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

An account is given of work published during the past 10 years incriminating species of phlebotomine sandflies as vectors of Leishmania species which infect man. An assessment is made of the degrees of certainty of the vectorial roles of eighty-one species and subspecies of sandflies (thirty-seven Old World and forty-four New World) in the transmission of twenty-nine leishmanial parasites of mammals. At least one species of sandfly is considered to be a proven vector of each of ten parasites. Of the eighty-one sandfly taxa, evidence is judged to be sufficient to incriminate nineteen as proven vectors (eleven Phlebotomus species and eight Lutzomyia species or subspecies) and evidence for a further fourteen (nine Phlebotomus species and five Lutzomyia species or subspecies) is considered to be strong. The suggested criteria for incrimination of a vector are anthropophily and common infection with the same leishmanial parasite as that found in man in the same place. More weight should be given to natural infections persisting after the digestion of a bloodmeal than those in the presence of blood. Supporting evidence is a concordance in the distribution of the fly and the disease in man, proof that the fly feeds regularly on the reservoir host, a flourishing development of the parasite in infected flies and the experimental transmission of the parasite by the bite of the fly.

Phlebotomine vectors of the leishmaniases: a review.

The biology and control of phlebotomine sand flies.

Recent epidemiologic studies indicate that leishmaniasis in the Americas is far more abundant and of greater public health importance than was previously recognized. The disease in the New World is caused by a number of different parasite species that are capable of producing a wide variety of clinical manifestations. The outcome of leishmanial infection in humans is largely dependent on the immune responsiveness of the host and the virulence of the infecting parasite strain. This article reviews current concepts of the clinical forms, immunology, pathology, laboratory diagnosis, and treatment of the disease as well as aspects of its epidemiology and control. Recommendations for future research on the disease and its control are made.

Leishmaniases of the New World: current concepts and implications for future research.

Background: The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale.
Methodology and Principal Findings
Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate?
Conclusions and Significance: We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites.

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A Historical Overview of the Classification, Evolution, and Dispersion of Leishmania Parasites and Sandflies

Evolution, classification and geographical distribution.

As the first species of Leishmania encountered were the agents of human visceral and cutaneous leishmaniasis, it is understandable that studies on these parasites for a long time concentrated on those organisms commonly causing disease in man. Epidemiological studies over the past 20 years or so, however, have led to the inescapable conclusion that the genus Leishmania is comprised of numerous species of well adapted parasites, in a wide range of mammals, throughout most of those tropical and subtropical regions of the world where phlebotomine sandflies exist (Diptera: Psychodidae). Many of the leishmanias probably never gain entrance into man: due either to an incapacity to survive in his tissues, or (more likely) because the natural sandfly vectors do not feed on him. The leishmanias that do infect man are, nevertheless, among the greatest protozoological scourges of mankind, and a better understanding of their life-cycles may well help in future prevention or control of the diseases they cause. With few exceptions the leishmaniases are zoonoses, with a major source of infection in wild or domestic animals. In the Americas, the disease is essentially a rural one, and most commonly acquired by those penetrating forested or wooded regions. The following paper deals with the better known human leishmaniases of the New World, and some new ones, and discusses the major historical events in the laborious task of elucidating their ecology and epidemiology.

The American leishmaniases: some observations on their ecology and epidemiology

Six species of Leishmania are at present known to cause cutaneous and/or mucocutaneous leishamniasis in Brazil, and they are all to be found in the Amazon region of this country. The eco-epidemiology of each is discussed, with the observation that the Amazonian leishmaniases are all zoonoses, with their source in silvatic mammals and phlebotomine sandfly vectors. With man's destruction of the natural forest in southern Brazil, some sandfly species have survived by adapting to a peridomestic or domiciliary habitat in rural areas. Some domestic animals, such as dogs and equines are seemingly now involved in the epidemiology of the disease. No such process has yet been reported in the Amazon region, but may well take place with the continuing devastation of its forest.

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The dermal leishmaniases of Brazil, with special reference to the eco-epidemiology of the disease in Amazonia

Keywords:

New World leishmaniasis;
neotropical cutaneous leishmaniasis (NCL)-seeming to be of great antiquity;
cutaneous leishmaniasis-widespread in Latin America;
NCL, a zoonosis-causative parasites, primarily those of wild animals;
anergic diffuse cutaneous leishmaniasis (ADCL) and American visceral leishmaniasis (AVL);
neotropical Leishmania species-as recorded in humans and resultant pathologies;
Leishmania-like parasites of uncertain taxonomic position;
cutaneous and mucosal leishmaniasis

New World Leishmaniasis

Quatro casos de doenca de Chagas sao registrados numa familia em Belem, Para, Brasil. Acredita-se que a infeccao foi adquirida em Belem. Como nao foram encontrados triatomineos na casa dos doentes, nem nas residencias vizinhas, sugere-se que outros meios de transmissao devem ser considerados, por exemplo a transmissao "per os".

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Ralph Lainson

Papers

Evolution, classification and geographical distribution.

The American leishmaniases: some observations on their ecology and epidemiology

The dermal leishmaniases of Brazil, with special reference to the eco-epidemiology of the disease in Amazonia

New World Leishmaniasis

Considerações sobre a epidemiologia dos primeiros casos autóctones de doença de Chagas registrados em Belém, Pará, Brasil