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Query: UMLS:C0019693 (HIV)
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Visceral leishmaniasis (VL) is a severe disease associated with infection of the reticuloendothelial system by Leishmania species. The infection is acquired through sandfly bites. Recent large scale epidemics of VL in east Africa and India and the emergence of a HIV epidemic make VL a priority for the World Health Organization. Pentavalent antimonials have been cornerstone of treatment for the last six decades. The appearance of antimonial-resistance and the development of lipid formulations of amphotericin B have changed the pattern of VL treatment. Within the past five years, miltefosine has been demonstrated as the first effective and safe oral treatment against VL. The price of miltefosine is yet to be determined. However, miltefosine will certainly be cheaper than lipid formulations of amphotericin B, which are beyond the financial capacity of the poor countries. Because it can be administered orally, miltefosine is suited for the treatment of large number of patients who get affected during epidemics, particularly in regions where the parasites are resistant to the currently used agents. Here, we recommend different treatment schedules according to the resistance pattern and the region-specific socio-economical and cultural factors.
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PMID:Recent understanding in the treatment of visceral leishmaniasis. 1286 73

Currently there are no effective orally administered drugs or visceral leishmaniasis or kala-azar, a parasitic disease affecting about 0.5 million people a year, majority of whom are in India and adjacent areas of Nepal. Symptoms of affected patients are fever, cachexia, hepatosplenomegaly and pancytopenia. The disease is usually fatal, if left untreated. Traditionally kala-azar is treated with four weeks of injections of sodium stibogluconate, a pentavalent antimonial. However, this treatment has not only shown resistance in 37-64% patients of the current Indian epidemic in Bihar (the epicentrre) but also life-threatening cardiotoxicity in 7-10% and treatment-related deaths in 5-10% cases, besides being unsuccessful at times. Parenteral amphotericin B is used as a secondary agent that shows 95% effectiveness but its toxicity and high cost of even the well tolerated liposomal complex precludes its wide use in the developing countries, where the disease is present in epidemic proportions. Recently, miltefosine (hexadecylphosphocholine), a compound originally developed as an antitumour agent has been shown to be an orally effective drugs against kala-azar. All clinical trials with this drug are conducted in India in patients of visceral leishmaniasis. A regimen of 100 mg per day or 50 mg twice daily for 3-4 weeks was observed to produce a cure rate of 100%. Gastrointestinal side effects were frequent (62%) but no patient discontinued the therapy. A phase III trial involving 300 HIV-negative adults and adolescents is underway in India and the drug is hoped to be licensed in the next 2-3 years. Few studies of phase II clinical trials mainly conducted in Kenya with another drug, sitamaquine or kalazaquine (WR 6026), an 8-aminoquinoline has also shown promise as an orally effective agent (in a dose of 1 mg/kg/day for two weeks) for visceral leishmaniasis. These Studies with two orally effective compounds, it appears, will open new vistas for orally effective, affordable and acceptable drugs in the armamentarium for the treatment of kala-azar. It is expected that in future we would have effective ways to prevent and treat all forms of leishmaniasis without discomforting the patient.
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PMID:Orally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine. 1462 Oct 30

Leishmania species can cause a wide spectrum of cutaneous disease in HIV-positive patients: asymptomatic, localized cutaneous, mucosal, muco-cutaneous, diffuse cutaneous or post-kala-azar leishmaniasis. In such cases, which are usually severely immunocompromised, the leishmanial parasites reach the skin of the human host by dissemination after either a new infection (resulting from the bite of infected sandfly or, probably, the sharing of contaminated syringes by intravenous-drug users) or the re-activation of a latent infection. Recent experience and past observations on the dermatology of leishmaniasis in those with Leishmania/HIV co-infection are reviewed here.
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PMID:Leishmania and HIV co-infection: dermatological manifestations. 1467 38

