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The visceral form of leishmaniasis (VL), due to infection by Leishmania infantum, is a neglected tropical disease. The accessible therapeutic options are limited. Artemisinin is an efficient antileishmanial product with poor biological availability that requires high repetition of therapeutic doses in VL. Solid lipid nanoparticles (SLNs) provide targeted delivery, increase bioavailability and reduce toxicity of the traditional therapeutic strategy. The spherical shape artemisinin-loaded SLNs were prepared in a particle diameter of 222.0 ± 14.0 nm. The SLNs showed no particular toxic effect on the parasites, whereas the native artemisinin demonstrated a significant toxicity rate of 31% in viability of the promastigotes at the 250 µg/ml concentration. The therapeutic efficacy of the artemisinin-loaded SLNs was demonstrated in the experimental VL, using the L. infantum-infected BALB/c mice, in the present study. The 10 and 20 mg/kg doses of artemisinin-loaded SLNs showed higher level of antileishmanial efficacy compared with the free artemisinin. There was a significant diminishing of the parasite burden in liver (84.7 ± 4.9%) and spleen (85.0 ± 3.1%) and hepatosplenomegaly by the artemisinin-loaded SLNs treated at 20 mg/kg compared to the free artemisinin. Therefore, the present study supports the superior efficacy of artemisinin-loaded SLNs over the free artemisinin and could be considered as a new therapeutic strategy in the treatment of leishmaniasis. [ABSTRACT FROM AUTHOR]

Leishmaniasis, an infectious disease, manifests itself mostly in two forms, cutaneous leishmaniasis (CL) and, a more severe and potentially deadly form, visceral leishmaniasis (VL). The current control strategy for leishmaniasis relies on chemotherapy drugs such as sodium antimony gluconate (SAG) and meglumine antimoniate (MA). However, all these chemotherapy compounds have poor efficacy, and they are associated with toxicity and other adverse effects, as well as drug resistance. While research in vaccine development for leishmaniasis is continuously progressing, no vaccine is currently available. However, some experimental vaccines such as LEISH-F1+MPL-SE (V) have demonstrated some efficacy when used as drugs for CL patients. In this paper we use a mathematical model to address the following question: To what extent vaccine shots can enhance the efficacy of standard chemotherapy treatment of leishmaniasis? Starting with standard MA treatment of leishmaniasis and combining it with three injections of V , we find, by Day 84, that efficacy increased from 29% to 65–91% depending on the amount of the vaccine. With two or just one injection of V , efficacy is still very high, but there is a definite resurgence of the disease by end-time. [ABSTRACT FROM AUTHOR]

Leishmania donovani causes the neglected tropical disease visceral leishmaniasis. There is currently no vaccine available to combat the disease. Therefore, chemotherapy is the only treatment option available. However, the available drugs have various adverse effects on the host. As a result, new drugs are needed to treat the disease; natural compounds can be used as an alternative to traditional drugs. This study examined apigenin, diosmin, and naringin as prospective inhibitors against the Leishmania donovani Sterol 24-C- methyltransferase enzyme (LdSMT). All three compounds have a high affinity for the LdSMT and remain stable for 100 ns during the molecular dynamics simulation. In the cell viability assays, these compounds showed excellent IC50 values, with apigenin having the best IC50 value of 16.11 µM against Leishmania donovani promastigote. The findings of this study showed that all three flavonoids could be used as a safe alternative to conventional anti-leishmanial drugs. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a neglected tropical disease that is defined by the World Health Organization as vaccine preventable. Although several new candidate vaccines are in development, no vaccine has successfully reached the market for human use. Several species of Leishmania cause human disease and have co-evolved with their respective sand fly vectors. These unique relationships have implications for initiation of infection and vaccine development. An approach to vaccine development for many infectious diseases is the use of controlled human infection models (CHIMs). We describe the history and recent development of experimental and deliberate infection using Leishmania in humans and the rationale for developing a new sand fly-initiated CHIM to progress leishmaniasis vaccine development. Examples from other infectious diseases are discussed in the context of the development of a new leishmaniasis CHIM. We also reflect upon the manufacture of the challenge agent, practical considerations, safety, ethics, and regulatory issues. A new cutaneous Leishmania CHIM is being developed to enable testing of vaccines in the development pipeline. Questions remain about the use of such CHIMs to determine effectiveness of vaccines against visceral leishmaniasis. However, such a CHIM will be invaluable in expediting time to market for vaccines. [ABSTRACT FROM AUTHOR]

