This timeline traces the history of the disease, starting with the first description of the disease, and all the epidemiological history, as well as that of case management, control of the disease, and WHO's involvement and its ongoing battle against the disease.
Bonanni, in Rome, Italy, gives the first recognizable description of a sandfly as a species of Culex, or mosquito.
Alexander Russell (1715–1768) provides the first description in English of a lesion resembling cutaneous leishmaniasis as the “Aleppo evil” after examining a Turkish patient from (what is now) the Syrian Arab Republic.
Scopoli describes the first member of the Diptera group of sandflies as papatasi.
Kala-azar is first noticed in an outbreak in Jessore in India (now Bangladesh) of a fever characterized by relapses and progressive emaciation that fails to respond to quinine; by 1862, the disease has spread to Burdwan where it reaches epidemic proportions and becomes known as “Burdwan fever”, “kala-azar” or “black disease”.
Rondani and Berte establish the genus of the sandflies Phlebotomus.
The earliest description of leishmaniasis in the Old World presents the disease as “Nile Pimple” in Pharaoh’s Papyrology.
David Douglas Cunningham (1843–1914) makes the first drawings of Leishmania amastigotes isolated from lesions of “Delhi boil” in India. As a Professor of Medicine and Pathology in India, he makes a number of contributions to parasitology including early accounts of Entamoeba coli and Trichomonas hominis.
The focal nature of the infection was noted in the 19th century by Rogers who introduced the practice of destroying villages and resiting them. The next method of control was finding all the cases and treating them, which was expensive and time-consuming but over period of time has proved successful.
Peter Fokich Borovsky (1863–1932), a physician in the Russian army, fully describes for the first time the causative organism of Old World leishmaniasis and accurately describes small bodies in the lesions of “Oriental sore” in Tashkent.
James Homer Wright (1969–1928), chief of pathology at Massachusetts General Hospital, comes across an Armenian girl suffering from “Delhi sore” from whose lesions he discovers numerous organisms that are indescribable to him. Wright names the organism Helicosoma tropicum (today known as Leishmania tropica).
William Leishman (1865–1926), a doctor in the Scottish army, publishes his identification of the parasite in the spleen of an English private who had died of Dumdum fever in Dum-Dum, India in 1900. Leishman becomes the first person to identify the causative agent of kala-azar; however, he identifies the organisms as trypanosomes.
Charles Donovan (1863–1951), serving in the Indian Medical Service but unaware of Leishman’s discovery, independently confirms what are known as Leishman–Donovan bodies and makes the first description of the link between Leishman–Donovan bodies and kala-azar.
Ronald Ross (1857–1932) investigates the causative parasite of kala-azar in Calcutta and realizes that the parasite discovered by Donovan is the same as that seen by Leishman; Ross creates the genus Leishmania and names the parasite Leishmania donovani in their honour. Born in India, Ross joins the Indian Medical Service in 1881, and wins the Nobel Prize in 1902 for his elucidation of malaria transmission by mosquitoes.
Cathoire and Laveran describe visceral leishmaniasis in children with infantile splenic anaemia as a different form of the disease that attacks only infants, does not occur in epidemics but that remains endemic. The parasite concerned is now known as L. infantum in the Old World.
Charles Jules Henry Nicolle, a French bacteriologist, describes species causing visceral leishmaniasis in children in Tunisia suffering from splenic anaemia. Together with Charles Comte, he discovers the parasite in dogs in Tunis, establishing them as important reservoir hosts for visceral leishmaniasis.
Adolpho Lindenberg first detects various skin lesions of humans in Latin America as due to species of Leishmania by showing Leishman–Donovan bodies (amastigotes) in patients with “úlcera de Bauru” in São Paulo State, Brazil.
Gaspar Vianna, a young physician in Rio de Janeiro, claims that the parasites in South America differ from those in Africa and India and creates a new species, Leishmania brazilienses (later amended to L. braziliensis by Matta in 1916).
