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Showing papers on "Visceral leishmaniasis published in 1998"


Journal ArticleDOI
TL;DR: In this paper, a prospective study was conducted to assess the diagnostic usefulness of non-invasive testing for antibody to the leishmanial antigen K39 by means of antigen-impregnated nitrocellulose paper strips adapted for use under field conditions.

264 citations


Journal ArticleDOI
TL;DR: Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.

233 citations


Journal ArticleDOI
TL;DR: Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involvement in the tissue damage seen in tegumentary leishmaniasis.
Abstract: The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. In humans, production of IFN-gamma is associated with the control of infection in children infected by Leishmania chagasi. In visceral leishmaniasis, an impairment in IFN-gamma production and high IL-4 and IL-10 levels (Th2 cytokines) are observed in antigen-stimulated peripheral blood mononuclear cells (PBMC). Moreover, IL-12 restores IFN-gamma production and enhances the cytotoxic response. IL-10 is the cytokine involved in down-regulation of IFN-gamma production, since anti-IL-10 monoclonal antibody (mAb) restores in vitro IFN-gamma production and lymphoproliferative responses, and IL-10 abrogates the effect of IL-12. In cutaneous and mucosal leishmaniasis, high levels of IFN-gamma are found in L. amazonensis-stimulated PBMC. However, low or absent IFN-gamma levels were observed in antigen-stimulated PBMC from 50% of subjects with less than 60 days of disease (24 +/- 26 pg/ml). This response was restored by IL-12 (308 +/- 342 pg/ml) and anti-IL-10 mAb (380 +/- 245 pg/ml) (P < 0.05). Later during the disease, high levels of IFN-gamma and TNF-alpha are produced both in cutaneous and mucosal leishmaniasis. After treatment there is a decrease in TNF-alpha levels (366 +/- 224 pg/ml before treatment vs 142 +/- 107 pg/ml after treatment, P = 0.02). Although production of IFN-gamma and TNF-alpha might be involved in the control of parasite multiplication in the early phases of Leishmania infection, these cytokines might also be involved in the tissue damage seen in tegumentary leishmaniasis.

212 citations


Journal ArticleDOI
TL;DR: The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.
Abstract: To assess the effect of removing leishmania-infected dogs on the incidence of visceral leishmaniasis, a controlled intervention study was performed in northeast Brazil. The attempted elimination of seropositive dogs resulted in an initial significant decrease in the annual incidence of seroconversion among dogs from 36% to 6% over the first two years. In the following two years, the incidence increased to 11% and 14%, respectively. In a control area in which dogs were surveyed but seropositive dogs were not removed, the cumulative incidence did not vary significantly from year to year, ranging from 16% to 27%. In the intervention area, the prevalence of dog seropositivity decreased from 36% before the intervention to 10% and remained stable. These findings suggest that attempting to remove seropositive dogs is insufficient as a measure for eradicating visceral leishmaniasis in dogs. However, the force of transmission of infection among dogs can be reduced by such programs. Also, when the number of human cases before and after the start of the intervention was calculated, a significant decrease in incidence of disease in the intervention area was observed among children less than 15 years of age (P < 0.01). The results of this intervention study suggest that the elimination of the majority of seropositive dogs may affect the cumulative incidence of seroconversion in dogs temporarily and may also diminish the incidence of human cases of visceral leishmaniasis.

208 citations


Journal ArticleDOI
TL;DR: Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3β-ol and not ergosterols as in the AmB-sensitive strain.
Abstract: Amphotericin B (AmB)-resistant Leishmania donovani promastigotes were selected by increasing drug pressure, and their biological features were compared with those of the wild-type parent strain. The 50% inhibitory concentration for resistant cells was 20 times higher than that for the wild-type. Resistance was stable after more than 40 passages in drug-free medium, and resistant promastigotes were infective to macrophages in vitro but lost their virulence in vivo. They had 2.5 times longer generation time, decreased AmB uptake, and increased AmB efflux in comparison to the wild type. Fluorescence measurement with a specific plasma membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3b-ol and not ergosterol as in the AmB-sensitive strain. Leishmania donovani, a protozoan parasite, is the causative agent of visceral leishmaniasis, a disease which is fatal in the absence of treatment. Its incidence is about 0.5 million cases annually (28). Pentavalent antimonials (Pentostam and Glucantime) are the first-line drugs, but refractory strains to these drugs are increasingly prevalent in areas of endemicity (26, 33). Amphotericin B (AmB) is a polyene antibiotic which binds preferentially to ergosterol, the major sterol of fungi, Leishmania, and Trypanosoma cruzi. This antibiotic is a second-line treatment for leishmaniasis (1), but side effects limit its use. Recently, AmB-lipid formulations (AmBisome and Amphocil) have been developed with reduced toxicity and an improved therapeutic index. They represent an alternative for the treatment of visceral leishmaniasis (6, 23, 31). As AmB formulations are increasingly being used for the treatment of visceral leishmaniasis and probably mucocutaneous leishmaniasis, we decided to investigate the development and mechanism of resistance. Resistance to AmB is uncommon in fungi but has been reported previously (16). The aim of our work was to establish a line of AmB-resistant L. donovani promastigotes in vitro and to study the molecular basis of this resistance.