Trypanothione synthetase (TryS) produces N1,N8-bis(glutathionyl)spermidine (or trypanothione) at the expense of ATP. Trypanothione is a metabolite unique and essential for survival and drug-resistance of trypanosomatid parasites. In this study, we report the mechanistic and biological characterisation of optimised N5-substituted paullone analogues with anti-TryS activity. Several of the new derivatives retained submicromolar IC50 against leishmanial TryS. The binding mode to TryS of the most potent paullones has been revealed by means of kinetic, biophysical and molecular modelling approaches. A subset of analogues showed an improved potency (EC50 0.5–10 µM) and selectivity (20–35) against the clinically relevant stage of Leishmania braziliensis (mucocutaneous leishmaniasis) and L. infantum (visceral leishmaniasis). For a selected derivative, the mode of action involved intracellular depletion of trypanothione. Our findings shed light on the molecular interaction of TryS with rationally designed inhibitors and disclose a new set of compounds with on-target activity against different Leishmania species. [ABSTRACT FROM AUTHOR]

Population-level proportions of individuals that fall at different points in the spectrum [of disease severity], from asymptomatic infection to severe disease, are often difficult to observe, but estimating these quantities can provide information about the nature and severity of the disease in a particular population. Logistic and multinomial regression techniques are often applied to infectious disease modeling of large populations and are suited to identifying variables associated with a particular disease or disease state. However, they are less appropriate for estimating infection state prevalence over time because they do not naturally accommodate known disease dynamics like duration of time an individual is infectious, heterogeneity in the risk of acquiring infection, and patterns of seasonality. We propose a Bayesian compartmental model to estimate latent infection state prevalence over time that easily incorporates known disease dynamics. We demonstrate how and why a stochastic compartmental model is a better approach for determining infection state proportions than multinomial regression is by using a novel method for estimating Bayes factors for models with high-dimensional parameter spaces. We provide an example using visceral leishmaniasis in Brazil and present an empirically-adjusted reproductive number for the infection. [ABSTRACT FROM AUTHOR]

Background:Natural Killer (NK) cell plays an important role in the innate immune system and is known to produce IFN-γ at an early stage of infection that is essential to eliminate intracellular infection likeLeishmaniaspp. It is already established thatLeishmaniaparasite inhibits the activity of NK cells, avoiding the encounter with the early innate immune response. This, in turn, favors establishment and further dissemination of the infection.Methods:In the present study, we have tried to measure the frequency of different phenotypic subsets of NK cells among visceral leishmaniasis (VL) patients.Results:We have phenotyped three distinct three distinct subsets (CD56–CD161+, CD56+CD161–, and CD56+CD161+) of NK (CD3–) cell using their specific markers CD161 and CD56.Conclusion:Interestingly, we observed selective loss of CD56+CD161+subset of circulating NK (CD3–) cells. Importantly, the other subsets (i.e., CD56−CD161+and CD56+CD161–) of circulating NK cells remain unaffected as compared with healthy subjects. [ABSTRACT FROM PUBLISHER]

