Showing papers on "Visceral leishmaniasis published in 1996"
TL;DR: RK39 seroreactivity correlated with active disease and the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease is demonstrated.
Abstract: The diagnosis of visceral leishmaniasis (VL), a serious and often fatal parasitic disease caused by members of the Leishmania donovani complex, remains problematic. Current methods rely on clinical criteria, parasite identification in aspirate material, and serology. The latter methods use crude antigen preparations lacking in specificity. A previously described cloned antigen, rK39, of Leishmania specific for all members of the L. donovani complex (L. chagasi, L. donovani, L. infantum) was very useful in the serodiagnosis by ELISA of both human and canine VL. The present study demonstrated that rK39 seroreactivity correlated with active disease. The sera from early or self-healing infected subjects reacted with leishmanial lysate and were generally nonreactive with rK39. These data demonstrate the utility of rK39 in the serodiagnosis of VL and as an indicator of active disease.
304 citations
TL;DR: Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs, and a dog vaccine is highly desirable in Europe, where vector control is less likely to be successful.
Abstract: Mathematical models are used to compare the effectiveness of various untested, unused, and undeveloped methods for controlling canine and human zoonotic visceral leishmaniasis (ZVL), including insecticides, vaccines, killing serologically positive and sick dogs, and drugs. For given percentage changes in control parameters, insecticides are the most effective control method. Where transmission occurs peridomestically and vectors are accessible to treatment, as in parts of tropical America, insecticides are expected to reduce the incidence of human ZVL even more effectively than they reduce the prevalence of canine leishmaniasis, a result that should encourage properly designed vector control trials. The second best strategy is to reduce susceptibility to leishmaniasis by vaccinating people or dogs, or by eliminating childhood malnutrition where it is common. Both killing vectors and reducing susceptibility (by whatever means) are more effective than killing dogs or treating them with drugs. In Europe, where vector control is less likely to be successful and canine leishmaniasis is a major veterinary problem, a dog vaccine is highly desirable. Better drugs for dogs will help case management but, with regard to bringing down the incidence in the dog population, immunization is the ultimate goal.
278 citations
TL;DR: This continuing epidemic of visceral leishmaniasis in Western Upper Nile has shown that VL can cause high mortality in an outbreak with astonishingly high infection rates.
Abstract: The syndrome of fever wasting and enlarged spleen or lymph glands resulting from visceral leishmaniasis (VL) is usually fatal unless treated. While VL is endemic in parts of southern Sudan it was first reported in Western Upper Nile (WUN) during a confirmed epidemic in 1989 among a population of mainly Nuer and Dinka people who had no immunity. Civil war has been a major contributing factor to the continuation and spread of the epidemic and continues to impede the provision of treatment data collection and control measures. The first of three clinics to treat VL was established in WUN in 1989. Data have since been collected in seven retrospective surveys in villages and among patients. Survey death rates were used to estimate mortality from VL and excess mortality above expected levels. Mortality was high at all ages. The overall death rate is estimated at 38-57% since the epidemic started in 1984 and up to 70% in the most affected areas. Approximately 100000 deaths among approximately 280000 people in the epidemic area may be attributable to VL.
217 citations
TL;DR: Both PCR and immunoblot are sensitive enough to detect asyptomatic infection and could be valuable tools for studies monitoring the transmission of the disease and vaccination trials.
Abstract: A major limitation to the study of the epidemiology of canine visceral leishmaniasis is the inability to identify and count asymptomatic carriers because classic diagnositc tests are insufficiently sensitive. We investigated the capacity of the polymerase chain reaction (PCR) to detect the parasite and immunoblotting to detect specific antibodies in samples from dogs living in an endemic area without any symptoms of leishmaniasis. Results of classic serologic tests (immunofluorescence and enzyme-linked immunosorbent assay) were negative. Two independent PCR assays detected the parasite in skin and conjunctival samples from 80% of the dogs. We found specific antibodies by immunoblot in 66% and 56% of the dogs had both specific antibodies and parasite DNA. As controls, samples from dogs with clinical manifestations of the disease before and after treatment were assayed. The frequency of positive PCR samples decreased after treatment, and although antibody levels decreased with cure of the disease, they remained detectable by immunoblot. Results showed that most of the dogs living in an endemic area had been exposed to Leishmania. Both PCR and immunoblot are sensitive enough to detect asyptomatic infection and could be valuable tools for studies monitoring the transmission of the disease and vaccination trials.
