more than three. The most common pathological features of the bone marrow were megakaryocytic dysplasia in 10 of the dogs, erythrophagocytosis in eight, erythroid dysplasia in two and emperipolesis in two. The megakaryocytic and erythroid dysplasia were probably related to an increased number of marrow macrophages producing high levels of tumour necrosis factor alpha and interferon gamma. Six of the dogs with clinical signs showed bone marrow dysplastic features and erythrophagocytosis, suggesting that leishmaniosis could be the unique cause of both conditions.
Animals↗
Failure of a multi-subunit recombinant leishmanial vaccine (MML) to protect dogs from Leishmania infantum infection and to prevent disease progression in infected animals.
We report results of a Phase III trial of the multi-subunit recombinant Leishmania polyprotein MML for the protection of dogs against infection by Leishmania infantum. The antigen, also known as Leish-111f, is the first antileishmanial human vaccine entered Phase I clinical testing. The study was performed in a leishmaniasis endemic area of southern Italy. Three groups of 15 Leishmania-free beagle dogs each, received 3 monthly injections with vaccines A (MML+MPL-SE adjuvant), B (sterile saline = control) and C (MML+Adjuprime adjuvant), respectively, before transmission season 2002. The surviving dogs received a second three-dose vaccine course 1 year later. The dogs were naturally exposed to sandfly bites for 2.5 months in 2002, and for 5 months in 2003. Every 2 months post vaccination, dogs were examined by clinical and immunological evaluation, and by specific serology, microscopy, culture and PCR. A weak lymphoproliferative response to MML was seen in A and C groups throughout the study period. One year after the first vaccine course, the cumulative incidence of leishmanial infections was 40% in group A, 43% in group B and 36% in group C. Two-year post-vaccination (1 year after the second vaccine course) the cumulative incidence was 87% in group A (with three symptomatic cases), 100% in group B (with no symptomatic cases) and 100% in group C (with two symptomatic cases). The efficacy of the MML vaccine as an immunotherapeutic agent for the prevention of disease progression (subpatent infection-->asymptomatic patent infection-->symptomatic patent infection) was evaluated through follow-up of dogs found infected prior to the second vaccination. Among 15 infected animals, progression to a subsequent stage of infection was found in 5/6 dogs of group A, 3/6 of group B and 2/3 of group C. We conclude that vaccination with MML is not effective to prevent leishmaniasis infection and disease progression in dogs under field conditions.
Animals↗
Papular-like glossitis in a dog with leishmaniosis.
Explore the source record for details and available documents.
Animals↗
Entomological and parasitological study on phlebotomine sandflies in central and northern Albania.
An entomological survey was carried out in two districts of central (Kruje) and northern (Lezhe) Albania. Six collecting sites, showing a variety of diurnal resting sites, were monitored for adult sandflies from June through October 2002. Flies were collected with CDC miniature light traps, sticky traps and mechanical or hand aspirators in peridomestic sites, in bedrooms and inside cow barns, chicken coops and pigpens. All collecting sites monitored were found positive for sandflies. A total of 849 specimens were caught (29.2% males) belonging to five Phlebotomus species. Phlebotomus neglectus (75.6%) was the most abundant species followed by P. perfiliewi (14.4%), P. papatasi (4.6%), P. tobbi (3.6%) and P. similis (1.8%). The first adult of P. neglectus appeared on June 11 and the last one was collected on October 16. The highest density for this species was observed at the end of July. A total of 111 blood-fed females were caught from the two areas studied. P. neglectus was the only species found blood fed in Lezhe and the same species was prevalent (56.1%) in Kruje followed by P. perfiliewi (30.3%), P. tobbi (10.6%); P. papatasi was represented by only two specimens. Blood meal origin was determined in 45/66 (68.2%) of the females tested from Kruie district. P. neglectus was found fed on four hosts, showing the following feeding patterns: cow (71.4%), dog (117.1%), chicken (5.7%) and human (5.7%); P. perfiliewi was found fed on cow (80.0%) and chicken (20.0%), P. tobbi on cow (50.0%), chicken (25.0%) and dog (25.0%). One specimen of P. papatasi was found fed on cow. When such prevalences were analysed by the available biomass for each host present at the collecting site, P. neglectus resulted to be an opportunistic feeder rather than exhibiting preferences for any specific animal. PCR analysis of 39 P. neglectus from the Lezhe district gave negative results for the presence of Leishmania DNA.