Visceral leishmaniasis (VL) is World Health Organization designated most serious leishmaniasis with an annual mortality rate of 50,000. Even after country specific eradication programs, the disease continues to multiply with added complexities like resistance development, drug hypersensitivity and associated infections. Newer therapeutic interventions are urgently warranted to control the spread. Present study aims to arrive at terpenoid andrographolide engineered gold nanoparticle (AGAunps) facile synthesis and its efficacy evaluations against wild and drug resistant VL strains for the first time. Molecular bio-organic conjugation of AGAunp was confirmed in FT-IR and EDAX studies. Nano-gold plasmon response was recorded at 543 nm and the average size in TEM was 14 nm. SAED pattern and XRD observations proved fcc crystalline structure of nano-gold. AGAunp recorded spherical geometry in AFM and TEM. PDI value of 0.137 revealed the monodisperse nature of the nano-scale population. AGAunp exhibited strong antileishmanicidal effect both against wild type (IC50 19 ± 1.7 µM) and sodium stibogluconate (IC50 55 ± 7.3 µM)/paromomycin (IC50 41 ± 6 µM) resistant strains. Complete macrophage uptake AGAunp's occured within two hours exposure. AGAunp macrophage cytotoxicity was significantly lower as compared to Amphotericin-B. Low toxic Andrographolide engineered gold nanoparticle emerged as promising alternatives in the control of wild and drug resistant VL. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop novel nanoemuslion core loaded nanocapsules (NCs) with high payload of doxorubicin (DOX) and to assess its efficacy against Leishmania donovani. The low energy emulsification method was used to obtained nanoemulsion core as template, followed by stepwise addition of additional layer components protamine sulphate and sodium alginate. Zeta potential studies revealed that there was reversal in charge after each layering. NCs were characterized on the basis of size (340 nm) and entrapment efficiency (>80%). The drug release behaviour was studied by in vitro method. The NCs loaded with DOX (NCs-DOX) is completely internalized into macrophages showing improved efficacy (IC50 of formulation is almost ≤ 1.9-fold as compared to plain drug, p < 0.05) against intracellular amastigotes. [ABSTRACT FROM AUTHOR]

The potential of chitosan microparticles as a carrier of doxorubicin for the treatment of visceral leishmaniasis was evaluated by macrophage-mediated drug targeting approach. Cationic charge of doxorubicin was masked by complexing it with dextran sulphate (a poly anion) in order to facilitate its incorporation into cationic chitosan microparticles. Prior to in  vitro and in  vivo studies, characterization studies were carried out systematically: particle size (∼∼1.049 µµm), surface morphology (fluorescence microscopy -- spherical structured microparticles), Fourier transform infrared spectroscopy (to characterize effective cross-linking) and differential scanning calorimetry. In  vitro studies were carried out in J774.1 in order to check the effective endocytotic uptake of microparticles by macrophages. In  vivo studies were conducted in Syrian golden hamsters as per well-established protocols and the results drawn from in  vivo studies displayed substantial reduction in leishmanial parasite load for doxorubicin-encapsulated chitosan microparticles: ∼∼78.2 ±± 10.4%%, when compared to the control (free doxorubicin): 33.3 ±± 2.4%%. [ABSTRACT FROM AUTHOR]

An 8-month-old boy was diagnosed with visceral leishmaniasis in the Ukraine, a non-endemic area. His mother had been treated for visceral leishmaniasis at 28–32 weeks gestation whilst working in Alicante, Spain and delivered her infant at 38 weeks gestation by elective caesarean section in Ukraine. It is presumed that the infant's infection was as a result of vertical transmission. [ABSTRACT FROM AUTHOR]

The present study evaluates the potential of surface functionalized gelatin nanoparticles ( f-GNPs) for efficient macrophage-specific delivery of amphotericin B (AmB) in the treatment of visceral leishmaniasis (VL). Further, the effect of spacer for macrophage targeting was also evaluated. Gelatin was functionalized either through conjugation to mannose via direct coupling (mGelatin) or via PEG spacer (m-Gelatin), and the synthesis was confirmed by FTIR. AmB-loaded f-GNPs, that is, mGNPs and m-GNPs prepared from mGelatin and m-Gelatin conjugates, respectively, were characterized. In vitro concanavalin A (Con-A) agglutination assay confirmed the availability of mannose on the surface of these f-GNPs. Kinetics of cellular uptake of AmB-loaded f-GNPs by J774A.1 macrophage cells assessed through flow cytometry demonstrated a steady increase and maximum cell-associated fluorescence was observed at 4h for m-GNPs and 6 h for m-GNPs. Measurement of cytotoxicity using Annexin-V–FITC/PI apoptosis assay delineated marginal changes (7–9%) in treated macrophages following 48 h incubation, establishing the safety of f-GNPs. m-GNPs showed a 5.4-fold reduction in IC50 in comparison with plain AmB suggesting significant enhancement of antileishmanial activity. Our results indicate that f-GNPs could be a promising carrier for specific delivery of AmB to macrophages for effective treatment of VL. Furthermore, spacer contributed significantly in reducing the cytotoxicity as well as increasing the uptake and activity of f-GNPs. [ABSTRACT FROM AUTHOR]