190 citations
TL;DR: The dog is the most important domestic source for infection of the vector, however it is not a primary reservoir, and the opossum Didelphis albiventris was found naturally infected with Le.
Abstract: The laboratory and field observations summarized in this paper on visceral leishmaniasis ecology in the State of Bahia, Brazil are based on the author's observations over the past 35 years in a number of state's foci, public health records and literature citations. The disease is endemic with epidemic outbreaks occurring every ten years and its geographical distribution is expanding rapidly in the last years. Leishmania chagasi is the main ethiologic agent of the visceral leishmaniasis but Le. amazonensis s. lato was the only leishmania isolated by other authors from some visceral leishmaniasis human cases in the state. Lutzomyia longipalpis (with one or two spots on tergites III and IV and two sized different populations) was epidemiologically incriminated as the main vector. It was found naturally infected with promastigotes, and it was infected with four species of leishmanias in the laboratory. Although the experimental transmission of Le. amazonensis by the bite of Lu. longipalpis to hamsters was performed, the author was not successful in transmitting Le. chagasi in the same way. The dog is the most important domestic source for infection of the vector, however it is not a primary reservoir. The opossum Didelphis albiventris was found naturally infected with Le. chagasi but its role as reservoir is unknown. Foxes and rodents were not found infected with leishmanias in Bahia.
187 citations
TL;DR: The appearance of the South American arenaviruses illustrates how exploitation of new areas for human settlement and agriculture increases the likelihood that new infectious diseases will emerge.
Abstract: Because of a complex array of factors, an increasing number of new and reemerging infectious diseases are being recognized in both industrialized and developing countries in the Americas (1,2). The expanding population, living in overcrowded conditions with inadequate housing and sanitary facilities, has been exposed to new diseases and human pathogens. For example, the appearance of the South American arenaviruses (Junin, Machupo, and Guanarito) illustrates how exploitation of new areas for human settlement and agriculture increases the likelihood that new infectious diseases will emerge. Cholera, plague, AIDS, dengue hemorrhagic fever, and urban/periurban visceral leishmaniasis are examples of new and reemerging diseases in the region.
154 citations
TL;DR: Southern Sudan is experiencing an epidemic of the classic visceral leishmaniasis syndrome, which is manifested by fever, cachexia, hepatosplenomegaly, and pancytopenia, and it is typically fatal if not appropriately treated.
Abstract: Objectives: 1] To determine the proportions of patients with visceral leishmaniasis who had various treatment outcomes when cared for under wartime conditions and with limited resources and 2) to i...
131 citations
Journal Article•
TL;DR: An Ag of Leishmania capable of eliciting a mixed cellular response that is skewed toward a Th1 phenotype in susceptible BALB/c mice with advanced infections is identified.
Abstract: BALB/c mice are highly susceptible to infection with the protozoan parasite Leishmania major. This susceptibility has been attributed, in part, to the expansion of parasite-specific CD4+ Th2 cells that antagonize Th1 responses and promote humoral immunity. In the present study, we have utilized sera from L. major-infected BALB/c mice to screen an L. major amastigote cDNA expression library. One of the clones detected encodes a novel Ag designated as L. major stress-inducible 1 (LmSTI1). LmSTI1 contains six copies of the tetratricopeptide consensus motif and is highly related to a family of stress-inducible proteins that is conserved from yeast to humans. Sera from L. major-infected BALB/c mice have LmSTI1-specific Ab titers in excess of 1:200,000, comprised predominantly of IgG1, IgG2A, and IgG2B isotypes. Recombinant LmSTI1 protein elicited strong proliferative responses from draining lymph node cells of L. major-infected BALB/c mice at both early (10 days) and late (28 days) stages of infection and elicited production of high levels of IFN-gamma and low levels of IL-4. In contrast, soluble leishmanial lysate elicited high levels of IL-4 and low IFN-gamma production. Thus, we have identified an Ag of Leishmania capable of eliciting a mixed cellular response that is skewed toward a Th1 phenotype in susceptible BALB/c mice with advanced infections. In addition, analyses of sera from human patients with cutaneous, visceral, and post-kala azar visceral leishmaniasis indicated that a majority of individuals from all three clinical groups mounted strong humoral responses against LmSTI1.