Albania↗
Development of recombinant chimeric antigen expressing immunodominant B epitopes of Leishmania infantum for serodiagnosis of visceral leishmaniasis.
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.
Adult↗
[Nitric oxide and anti-protozoan chemotherapy].
Constitutive nitric oxide (NO) is generated by constitutively expressed types of NO-synthase enzymes (NOS-I and -III), being involved in physiological processes such as nervous transmission and vasodilatation. Inducible NO, synthesized by the NO-synthase isoform NOS-II, is an anti-pathogen and tumoricidal agent. However, inducible NO production requires a tight control because of cytotoxic and immune-modulation activity. NO produced by human and canine macrophages has long been demonstrated to be involved in the intracellular killing of Leishmania. Mechanisms of parasite survival and persistence in the host have been throughly investigated, and include suppression of NOS-II and the parasite entry into NOS-II negative cells. Both intracellular and extracellular morphotypes of Trypanosoma cruzi are killed by NO in vitro and in vivo, although a role of NO in the pathogenesis of heart disease has been reported. Killing of extracellular protozoa such as Trichomonas vaginalis and Naegleria fowleri by activated macrophages is also mediated by NO. The main control of Plasmodium spp infection in human and murine hepatocytes, and in human monocytes is achieved by NO-mediated mechanisms. Protection from severe malaria in African children has been found associated with polymorphisms of the NOS-II promoter; however, a pathogenic role of endogenous NO has been documented in cerebral malaria. Although several macromolecules are putative NO targets, recent experimental work has shown that NO-releasing compounds inhibit cysteine proteases (CP) of P. falciparum, T. cruzi and L. infantum in a dose-dependent manner. CPs are present in a wide range of parasitic protozoa and appear to be relevant in several aspects of the life cycle and of the parasite-host relationships. Comparative analysis of 3-D amino acid sequence models of CPs from a broad range of living organisms, from viruses to mammals, suggests that the Sy atom of the Cys catalytic residue undergoes NO-dependent chemical modification (S-nytrosilation and disulfide bridge formation), with the concomitant loss of enzyme activity. The NO-donor S-nitroso-N-acetilpenicillamine (SNAP) was shown to kill T. cruzi epimastigotes and L. infantum promastigotes in culture, while a combination of nitrite plus acid organic salts was highly effective against L. major amastigotes in mouse macrophages. A parasitostatic effect--with both encystation and excystation inhibition--of S-nitrosoglutathione and spermine-NONOate was documented in trophozoite cultures of Giardia duodenalis. Recently, a novel formulation of metronidazole bearing a NO-releasing group was found to enhance significantly the in vitro killing of Entamoeba histolytica trophozoites, compared to metronidazole. So far, only two clinical studies were performed on human patients, suffering from cutaneous leishmaniasis. In one study, 16 Ecuadorean patients were treated with a SNAP cream administered on lesions for 10 days. All lesions were parasitologically cured and clinically healed by day 30. In the second study, a different NO-producing cream (basically nitrite in acidic environment) was employed to treat 40 Syrian patients. Only 28% of them showed improvement and 12% were cured by day 60. In conclusion, despite the wide evidence that NO can be regarded as a natural anti-protozoal weapon, little efforts have been made to develop and test NO-based drugs in human medicine. This is mainly due to the difficulty in designing suitable chemical carriers able to release the right amount of NO, in the right place and in the right time, to avoid toxic effects against non-target host cells.
