Leishmaniasis
Leishmaniasis is a disease that is caused by infection with protozoan leishmania parasites which are transmitted through the bite of infected female phlebotomine sand flies.
There are three main forms of leishmaniasis in people:
- cutaneous leishmaniasis, which causes skin sores
- mucosal leishmaniasis, which damages the skin and mucous membranes, especially in the nose and throat area
- visceral leishmaniasis, also known as kala-azar and the most serious form of the disease, which affects several internal organs like spleen, liver and bone marrow
What is canine leishmaniasis?
Leishmaniasis caused by the protozoan parasite Leishmania infantum (known in South America as Leishmania chagasi) is a true zoonosis and impacts on the health, well-being and life of predominantly dogs and cats. In veterinary medicine, one would speak of canine leishmaniasis. The transmission follows equivalent pattern as for humans, an infected phlebotomine sand fly. In Europe the predominant vector species is Phlebotomus perniciosus, in Latin America Lutzomyia longipalpis. While the infective Leishmania species is the same as in humans, in dogs one cannot differentiate as L. infantum causes clinical signs in skin as well as infecting inner organs of the dog.
Please find more information on this disease in the text below or watch expert interview:
Leishmaniasis
What is the disease?
How dangerous is leishmaniasis?
Only a small fraction of persons infected by Leishmania parasites will actually develop the disease.
If not treated, severe cases of visceral leishmaniasis also known as kala-azar are fatal in over 95 percent of cases.
The skin sores of cutaneous leishmaniasis usually heal on their own. But this can take months or even years, and the sores can leave lifelong scars.
Certain types of parasites found in parts of Latin America might spread from the skin and cause mucosal leishmaniasis with sores in the mucous membranes of the nose, mouth, or throat.
How dangerous is leishmaniasis to dogs?
Canine leishmaniosis is a life threatening disease in canids. In Leishmania endemic regions investigations have shown, that unprotected dogs are tested positive following two seasons of sand fly exposure.
Who is at risk?
People of all ages are at risk for infection if they live or travel where leishmaniasis is endemic.
The transmission risk is highest from dusk to dawn because this is when sand flies generally are the most active.
Which animals are at risk?
Infection with Leishmania is reported from a wide variety of mammalian animal species. These include e.g. horses. However in terms of medical importance leishmaniasis is a serious disease for dogs as well as cats. All dogs in sand fly, resp. Leishmania endemic regions of the world, esp. around the Mediterranean sea and South America are at risk to acquire the parasite and subsequently develop the disease. There are reports on either certain dogs breeds in Spain that are resistant against the disease. This is explained by the variation of the immune response, in general terms dogs that develop the disease have a humeral immune response, while those that are either resistant or are able to suppress, even eliminate the parasite have a strong cellular immune response. Transmission to dogs, like to humans is high in endemic regions especially during dusk and dawn, as sand flies try to avoid the heat of the day.
How many people are affected by leishmaniasis?
- For cutaneous leishmaniasis, estimates of the number of cases range from approximately 700,000 to 1,200,000 per year
- For visceral leishmaniasis, estimates of the number of cases range from approximately 200,000 to 400,000 per year
- An estimated 20 000 to 30 000 deaths occur annually
How many dogs are affected by Leishmania?
There are no such figures as those for humans reported via the WHO. In Southern Italy studies have shown the high prevalence, and even more important incidence of leishmaniasis. 100% of unprotected dogs developed an immune response to the infection following two seasons of exposure. Canine leishmaniasis, the protection, diagnosis and therapy is the major clinical disease in small animal clinics in respective countries such as Italy, Spain or Portugal.
Where is leishmaniasis found?
Leishmaniasis usually is more common in rural than in urban areas, but it is found in the outskirts of some cities.
- Leishmaniasis is found in parts of more than 90 countries
- Visceral leishmaniasis is highly endemic in the Indian subcontinent and in East Africa
- Cutaneous leishmaniasis occurs in the Americas, the Mediterranean basin, the Middle East and Central Asia. Over two thirds of new Cutaneous leishmaniasis cases occur in six countries: Afghanistan, Algeria, Brazil, Colombia, Iran and Syria
- Mucocutaneous leishmaniasis occurs in Bolivia, Brazil, Ethiopia and Peru
- In 2015, more than 90 percent of new cases reported to WHO occurred in seven countries: Brazil, Ethiopia, India, Kenya, Somalia, South Sudan and Sudan
- Leishmaniasis is not found in Australia or the Pacific Islands
Where is canine leishmaniasis found?