Splendore demonstrates the presence of the parasite in mucocutaneous lesions of espundia, a mucosal leishmaniasis
Wenyon demonstrates incrimination of Phlebotomus as the probable vector of diseases caused by Leishmania in the Old World.
Gaspar Vianna (1885–1914), a Brazilian clinician and scientist, introduces the use of tartar emetic (trivalent antimony) as treatment for cutaneous and muco-cutaneous leishmaniasis.
Migone reports the first documented case, which was from Paraguay. The history of viceral leishmaniais in South America is relatively short and dominated by arguments about whether or not it was imported from the Old World in relatively recent times.
Differentiation of parasites causing “dry urban” and “wet rural” cutaneous leishmaniasis
G. Di Cristina and G. Caronia, demonstrate efficacy of antimony (III) potassium tartarate (tartar emetic) in the treatment of visceral leishmaniasis
Upendranath Brahmachari, an Indian professor and scientist, synthesizes the pentavalent antimony compound urea stibamine as an effective chemotherapeutic agent against Indian kala-azar. For this discovery he is nominated for the Nobel Prize in 1929.
The Sergent brothers Edouard (1876–1969) and Etienne (1878–1948) demonstrate experimental proof of transmission to humans by sandflies of the genus Phlebotomus. Mosquito bites were already suspected of being the cause of oriental sore in the 16th century by Arabian physicians in the Middle East.
Aragão discovers Lutzomyia as the genus involved in sandfly transmission of Old World leishmaniasis after which the vectors in the New World are also assumed to belong to the genus Phlebotomus.
Sir Upendranath Brahmachari first reports human cases of non-ulcerative nodular skin lesions which he terms “dermal leishmanoid”, a dermatological manifestation usually occurring months to years after resolution of visceral leishmaniasis caused by Leishmania donovani. In 1927, Action and Naier term this condition “post-kala-azar dermal leishmaniasis”.
Noguchi, Adler and Theodor introduce the Noguchi-Adler test as a serological test to differentiate strains of Leishmania. The test is based on the species-specific determinants, which are on Leishmania recognized by polyclonal immune sera. This method is used to distinguish between the Mediterranean form of L. major and L. tropica.
Montenegro develops an intradermal leishmanin skin test, or “Montenegro test”, by experimental inoculation of L. braziliensis. This delayed hypersensitivity test is useful in epidemiological studies.
Penna provides the first record of visceral leishmaniasis in the Amazon.
Hans Schmidt, in Germany, synthesizes sodium antimony gluconate under the name “solustibosan”, a pentavalent antimonial, in which gluconic acid replaces tartaric acid. Stable in solution and less toxic than the previous form, sodium stibogluconate and the closely related meglumine antimoniate (Glucantime) introduced by Rhone-Poulenc in 1946 remain the standard treatment for all forms of leishmaniasis. The pentavent antimonials were only available as injection until today. They are now included in WHO’s List of Essential Medicines.
Saul Adler (1895–1966) continues the search for a vector and the actual mode of infection through the bite of the sandfly when volunteers are exposed to Phlebotomus papatasi infected with leishmanial flagellates. The volunteers finally develop individual leishmanial lesions.
Henry Edward Shortt (1887–1987), a Colonel in the Indian Army Medical Service, demonstrates transmission of kala-azar by Phlebotomus argentipes
Biagi names the causative agent of “Chicleros ulcer” in Belize, Guatemala and Yucatán as Leishmania tropica mexicana. In French Guyana, Floch adopts the same trinomial nomenclature in 1954 by referring to the cause of “pian-bois” as L. tropica guyanensis. Similarly, in other parts of South America, he attributes cutaneous leishmaniasis to L. tropica braziliensis. However, in 1959, Medina and Romero, as well as other researchers, give the name to the parasite associated with 81 cases of diffuse cutaneous leishmaniasis in (what is now) the Bolivarian Republic of Venezuela.
