Uma história das leishmanioses no novo mundo: anos 1960 ao século XXI: Amazônia / A history of leishmaniasis in the new world: 1960s to the 21st century: Amazon

Analisam os fatores biológicos, sociais e ambientais responsáveis pela ocorrência da doença na Amazônia mostrando os cientistas e sanitaristas que tiveram papel fundamental nas pesquisas sobre essa e outras endemias

Uma história das leishmanioses no Novo Mundo: fins do século XIX aos anos 1960

Apanhado dos estudos sobre as leishmanioses no Brasil englobando a descoberta dos seus agentes etiológicos, diversas espécies associadas às diferentes formas clínicas da doença, seus hospedeiros reservatórios e os flebotomíneos vetores, bem como aspectos da epidemiologia e ações de controle implementadas em contextos sociopolíticos e momentos diversos

Historical overview of infantile visceral leishmaniasis in El Agamy, Alexandria, Egypt.

Infantile visceral leishmaniasis (IVL) is considered a rare and neglected disease in Egypt. An outbreak of the disease in El Agamy, Alexandria occurred in 1982 although the disease was previously reported 80 years before. Epidemiological and entomological studies were conducted ever since the 1982 outbreak to identify human cases, the parasite, reservoir host and the sand fly vector. Leishmania infantum MON-98, a new and unique zymodeme, was responsible of the disease. Stray dogs acted as the reservoir host and Phlebotomus langeroni was the proven vector. The parasite isolates from human cases were identical to the parasite isolates from the reservoir host and the sand fly vector. The El Agamy focus in 1982 was basically a rural Bedouin setting of recently built cement houses surrounded by lime stone fences. The numbers of human cases of IVL in this area have been declining, with the last reported case in 2005. This coincides with the completion of irregular urbanization of El Agamy which resulted in the disappearance of P. langeroni. In this review, we characterize the old focus of IVL in El Agamy based on published literature to identify factors underlying the appearance and disappearance of the disease.

Visceral leishmaniasis epidemiologic evolution in timeframes, based on demographic changes and scientific achievements in Brazil.

Visceral leishmaniasis (VL) is a disease of chronic evolution which could be uniformly fatal, if left untreated. Human VL was first described in the Americas in 1913 and in 1936 in Brazil. The number of VL cases in Brazil is increasing steadily in the last three decades. Medical literature highlights this change in the disease epidemiology as a recent urbanization phenomenon, with most of the cases occurring in large cities since 1981, different to that observed previously, like a typical rural endemic. The aim of this study was to create a narrative review of the evolution of VL epidemiology since its first description in Brazil. To describe the process of urbanization of VL, timeframes were created historically consistent with the scientific and public health knowledge obtained about the VL and the demographics changes in Brazil, especially considering the extensive migratory movements in the country due to political or economic events. The first phase of VL was the decades of 30-50 when industrialization triggered internal migration process from countryside to the cities; during this period VL was studied for the first time and described as a rural endemic disease with no relevance to public health. Until the second phase, between the 50s and 80s of the 20th century, demography was characterized by expansion of immigration to the large cities and increase in population density in the suburbs with poor living standards. In this period, there was an advancement in the knowledge of the transmission of the disease being described as the first case acquired in the urban environment. The third phase was characterized by the explosion of cases in Brazilian cities and consolidation of urban endemic transmission. The possibility of urban transmission has been known since the 50s; however, the current phenomenon was due to the creation of ideal conditions for the establishment of transmission cycle in Brazilian cities.

Quantification of the natural history of visceral leishmaniasis and consequences for control.

BACKGROUND: Visceral leishmaniasis has been targeted for elimination as a public health problem (less than 1 case per 10,000 people per year) in the Indian sub-continent by 2017. However, there is still a high degree of uncertainty about the natural history of the disease, in particular about the duration of asymptomatic infection and the proportion of asymptomatically infected individuals that develop clinical visceral leishmaniasis. Quantifying these aspects of the disease is key for guiding efforts to eliminate visceral leishmaniasis and maintaining elimination once it is reached. METHODS: Data from a detailed epidemiological study in Bangladesh in 2002-2004 was analysed to estimate key epidemiological parameters. The role of diagnostics in determining the probability and rate of progression to clinical disease was estimated by fitting Cox proportional hazards models. A multi-state Markov model of the natural history of visceral leishmaniasis was fitted to the data to estimate the asymptomatic infection period and the proportion of asymptomatic individuals going on to develop clinical symptoms. RESULTS: At the time of the study, individuals were taking several months to be diagnosed with visceral leishmaniasis, leading to many opportunities for ongoing transmission. The probability of progression to clinical disease was strongly associated with initial seropositivity and even more strongly with seroconversion, with most clinical symptoms developing within a year. The estimated average durations of asymptomatic infection and symptomatic infection for our model of the natural history are 147 days (95 % CI 130-166) and 140 days (95 % CI 123-160), respectively, and are significantly longer than previously reported estimates. We estimate from the data that 14.7 % (95 % CI 12.6-20.0 %) of asymptomatic individuals develop clinical symptoms-a greater proportion than previously estimated. CONCLUSIONS: Extended periods of asymptomatic infection could be important for visceral leishmaniasis transmission, but this depends critically on the relative infectivity of asymptomatic and symptomatic individuals to sandflies. These estimates could be informed by similar analysis of other datasets. Our results highlight the importance of reducing times from onset of symptoms to diagnosis and treatment to reduce opportunities for transmission.