Animals↗
[Monitoring of canine leishmaniasis in northern Italy: an update from a scientific network].
Canine leishmaniasis (CanL) due to Leishmania infantum is a disease of great veterinary importance and a serious public health problem. In humans, L. infantum causes visceral (VL) and cutaneous leishmaniasis (CL) and the distribution of VL overlaps that of CanL. Currently, VL is considered by WHO as an emerging zoonosis in southern Europe. The dog is the only domestic reservoir of the infection and phlebotomine sandflies are the only proven vectors of leishmaniasis for dogs and humans. CanL is endemic in Italy, particularly in central and southern regions, including islands. Until 1983, all regions of northern Italy but Liguria and some territories of Emilia Romagna were considered free from CanL. From early '90s new stable foci of CanL have appeared, most of them located within classical endemic areas including territories of Emilia Romagna, Tuscany, Umbria, Marche, and Abruzzi regions. But the most relevant aspect, from an epidemiological point of view, has been the appearance of stable CanL foci in northern Italy, namely in Veneto and Piedmont regions. In these two foci, entomological surveys showed the presence of P. perniciosus and of a second phlebotomine vector, P. neglectus, which may have played a role in the CanL diffusion in some parts of northern Italy. Furthermore, in these areas, autochthonous human VL cases have occurred. There is therefore a realistic risk that CanL infection could rapidly spread through northern latitudes and a surveillance activity is strongly needed. For this reason, in October 2002, thanks to the collaboration and support of Intervet Italia, the network "LeishMap" was created, with the main purpose of monitoring the spread of CanL and vectors in northern Italy. LeishMap consists of scientific and sanitary institutions with proven experience both in field surveys and diagnostic methodologies on CanL and phlebotomine vector. It is organised in 4 Operational Units (OU), represented by researchers of the Veterinary Faculties of the University of Bologna, Padua, Milan and Turin, under the scientific coordination of the MIPI Department, ISS of Rome and with the collaboration of private and public veterinarians operating in the regions under study. During the first year of activity, each OU was involved in the serological and entomological surveillance of several territories in the respective regions, where recent autochthonous CanL cases were registered. The studies have involved five regions, namely Valle D'Aosta, Piedmont, Lombardia, Veneto, Trentino-Alto Adige and Emilia Romagna. In the Symposium 6 of this Congress we report detailed results of a retrospective analysis of data concerning CanL and vectors in northern Italy till 2002 and the preliminary results of 2003 on the seroprevalence rates observed in foci studied and on the entomological surveys carried out. In summary, the results outlined that already known foci of CanL are expanding from the original sites. Several new foci have been identified and many others are at high risk of evolving toward a stable endemicity. P. perniciosus has been found in all but one the suspected new foci. In Emilia Romagna region P. perfiliewi was identified in 2 areas and in one was the only species present. The occurrence of P. neglectus was confirmed in three regions, Veneto, Lombardia and Piedmont. In conclusion, from the 2002-2003 LeishMap activities it appears that further monitoring activities are necessary to identify new endemic foci of CanL, this representing the prerequisite for the implementation of programs for leishmaniasis control in northern Italy.
Animals↗
[Change in human visceral leishmaniasis treatment in Italy: retrospective study of 630 patients].