With expanding travel activities, visceral leishmaniasis increasingly occurs in non-endemic areas and affects immunocompetent individuals with no other risk factor than holidays at the Mediterranean coast. We report 3 instructive Swiss cases of visceral leishmaniasis presenting with fever of unknown origin and pancytopenia and review current diagnostic and therapeutic concepts. [ABSTRACT FROM AUTHOR]

Cases of human visceral leishmaniasis (VL) are often found to have bacterial infections. Between 1997 and 2007, 60 cases of VL were admitted to the paediatric ward of the Afzalipour Medical Centre, which forms part of the Kerman University of Medical Sciences, in southern Iran. On admission, the 60 cases (39 boys and 21 girls), each of which was confirmed by the demonstration of amastigotes in a bone-marrow aspirate, had a mean (S.D.) age of 48.8 (44.4) months and a mean (S.D.) erythrocyte sedimentation rate of 53.2 (34.2) mm/h. Twenty-five (42%) of the cases (14 boys and 11 girls) were found to have bacterial infections. Urinary infections (seen in 36% of the cases with bacterial infection) were the most common, followed by blood (28%), respiratory (16%), gastro-intestinal (12%) and skin infections (8%). Despite treatment of all the VL cases with meglumine antimoniate, four (7%) died on the paediatric ward, all four having concurrent bacterial infections. The leucopenia and immunosuppression associated with VL probably facilitate the development of fatal bacterial co-infections. The prompt diagnosis and treatment of both the VL and any bacterial co-infections should therefore reduce mortality among VL cases. [ABSTRACT FROM AUTHOR]

A century of publications on leishmaniasis in Alpes-Maritimes, in southern France, is here reviewed. Autochtonous human and canine leishmaniasis were first recognised in this département, which lies by the Mediterranean Sea and near the Italian border, in 1918 and 1925, respectively. The parasite responsible for the leishmaniasis, Leishmania infantum, is transmitted by Phlebotomus perniciosus and P. ariasi. The human leishmaniasis is zoonotic, with domestic dogs acting as the main 'reservoir' hosts. In prospective surveys over the last two decades, a mean of 12% of the domestic dogs checked in Alpes-Maritimes have been found seropositive for L. infantum but only about 50% of the seropositive animals showed any clinical signs of infection at the time of the surveys. During the last 30 years, 178 cases of human visceral leishmaniasis have been recorded in the area. Such cases are sporadic and often opportunistic, occurring predominantly in children (29% of the 178 cases) or HIV-positive subjects (31%). Recently, it has been demonstrated that, in Alpes-Maritimes, approximately 20% of those found seropositive in leishmanin skin tests are asymptomatic carriers, with amastigotes in their peripheral blood. [ABSTRACT FROM AUTHOR]

