Leishmaniasis Worldwide and Global Estimates of Its Incidence
TL;DR: 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.
Abstract: 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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TL;DR: The functions of cytokines secreted by macrophages are discussed, and what is known about their release mechanisms are summarized to delve into how selected pathogens subvert cytokine release for their own survival.
Abstract: The evolution of macrophages has made them primordial for both development and immunity. Their functions range from the shaping of body plans to the ingestion and elimination of apoptotic cells and pathogens. Cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. A portfolio of cytokines is central to the role of macrophages as sentries of the innate immune system that mediate the transition from innate to adaptive immunity. In concert with other mediators, cytokines bias the fate of macrophages into a spectrum of inflammation-promoting "classically activated," to anti-inflammatory or "alternatively activated" macrophages. Deregulated cytokine secretion is implicated in several disease states ranging from chronic inflammation to allergy. Macrophages release cytokines via a series of beautifully orchestrated pathways that are spatiotemporally regulated. At the molecular level, these exocytic cytokine secretion pathways are coordinated by multi-protein complexes that guide cytokines from their point of synthesis to their ports of exit into the extracellular milieu. These trafficking proteins, many of which were discovered in yeast and commemorated in the 2013 Nobel Prize in Physiology or Medicine, coordinate the organelle fusion steps that are responsible for cytokine release. This review discusses the functions of cytokines secreted by macrophages, and summarizes what is known about their release mechanisms. This information will be used to delve into how selected pathogens subvert cytokine release for their own survival.
1,829 citations
Cites background from "Leishmaniasis Worldwide and Global ..."
...Mucocutaneous and visceral disease can be lethal if untreated, but most deaths are attributable to visceral leishmaniasis (103)....
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TL;DR: 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 is proposed.
Abstract: 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.
583 citations
TL;DR: This review focuses on the two parasites causing most human visceral leishmaniasis (VL), which leads to substantial health problems or death for up to 400,000 people per year, and compares and contrasts continental differences.
Abstract: Leishmania species are the causative agents of leishmaniasis, a neglected tropical disease. These parasitic protozoans are usually transmitted between vertebrate hosts by the bite of blood sucking female phlebotomine sand flies. This review focuses on the two parasites causing most human visceral leishmaniasis (VL), which leads to substantial health problems or death for up to 400,000 people per year. Except for travel cases, Leishmania donovani infections are restricted to the (sub-)tropics of Asia and Africa, where transmission is mostly anthroponotic, while Leishmania infantum occurs in the drier parts of Latin America as well as in the Mediterranean climate regions of the Old World, with the domestic dog serving as the main reservoir host. The prevalence of VL caused by L. infantum has been declining where living standards have improved. In contrast, infections of L. donovani continue to cause VL epidemics in rural areas on the Indian subcontinent and in East Africa. The current review compares and contrasts these continental differences and suggests priorities for basic and applied research that might improve VL control. Transmission cycles, pathogenesis, diagnosis, treatment and prognosis, prevention (including vector control), surveillance, transmission modeling, and international control efforts are all reviewed. Most case detection is passive, and so routine surveillance does not usually permit accurate assessments of any changes in the incidence of VL. Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors because of the limitations of survey methods. Consequently, transmission modeling rarely passes beyond the proof of principle stage, and yet it is required to help develop risk factor analysis for control programs. Anthroponotic VL should be susceptible to elimination by rapid case detection and treatment combined with local vector control, and one of the most important interventions may well be socioeconomic development.
359 citations
Cites background from "Leishmaniasis Worldwide and Global ..."