Since the 1940s meglumine antimoniate (MA) has been the only first-line drug for visceral leishmaniasis (VL) treatment in Italy. From 1991 through 1994, several patients of all ages, representing 1/3 of all immunocompetent VL patients reported during that period, were enrolled in clinical trials of liposomal amphotericin B (L-AmB), which led to a novel, safe, short course of VL treatment as an alternative to MA. In the same period, other lipid-associated AmB drugs were registered in Italy for the treatment of fungal infections, i.e., AmB colloidal dispersion (ABCD) and AmB lipid complex (ABLC). A retrospective analysis was performed on data collected at the Unit of Protozoology of Istituto Superiore di Sanità, Rome, to assess whether changes have occurred in first-line drug regimens adopted in Italy for routine VL treatment, during the 1995-2002 period. The sample consisted of immunocompetent individuals clinically suspected for VL, in whom the disease was confirmed by the examination of serum and bone marrow specimens sent to the Unit by hospitals from throughout the country. Relevant information on patients was then recorded, which included drug regimens used and post-therapy results. We recorded treatment information for 630 patients, representing a large proportion (55.5%) of 1,135 immunocompetent individuals with VL reported in Italy from 1995 through 2002. About half were children (306). Every year, patients were referred by 19 to 42 hospitals, with a range of 1 to 30 patients per hospital. MA was the first-line drug used in 159 patients (25.2%). However, the proportion of MA-treated patients has steadily decreased from 55.9% in 1995 to 1.0% in 2002. We recorded the failure of MA therapy in 16 patients (10.1%), who were successfully retreated with a L-AmB regimen. The rate of MA failures significantly increased in recent years, from 5.3% in 1995 to 36.4% in 2000 (p = 0.01). AmB drugs have been the only alternative drugs used in the remaining 471 patients (74.8%). L-AmB accounted for most regimens (441, 93.6%). The proportion of patients treated with any AmB-based drugs increased from 44.1% in 1995 to 99.0% in 2002. Drug treatment was unsuccessful in 15 patients (3.2%), who were successfully retreated with a high-dose L-AmB regimen. This rate was significantly lower than the MA failure rate (p = 0.001). Results have shown a countrywide change in therapy over the period considered. A traditionally effective, but moderately toxic drug (MA) has been almost fully replaced by a new compound (L-AmB) with negligible toxicity, in an epidemiologic context of disease reemergence. Furthermore, short courses of 6 to 7 days, as required for lipid-associated AmB, are highly cost-effective if compared with 21- to 28-day courses needed for standard MA treatment.
Adult↗
[Infantile visceral leishmaniasis in the Campania region, Italy: experience from a Paediatric Referral Centre].
In the first half of the 20th century, visceral leishmaniasis (VL) was a common infantile syndrome in coastal territories of the Campania region of Italy. After World War II, the incidence dropped to a few cases/year for three decades; in late 1980s the disease reemerged among both children and adults. To face the VL recrudescence, a Paediatric Reference Centre was established at the Santobono-Pausilipon hospital in Naples, for the clinical diagnosis, care and drug treatment of all infantile VL cases occurred in the Campania region. Rapid laboratory diagnosis was secured by a Diagnostic Reference Centre established at the Istituto Superiore di Sanità. Here, we report on the epidemiological and parasitological features of all cases referred to the Centre in the past 15 years. From 1990 to March 2004, a total of 255 cases were diagnosed and treated at the Centre. The Figure shows the yearly trend of patients (min. 3 cases in 1990 and 1991, max. 30 cases in 2000). There were 135 males (52.9%); the age ranged 4 months-14 years, but 189 patients (74.1%) were < or = 3 years old. The majority of the patients (189, 74.1%) were from the Naples province, with a cluster of 102 cases (40% of total patients) from the towns and districts surrounding Vesuvius. Twenty-seven cases (10.6%) were from the town of Maddaloni, Caserta province, whereas 15 cases (5.9%) were from coastal villages of the Salerno province. Only 1 and 2 cases were from Benevento and Avellino provinces, respectively. All patients but seven, who have been treated with antimonial drugs in the 1990-1993 period, were successfully treated with a liposomal amphotericin B regimen. From bone-marrow aspirate samples, 138 Leishmania cultures were obtained in EMTM and Sloppy Evans' media, of which 134 have been typed by the electrophoretic analysis of 13 isoenzymes. Two zymodemes (Z) of L. infantum were routinely identified over the study period, ZMON-1 (the commonest zymodeme in the Mediterranean area) and ZMON-72, variant from MON-1 in PGM mobility and detected only in our region. The latter, identified in 61 patients (45.5%), was found exclusively distributed in towns of the Vesuvius area and in Maddaloni until 1996, but in recent years it appears to have spread to other areas of the Naples (including the island of Ischia) and Caserta provinces, but not to Salerno province. In conclusion, the VL macrofocus of the Naples-Caserta area is probably responsible for the highest number of infantile cases among any VL macrofoci described in southern Europe. Considering the limited efforts paid to control the canine reservoir, rapid diagnosis and appropriate treatment of patients still remain the first-line control measures aimed at reducing the health impact of the disease.