111 citations
TL;DR: The seroprevalence of canine Leishmania antibodies was investigated using an enzyme-linked immunosorbent assay as a screening test since its sensitivity was significantly higher than that of an indirect immunofluorescence assay, which found no correlation with the intracluster densities of canine populations, or with the distances from individual clusters to the town center.
Abstract: Jequie, a community of about 144,500 inhabitants located in the State of Bahia, Brazil, is endemic for both visceral and cutaneous leishmaniases. In the present epidemiologic study, the urban and inhabited periurban areas of the town were divided into 140 clusters of 0.25 km2 each. The seroprevalence of canine Leishmania antibodies was investigated using an enzyme-linked immunosorbent assay as a screening test since its sensitivity was significantly higher than that of an indirect immunofluorescence assay. A total of 1,681 dogs was surveyed in 34 randomly sampled clusters. The overall prevalence of Leishmania antibodies in the dog population was 23.5%, with intracluster prevalences ranging from 0% to 67%. There was no correlation of these seroprevalences with the intracluster densities of canine populations, or with the distances from individual clusters to the town center. Moreover, the Leishmania transmission did not seem to follow any clear-cut spatial pattern, since large disparities in the seroprevalences of contiguous clusters were found. Curiously, human cases of visceral leishmaniasis have never been observed in some clusters with a relatively high prevalence of canine seroprevalences. Eight parasite isolates from seropositive dogs were found to belong to the same serodeme and zymodeme as Leishmania (L.) chagasi. The implications of these findings with respect to the epidemiology and control of American visceral leishmaniasis are discussed.
109 citations
TL;DR: Ten HIV infected patients with parasitologically confirmed VL with liposomal amphotericin B with L-AMB were treated with a dose of 4 mg/kg/day and only one patient remained alive 26 months after treatment.
99 citations
TL;DR: Since 1980, the development of leish maniasis in Algeria has been marked by a considerable increase in the number of cases of both visceral leishmaniasis and cutaneous leishManiasis (more than 2000 cases per year), with major foci in the north and south of the country.
Abstract: Since 1980, the development of leishmaniasis in Algeria has been marked by a considerable increase in the number of cases of both visceral leishmaniasis (1121 cases recorded) and cutaneous leishmaniasis (more than 2000 cases per year). New Leishmania infantum and L. major foci have appeared in the north and south of the country. During this period, 100 strains of Leishmania isolated from humans, other mammals and sandflies have been identified. The presence of L. major mon -25 in Psammomys obesus and Phlebotomus papatasi has identified these species as the main reservoir and vector, respectively, of zoonotic cutaneous leishmaniasis. Similarly, the presence of L. infantum mon -1 in Ph. perniciosus and dogs has implicated them as the vector and reservoir of visceral leishmaniasis. The isolation of the dermotropic zymodeme mon -24 of L. infantum from Ph. perfiliewi suggested that it was one of the main vectors of cutaneous leishmaniasis in the north of the country; the reservoir has not been identified. In addition, other zymodemes of Leishmania have been identified in visceral leishmaniasis patients, frequently associated with human immunodeficiency virus ( mon -24, mon -33, mon -34 and mon -78), in patients with cutaneous leishmaniasis ( mon -80), and in dogs with leishmaniasis ( mon -34 and mon -77).
TL;DR: Pentavalent antimony given once a month is effective in the prevention of VL relapses in HIV-infected individuals and is a low-cost treatment that proved to be well tolerated.
Journal Article•
TL;DR: Through immunostaining, it was established that sialoadhesin-positive stromal bone marrow macrophages contain parasites; such long-lived mononuclear phagocytes could be the host cells where the parasite can find "safe targets" unreactive to the dominant effector immune mechanism triggered by the replicative stage of the parasites.