Visceral leishmaniasis is basically a disease of healthy infants and adults. However, in the last decade an increasing number of cases of kala azar in immunocompromised patients have been reported with emphasis on atypical manifestations of the disease. During a period of 11 years, 20 immunocompromised patients with AIDS (12 patient), haematological neoplasia (3 patients), corticosteroid therapy (3 patients) or renal transplantation (2 patients) were studied by one or more of the authors. We did not find differences in the presentation of leishmaniasis between patient with or without AIDS and most patients had fever, enlargement of the liver and spleen, blood cytopenias and biochemical abnormalities. Serology was more frequently positive in HIV-negative than in HIV-positive patients (100% versus 63.6%; P=0.13). Bone marrow biopsy was diagnostic in 66% and 87% of patients with and without AIDS, respectively. Failure of anti-leishmanial therapy occurred in 6 of 19 patients treated (31.5%), and 3 patients with AIDS and another 3 without AIDS died during the first episode of leishmaniasis. Of 12 survivors, relapses occurred in five (41.6%). Only patients in whom immunosuppression was ameliorated by means of antiretroviral therapy or by reduction of corticosteroid and other immunosuppressive drugs did not relapse. Treatment of kala azar in immunocompromised host is in satisfactory and new drugs or strategies are urgently needed.
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PMID:Visceral leishmaniasis in immunocompromised patients with and without AIDS: a comparison of clinical features and prognosis. 1473 17

Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis (VL) is of higher priority than cutaneous leishmaniasis (CL) as it is a fatal disease in the absence of treatment. Anthroponotic VL foci are of special concern as they are at the origin of frequent and deathly epidemics (e.g. Sudan). Leishmaniasis burden remains important: 88 countries, 350 million people at risk, 500,000 new cases of VL per year, 1-1.5 million for CL and DALYs: 2.4 millions. Most of the burden is concentrated on few countries which allows clear geographic priorities. Leishmaniasis is still an important public health problem due to not only environmental risk factors such as massive migrations, urbanisation, deforestation, new irrigation schemes, but also to individual risk factors: HIV, malnutrition, genetic, etc em leader Leishmaniasis is part of those diseases which still requires improved control tools. Consequently WHO/TDR research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines. The ongoing effort has already produced significant results. The newly available control tools should allow a scaling up of control activities in priority areas. In anthroponotic foci, the feasibility of getting a strong impact on mortality, morbidity and transmission, is high.
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PMID:Leishmaniasis: current situation and new perspectives. 1522 81

Visceral leishmaniasis represents a serious public health concern in endemic regions and is rapidly emerging as an opportunistic infection in HIV patients. The disease is difficult to diagnose and prevent, and available treatment is associated with toxicity and drug resistance. Even though significant headway has been made in the development of vaccines against cutaneous leishmaniasis, visceral leishmaniasis has received limited attention. The fact that a large proportion of the people living in endemic areas have self-resolving subclinical infection and individuals once recovered are immune to reinfection provides a rationale for designing immunoprophylactic strategies against visceral leishmaniasis. The primary aim of this paper is to review advances in vaccination strategies against visceral leishmaniasis, suggesting possible effector mechanism leading to resistance. It also covers the role of immunostimulators and gives an account of the adjuvants used against visceral leishmaniasis. Vaccine strategies in different established experimental models have also been dealt with which can provide potential leads for their application in humans. In light of the available observations made during the course of studies performed on experimental models of visceral leishmaniasis there is increasing evidence that a successful approach towards a vaccine involves the requirement of Th1 subset of CD4+ cells along with Th2, CD8+, and B cells. In this review we present the possible mechanism of interaction of these cells and their effector molecules in providing resistance against visceral leishmaniasis for the future design of effective vaccine against this disease.
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PMID:Progress in vaccine research and possible effector mechanisms in visceral leishmaniasis. 1535 18