194 citations


Journal ArticleDOI
TL;DR: The purpose of this study was to define the vector of AVL in the region and to highlight the areas considered to be hyperendemic, as well as the urbanization of the disease.
Abstract: Leishmania chagasi (Cunha & Chagas), the aetiologic agent of American visceral leishmaniasis (AVL), is transmitted by Lutzomyi longipalpis(Lutz & Neiva) throughout the Americas, from Northern Argentina to Southern Mexico (Arias et al. 1996b). In at least one previously reported case, another species of sand fly,Lu. evansi(Nuñez-Tovar), has been reported to be a suspected vector, in a specific focus of the disease, in San Andrés de Sotavento, Department of Cordoba, Colombia (Travi et al., 1990) Classically, in Brazil, AVL has been a major problem in the states in the north-east of the country, specifically in Ceara ́ and Bahia (Deane & Deane, 1962), manifesting itself in a pattern suggestive of a 10-year cycle (I. A. Sherlock, personal communication, Akhavan, 1996). During the past few years, many countries have witnessed the re-emergence of AVL, as well as the urbanization of the disease (Ariaset al. 1996a). What we have witnessed in Corumbáand Lada ́rio, Mato Grosso do Sul State, Brazil is an example of what is occurring in many cities. Here, canines infected withLe. chagasiwere first reported in 1983 after a serological survey was carried out (Rego et al., 1983), even though human cases of AVL had been reported as early as 1980 in Corumba ́’s hospitals and health centres. As can be seen in Table 1, in a city with a population of c. 96 000 the first human cases were reported in 1993 and since then, there has been an increase in the number of cases. Even though this area is considered to be hyperendemic (Anon, 1994), previous entomological studies (Galati et al., 1985, 1989) did not reveal the presence of Lu. longipalpis. Control interventions were initiated in midto late-1995. However, they were not sustained, and the coverage was only μ 45%. The purpose of this study was to define the vector of AVL in the region.

192 citations


Journal ArticleDOI
18 Apr 1998-BMJ
TL;DR: A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar and no significant clinical or laboratory toxicity occurred in any treatment group.
Abstract: Objectives: To assess the efficacy and tolerability of aminosidine compared with sodium stibogluconate for treating visceral leishmaniasis. Design: Randomised, unblinded, controlled trial with 180 day follow up. Setting: Kala-Azar Research Centre, Brahmpura, Muzaffarpur, Bihar, India. Subjects: People of either sex aged 6-50 years with symptoms and signs suggestive of visceral leishmaniasis (fever, loss of appetite, enlarged spleen) with leishmania amastigotes detected in Giemsa stained aspirates of spleen or bone marrow. Interventions: Aminosidine at three daily doses (12, 16, and 20 mg/kg) for 21 days and sodium stibogluconate 20 mg/kg/day for 30 days. Main outcome measures: Laboratory measures of efficacy: parasite count, haemoglobin concentration, white cell count, platelet count, serum albumin concentration. Clinical measures of efficacy: spleen size, fever, body weight, and liver size. Measures of safety: liver and renal function tests, reports of adverse events. Results: Of the 120 patients enrolled (30 per treatment arm), 119 completed treatment and follow up. Cure at end of follow up was achieved in 23 (77%), 28 (93%), and 29 (97%) patients treated with 12, 16, and 20 mg aminosidine/kg/day respectively, and in 19 (63%) patients given sodium stibogluconate. At 16 and 20 mg/kg/day, aminosidine was significantly more active than sodium stibogluconate in both clinical and laboratory measures of efficacy. No significant clinical or laboratory toxicity occurred in any treatment group. Conclusions: A 21 day course of aminosidine 16 or 20 mg/kg/day should be considered as first line treatment for visceral leishmaniasis in Bihar. Key messages Bihar in north east India accounts for about half the annual worldwide cases of visceral leishmaniasis, and resistance to standard treatment with sodium stibogluconate has been increasing We compared the safety and efficacy of three doses of aminosidine with standard regimen of sodium stibogluconate for treating visceral leishmaniasis in Bihar Aminosidine given at 16 or 20 mg/kg/day for 21 days was significantly more effective in producing final cure than sodium stibogluconate 20 mg/kg/day for 30 days Aminosidine had a low incidence of adverse reactions, including ototoxicity and renal toxicity, and was well tolerated Intramuscular injection of aminosidine 16 mg/kg/day for 21 days should be considered as a new first line treatment for visceral leishmaniasis in Bihar