Abstract: Human visceral leishmaniasis is mainly due to intracellular protozoan parasites of the Leishmania donovani complex, i.e., L. donovani and L. infantum (or L. chagasi). A mouse model has been established to monitor 1) the parasitic process initiated by L. infantum in three tissues they invade, and 2) parameters of the acquired immune response they trigger. Mice congenic at the Lsh locus and mice of inbred strains differing at the MHC locus have been inoculated by the i.v. route with L. infantum. The parasitic process has been evaluated by the follow-up of the parasitic load in the liver, the spleen, and, for the first time, in the bone marrow using a very sensitive limiting dilution assay. As previously established for L. donovani, the early outcome of L. infantum is also under the control of the Lsh locus in the liver; genes of the MHC complex are involved in the development of the subsequent acquired immune response. "Cure" or "noncure" haplotypes are the same for the two species of Leishmania; as far as the cure haplotype is concerned, whatever the tissues being screened, the parasites are never totally cleared, although the liver is the tissue in which the best parasite load reduction is achieved. Through immunostaining, it was established that sialoadhesin-positive stromal bone marrow macrophages contain parasites; such long-lived mononuclear phagocytes could be the host cells where the parasite can find "safe targets" unreactive to the dominant effector immune mechanism triggered by the replicative stage of the parasites.
TL;DR: These findings demonstrate an unexpected resistance of BALB/c mice to the infection with L. amazonensis isolated from patients with visceral leishmaniasis, due to differences in these parasites that may be related to the altered course of the disease in humans and in isogenic BALB /c mice.
Abstract: Leishmania amazonensis causes a wide spectrum of disease in humans. In this study, we evaluated BALB/c mice infected with five strains of L. amazonensis isolated from patients with either cutaneous, mucosal, or visceral leishmaniasis. Mice infected with cutaneous and mucosal isolates developed ulcerating footpad lesions with parasite-loaded macrophages and extensive tissue destruction. Skin metastases, early dissemination of parasites to the spleen, and high anti-Leishmania antibody levels were also noted. Mice infected with L. amazonensis strains isolated from patients with visceral disease had a controlled infection, with small footpad lesions with mononuclear cell infiltration, few infected macrophages, and granuloma formation. They had no skin metastases, delayed dissemination of the parasite to the spleen, lower levels of IgG and higher levels of IgG2a against L. amazonensis. These findings demonstrate an unexpected resistance of BALB/c mice to the infection with L. amazonensis isolated from patients with visceral leishmaniasis. This resistance seems to be due to differences in these parasites that may be related to the altered course of the disease in humans and in isogenic BALB/c mice.
TL;DR: Data indicate that following successful chemotherapy of visceral leishmaniasis, leishmania parasites are killed by macrophages activated by gamma interferon-producing lymphocytes via an NO-dependent mechanism.
Abstract: Following successful chemotherapy in canine visceral leishmaniasis, monocyte-derived macrophages can induce antileishmanial activity via a gamma interferon-dependent mechanism in the presence of autologous lymphocytes. The killing of leishmania correlated with the induction of the NO synthase pathway, because it correlated with the generation of nitrogen derivative production and was abrogated in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of the NO synthase pathway. The level of L-citrulline in serum, which was produced after activation of the NO synthase pathway, was markedly enhanced in dogs receiving successful chemotherapy. Taken together, these data indicate that following successful chemotherapy of visceral leishmaniasis, leishmania parasites are killed by macrophages activated by gamma interferon-producing lymphocytes via an NO-dependent mechanism.
Journal Article•
TL;DR: Visceral leishmaniasis is an important opportunistic infection in patients with acquired immunodeficiency syndrome and it must be ruled out in every patient with fever and/or pancytopenia and an appropriate travel history.
Abstract: . Background.-Visceral leishmaniasis is an important infection in patients infected with human immunodeficiency virus and living in areas endemic for Leishmania sp. Leishmaniasis, however, is rarely suspected in patients residing in nonendemic countries. Methods.-Retrospective case analysis of 15 patients with human immunodeficiency virus infection and leishmaniasis treated at seven German clinics. The clinicopathological features and the diagnostic role of biopsy and/or cytology as compared to serology were evaluated. Results.-All patients were severely immunocompromised. One patient was first diagnosed at autopsy. One patient with mucocutaneous disease was diagnosed by nasal biopsy. All others had amastigotes detected in bone marrow (13/13), liver (3/3), and gastrointestinal mucosa (4/4). Serology was positive in only 6 of 13. Conclusion.-Visceral leishmaniasis is an important opportunistic infection in patients with acquired immunodeficiency syndrome and it must be ruled out in every patient with fever and/or pancytopenia and an appropriate travel history. Because serological diagnosis is often insufficient, pathologists must be aware of the association between human immunodeficiency virus infection and leishmaniasis. Diagnosis depends on detection of the parasite in submitted specimens.