...Among the few published empirical Clinical Epidemiology 2014:6 submit your manuscript | www.dovepress.com Dovepress Dovepress 153 visceral leishmaniasis assessments of under-reporting in surveillance data, two from Bihar, India, compared VL case numbers estimated by house-to-house surveys with official data, which were 4.2- fold and 8.1-fold lower.6 The incidence of VL associated with the transmission of L. infantum by sand flies has been declining in many foci where living standards have improved, with better nutrition believed to mitigate the progression of debilitating or fatal infantile visceral leishmaniasis.6 Also, there has been a decline or stabilization in the incidence of VL resulting from the transmission of L. infantum by needles or blood transfusion through better awareness and drugs to combat coinfecting HIV.6 International collaboration for sustainable integrated control of VL The paradigm for controlling vector-borne diseases should be prevention at source using an integrated set of intervention measures,34 not detection and response....
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...budgets, with fewer uncomplicated cases being resolved in East Africa and India than in southern Europe and Brazil.(1,6) Malnutrition is one of the important risk factors for VL, and a fall in disease incidence in southern Europe during the last 50 years coincided with better nutrition....
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...infantum by sand flies has been declining in many foci where living standards have improved, with better nutrition believed to mitigate the progression of debilitating or fatal infantile visceral leishmaniasis.(6) Also, there has been a decline or stabilization in the incidence of VL resulting from the transmission of L....
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...Surveillance, transmission modeling, risk factors, and predictive modeling Routine surveillance is usually too insensitive to assess accurately any changes in the prevalence or incidence of VL,(15,27) with most case detection being passive.(6) Also, it is not usually possible to estimate the human inoculation rate of parasites by the sand fly vectors(2) because most sand fly surveys use light and sticky traps that do not target host-seeking female flies, and the reports often mention only the relative abundances of species without distinguishing males from females....
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...donovani is found only in the Old World, where it is notoriously associated with VL (kala-azar or black death) of the rural poor in the northeast of the Indian subcontinent and with VL of displaced persons in East Africa.(1,6) Most transmission is believed to be anthroponotic, from human to human, and this contrasts with the zoonotic transmission of L....
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TL;DR: The early events associated with infection, the CD4- T cells that mediate protective immunity and the pathological role that CD8+ T cells can have in cutaneous leishmaniasis are discussed.
Abstract: Cutaneous leishmaniasis is a major public health problem and causes a range of diseases from self-healing infections to chronic disfiguring disease. Currently, there is no vaccine for leishmaniasis, and drug therapy is often ineffective. Since the discovery of CD4(+) T helper 1 (TH1) cells and TH2 cells 30 years ago, studies of cutaneous leishmaniasis in mice have answered basic immunological questions concerning the development and maintenance of CD4(+) T cell subsets. However, new strategies for controlling the human disease have not been forthcoming. Nevertheless, advances in our knowledge of the cells that participate in protection against Leishmania infection and the cells that mediate increased pathology have highlighted new approaches for vaccine development and immunotherapy. In this Review, we discuss the early events associated with infection, the CD4(+) T cells that mediate protective immunity and the pathological role that CD8(+) T cells can have in cutaneous leishmaniasis.
349 citations
TL;DR: In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression, and is highlighted as a potential target to treat inflammatory related diseases.
Abstract: Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors-P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels). Among the P2 receptors, the P2X7 receptor is the most extensively studied from an immunological perspective, being involved in both innate and adaptive immune responses. P2X7 receptor activation induces large-scale ATP release via its intrinsic ability to form a membrane pore or in association with pannexin hemichannels, boosting purinergic signaling. ATP acting via P2X7 receptor is the second signal to the inflammasome activation, inducing both maturation and release of pro-inflammatory cytokines, such as IL-1β and IL-18, and the production of reactive nitrogen and oxygen species. Furthermore, the P2X7 receptor is involved in caspases activation, as well as in apoptosis induction. During adaptive immune response, P2X7 receptor modulates the balance between the generation of T helper type 17 (Th17) and T regulatory (Treg) lymphocytes. Therefore, this receptor is involved in several inflammatory pathological conditions. In infectious diseases and cancer, P2X7 receptor can have different and contrasting effects, being an angel or a demon depending on its level of activation, cell studied, type of pathogen, and severity of infection. In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression. In this review, we deeply discuss P2X7 receptor dual function and its pharmacological modulation in the context of different pathologies, and we also highlight the P2X7 receptor as a potential target to treat inflammatory related diseases.