169 citations


Journal Article
TL;DR: It is concluded that locally secreted TGF-beta inhibits Th1-associated cure of murine visceral leishmaniasis caused by L. chagasi, independently of Th2-type cytokines.
Abstract: IFN-gamma is critical for the cure of leishmaniasis in humans and mice. BALB/c mice are genetically susceptible to infection with the visceralizing species of Leishmania, L. chagasi. We have evidence that a soluble factor(s) inhibits IFN-gamma production by cultured liver granuloma cells from BALB/c mice during L. chagasi infection. In contrast, liver granulomas from C3H.HeJ mice, which are genetically resistant to L. chagasi infection, produce abundant IFN-gamma. According to ELISAs and neutralization studies, there was not evidence that the Th2-type cytokines IL-10 or IL-4 contributed to IFN-gamma suppression. However, both Ab neutralization and immunohistochemistry showed that granuloma-derived TGF-beta was, at least in part, responsible for inhibiting IFN-gamma release by CD4+ cells in BALB/c liver granuloma cultures. Consistently, TGF-beta levels were high in liver granulomas from susceptible BALB/c mice but low in resistant C3H mice or in BALB/c mice that were immunized against L. chagasi disease. Administration of recombinant adenovirus expressing TGF-beta (AdV-TGFbeta) but not IL-10 (AdV-IL10) caused genetically resistant C3H mice to become significantly more susceptible to L. chagasi infection. In contrast, either AdV-TGFbeta or AdV-IL10 could abrogate the protective immune response achieved by immunization of BALB/c mice. We conclude that locally secreted TGF-beta inhibits Th1-associated cure of murine visceral leishmaniasis caused by L. chagasi, independently of Th2-type cytokines.

151 citations


Journal ArticleDOI
TL;DR: It is reported here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL‐10 is involved in the pathogenesis.
Abstract: Some patients develop post-kala-azar dermal leishmaniasis (PKDL) after they have been treated for the systemic infection kala-azar (visceral leishmaniasis). It has been an enigma why the parasites cause skin symptoms after the patients have been successfully treated for the systemic disease. We report here that PKDL development can be predicted before treatment of visceral leishmaniasis, and that IL-10 is involved in the pathogenesis. Before treatment of visceral leishmaniasis, Leishmania parasites were present in skin which appeared normal on all patients. However, IL-10 was detected in the keratinocytes and/or sweat glands of all patients who later developed PKDL (group 1) and not in any of the patients who did not develop PKDL (group 2). Furthermore, the levels of IL-10 in plasma as well as in peripheral blood mononuclear cell culture supernatants were higher in group 1 than in group 2.

135 citations


Journal ArticleDOI
TL;DR: The use of the rK39 ELISA as a sensitive tool makes it possible to demonstrate coendemicity of canine and human VL, as expected in the case of IVL, and points to the possible presence of additional VL types in western Turkey and cutanovisceral type in the southeast part of this country.
Abstract: Infantile Mediterranean visceral leishmaniasis (IVL) and anthroponotic cutaneous leishmaniasis (ACL) have long been known to exist in the western and southeastern Turkey, respectively. To further study these and other related diseases, a recombinant antigen (rK39) specific to VL was used in an ELISA for serodiagnosis of selected patients and for screening dog reservoir populations in several endemic sites. Among 24 confirmed VL cases from western Turkey, the rK39 ELISA proved to be more sensitive than a combination of cultivation and microscopy of bone marrow aspirates. The specificity of rK39 for leishmaniasis was demonstrated by its lack of cross-reactivity with sera from other human diseases in the same sites. Interestingly, six of the 83 parasitologically proven ACL cases from southeast Turkey were also rK39 positive. The end point titers of the positive VL and CL cases vary from 10(-2) to 10(-5) and from 10(-2) to 10(-3), respectively. The rK39 ELISA was also used to screen 494 apparently healthy dogs from Urfa in southeast Turkey, Manisa/Alasehir near the Aegean Sea, and Karabuk near the Black Sea. Eighteen rK39-positive cases (3.6%), all from the latter two areas, were found to have varying endpoint titers (10(-2)-10(-4)). The high titers predicted increased severity and frequency of the clinical symptoms (i.e., lymphadenopathy, depilation, skin lesion, weight loss and/or death), which were manifested subsequently in 16 of these 18 cases. In addition, more positive canine cases were diagnosed by the rK39 ELISA preclinically than the procedures to detect parasites postsymptomatically in the lymph node aspirates. The use of the rK39 ELISA as a sensitive tool makes it possible to demonstrate coendemicity of canine and human VL, as expected in the case of IVL. The results also point to the possible presence of additional VL types in western Turkey and cutanovisceral type in the southeast part of this country.