TL;DR: The complex epidemiology combined with the problems associated with drug treatment (prolonged treatment time and numerous side effects, in addition to drug resistance) make prophylaxis against ACL a serious health problem in countries affected by the disease.
TL;DR: There is a difference in the activation of CD18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.
Abstract: The objective of this study was to compare the histopathological changes and expression of CR3 and CR4 in the liver and spleen of dogs naturally and experimentally infected with L. chagasi. The basic histopathological lesions observed mainly in naturally infected dogs were: epithelioid hepatic granulomas, hyperplasia and hypertrophy of Kupffer cells, Malpigui follicles and mononucleated cells of the red pulp of the spleen. Sections from the liver and spleen by immunocytochemistry technique showed the presence of CD11b, c/CD 18 antigens in the control and infected animals and no qualitative or quantitative differences in the liver. Nevertheless, CD18 was always increased in the spleen of naturally and experimentally infected dogs. These results indicate that there is a difference in the activation of CD18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.
TL;DR: Administration of AmBisome at the well-tolerated doses of 5 or 50 mg/kg of body weight completely eradicated the parasites from the tissues and seemed to account for the remarkable efficacy of the liposomal formulation ofAmB in the treatment of visceral leishmaniasis due to L. infantum.
Abstract: The tolerance and efficacy of amphotericin B (AmB) deoxycholate (Fungizone) were compared with those of liposomal AmB (AmBisome) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Control groups consisted of untreated mice and mice treated with a pentavalent antimonial (Glucantime). BALB/c mice were infected intravenously on day 0 with 10(7) promastigotes of L. infantum and then treated from day 7 to 17 (early treatment group) or from day 60 to 70 (delayed treatment group). The pentavalent antimonial was administered daily by intraperitoneal injection, whereas AmB formulations were administered intravenously on alternate days. On days 20, 60, and 120 (early treatment group) and on days 72 and 125 (delayed treatment group), parasite burdens in the liver, spleen, and lungs were determined by subculturings using a microtitration method. A dose range study showed that administration of AmBisome at the well-tolerated doses of 5 or 50 mg/kg of body weight completely eradicated the parasites from the tissues. At 0.8 mg/kg, AmBisome proved more efficacious than AmB deoxycholate administered at the same dose. We also compared the levels of AmB deoxycholate and AmBisome in plasma and tissue. Mice treated with AmBisome had levels of AmB in tissue much higher than did AmB deoxycholate-treated mice with persistent detectable levels 14 weeks after treatment. These results seem to account for the remarkable efficacy of the liposomal formulation of AmB in the treatment of visceral leishmaniasis due to L. infantum.
01 Jan 1996
Journal Article•
TL;DR: The most affected breed was the Doberman, and the least affected was the Collie, while dogs from outlying areas of the Athens basin had higher infection rates than dogs from the city.
Abstract: A survey of 1,175 dogs with suspected visceral leishmaniasis (VL), was carried out to investigate canine leishmaniasis in the Athens basin, the largest metropolitan area of Greece. The dogs examined were not a random sample since animals were selected on the basis of symptoms indicating the disease. Dog sera were tested using the indirect fluorescent antibody technique (IFAT), with titres greater than or equal to 1/200 considered positive for VL. On this basis 569 dogs (48.4%) were found positive for VL and 69 (5.9%) borderline (with titres of 1/100). Additionally, 218 of these sera were also tested by enzyme-linked immunosorbent assay (ELISA). Of this sample, 120 were negative and 88 were positive with both IFAT and ELISA (according to the stated criteria), and thus the concordance of the two methods was 98.6%. Dogs positive for VL were classified according to age, sex, breed, and area of residence. Dogs from outlying areas of the Athens basin had higher infection rates than dogs from the city. The most affected breed was the Doberman, and the least affected was the Collie.
TL;DR: A 10-year-old boy suffering from kala-azar (visceral leishmaniasis) for two and a half years was finally cured with a course of amphotericin B, a drug known to cross the blood-brain barrier.