Jacinto Convit, a Venezuelan physician, and his colleague Lapenta describe a condition referred to as diffuse cutaneous leishmaniasis, the causative agent of which in Venezuela was later named Leishmania pifanoi.
Lainson and Strangways-Dixon establish that forest rodents are the reservoir host of the leishmanial parasite, and show visible lesions on their tails. A volunteer is successfully infected with the rodent parasite, representing the first conclusive association of a neotropical leishmanial parasite known to infect man with a sylvatic reservoir in wild animals.
Biochemical tests are introduced to differentiate strains of Leishmania. This technique is useful for epidemiological studies in humans and, from the 1980s, is recommended also to designate reference strains and to protect them in cryobanks. Recently, polymerase chain reaction methods have improved their diagnostic sensitivity, allowing identification of the parasite DNA. Today, molecular genetics are used to elucidate the evolution of Leishmania. Besides the Noguchi-Adler test, other techniques emerge for differentiating strains of Leishmania.
WHO publishes the first report of the WHO Expert Commitee on control of the leishmaniases.
A simpler direct agglutination test is introduced in the diagnosis of visceral leishmaniasis. This semi-quantitative test uses microtitre plates in which increasing dilutions of a patient’s serum or blood are mixed with killed L. donovani promastigotes. Agglutination is visible after 18 hours with the naked eye. The test is extensively validated in most endemic areas. Indirect fluorescent antibody techniques and the enzyme linked immunosorbent assay are introduced, improving diagnostic accuracy but are poorly adapted for field settings.
WHO publishes the second report of the WHO Expert Committee on control of the leishmaniases.
Until the 1990s, the classical confirmatory test was used for diagnosis of visceral leishmaniasis is a parasitological test confirmed by microscopy or culture of blood, bone marrow, lymph nodes or spleen. However, splenic aspiration can be complicated and requires strict precautions, training and technical expertise. Thus, the high risk associated with splenic aspiration motivates the development of non-invasive serological tests such as the direct agglutination test and the lateral flow immunochromatographic test, commonly referred to as rapid diagnostic tests.
The first form of liposomal amphotericin B (L-AmB) is introduced into the market by Vestar under the brand name AmBisome. In 1997, the United States Food and Drug Administration approves its use for treatment of visceral leishmaniasis.
WHO categorizes the Leishmania species intro three subgenera: Leishmania, Sauroleishmania, and Viannia.
Dr Philippe Desjeux publishes a document presenting for the first time data, as countries profiles, on the epidemiology and control of the leishmaniases.
WHO establishes a global surveillance network of 28 institutions, named Leishnet, to document the extent of HIV–Leishmania coinfection and monitor trends. Subsequently, the network expands to all endemic areas and includes Africa, South America and Asia.
WHO publishes the report of a consultative meeting on coinfection with Leishmania and HIV. The main objectives of the meeting were: to evaluate the real extent of the problem and identify the main populations at risk; to issue guidelines for diagnosis and treatment; to set up a network of institutions that can promote systematic detection of both infections and improve the management and follow up of coinfected patients; to set up a central registry at WHO headquarters to centralize, analyse and periodically disseminate basic epidemiological information on Leishmania–HIV coinfection; and, finally, to secure the recognition of visceral leishmaniasis as an AIDS-defining disease.
In the 1990s, a second serological test that does not require a laboratory is developed for field use. This technique is based on immunochromatographic detection by dip-stick of a cloned recombinant rK39 antigen.
WHO publishes an epidemiological analysis of 692 retrospective cases of coinfection with Leishmania and HIV in the Weekly Epidemiological Record.
Desjeux and colleagues publish Leishmania/HIV co-infection in south-western Europe 1990–1998: retrospective analysis of 965 cases.
Miltefosine is introduced as the first oral treatment against leishmaniasis. The Weekly Epidemiological Record dedicates a paragraph to miltefosine.
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