Infection by L. infantum can be found in large parts of South America, esp. Brazil, as well as all round the Mediterranean Sea. Due to re-homing of dogs, in non-endemic countries such as, e.g. Germany or UK, large numbers of patent infected dogs are present.
How do people get leishmaniasis?
The main way is through the bite of infected female phlebotomine sand flies. Sand flies become infected by sucking blood from an infected animal or person. People might not realize that sand flies are present because:
- they do not make any noise
- they are very small, about one third the size of typical mosquitoes or even smaller
- their bites might not be noticed because they can be painless
- contaminated needles
- blood transfusions
- congenital transmission from a pregnant woman to her baby
How do dogs get infected?
There is no difference between the infection with Leishmania in humans or animals. Infected blood feeding female sand flies transmit the parasite to the host. There is one difference due to the biology of the sand fly and the canine host. As dogs, different to humans have the skin covered by hair, sand flies approach the dog, land anywhere on the dog and for there the sand fly is moving, hopping around on the dog to find skin areas with less hair. Sand flies do not ‘crawl’ through the hair coat to get to the skin for a blood meal. Sand flies search for hair-less regions, like e.g. around the nose, mouth or eyes of the dog. Thus these feeding sides are also the deposit sides of the Leishmania parasite and subsequently the side with the first clinical signs.
Like in humans, in veterinary medicine, non vectorial transmission are possible, thus veterinary associations have defined by guidelines on how to avoid, e.g. transmission during blood transfusion. Dog breeder associations are advised to test e.g. male dogs for Leishmania, as the parasites can be transmitted with the semen.
What are the signs and symptoms of cutaneous leishmaniasis?
Cutaneous leishmaniasis causes skin lesions, mainly ulcers, on exposed parts of the body, leaving life-long scars and serious disability.
Some people have a silent infection, without any symptoms or signs but most people usually develop symptoms within a few weeks or months of the sand fly bite.
What are the signs and symptoms of mucosal leishmaniasis?
Mucocutaneous leishmaniasis leads to partial or total destruction of mucous membranes of the nose, mouth and throat.
After the sores of cutaneous leishmaniasis have healed affected people may notice frequent nose bleeding and restricted breathing through the nose.
What are the signs and symptoms of visceral leishmanias?
Visceral leishmaniasis, also known as kala-azar, is fatal if left untreated in over 95 percent of cases. It is characterized by irregular bouts of fever, weight loss, enlargement of the spleen and liver, and anaemia.
Some people have a silent infection without any symptoms but most people become sick within months of when they were bitten.
What are the clinical signs in canine leishmaniasis?
Infection following the transmission of the Leishmania infantum parasite during the blood meal of sand flies can be clustered into:
Dogs that are either exposed while without any clinical signs and detection via serology, or infected with serology and clinical signs. These clinical signs are differentiated into four stages:
-
Stage I (Mild disease):
The dog shows either no or low antibody titers in serology. The clinical signs are mild with e.g. single lymph nodes affected. -
Stage II (moderate disease):
The dog shows low to high antibody titer and is positive under clinical examination. Lesion are either on the skin, inner organs and the dogs shows loss of appetite and weight loss. -
Stage III (servere disease):
The serology of the severely sick dog shows medium to high antibody titers. Under clinical examination the dogs shows lesions in addition to those listed under stage I & II in the eyes (e.g. uvetitis) and the kidney (e.g. glomerulonephritis): -
Stage IV (very severe disease):
The antibody titers are medium to high and the clinical signs are severe.
The stages indicate the prognosis of the dog to recover under therapy. The prognosis is good, fair, and critical (in faust) in stages III and esp. IV.
How is the disease developing?
The period of time between infection and first symptoms is two weeks to three months for cutaneous leishmaniasis, and three to six months to several years for visceral leishmaniasis.
- The sores of cutaneous leishmaniasis can change in size and appearance over time. They may start out as papules or nodules and may end up as ulcers. Skin ulcers may be covered by scab or crust. The sores usually are painless but can also be painful. Some people have swollen glands near the sore.
- Mucosal leishmaniasis usually starts with a skin ulcer, such as cutaneous leishmaniasis. After it has healed, the disease affects the mucous membranes of some patients - especially the nasal and pharyngeal mucous membranes. Other mucous membranes, such as the mouth, larynx, windpipe or genitalia, may also be affected.
If he disease is not treated, it gradually destroys skin, cartilage and connective tissue, so that in the worst case the affected person suffers disfigured facial features.