Abstract: A 10-year-old boy had been suffering from kala-azar (visceral leishmaniasis) for two and a half years. He failed to respond to all known anti-leishmanial treatment regimens. Even the drastic step of splenectomy failed to cure him. In November 1991, he presented with symptoms of meningitis. A diagnostic lumbar puncture revealed leishmanial amastigotes in his cerebrospinal fluid. The patient was finally cured with a course of amphotericin B, a drug known to cross the blood-brain barrier.
TL;DR: The first case of co-infection with herpes zoster and leishmania in the same lesion is reported, on the face of a 29-year-old female who was an intravenous drug user and who was HIV positive, and who died due to severe internal complications, not attributed to visceral leishmaniasis.
Abstract: We report the first case of co-infection with herpes zoster and leishmania in the same lesion, on the face of a 29-year-old female, who was an intravenous drug user and who was HIV positive. The infection was initially resistant to acyclovir and itraconazole, and the patient died due to severe internal complications, not attributed to visceral leishmaniasis. The prevalence of leishmania infection in the Mediterranean countries is increasing among the HIV-positive population because of the existence of human carriers. Paradoxically, most of these patients show mild forms of visceral leishmaniasis.
TL;DR: The results suggest that L. infantum Hsp83 and particular protein subfragments may be useful in serodiagnostic assays for canine leishmaniasis.
TL;DR: Chemically defined peptide-protein conjugates improve the reproducibility and reliability of ELISA for the serodiagnosis of L. donovani infection.
Abstract: Synthetic peptides, derived from the amino acid sequence of a Leishmania donovani clone, were used to develop an enzyme-linked immunosorbent assay (ELISA) for detecting antibodies against L. donovani. For this purpose, five peptides were conjugated to a protein carrier, human serum albumin (HSA), by using a heterobifunctional reagent, epsilon-maleimidocaproic acid N-hydroxysuccinimide ester, to obtain a well-defined product. The sensitivity and the specificity of the peptide-specific ELISA were determined with a panel of 106 serum samples from individuals living in areas where visceral leishmaniasis is endemic; sera from post-kala azar dermal leishmaniasis-infected patients and from individuals suffering from other infectious diseases were also included. ELISAs were performed with either a single peptide-HSA conjugate or a mixture of two peptide-HSA conjugates. Ninety-seven percent of the serum samples from patients with visceral leishmaniasis had detectable antibodies to one or more of the single synthetic peptides. ELISA with a single peptide-HSA conjugate proved to be less sensitive (less than 71%) but more specific (up to 93%) than ELISA with crude promastigote antigens (80% sensitivity and 79% specificity); when a combination of two different peptide-HSA conjugates was used, the test increased both in sensitivity and in specificity. Chemically defined peptide-protein conjugates improve the reproducibility and reliability of ELISA for the serodiagnosis of L. donovani infection.
TL;DR: The Fucose-Mannose Ligand of Leishmania donovani is a complex glycoproteic fraction and its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil.
Abstract: The Fucose-Mannose Ligand (FML) of Leishmania donovani is a complex glycoproteic fraction. Its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil. The FML-ELISA test, showed 100% sensitivity and 96% specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. More than 20% apparently healthy subjects with positive reaction to FML developed overt kala-azar during the following 10 months. In the screening of human blood donnors, a prevalence of 5% of sororeactive subjects was detected, attaining 17% in a single day. The GP36 glycoprotein of FHL is specifically reconized by human kala-azar sera. The immunoprotective effect of FML on experimental L. donovani infection was tested in swiss albino mice. The protection scheemes included three weekly doses of FML, supplemented or not with saponin by the subcutaneous or intraperitoneal routes and challenge with 2 x 10(7) amastigotes of Leishmania donovani. An enhancement of 80.0% in antibody response (p < 0.001) and reduction of 85.5% parasite liver burden (p < 0.001) was detected in animals immunized with FML saponin, unrespectively of the immunization route.
TL;DR: The results of the prevalence of anti‐histone H3 antibodies in canine VL sera together with the sequence‐specific characteristics of the amino‐terminal region of L. infantum hist one H3 indicate that the recombinant protein rLiH3‐Nt may be of use for diagnosis of canine V L.