105 citations


Journal ArticleDOI
TL;DR: It is demonstrated that antibodies to rK 39 were also detectable in HIV-seropositive patients coinfected with Leishmania infantum and the rK39 ELISA was more sensitive than an IFA for detecting L. infantum infections in patients with AIDS.
Abstract: Serologic assays using crude antigens for the diagnosis of visceral leishmaniasis in human immunodeficiency virus type 1 (HIV)-seropositive patients have been shown to lack sensitivity and specificity, particularly in AIDS patients. Antibodies to a cloned antigen, recombinant (r) K39, of Leishmania chagasi are specific for members of the Leishmania donovani complex and have been shown to indicate active disease in immunocompetent persons. This study demonstrated that antibodies to rK39 were also detectable in HIV-seropositive patients coinfected with Leishmania infantum. Furthermore, the rK39 ELISA was more sensitive than an IFA for detecting L. infantum infections in patients with AIDS. In addition, antibody titers to rK39 in HIV-negative patients infected with L. infantum or L. chagasi declined during treatment with meglumine antimoniate or liposomal amphotericin B. In contrast, most patients who clinically relapsed showed increased antibody titers to rK39. These data demonstrate the diagnostic and prognostic utility of rK39 in detecting active visceral leishmaniasis.

Journal ArticleDOI
TL;DR: The discovery of VL close to major urban centers is an important public health issue and the presence of seropositive wild canids, jackals and red foxes in central Israel, and the reappearance of the jackal population after near extinction suggests thatWild canids may play a role in spreading this disease.
Abstract: In 1994-1995, a child and five dogs from villages located between Jerusalem and Tel-Aviv, Israel were diagnosed with visceral leishmaniasis (VL). Based on these findings, the distribution of VL in domestic and wild canids in central Israel was examined. In the two villages where canine index cases were identified, a substantial proportion (11.5%, 14 of 122) of the dogs examined were seropositive. However, the rate of infection in five neighboring villages was only 1% (1 of 99). Parasites were cultured from 92% (12 of 13) of the seropositive dogs biopsied and the strains were characterized as Leishmania infantum by a clamped polymorphic-polymerase chain reaction, monoclonal antibodies, and/or excreted factor serology. The discovery of VL close to major urban centers is an important public health issue. The disease appears to have emerged recently in this area, and it is unclear whether the parasite was re-introduced or was continuously present at low levels in this region. The presence of seropositive wild canids, jackals (7.6%, 4 of 53) and red foxes (5%, 1 of 20), in central Israel, and the reappearance of the jackal population after near extinction suggests that wild canids may play a role in spreading this disease.

Journal ArticleDOI
TL;DR: Recent data provide increasing evidence that L infantum is an important agent of cutaneous leishmaniasis, and this species is the only agent that has long been identified from autochthonous CL in southwestern Europe.
Abstract: Background Leishmania infantum recently has been identified as a possible agent of cutaneous leishmaniasis (CL). This species has been isolated from cutaneous lesions of patients from the Mediterranean Basin. However, little is known about the clinical, biological, or therapeutic features of this newly recognized CL. Observations Six patients aged 9 months to 85 years in southeastern France were found to have autochthonous leishmaniasis. Parasitological identification showed that the agent was L infantum, zymodemes Montpellier-1 for 2 patients and Montpellier-24 for 1 patient. Five patients who underwent testing with a Western blot assay were found to have antibodies against 4 antigens with molecular masses of 18, 21, 23, and 31 kd. Five patients were successfully treated with local injections of N -methylglucamine, and 1 patient was successfully treated with topical paromomycin sulfate. No patient had visceral disease at diagnosis or after follow-up. Conclusions Recent data provide increasing evidence that L infantum is an important agent of CL. In southwestern Europe, this species is the only agent that has long been identified from autochthonous CL. Leishmania infantum should be considered an agent of CL in areas in which visceral leishmaniasis is endemic. Western blot assay could be a useful test for the diagnosis, but precise parasitological identification is important to having a better knowledge of the disease. The relationships between CL and the visceral disease have to be explored.