The antifungal and antileishmanial agent amphotericin B (AmB) has been complexed with lipids to develop a less toxic formulation of AmB. Because lipid particles are phagocytized by the reticuloendothelial system, lipid associated AmB should be concentrated in infected macrophages of liver and spleen and be very effective against visceral leishmaniasis (VL) and systemic fungal infections. Therefore, AmB was formulated in trilaurin based nanosize lipid particles (emulsomes) stabilized by soya phosphatidylcholine (PC) as a new intravenous drug delivery system for macrophage targeting. Emulsomes were prepared by cast film technique followed by sonication to obtain particles of nanometric size range. Formulations were optimized for AmB to lipid ratio, sonication time and PC to trilaurin ratio. Emulsomes were modified by coating them with macrophage-specific ligand (O-palmitoyl mannan, OPM). The surface modified emulsomes and their plain counterparts were characterised for size, shape, lamellarity and entrapment efficiency. Fluorescence microscopy study showed significant localization of plain and coated emulsomes inside the liver and spleen cells of golden hamsters. In vivo organ distribution studies in albino rats demonstrated that extent of accumulation of emulsome entrapped AmB in macrophage rich organs, particularly liver, spleen and lungs was significantly high when compared against the free drug (AmB-deoxycholate or AmB-Doc). The rate and extent of accumulation were found to increase further on ligand anchoring. Further, a significantly higher (P < 0.05) drug concentration in the liver was estimated over a period of 24 h for OPM coated emulsomes than for plain emulsomes. We concluded that OPM coated emulsomes could fuse with the macrophages of liver and spleen due to ligand-receptor interaction and could target the bioactives inside them. The proposed plain and OPM coated emulsome based systems showed excellent potential for passive and active intramacrophage targeting, respectively and the approach could be a successful alternative to the currently available drug regimens of VL and systemic fungal infections. [ABSTRACT FROM AUTHOR]

Background: Untreated visceral leishmaniasis (VL) is an inevitably fatal childhood disease. First-generation candidate vaccines for VL [autoclaved Leishmania major (ALM) + BCG] have been found to be safe and immunogenic but not superior to BCG alone. Modulation of ALM by adsorption to Alum significantly increases the immunogenicity. The Alum-adsorbed ALM vaccine was found to be safe and strongly immunogenic in healthy adult volunteers in a non-VL-endemic area. This study aimed at establishing the safety and immunogenicity of Alum-precipitated autoclaved L. major + BCG vaccine in children under field conditions. Methods: A total of 544 healthy, leishmanin non-reactive children (<15 y) were randomly allocated to receive either a single intradermal injection of Alum/ALM + BCG or vaccine diluent (placebo). Volunteers were closely followed for 2 years at 6-month intervals for vaccine safety and immunogenicity. Results: The vaccine was well tolerated with minimal side-effects. Leishmanin skin test conversion (≥5 mm) was seen in 56%, 50%, 25% and 31% at 6, 12, 18 and 24 months post-vaccination, respectively; conversion in the placebo group was 4%, 12%, 3% and 13% at the same follow-up visits. There was no significant increase in anti-leishmanial antibodies in either study arm at any of the follow-up visits. During the study, four patients in the placebo arm developed parasitologically confirmed VL. Conclusion: Alum/ALM + BCG vaccine is safe and immunogenic in children under field conditions. Multiple injections might be needed to obtain results similar to those obtained in healthy volunteers. [ABSTRACT FROM AUTHOR]

The article presents three clinical cases of visceral leishmaniasis with duodenal involvement. Human visceral leishmaniasis (VL), caused by Leishmania infantum is endemic in southern and north-eastern Iran. The disease is diagnosed by the detection of smears of bone-marrow or splenic aspirates. Cases of intestinal leishmaniasis found to be in young immunocompetent children, is also described.

The first two patients to be treated with miltefosine for post-kala-azar dermal leishmaniasis (PKDL) are reported. One was a 26-year-old Ethiopian man who had been treated with sodium stibogluconate, for relapsing visceral leishmaniasis (VL), four times between August 2002 and March 2004. In January 2004 this patient was found to be seropositive for HIV and began antiretroviral treatment with stavudine, lamivudine and nevirapine. Five months later he developed clinical PKDL, with extensive cutaneous, conjunctival and oral mucosal involvement. The second patient was a 42-year-old Ethiopian man who was treated for relapsing VL in November 2003. He too was subsequently found to be seropositive for HIV and was treated with stavudine, lamivudine and nevirapine from May 2004. He developed a nodular rash of PKDL over his face and upper body 2 weeks after starting the antiretroviral therapy. Treatment of both patients with oral miltefosine, at 100 mg/day for 28 days, led to the complete regression of their PKDL lesions. When checked 3–6 months after the end of the miltesofine treatment, neither patient showed any signs of VL, PKDL or other HIV-associated disease. [ABSTRACT FROM AUTHOR]