Abstract: In the present study we show that sera from dogs naturally infected with the protozoan parasite Leishmania infantum contain antibodies that specifically react with the parasite histone H3. Using synthetic peptides covering the complete sequence of the protein we located the linear antigenic determinants within the 40 amino-terminal amino acids of the molecule. In addition to the complete form of the protein (rLiH3), two regions of the Leishmania histone H3 were expressed as recombinant proteins: the rLiH3-Nt fragment containing the 39 amino-terminal amino acids and the rLiH3-Ct fragment containing the 90 carboxyl-terminal residues. Competition experiments using the protein fragment rLiH3-Nt as competitor confirmed that the antigenic determinants of histone H3 are confined to the amino-terminal domain. This domain, which is believed to be exposed on the nucleosome surface, is also the most evolutionarily divergent region of the L. infantum histone H3. Visceral leishmaniasis (VL) sera do not react with mammalian histones, an indication that the anti-histone response elicited during Leishmania infection is triggered by the parasite histone. The results of the prevalence of anti-histone H3 antibodies in canine VL sera together with the sequence-specific characteristics of the amino-terminal region of L. infantum histone H3 indicate that the recombinant protein rLiH3-Nt may be of use for diagnosis of canine VL.
TL;DR: The results show that while the modified recombinant proteins r LiP2a-Q and rLiP2b-Q, in which the five carboxyl-terminal amino acids had been deleted, maintain the leishmaniasis-specific epitopes, they do not react with sera from patients with autoimmune disease and Chagas' disease.
Abstract: The Leishmania P2 proteins have been analyzed as potential tools for the immunodiagnosis of human mucocutaneous and visceral leishmaniasis. Two recombinant Leishmania infantum proteins, rLiP2a and rLiP2b, were used. The analysis indicated that the rLiP2a and rLiP2b proteins are recognized by 76% (16 of 21) and 42% (9 of 21), respectively, of sera from patients with mucocutaneous leishmaniasis and by 50% (5 of 10) and 40% (4 of 10), respectively, of sera from patients with visceral leishmaniasis. The Leishmania P2 proteins were engineered to have deletions of particular amino acids from the carboxyl-terminal region in ordertoavoidcross-reactivitywithserafrompatientswithsystemiclupuserythematosusandChagas’disease, since it is known that this region is the main target of the autoantibodies present in sera from these patients. The results show that while the modified recombinant proteins rLiP2a-Q and rLiP2b-Q, in which the five carboxyl-terminalaminoacidshadbeendeleted,maintaintheleishmaniasis-specificepitopes,theydonotreact with sera from patients with autoimmune disease and Chagas’ disease. For this reason, and also because the sera from patients with tuberculosis and leprosy, diseases that have to be considered in a differential clinical diagnosis of infectious diseases, do not react with the rLiP2a-Q or rLiP2b-Q protein, we think that the engineered proteins may be considered specific tools for the immunodiagnosis of mucocutaneous and visceral leishmaniasis. Leishmaniasis, which has a worldwide distribution, is associated with a large number of clinical symptoms. The causative agents of leishmaniasis are the protozoan parasites of the genus Leishmania, which are transmitted to a variety of animal hosts by sandflies. Most forms of the disease are zoonotic. There are three main categories of human leishmaniasis: cutaneous leishmaniasis, mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL). The leishmanial diseases, except for cutaneous leishmaniasis, have a lengthy incubation period,aninsidiousonset,andachroniccourse.VL,causedby members of the Leishmania donovani complex, namely, L. donovani and Leishmania infantum in the Old World and Leishmania chagasiin the New World (2), is characterized by irregular fever, hepatosplenomegaly, anemia, and weight loss. The VL disease, with approximately 100,000 new cases annually (1), has a high mortality rate for untreated cases and is often complicated by recurrent infections. MCL is characterized by metastasis to the oronasal or pharyngeal mucosa after a few years of primary skin lesions. The degenerative mucocutaneous lesions, occurring mostly in patients in the Latin America area, are caused by infection with the Leishmania braziliensis complex and can be confounded with leprosy. For the differential diagnosis of VL, other diseases, among which malaria, trypanosomiasis, tuberculosis, and brucellosis are the main ones, have to be considered because the signs and symptomsareveryconfusingandoftensimilartothoseofVL.Thus, a specific method for the diagnosis of human leishmaniasis is
TL;DR: A careful dissection of immune responses in hepatic granuloma cells from susceptible or resistant mice infected with L. chagasi may lead to a better understanding of murine immune responses to these important pathogens.