As part of a World Health Organization-led effort to update the empirical evidence base for the leishmaniases, national experts provided leishmaniasis case data for the last 5 years and information regarding treatment and control in their respective countries and a comprehensive literature review was conducted covering publications on leishmaniasis in 98 regional level between 2007 and 2011. Two questionnaires regarding epidemiology and drug access were completed by experts and national program managers. Visceral and cutaneous leishmaniasis incidence ranges were estimated by country and epidemiological region based on reported incidence, underreporting rates if available, and the judgment of national and international experts. Based on these estimates, approximately 0.2 to 0.4 cases and 0.7 to 1.2 million VL and CL cases, respectively, occur each year. More than 90% of global VL cases occur in six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. Cutaneous leishmaniasis is more widely distributed, with about one-third of cases occurring in each of three epidemiological regions, the Americas, the Mediterranean basin, and western Asia from the Middle East to Central Asia. The ten countries with the highest estimated case counts, Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, North Sudan, Costa Rica and Peru, together account for 70 to 75% of global estimated CL incidence. Mortality data were extremely sparse and generally represent hospital-based deaths only. Using an overall case-fatality rate of 10%, we reach a tentative estimate of 20,000 to 40,000 leishmaniasis deaths per year. Although the information is very poor in a number of countries, this is the first in-depth exercise to better estimate the real impact of leishmaniasis. These data should help to define control strategies and reinforce leishmaniasis advocacy. Funding: The Spanish Agency for International Cooperation for Development (AECID) has provided generous support to the WHO Leishmaniasis program since 2005. This support permitted among many other activities regional meetings with the AFRO, EURO, PAHO and SEARO countries, and provided for short term contracts for IDV, MdB, MH and JS related to the preparation of the country profiles. Sanofi provided a grant for a regional meeting with the EMRO countries and various activities related to the control of cutaneous Leishmaniasis in the EMRO region. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: alvarj@who.int . These authors contributed equally to this work " For a full list of the members of the WHO Leishmaniasis Control Team please see the Acknowledgments section.

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Leishmaniasis Worldwide and Global Estimates of Its Incidence

A rapid, semiautomated microdilution method was developed for measuring the activity of potential antimalarial drugs against cultured intraerythrocytic asexual forms of the human malaria parasite Plasmodium falciparum. Microtitration plates were used to prepare serial dilutions of the compounds to be tested. Parasites, obtained from continuous stock cultures, were subcultured in these plates for 42 h. Inhibition of uptake of a radiolabeled nucleic acid precursor by the parasites served as the indicator of antimalarial activity. Results of repeated measurements of activity with chloroquine, quinine, and the investigational new drug mefloquine demonstrated that the method is sensitive and precise. Several additional antimalarial drugs and compounds of interest were tested in vitro, and the results were consistent with available in vivo data. The use of P. falciparum isolates with known susceptibility to antimalarial drugs also permitted evaluation of the cross-resistance potential of each compound tested. The applications and expectations of this new test system within a drug development program are discussed.

Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique.

Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to ‘second-generation liposomes’, in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.

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Liposome: classification, preparation, and applications

Commentary. Lysosomotropic agents.

125I-labeled human epidermal growth factor (hEGF) binds in a specific and saturable manner to human fibroblasts. At 37 degrees C, the cell-bound 125I-hEGF initially may be recovered in a native form by acid extraction; upon subsequent incubation, the cell-bound 125I-hEGF is degraded very rapidly, with the appearance in the medium of 125I-monoiodotyrosine. At 0 degrees C, cell-bound 125I-hEGF is not degraded but slowly dissociates from the cell. The data are consistent with a mechanism in which 125I-hEGF initially is bound to the cell surface and subsequently is internlized before degradation. The degradation is blocked by inhibitors of metabolic energy production (azide, cyanide, dinitrophenol), some protease inhibitors (Tos-Lys-CH2Cl, benzyl guanidobenzoate), a lysosomotropic agent (chloroquine) various local anesthetics (cocaine, lidocaine, procaine), and ammonium chloride. After the binding and degradation of 125I-hEGF the fibroblasts are no longer able to rebind fresh hormone. The binding capacity of these cells is restored by incubation in a serum-containing medium; this restoration is inhibited by cycloheximide or actinomycin D.

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125I-labeled human epidermal growth factor. Binding, internalization, and degradation in human fibroblasts.

Data are provided on the activity of a variety of antimalarial drugs against drug-sensitive and drug-resistant lines of Plasmodium berghei in albino mice. Parallel data for the response of the drug-sensitive parasites to these compounds in vitro indicate whether the drugs have a chloroquine-like or quinine-like type of action, or neither. The value of this test system for drug evaluation is debated. It is concluded that the in vivo tests do provide a valuable indication of the potential use of a compound against drug-resistant malaria parasites of man. The tests may also provide a good indication of the future value of new compounds against strains of parasites that are already resistant to chloroquine. Where necessary, steps should be taken to protect promising new compounds.

The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity.

MALARIA parasites1 or mammalian liver2 suitably exposed to chloroquine rapidly form autophagic vacuoles; in the case of the parasites, these are visible under the light microscope because they contain clumps of pigment, the remains of haemoglobin digestion (Fig. 1). These striking morphological changes are well known but not correspondingly well understood.

Lysosomes, pH and the Anti-malarial Action of Chloroquine

The Leishmaniases in biology and medicine , The Leishmaniases in biology and medicine , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی

The Leishmaniases in biology and medicine

THE use of liposomes in chemotherapy as a method of ensuring that drugs reach the diseased or defective tissues suffers from the drawback that, on intravenous injection, the bulk of the material is rapidly cleared by the phagocytic cells of the liver1, and does not reach the desired target. We report here a system in which advantage is taken of this behaviour to treat visceral leishmaniasis in mice, in which the amastigote parasites reside unharmed in vacuoles inside the Kupffer cells of the liver2.

Antileishmanial activity of antimonials entrapped in liposomes

The micro-scale Enzyme-linked Immunosorbent Assay (micro-ELISA) technique, with alkaline phosphatase as a marker enzyme, has been used for the serodiagnosis of human and canine visceral leishmaniasis, from foci in southern France. This technique which uses a soluble antigen is highly sensitive, with a degree of specificity slightly higher than that of the IFA. It is suggested that the micro-ELISA procedure can be added to the battery of serological techniques and would be particularly useful for large scale epidemiological studies of leishmaniasis.

W. Peters

Papers

The chemotherapy of rodent malaria, XXII. The value of drug-resistant strains of P. berghei in screening for blood schizontocidal activity.

Lysosomes, pH and the Anti-malarial Action of Chloroquine

The Leishmaniases in biology and medicine

Antileishmanial activity of antimonials entrapped in liposomes

The micro-ELISA technique in the serodiagnosis of visceral leishmaniasis