Journal ArticleDOI
TL;DR: A serological evaluation of this multiple-epitope protein by Falcon assay screening test-ELISA revealed a sensitivity of 79 to 93% and a specificity of 96 to 100% in diagnosis of canine visceral leishmaniasis, indicating that this protein represents a valuable tool for serodiagnosis.
Abstract: In this work, we describe the assembly of a synthetic gene coding for several antigenic determinants found in different Leishmania infantum antigens. Selected epitopes were derived from the ribosomal proteins LiP2a, LiP2b, and LiP0 and from the histone H2A. The resulting gene was overexpressed in Escherichia coli either as a fusion protein (with the vector pMAL-c2) or alone (with the vector pQE). In both cases, high-level bacterial production of the recombinant protein was achieved and the products were found to be stable. Enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments confirmed that the corresponding epitopes are present in the engineered protein. Finally, a serological evaluation of this multiple-epitope protein by Falcon assay screening test-ELISA revealed a sensitivity of 79 to 93% and a specificity of 96 to 100% in diagnosis of canine visceral leishmaniasis, indicating that this protein represents a valuable tool for serodiagnosis.

Journal ArticleDOI
TL;DR: In endemic areas, visceral leishmaniasis may complicate the clinical course of organ transplantation and can have fatal consequences, particularly when untreated.
Abstract: Background. In endemic areas, visceral leishmaniasis has been identified as an opportunistic infection in patients with derangements in their cellular immune system. Methods. We report a renal transplant patient with visceral leishmaniasis. We also reviewed the previously published cases of 17 organ transplant recipients with this parasitic disease. Results. Visceral leishmaniasis occurred a median time of 8 months after transplantation, and the clinical picture was characterized by fever, splenomegaly, and blood cytopenias. Leishmaniae were detected in bone marrow in 16 of 18 patients and diagnostic serology results were found in 8 of 10 tested patients. Pentavalent antimonials were used to treat 16 patients, five of which developed pancreatitis. Five of 18 patients died, including two untreated patients. Relapses of visceral leishmaniasis occurred in 4 of 13 survivors. Conclusions. In endemic areas, visceral leishmaniasis may complicate the clinical course of organ transplantation and can have fatal consequences, particularly when untreated.

Journal ArticleDOI
TL;DR: An HIV positive patient presenting a clinical picture of visceral leishmaniasis co-infection was submitted to a bone marrow aspiration and the parasite grew in culture as promastigotes and molecular analyses showed that the flagellates isolated did not belong to the genera Leishmania, Trypanosoma or Sauroleishmania.
Abstract: An HIV positive patient presenting a clinical picture of visceral leishmaniasis co-infection was submitted to a bone marrow aspiration after admission to hospital. Amastigotes forms were seen in the bone marrow aspirate and the parasite grew in culture as promastigotes. Molecular analyses showed that the flagellates isolated did not belong to the genera Leishmania, Trypanosoma or Sauroleishmania. It was not possible to establish infection in laboratory animals. In vitro culture of mouse peritoneal macrophages revealed the invasion of the host cells by the flagellates and their killing 48 hr after infection. Opportunistic infection with an insect trypanosomatid was suspected. Further hybridization analyses against a panel of different monoxenous and heteroxenous trypanosomatids showed kDNA cross-homology with Leptomonas pulexsimulantis a trypanosomatid found in the dog's flea.

Journal ArticleDOI
TL;DR: In coinfected patients with human immunodeficiency virus type-1 (HIV-1) infection, immunoblotting could be a useful tool for studying the natural course of leishmaniasis, although it has limited value for diagnosis or treatment control.
Abstract: To define the possible role of serology in the diagnosis and prognosis of visceral leishmaniasis (VL) in patients with human immunodeficiency virus type-1 (HIV-1) infection, the dynamics of humoral immune responses was investigated in 20 coinfected patients. Sequential sera obtained before, during, and after VL diagnosis were analyzed by an indirect immunofluorescent antibody test (IFAT), a recombinant ELISA (using the rK39 protein), and immunoblotting. During the active course of the disease, positive results were found by IFAT or ELISA in 22% of the cases and by immunoblotting in 78% of the cases. A great variability in the response was observed during the follow-up with a trend to more positive results near the time of VL diagnosis. Forty-six percent of the patients were positive by IFAT or ELISA on at least one time point before VL and 37.5% were positive during the period following treatment. These results confirm the limited usefulness of the IFAT and ELISA in the diagnosis of VL in coinfected patients and demonstrate their low ability to predict the development or the outcome of disease. In these patients, immunoblotting could be a useful tool for studying the natural course of leishmaniasis, although it has limited value for diagnosis or treatment control.