The race to discover the insect vector of kala-azar: a great saga of tropical medicine 1903-1942.

In the 19(th) century, a devastating epidemic of visceral leishmaniasis (kala-azar) swept through northeast India. After identification of the pathogenic agent, Leishmania donovani, in 1903, the question of its transmission remained to be resolved. In 1904, thanks to work by L. Rogers on cultures of this parasite it became probable that a haematophagous arthropod was responsible for transmission. J.A. Sinton suggested, in 1925, the distribution of the sand fly Phlebotomus argentipes was similar to that of the disease and, thereafter, two independent teams led by H.E. Shortt in Assam and R. Knowles and L. Napier in Calcutta concentrated on this potential vector. Parallel work was in progress in China, directed by E. Hindle and W. S. Patton for the Royal Society Kala-azar Commission, on another species of sand fly. In 1942 the Assam workers transmitted L. donovani to five human volunteers by the bites of colonised P. argentipes and the race was over.

Editorial: A 101 años del primer caso de leishmaniosis visceral en las Américas / Editorial: 101 years from the first case of visceral leishmaniosis in the Americas

En 1911 se reportó el primer caso de leishmaniosis visceral en las Américas (LVA), y no es de extrañar que haya transcurrido el centenario del descubrimiento realizado por el Prof. Dr. Luis Enrique Migone Mieres (1876-1954) y publicado dos años más tarde en el Boletín de la Sociedad de Patologías Exóticas de Francia (1) y 15 años después en la revista Anales del Instituto Nacional de Parasitología de Paraguay (2), sin que se haya hecho hincapié en este relevante suceso, pues nos encontramos frente a una de las enfermedades tropicales consideradas como enfermedades infecciosas desatendidas (EID) del mundo entero. Se estima que hay unas 12 millones de personas infectadas y cada año se registran aproximadamente entre 1,5 y 2 millones de nuevas infecciones (3), representando un estigma para las regiones pobres del mundo, con una carga bastante pesada para las poblaciones afectadas.

[Contribution of palaeopathology to defining the pathocoenosis of infectious diseases (Part two)]. / Apporti della paleopatologia alla definizione della patocenosi delle malattieinfettive (II parte).

In the second part of their review the authors focus on palaeopathological studies, performed in mummified tissues, with reference to infectious diseases. The analysis of samples obtained from both natural and artificial mummies may provide, in some favourable events, a more complete knowledge of these findings in comparison to information obtained from only comprehensive examination of the skeleton. The acquired data enable us to understand not only the diseases which afflicted mankind, but also dietary and hygiene conditions of ancient populations. We report knowledge acquired regarding some palaeopathological conditions, including schistosomiasis, smallpox, cisticercosis, trichinosis, ascaridiasis, echinococcosis, filariasis, hepatitis E virus, condylomatosis, pulmonary tubercolosis, pediculosis, visceral leishmaniasis as well as Diphyllobotrium sp., Dicrocoelium dendriticum and Fasciola hepatica infestations. In addition some interesting findings concerning the relationship between dietary and food intake colonized by streptomyces are described. This review reports the discovery of human remains from different geographic areas: while most of these studies describe findings in two Mediterranean countries (Italy and Egypt), some refer to Britain and German-speaking countries (Austria and Germany) as well as the area in Africa known as Nubia, along the Nile. Both histological and biomolecular diagnosis are useful not only to identify a specific disease in a subject from the remote past, but also to achieve information concerning its frequency and evolution. Such knowledge may thus allow us to understand the intensity of cultural exchanges and links among different populations and the role of these relationships in transmitting and spreading infectious diseases in a certain geographic area.

Pursuit of medical knowledge: Charles Donovan (1863-1951) on kala-azar in India.

Kala-azar was a lethal disease in colonial India. Charles Donovan of the Indian Medical Service (IMS) in Madras discovered the parasite independently in 1903 while William Boog Leishman was carrying out his research in Great Britain. Donovan's discovery ended the confusion prevalent over the anomalous and puzzling cases of malarial fevers in India and proved they were not related to malaria. This added to the promotion of medical knowledge, initiated further research and created enthusiasm among medical scientists throughout the world. Donovan was the first person to see the kala-azar parasite in the peripheral blood and thus provided a clue to the carriage and transmission of the kala-azar parasite by the insect through peripheral blood. Donovan's research on kala-azar also convinced the government of its utility and the need for further investigation; he fell victim to professional rivalry.