The incidence of human visceral leishmaniasis (VL) caused by Leishmania infantum, which is endemic in several parts of Iran, has recently increased in the Nourabad-Mamassani district of Fars province, in the south of the country. Between 2003 and 2005, 12,688 sandflies were caught in this focus, using CDC miniature light traps, sticky traps and aspirators, in an attempt to identify the main vector of L. infantum. When 120 of the parous, female Phlebotomus (Paraphlebotomus) alexandri caught were individually checked for Leishmania infection, in an assay based on PCR and kinetoplast minicircle primers (LINR4 and LIN17), five (4.2%) of the flies were found to be infected with L. infantum. Thirty-nine (32.5%) of the 120 blood-fed Ph. alexandri checked in an ELISA were found positive for human blood. Since Ph. alexandri was the third-most common species caught (representing over 17% of the total catch), was clearly anthropophilic, and was not infrequently infected with L. infantum, it is probably an important vector in the Nourabad-Mamassani focus. Although other sandfly species have been found naturally infected with promastigotes in Iran, Ph. alexandri is the first that has been proven to harbour L. infantum in the country. [ABSTRACT FROM AUTHOR]

Kala-azar is an intracellular parasitic infection that infects and multiplies in the macrophages of the liver, the spleen, and the bone marrow. It is characterized by intermittent fever, hepatosplenomegaly, pancytopenia, and hypergammaglobulinemia. Although anemia is a usual finding, Coombs-positive autoimmune hemolytic anemia (AIHA) has rarely been reported with this disease. Pentavalent antimonial compounds remain the mainstay of treatment worldwide. Liposomal amphotericin B (L-AmB) is currently preferred in the treatment of kala-azar because of the resistance to pentavalent antimonals. The authors diagnosed kala-azar associated with Coombs-positive AIHA in 3 patients and treated them with L-AmB (1–5 mg/kg/day) for 30–36 days. Now, all of these patients are healthy following up at the outpatient base for 18–34 months. Kala-azar must be considered in patients with Coombs-positive AIHA and living in and coming from the endemic region for this disease, and it can be successfully treated with L-AmB. [ABSTRACT FROM AUTHOR]

The antileishmanial property of a Benzyl derivative of a new antibiotic MT81 (Bz 2 MT81), isolated and purified from a fungal strain of Penicillium nigricans NRRL 917 was tested in free, liposome intercalated and mannose coated liposome intercalated forms in vivo against visceral leishmaniasis in hamsters. Mannose grafted liposome intercalated Bz 2 MT81 eliminated intracellular amastigotes of Leishmania donovani within splenic macrophages more efficiently than the liposome intercalated Bz 2 MT81 or free Bz 2 MT81. At a dose equivalent to 7.5 μg/Kg body weight when injected subcutaneously (s.c) in mannose grafted liposome intercalated form for 15 days in an interval of three days, the splenic parasitic load decreased to the extent of 79.1% of the total parasite present in infected control animals. Whereas, an identical amount (7.5 μg/Kg body weight) of Bz 2 MT81 in free or liposome intercalated form was found less effective in controlling the parasite in spleen (in free Bz 2 MT81 form, suppression of parasitic load is 49.8% and in liposome intercalated form, it is 55.1%). Both mannosylated liposomes and Bz 2 MT81 were noted non-toxic to the host peritoneal macrophages. Histological examinations of spleen and liver, kidney function tests (SGPT, alkaline phosphatase, creatinine and urea in blood plasma) showed that the toxicity of Bz 2 MT81 was reduced up to normal level when mannose grafted liposomal Bz 2 MT81 were administered. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) caused by Leishmania chagasi is a growing public-health problem in many parts of the New World. Although several studies have focused on the consequences of environmental damage, human migration and land occupation on the incidence of VL, the effects on the disease of the substandard living conditions that often result from the process of urbanization have not been investigated in detail. The present study was based in the Brazilian city of Teresina, where, since 1980, there have been two large outbreaks of VL (one in 1981–1985 and the other in 1993–1996), each involving at least 1000 newly reported cases. The role of household structure and the provision of urban services in the city, as predictors of the occurrence of VL, was studied in a case–control investigation. After controlling for age, crowding, and the background incidence of VL in the area where the subjects lived, the risk of acquiring the disease was found to be significantly higher for those who lived in houses with an inadequate sewage system and those who had no regular rubbish collection. Improving household structure and providing basic urban services might be effective strategies for controlling the spread of VL in urban areas. [ABSTRACT FROM AUTHOR]