Journal ArticleDOI
TL;DR: V visceral leishmaniasis is a very prevalent disease among HIV-1-infected patients in southern Spain, with a high proportion of cases being subclinical, and there is also an association of this disease with male sex and intravenous drug use.
Abstract: The actual prevalence of visceral leishmaniasis among human immunodeficiency type 1 (HIV-1)-infected patients in the Mediterranean basin remains unknown. There is also controversy about the risk factors for Leishmania infantum and HIV-1 coinfection. To appraise the prevalence of visceral leishmaniasis in patients infected with HIV-1 in southern Spain and to identify factors associated with this disease, 291 HIV-1 carriers underwent a bone marrow aspiration, regardless of their symptoms. Giemsa-stained samples were searched for Leishmania amastigotes. Thirty-two (11%) patients showed visceral leishmaniasis. Thirteen (41%) patients had subclinical cases of infection. Centers for Disease Control and Prevention (CDC) clinical category C was the factor most strongly associated with this disease (adjusted odds ratio [OR], 1.88 [95% confidence interval, 1.22 to 2.88]), but patients with subclinical cases of infection were found in all CDC categories. Female sex was negatively associated with visceral leishmaniasis (adjusted OR, 0.42 [95% confidence interval, 0.18 to 0.97]). Intravenous drug users showed a higher prevalence than the remaining patients (13.3 versus 4.9%; P = 0.04), but such an association was not independent. These results show that visceral leishmaniasis is a very prevalent disease among HIV-1-infected patients in southern Spain, with a high proportion of cases being subclinical. Like other opportunistic infections, subclinical visceral leishmaniasis can be found at any stage of HIV-1 infection, but symptomatic cases of infection appear mainly when a deep immunosuppression is present. There is also an association of this disease with male sex and intravenous drug use.

Journal ArticleDOI
TL;DR: Orally administered HDPC—the safe doses and side effects of which are at least partially known—appears to be a promising candidate for the treatment of VL.
Abstract: In the immunocompetent host, visceral leishmaniasis (VL) is a fatal disease if untreated. In immunosuppressed patients, VL is an opportunistic infection for which there is no effective treatment for relapses. Here we report on the long-term activity of orally administered hexadecylphosphocholine (HDPC) against established Leishmania infantum infection in BALB/c mice. HDPC is a synthetic phospholipid with antiproliferative properties that has been extensively studied for its cancerostatic activity. Its short-term leishmanicidal effects in mice recently infected with viscerotropic Leishmania species have been previously reported. First, we show that 5 days of oral therapy with HDPC (20 mg/kg of body weight/day) led to amastigote suppression in the liver and the spleen of 94 and 78%, respectively (versus 85 and 55% suppression by meglumine antimonate in the liver and spleen, respectively), in mice infected 6 weeks before treatment and examined 3 days after the end of treatment. These results demonstrate the short-term efficacy of HDPC against an established Leishmania infection. Next, the long-term efficacy of HDPC was examined. In HDPC-treated mice both the hepatic and splenic amastigote loads were significantly reduced (at least 89%) 10, 31, and 52 days after the end of the treatment. In the treated mice, the increase of the splenic load was significantly slower than that in the untreated mice, demonstrating that the HDPC-exerted inhibition of Leishmania growth persisted for at least 7 to 8 weeks. Orally administered HDPC--the safe doses and side effects of which are at least partially known--appears to be a promising candidate for the treatment of VL.


Journal ArticleDOI
TL;DR: Results indicate that a specific IgE response is useful in the diagnosis of active disease and to evaluate response to treatment.
Abstract: Visceral leishmaniasis (VL) is characterized by a depression of the T helper cell type 1 immune response. Although mRNA expression for interleukin-4 (IL-4) is observed, evidence of the role of this cytokine in the pathogenesis of VL has been lacking. Since IL-4 is involved in IgE synthesis, we measured the total IgE and Leishmania antigen-specific IgE antibody levels in sera from patients with VL. Specific IgE antibodies detected by an ELISA technique after absorbing the sera with purified sheep IgG anti-human IgG were found in all 23 patients with VL and were not detected in subjects with subclinical Leishmania chagasi infection (n = 10), Chagas' disease (n = 10), atopic patients (n = 10), and healthy controls (n = 10). Levels of Leishmania-specific IgE (optical density values) before and after treatment were 0.100 +/- 0.03 (mean +/- SD) and 0.028 +/- 0.002, respectively (P < 0.05). These results indicate that a specific IgE response is useful in the diagnosis of active disease and to evaluate response to treatment.