271 citations
Cites background from "Leishmaniasis Worldwide and Global ..."
...Over the last decade, our laboratory has been exploring the role of P2X7 receptor in Leishmaniasis, a neglected tropical disease caused by a parasite of the genus Leishmania (Alvar et al., 2012)....
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...P2X7 receptor expression is upregulated in Leishmania amazonensis-infected macrophages and its activation reduces parasitic load in these cells (Chaves et al., 2009)....
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...P2X7 Receptor in Protozoa Infections Over the last decade, our laboratory has been exploring the role of P2X7 receptor in Leishmaniasis, a neglected tropical disease caused by a parasite of the genus Leishmania (Alvar et al., 2012)....
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References
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Book•
01 Jan 1996
TL;DR: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors" and use historical trends in main determinants to project mortality and disease burden forward to 2020.
Abstract: This is the first in a planned series of 10 volumes that will attempt to "summarize epidemiological knowledge about all major conditions and most risk factors;...generate assessments of numbers of deaths by cause that are consistent with the total numbers of deaths by age sex and region provided by demographers;...provide methodologies for and assessments of aggregate disease burden that combine--into the Disability-Adjusted Life Year or DALY measure--burden from premature mortality with that from living with disability; and...use historical trends in main determinants to project mortality and disease burden forward to 2020." This first volume includes chapters summarizing results from the project as a whole. (EXCERPT)
7,154 citations
01 Jan 2006
TL;DR: This first edition provides information on disease control interventions for the most common diseases and injuries in developing countries to help them define essential health service packages and offers preventive and case management guidelines critical to improving the quality of care.
Abstract: This first edition provides information on disease control interventions for the most common diseases and injuries in developing countries to help them define essential health service packages. Life expectancy in developing countries increased from forty to sixty-three years between 1950 and 1990 with a concommitant rise in the incidence of noncommunicable diseases of adults and the elderly. It is still necessary to deal with under nutrition and communicable childhood diseases. Also, new epidemic diseases like AIDS are emerging, and the health of the poor during economic crisis is a growing concern. These health developments intensify the need for better information on the effectiveness and cost of health interventions. The information is intended for health practitioners at every level. Individual chapters offer preventive and case management guidelines critical to improving the quality of care. The need for health sector reform is global. Both developed and developing countries, and centrally planned and market oriented health systems share basic dissatisfaction with the present organization and financing of health care delivery and a conviction that there are better ways to obtain results with the available resources. This book attempts to assist health sector reformers to review existing services and adapt them to provide the most cost effective interventions available.
2,381 citations
TL;DR: Research for leishmaniasis has been more and more focusing on the development of new tools such as diagnostic tests, drugs and vaccines, and the newly available control tools should allow a scaling up of control activities in priority areas.
Abstract: 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.
2,150 citations
"Leishmaniasis Worldwide and Global ..." refers background in this paper
...Reported leishmaniasis case figures are widely acknowledged to represent gross underestimates of the true burden, but studies that measure the degree of underreporting are rare [23]....
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TL;DR: In depth topics with major scientific challenges and institutional and cultural barriers that are slowing the development of the field are explored.
884 citations
TL;DR: A raised estimate of 2-15% disability seems evident in different functional domains of a person with schistosomiasis, if confirmed in formal patient-preference studies, indicates a need to reassess the authors' priorities for treating this silent pandemic of schistOSomiasis.
836 citations
"Leishmaniasis Worldwide and Global ..." refers background in this paper
...The accuracy of this measure depends on the reliability of the incidence, duration, severity and mortality data for a given condition, as well as the underlying assumptions used in the calculations [7,14]....
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