Although visceral leishmaniasis is often fatal in the developing world, Leishmania-attributable deaths in Europe are relatively rare and nowadays almost always linked to HIV infection. In Spain, however, a HIV-negative man with a history of chronic obstructive pulmonary disease and prednisone treatment was recently hospitalized because of hypotension and asthenia. Although the patient was afebrile, a bone-marrow aspirate, collected after thrombo- and leuco-cytopenia had been observed, was found to contain huge numbers of amastigotes. A course of antileishmanial treatment with meglumine antimoniate was initiated but the patient went into refractory shock and died within 6 h. The significance of this case, in terms of the routine investigation and treatment of immunosuppressed patients who may have leishmaniasis, is discussed. [ABSTRACT FROM AUTHOR]

In the present study, 67 patients suspected to be cases of visceral leishmaniasis (VL) were each checked for leishmanial infection by the microscopical evaluation of various biological specimens, in-vitro culture, serology and an assay based on nested PCR. Most (35) of the subjects were immunocompetent (IC) but 32 were immunodeficient (ID) as the result of HIV infection (18 cases), treatment to prevent transplanted organs being rejected (six) or haematological malignancies (eight). Forty-one (61.2%) of the subjects (19 IC subjects, 12 HIV-positive patients, four transplant patients and six patients with malignancies) were considered true cases of VL. For the IC subjects, only the production and microscopical examination of leucocytoconcentrates and cultures of Buffy coats gave sensitivities of< 80%, the results of the other methods showing higher sensitivities and almost perfect agreement with the 'gold-standard' diagnoses. For the ID subjects, however, only the serological tests and the PCR gave reasonable sensitivities (of > 80%). For the initial diagnosis of leishmaniasis in ID patients, IFAT and western blots may be useful, as, among the present ID patients, they gave sensitivities (of 80.9% and 88.2%, respectively) that were almost as high as that for the PCR, and specificities of 100%. In the diagnosis of VL in either IC or ID patients, the assay based on a nested PCR appeared to be particularly reliable, with sensitivities of 88.9% and 95.2%, respectively, and a specificity of 100% in both groups of patients. The testing of bone-marrow aspirates by PCR revealed very few VL cases who were not found positive when samples of their peripheral blood were checked in the same assay. For both IC and ID subjects therefore, the use of the PCRbased method to test samples of peripheral blood (which can be collected much more easily than bone-marrow aspirates and with much less pain for the subject) is recommended. [ABSTRACT FROM AUTHOR]

Peri-urban visceral leishmaniasis (VL) caused by Leishmania chagasi is emerging in a new epidemiologic pattern in Brazilian cities. We studied peri-urban VL in endemic neighborhoods surrounding Natal, Brazil, identified through hospitalized individuals with VL. Clinical and environmental information obtained for 1106 members of 216 families living in endemic neighborhoods enabled us to identify 4 groups: VL: individuals with current or prior symptomatic visceral leishmaniasis ( n =135); DTH+: individuals with positive delayed-type hypersensitivity response with no history of VL ( n =390); Ab+: individuals with negative DTH response and seropositive ( n =21); DTH-: individuals with negative DTH and seronegative ( n =560). The mean±SD age of VL was 9.3±12.3 y. The gender distribution was nearly equal below age 5, but skewed toward males at higher ages. Acutely infected VL subjects had significantly lower hematocrits, neutrophils, and eosinophils than other categories. AB+ subjects also had lower eosinophil counts than others, a possible immune marker of early infection. VL was not associated with ownership of dogs or other animals, raising the question whether the reservoir differs in peri-urban settings. This new pattern of L. chagasi infection enables us to identify epidemiological and host factors underlying this emerging infectious disease. [ABSTRACT FROM AUTHOR]