Journal ArticleDOI
TL;DR: It is suggested that liposomal amphotericin B is effective therapy for visceral leishmaniasis in children and to evaluate a new scheme of therapy.
Abstract: Purpose. The purposes of this study were to describe the characteristics of pediatric visceral leishmaniasis in southern France and to evaluate a new scheme of therapy. Methods. Hospital records of 59 children with visceral leishmaniasis were retrospectively reviewed. The period of the study was from 1981 to 1997. Results. All children but one lived or had previously dwelled in the south of France. None was coinfected with human immunodeficiency virus or known to be immunocompromised. The mean age was 31 months; 10 children were younger than 1 year when admitted to the hospital. The male:female ratio was 0.73. Fever and splenomegaly were present in 90 and 100%, respectively. Anemia, leukopenia and thrombocytopenia were commonly observed, especially in the youngest patients. Hypergammaglobulinemia was noted in 64%. A biopsy sample of the bone marrow was always performed, but direct microscopic examination failed to identify Leishmania in 13 (22%) cases. In these patients specific serology and genomic amplification with polymerase chain reaction were useful tools for the diagnosis. All patients were initially treated with meglumine antimonate (Glucantime®). Twenty-six (44%) patients receiving the drug experienced at least one adverse event during treatment. Treatment failure occurred in six children (10%), who were subsequently cured with liposomal amphotericin B. Three additional children were treated with liposomal amphotericin B. All the children were finally cured and no death was observed. Conclusion. Our experience suggests that liposomal amphotericin B is effective therapy for visceral leishmaniasis in children.

Journal ArticleDOI
TL;DR: A nested PCR method based on amplification of the mini-exon gene, which is unique and tandomly repeated in the Leishmania genome, which represents a new tool for the diagnosis of kala-azar with patient blood samples instead of bone marrow or spleen aspirates obtained by more invasive procedures.
Abstract: To diagnose visceral leishmaniasis (kala-azar), we have developed a nested PCR method based on amplification of the mini-exon gene, which is unique and tandomly repeated in the Leishmania genome. Nested PCR was sufficiently sensitive for the detection of DNA in an amount equivalent to a single Leishmania parasite or less. We examined the usefulness of this PCR method using bone marrow aspirates and buffy coat cells collected from kala-azar patients who had or had not received chemotherapy in northwest China. We obtained PCR positivity for all of the parasitologically positive bone marrow samples from the patients. Some ambiguities with the primary PCR results were eliminated by the subsequent nested PCR. The buffy coat samples from 7 of 12 patients with splenomegaly were positive by the nested PCR, although only 2 of them were positive for parasites by culture. However, buffy coat samples from nine children, whose splenomegaly has been reduced and clinically cured by antimony treatment, were all negative. Thus, this nested PCR method represents a new tool for the diagnosis of kala-azar with patient blood samples instead of bone marrow or spleen aspirates obtained by more invasive procedures.

Journal ArticleDOI
TL;DR: The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.
Abstract: In this study, treatment efficacies of a nonionic surfactant vesicle formulation of sodium stibogluconate (SSG-NIV) and of several formulations of amphotericin B were compared in a murine model of visceral leishmaniasis. Treatment with multiple doses of AmBisome, Abelcet, and Amphocil (total dose, 12.5 mg of amphotericin B/kg of body weight) resulted in a significant suppression of parasite burdens in liver (P 98% suppression in all three sites). Free-SSG treatment failed to suppress spleen or bone marrow parasites. Infection status influenced treatment outcome. In the chronic-infection model, the AmBisome single-dose treatment was less effective in all three infection sites and the SSG-NIV single-dose treatment was less effective in the spleen. The results of this study suggest that the antileishmanial efficacy of SSG-NIV compares favorably with those of the novel amphotericin B formulations.