Visceral leishmaniasis (VL) is a major public health problem in many tropical countries of the world. The available chemotherapeutics require parenteral administration and have other limitations like cost, toxicity, variable efficacy or restricted supplies. There is no effective treatment for immunosuppressed patients with leishmaniasis- HIV co-infection. Hence, new therapies, that are effective when treatment with the currently available drugs fails, must be developed. One of the major strategies for effective and safe treatment of leishmaniasis and other infectious diseases, in the last decade, involves the use of immunomodulators as adjunct to chemotherapy. In this context, we studied the immunomodulatory activity of a hexapeptide Val-Glu-Pro-Ile-Gly-Tyr (CDRI compound 89-215) corresponding to (54-59) fragment of human beta-casein in mice and its efficacy in adjunct chemotherapy with SSG using L. donovani/hamster model. The hexapeptide was found to enhance both humoral and CMI responses. In animal model the hexapeptide per se showed no antileishmanial activity. However, when given alongwith suiboptimal dose of SSG, it enhanced the efficacy of SSG from 24% to 80%. The activity was very close to the efficacy (85%) recorded for curative dose of SSG. Adjunct chemotherapy with immunomodulator in visceral leishmaniasis appears to be a fruitful preposition.
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PMID:Adjunct effect of immunostimulating hexapeptide analogous to human beta-casein fragment (54-59) to sodium stibogluconate against experimental visceral leishmaniasis. 1551 75

Disseminated cutaneous leishmaniasis is characterized by the presence of a large (> or =10) number of lesions at several anatomic sites (head, limbs, and trunk). Most of the lesions are small, papular, and appear simultaneously with or secondarily to one or several ulcerated lesions of localized cutaneous leishmaniasis. We report the first case of disseminated cutaneous leishmaniasis in French Guiana. It concerns a 24-year-old woman who tested negative for human immunodeficiency virus (HIV). The disease began with three lesions that became ulcerated. One week later, multiple papulo-nodular lesions appeared. We counted a total of 425 lesions. Leishmania were observed in the lesions. The species involved was L. guyanensis, which has never been described in a case of disseminated cutaneous leishmaniasis. The patient was rapidly cured by a single course of pentamidine. Disseminated cutaneous leishmaniasis should be distinguished from other types of leishmaniasis with multiple lesions. These include anergic diffuse cutaneous leishmaniasis, post-kala-azar leishmaniasis, and leishmaniasis associated with HIV infection.
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PMID:Disseminated cutaneous leishmaniasis due to Leishmania guyanensis: case of a patient with 425 lesions. 1556 84

Leishmaniasis is a typical example of a worldwide diffused zoonosis. Geographic distribution depends on the presence of sand fly vectors and animal reservoirs. In Southern Europe, canines are considered the main reservoir of infection, and the phlebotomines are the vectors. In Sicily, as in all Mediterranean areas, sand flies are present almost all year around because the climate permits an uninterrupted lifecycle for the vectors. Visceral leishmaniasis is becoming a real public health concern especially in endemic areas; in fact, it is an opportunistic infection in immunocompromised patients and in HIV-positive subjects. In Italy, the visceral form of the disease is due exclusively to Leishmania infantum ZMON1, and its prevalence is growing. We have developed a highly accurate, reproducible, and sensible real-time polymerase chain reaction (PCR) assay. In a procedure that used a specific couple of primers, a 117-bp fragment was amplified from minicircle kinetoplast DNA (kDNA). The assay was able to detect even a single parasite (200 fg of DNA). In fact, a single parasite contains hundreds of kinetoplast minicircles for each class. We applied a rapid extraction method coupled with the real-time PCR assay. It was not only as sensitive as a conventional PCR assay for detection of Leishmania kDNA, but also more rapid. The assay is useful for the diagnosis of leishmaniasis in dogs and humans, and it facilitates the monitoring of parasite levels during pharmacological treatment.
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PMID:TaqMan-based detection of Leishmania infantum DNA using canine samples. 1560 81

Unsafe injection practices have been implicated in the worldwide spread of hepatitis B, hepatitis C, HIV or any parasitic disease with a blood phase, such as malaria, filaria and syphilis. Review of injection safety in India also revealed that use of injection is often inappropriate, injections are administered with unreliable safety measures. Studies in India have documented the association of injection use and spread of hepatitis C and kala-azar also. Some measures to address the issue are also discussed.
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PMID:Injection safety and its impact in India: a literature analysis. 1570 25


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