Adolescent↗
Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice.
Little progress has been made in the treatment of African trypanosomiasis over the past decades. L-carnitine has a major role in glycolysis-based energy supply of blood trypanosomes for it stimulates constant ATP production. To investigate whether administration of the isomer D-carnitine could exert a competitive inhibition on the metabolic pathway of the L-form, possibly resulting in parasite replication inhibition, several formulations of this compound were tested on Trypanosoma lewisi and T. brucei rhodesiense in rodent models. High oral dosages of D-cornitine inner salt and proprionyl-D-carnitine were not toxic to animals and induced about 50% parasite growth inhibition in reversible, i.e. competitive, fashion. A putative mechanism could be an interference in pyruvate kinase activity and hence ATP production. Considering both, lack of toxicity and inhibitory activity, D-carnitine may have a role in the treatment of African trypanosomiasis, in association with available trypanocidal drugs.
Adenosine Triphosphate↗
Prokaryotic expression and antigenic characterization of three recombinant Leishmania antigens for serological diagnosis of canine leishmaniasis.
Three recombinant antigens of Leishmania chagasi (= L. infantum) were expressed in prokaryotic systems and evaluated (using a panel of dog sera characterized by parasitological and serological immunofluorescent antibody test [IFAT] techniques) as diagnostic markers of infection. The whole open reading frame encoding K9, the gene fragment encoding the repetitive sequence of K26, and the 3'-terminal gene fragment encoding a single 39-amino-acid subunit of the kinesin-related protein K39 (K39sub) were amplified from L. infantum DNA and cloned into a pGEX-2T expression vector in frame with glutathione S-transferase (GST). The sensitivity and specificity of enzyme-linked immunosorbent assays (ELISAs) using K26 as an antigen (evaluated with sera from 20 parasitologically positive and 20 parasitologically negative dogs) were both 100% (95% confidence interval [CI] = 83.2 to 100). When K9 and K39sub were used, sensitivity was 95% (95% CI = 75.1 to 99.9) and specificity was 100% (95% CI = 83.2 to 100). Using 182 field sera, a good agreement was found between the recombinant K26 ELISA and IFAT (K = 0.92; 95% CI = 0.86 to 0.98) results and between the K9 and K39sub ELISA (used in parallel) and IFAT (K = 0.87; 95% CI = 0.80 to 0.95) results. The results demonstrate that each antigen carries immunodominant epitopes and that their combination may further increase the sensitivity of currently available serological tests.
Animals↗
HIV and the transmission of Leishmania.
In many countries, Leishmania/HIV co-infection is now changing the epidemiology of visceral leishmaniasis. The levels of transmission of the parasites causing such leishmaniasis were previously dependent on the conventional zoonotic cycle, in which sandflies transmitted the parasites from infected canids to other canids or humans. The co-infection, however, has led not only to marked increases in the sandfly transmission of the parasites from immunodepressed individuals directly to other humans but also, probably, to artificial transmission between immunodepressed intravenous-drug users, as the result of needle sharing.
AIDS-Related Opportunistic Infections↗
Unusual presentation of leishmaniasis as an adrenal cystic mass.