Panorama histórico do diagnóstico laboratorial da leishmaniose visceral até o surgimento dos testes imunocromatográficos(rk39) / Historical panorama of laboratorial diagnostic of visceral leishmaniasis until the appearance of immunochromatographic tests

Este estudo faz uma revisão do diagnóstico da Leishmaniose visceral humana no Brasil e no mundo. O diagnóstico parasitológico direto, utilizado a partir de 1930, possui elevada especificidade e sensibilidade, entre 60por cento e 95por cento. A Reação de Fixação do Complemento (em desuso), desenvolvida na década de 1940, apresentou resultados promissores, porém demonstrou reações cruzadas com doença de Chagas, sífilis e blastomicose. A reação de Imunofluorescência Indireta (RIFI), empregada a partir dos anos 60, utiliza formas promastigotas do parasito que a limitam em termos de especificidade e reprodutibilidade. Nos anos 70, a técnica de Enzimaimunoensaio (com antígenos crus ou purificados), assim como suas variações (Dot-ELISA, Fast-ELISA, e micro ELISA, entre outras), começou a ser utilizada e mostrou-se mais sensível e menos específica que a RIFI. Nos anos 80, a Reação em Cadeia da Polimerase foi empregada, apresentando boa sensibilidade, contudo, em virtude do elevado custo operacional não está adaptada ao diagnóstico de rotina. Nos anos 90, o Teste Rápido Anticorpo L. donovani, marcado com o antígeno rK39, apresentou limitações, pois não detectava infecção em animais com títulos de RIFI de 1:40 a 1:320. Atualmente, um novo método de Teste Rápido para detecção de Leishmania spp. (TRL), marcado com o antígeno rK39, está sendo utilizado no Brasil. Neste estudo o TRL demonstrou sensibilidade de 95,8por cento e especificidade de 99,7por cento. Este teste pode ser utilizado na área de campo, visto que apresenta resultados em curto espaço de tempo e tem baixo custo operacional.

LeishmanioseTegumentar Americana no Estado de São Paulo: Situação epidemiológica 2001-2002 / American cutaneous leishmaniasis em São Paulo State: Epidemiological situation 2001-2002

No Estado de São Paulo a Leishmaniose Tegumentar Americana (LTA) foi descrita pela primeira vez no final do século passado com ocorrência de grande número de casos, porém essas áreas estavam restritas às regiões Oeste e Noroeste do Estado onde o agente identificado foi Leishmania leishmania braziliensis; durante várias décadas a doença perdeu sua importância, porém na década de 70 sua ocorrência foi assinalada no Sul do Estado, região considerada anteriormente indene. Nestas áreas, tendo sido identificados manifestações endêmicas e a transmissão humana vem sendo detectada fora do ambiente florestal, ocorrendo nas zonas; rural e periurbana. Neste ambiente, a transmissão ocorre no intra, mas principalmente, no peridomicílio ( Camargo-Neves 1999). A transmissão no Estado de São Paulo é caracterizada pela ocorrência de casos esporádicos e surtos epidêmicos são característicos de algumas regiões como o Vale do Ribeira, Campinas e Sorocaba, geralmente ligados à ocupação do solo por novas áreas de plantio ou invasão de mata por extensão urbana ( Camargo-Neves 1999, Gomes e Camargo Neves 1998)...

Drug resistance in Indian visceral leishmaniasis.

Throughout the world, pentavalent antimonial compounds (Sb(v)) have been the mainstay of antileishmanial therapy for more than 50 years. Sb(v) has been highly effective in the treatment of Indian visceral leishmaniasis (VL: kala-azar) at a low dose (10 mg/kg) for short durations (6-10 days). But in the early 1980s reports of its ineffectiveness emerged, and the dose of Sb(v) was eventually raised to 20 mg/kg for 30-40 days. This regimen cures most patients with VL except in India, where the proportion of patients unresponsive to Sb(v) has steadily increased. In hyperendemic districts of north Bihar, 50-65% patients fail treatment with Sb(v). Important reasons are rampant use of subtherapeutic doses, incomplete duration of treatment and substandard drugs. In vitro experiments have established emergence of Sb(v) resistant strains of Leishmania donovani, as isolates from unresponsive patients require 3-5 times more Sb(v) to reach similarly effectiveness against the parasite as in Sb(v) responders. Anthroponotic transmission in India has been an important factor in rapid increase in the Sb(v) refractoriness. Pentamidine was the first drug to be used and cured 99% of these refractory patients, but over time even with double the amount of initial doses, it cures only 69-78% patients now and its use has largely been abandoned in India. Despite several disadvantages, amphotericin B is the only drug available for use in these areas and should be used as first-line drug instead of Sb(v). The new oral antileishmanial drug miltefosine is likely to be the first-line drug in future. Unfortunately, development of newer antileishmanial drugs is rare; two promising drugs, aminosidine and sitamaquine, may be developed for use in the treatment of VL. Lipid associated amphotericin B has an excellent safety and efficacy profile, but remains out of reach for most patients because of its high cost.