The article reports on a study which examined the isolation and identification of Leishmania donovani from Phlebotomus orientalis. The study, which focused on an area in eastern Sudan with endemic visceral leishmaniasis (VL), analyzed the molecular detection of Leishmania DNA in wild-caught sandflies. These sandflies were examined for the presence of Leishmania promastigotes. A combination of microscopy and polymerase chain reaction (PCR) was used to determine the prevalence of infection among P. orientalis.

The article discusses the research on the ecology of sandflies, due to the endemic that claimed thousands of lives in Sudan. It is stated that the human visceral leishmaniasis is an endemic in eastern and southern part of the country, while the human cutaneous leishmaniasis is known to be the endemic in Surogia. However, it is considered possible that the distribution of these two species in northern Sudan is restricted to certain habitats that have not previously been explored by entomologists, or these two species have not previously been detected because they only occur in the area in very low numbers. Thus, more studies are now needed to determine the distributions, seasonality and relative epidemiological importance.

The article discusses the significance of miltefosine in the treatment of a case of visceral leishmaniasis (VL) with renal dysfunction in India. A 45-year-old man from an area of Bihar with endemic VL has been presented at the Out-patient Department of the Rajendra Memorial Research Institute of Medical Sciences in Patna. After haematology tests, the patient was found to have normal blood sugar and results of liver-function tests fell within the normal range. However, in renal-function tests, he was found to have 57.83 mml urea/liter of blood and 194.48 μmol creatinine, 136 mmol sodium and 3.5 mmol potassium/liter of serum. Thus, after VL was confirmed, he was given oral miltefosine for 28 days, and at the end of the therapy, the patient was afebrile and feeling well.

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniasis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis typically presents with symptoms such as fever, enlargement of the spleen and the liver, hypergammaglobulinaemia and infection of the bone marrow resulting in anaemia and leukopenia. The disease is sporadic in the countries of the Mediterranean basin. We report an unusual case of acute tonsillitis due to tonsillar leishmaniasis, in an immunocompetent 34-y-old male patient. Diagnosis was confirmed by serological tests and histopathological examination following biopsy of the right tonsil. The patient was successfully treated with liposomal amphotericin-B. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis is endemic in some areas of Turkey; however, it has not been reported previously from the eastern part of the country. We reviewed 21 cases of visceral leishmaniasis admitted from eastern Turkey, 60% of whom were from the same region, Kağızman. [ABSTRACT FROM AUTHOR]

Kala-azar (visceral leishmaniasis) is a common problem in various well-defined areas of India. It is characterized by fever of long duration, enlarged liver and spleen, anaemia and leucopoenia. Bleeding is an uncommon manifestation of kala-azar. We report 2 cases, in which disseminated intravascular coagulation was an unusual complication. [ABSTRACT FROM AUTHOR]

The article provides information on the study concerning the revival of a focus of visceral leishmaniasis in central Sudan. The author infers that visceral leishmaniasis caused by Leishmania donovani is endemic over vast areas of eastern, western, and southern part of the country. The obvious revival of visceral leishmaniasis focus in the central part of the country is curious. A savannah belt once stretched across the central part from visceral leishmaniasis-endemic areas in the west to likewise endemic areas in the east.

Acquired aplastic anaemia (AAA) is caused by aetiologies ranging from infectious agents, chemical toxins, drugs, and autoimmune disorders. Few reports exist which establish a causal association of parasites in AAA. Causal association of Leishmania donavani infection in AAA has not been reported to date. [ABSTRACT FROM AUTHOR]