An unusual presentation of leishmaniasis that occurred in an Italian immunocompetent woman is described. The patient had a long history of coagulopathy due to factor VIII deficiency and pain in the right lumbar region. Computed axial tomography demonstrated a cystic mass in the right adrenal gland. Histological examination of the surgically removed cyst showed the presence of histiocytes containing Leishmania amastigotes. Serodiagnosis for leishmaniasis performed through immunofluorescent antibody testing and the rK39 enzyme immunoassay was positive, whereas a bone marrow aspirate did not reveal any parasite. The patient was not treated for leishmaniasis and recovered well after surgery. Serological testing was still positive 2 years after surgery, but clinical follow-up did not reveal the signs typical of visceral leishmaniasis.
Adrenal Gland Diseases↗
Evaluation of the Leishmania recombinant K39 antigen as a diagnostic marker for canine leishmaniasis and validation of a standardized enzyme-linked immunosorbent assay.
Canine infections with Leishmania infantum are important as a cause of serious disease in the dog and as a reservoir for human visceral leishmaniasis (VL). Accurate diagnosis of canine infections is essential to the veterinary community and for VL surveillance programs. A standardized ELISA using a purified recombinant antigen (rK39) specific to VL was compared to the immunofluorescent antibody test (IFAT) as the standard. The ELISA was developed, optimized and evaluated using sera from 6368 dogs. The standardized ELISA and IFAT results were highly concordant. The timing and pattern of ELISA and IFAT seroconversion in dogs followed prospectively after natural infections were very similar. Antibodies reacting with rK39 were more common in asymptomatic canine infections than reported for subclinical human VL. The rK39 ELISA is a relatively simple and rapid assay for assessing the infection status of dogs, and is an alternative to IFAT, especially when screening large numbers of samples.
Animals↗
An update on antileishmanial vaccine candidates and prospects for a canine Leishmania vaccine.
Dogs are the domestic reservoir for Leishmania infantum, the parasite causing zoonotic visceral leishmaniasis (VL) in both the Old and New Worlds. Since the available methods for canine leishmaniasis treatment and control have limited efficacy, the development of a canine Leishmania vaccine is highly desirable. Mechanisms of antileishmanial immune responses in murine, human, and canine infections are briefly presented. Vaccine candidates, including live or killed parasites, Leishmania purified fractions, defined recombinant parasite antigens, live recombinant bacteria expressing Leishmania antigens and antigen-encoding DNA plasmids, are reviewed. Finally, some practical requirements for the evaluation of vaccine candidates in dogs are indicated.
Animals↗
NO donors inhibit Leishmania infantum cysteine proteinase activity.
Nitric oxide (NO) releasing drugs (e.g., glyceryl trinitrate) were successfully used in the treatment of cutaneous leishmaniasis in man. In the present study, the effect of NO donors on the catalytic activity of the cysteine proteinase from promastigotes of Leishmania infantum, an agent of Old World visceral and cutaneous leishmaniases, is reported. In particular, one equivalent of NO, released by the NO donors S-nitrosoglutathione, glyceryl trinitrate, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide, 3-morpholinosydnonimine, S-nitrosoacetylpenicillamine and sodium nitroprusside, inhibited one equivalent of the parasite cysteine proteinase. As expected, NO-deprived compounds did not affect the catalytic activity of the parasite cysteine proteinase. Furthermore, the absorption spectrum of the (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide-treated inactive L. infantum enzyme displayed a maximum in the 330-350 nm wavelength range. The reducing agents dithiothreitol and L-ascorbic acid completely prevented parasite cysteine proteinase inhibition by NO, fully restored the catalytic activity, and reversed the NO-induced absorption spectrum of the inactive enzyme. Moreover, S-nitrosoacetylpenicillamine displayed a leishmanicidal effect, inhibiting the cysteine proteinase activity in vivo. As expected, the NO-deprived compound N-acetylpenicillamine did not affect significantly the parasite viability and the enzyme activity in vivo. These data suggest that the L. infantum cysteine proteinase undergoes NO-mediated S-nitrosylation, thereby representing a possible mechanism of antiparasitic host defence.
Animals↗