Journal ArticleDOI
TL;DR: Almost all (98%) of visceral leishmaniasis patients treated with sodium stibogluconate (Pentostam) in Sudan between 1989 and 1995 and follow-up responded well to treatment, however, the other 33 patients, all of whom were seronegative for HIV, showed partial or no response.
Abstract: Almost all (98%) of 1593 visceral leishmaniasis (VL) patients treated with sodium stibogluconate (Pentostam; Wellcome) in Sudan between 1989 and 1995 and follow-up responded well to treatment. However, the other 33 patients, all of whom were seronegative for HIV, showed partial or no response. The two main causes of unresponsiveness were primary drug resistance (39.3%) and low drug dosages given at peripheral dispensaries (30.3%). All of those who had been sub-optimal doses were cured when adequate doses of the drug were given. A third cause was concurrent disease, particularly pulmonary tuberculosis (18%). With treatment of the concurrent disease, patients responded well to Pentostam. Eight patients who failed to respond to repeated courses of Pentostam did not benefit from pentamidine or sterol inhibitors. Three of these patients responded to liposomal amphotericin B, two responded to splenectomy in association with Pentostam therapy, and three died. Pentostam, given in adequate doses, still appears to be the drug of choice for the treatment of VL in the Sudan Liposomal amphotericin B is a suitable second-line drug.

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01 Dec 1998-Parasite
TL;DR: The results suggest that after almost 30 years of epidemiological silence, American visceral leishmaniasis has re-emerged in this focus.
Abstract: The report of a new autochthonous case of human American Visceral Leishmaniasis (AVL) in 1992 in the village of Guayabita, Aragua State, Venezuela (10 degrees 16'N, 67 degrees 28'W; 500 m asl), led us to undertake an epidemiological study in this locality. A demographic survey was conducted using a structured questionnaire in which data was collected regarding sex, age, occupation, length of residence in the area and migratory history. A leishmanin skin test (LST) was applied and samples of venous blood for counter immunoelectrophoresis (CIEP) and immunofluorescent antibodies (IFAT) tests were drawn. The prevalence of positive LST was 11.4%. The positivity was highest among males and increased with age. Young males seemed to be more exposed to infection than females. Since occupation per se did not seem to account for this association, it may be explained as a gender-associated behavior, leading to different degrees of exposure to sand flies. The canine population was also screened for leishmanial infection. One dog was shown to be parasitologically infected with Leishmania sp. Four out of 71 dogs (5.6%) were positive for FG, CIEP, IFAT and Western Blot and 11 (15.5%) were positive for CIEP. These results suggest that after almost 30 years of epidemiological silence, American visceral leishmaniasis has re-emerged in this focus.

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TL;DR: Promastigote-conditioned media could be the source of cheap antigen for the immunodiagnosis of leishmaniasis.
Abstract: Leishmania donovani promastigotes were cultured in a protein-free medium for 3-5 days and the spent medium used to prepare antibody-detection ELISA plates. When the plates were used to test 29 Kenyan and 16 Nepalese patients with visceral leishmaniasis (VL; kala-azar), all the sera collected at diagnosis were found to have high levels of parasite-specific IgG. The levels of these antibodies dropped 6-12 months post-initiation of antileishmanial therapy in all but one of the patients. Although the levels in sera from 59% of the treated patients fell to those measured in sera from healthy controls, those in sera from 17% of the patients did not drop below those seen at diagnosis. The antigen used did not cross-react with sera from patients with parasitological diagnosis of malaria, filariasis, African trypanosomiasis or echinococcosis. Antibodies to antigens in the spent medium were detected, by western blot, in all the sera from Nepalese patients with VL. Promastigote-conditioned media could be the source of cheap antigen for the immunodiagnosis of leishmaniasis.

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TL;DR: Infection rates of Leishmania donovani in Phlebotomus orientalis from a focus of visceral leishmaniasis in eastern Sudan are studied.
Abstract: (1998). Infection rates of Leishmania donovani in Phlebotomus orientalis from a focus of visceral leishmaniasis in eastern Sudan. Annals of Tropical Medicine & Parasitology: Vol. 92, No. 2, pp. 229-232.

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TL;DR: The clinical features, diagnosis and treatment of 6 patients with post kala-azar ocular leishmaniasis are described and the causative parasite was characterized as Leishmania donovani in 2 of these 4 patients.
Abstract: The clinical features, diagnosis and treatment of 6 patients with post kala-azar ocular leishmaniasis are described. The eye lesions were associated with past or concomitant post kala-azar dermal leishmaniasis (PKDL). Four patients had post kala-azar leishmanial conjunctivitis and blepharitis. Using the polymerase chain reaction, the causative parasite was characterized as Leishmania donovani in 2 of these 4 patients. Two patients had post kala-azar anterior uveitis. The diagnosis of uveitis was based on the clinical manifestations, temporal relation to treated visceral leishmaniasis, the association with PKDL and positive anti-Leishmania serology. All patients were treated with systemic sodium stibogluconate. Patients with anterior uveitis were also treated with steroid and atropine eyedrops. The response to treatment was good. The importance of early diagnosis and treatment of ocular leishmaniasis is stressed.