- The condition of the patients with visceral leishmaniasis usually is progressively creeping over a longer period of time with rather unspecific symptoms like
- swelling of the lymph nodes
- fever spikes
- loss of weight
- weakness
- abdominal pain
- vomiting
- diarrhea
- markedly dark palms, soles and mucous membranes
- swelling of liver and spleen
- anemia
- increased susceptibility to infection
- impaired blood clotting
How is the disease developing in dogs?
Between infection following the sand fly blood meal and the first clinical, resp. laboratory diagnostic findings, there may be several months. First signs are often around the initial sand fly feeding site, resp. deposit of the Leishmania, on the skin. In general the major clinical findings in canine leishmaniasis are 90% dermal, followed by 80% lymphadenopathy, ocular and splenomegaly. In the terminal stage dogs dye of immunopathology, immune complex disease as e.g. Glomerolonephritis. The lag between infection and findings is predominantly important in those animals that are traveling between non-endemic and endemic regions.
How is Leishmaniasis diagnosed?
In visceral leishmaniasis, diagnosis is made by combining clinical signs with parasitological or serological tests.
In cutaneous and mucocutaneous leishmaniasis serological tests have limited value. In cutaneous leishmaniasis, clinical manifestation with parasitological tests confirms the diagnosis.
Tissue specimens – for example, from skin sores for cutaneous leishmaniasis or from bone marrow for visceral leishmaniasis – can be examined for the parasite under a microscope.
Blood tests that detect antibody to the parasite can be helpful for cases of visceral leishmaniasis. Tests to look for the parasite itself usually also are done.
How is leishmaniasis diagnosed in veterinary medicine?
Canine leishmaniasis is always a combination of the anamnesis, thus has the animal been in sand fly endemic regions (travel history) and thus often unknown in animals under re-homing scheme; the clinical and serological examination. Clear recommendations are given today, by when a leishmaniasis therapy to start, a combination of antibody titer and clinical signs. The gold standard in canine medicine remains the serology, the IFA followed by PCR.
How is Leishmaniasis treated?
Leishmaniasis requires an immunocompetent system because medicines will not get rid of the parasite from the body, thus the risk of relapse if immunosuppression occurs.
The treatment of leishmaniasis depends on several factors including type of disease, concomitant pathologies, parasite species and geographic location.
Detailed information on treatment of the various forms of the disease by geographic location is available in the WHO technical report series 949 and in the resources for health professionals at the CDC .
In general, all clinically manifest cases of visceral leishmaniasis and mucosal leishmaniasis should be treated, whereas not all cases of cutaneous leishmaniasis require treatment.
Special groups such as young children, elderly persons, pregnant/lactating women, and persons who are immunocompromised or who have other comorbidities may need different medications or dosage regimens.
How is canine leishmaniasis treated?
Todays recommendations are combination of actives such as allopurinol and meglumine antimoniate, resp. miltefosine. Treatment regimes, dosages, durations and veterinary consultations are defined.
How can I prevent infection?
No vaccines or drugs to prevent Leishmaniasis infection are available. The best way to prevent infection is to protect yourself from sand fly bites, especially from dusk to dawn, when sand flies generally are the most active.
When outdoors or in unprotected quarters:
- wear long-sleeved shirts, long pants, and socks and tuck your shirt into your pants
- apply insect repellent to exposed skin and under the ends of sleeves and pant legs
The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide)
When indoors:
- stay in well-screened or air-conditioned areas
- spray insecticides to kill insects
- use a bed net, preferably one that has been soaked in or sprayed with a pyrethroid-containing insecticide
- spray also screens, curtains, sheets and clothing
How is the infection with Leishmania prevented in veterinary medicine?
Unlike for humans, there are registered veterinary medicinal products that are capable to prevent the infection with Leishmania. The prevention is the most important way in todays veterinary medicine and in the recommendations to dog and cat owners. Prevention of Leishmania infection is based on the application of insecticides to the respective animal patient on a regular base throughout the sand fly season. These insecticides are synthetic pyrethorids, as this is the only chemical class that combines insecticidal with repellent properties. The actives registered as veterinary medicinal products are those containing permethrin (such as Advantix™) in high concentrated liquid form for dermal application to dogs only or insecticidal collars (such as Seresto™) containing a combination of imidacloprid and flumethrin registered for cats and dogs. In addition there are vaccines against Leishmania infantum registered for dogs. These vaccines are recommended to be combined with additional insecticidal treatment to increase the protection level.
How is Leishmania transmitted?
Leishmaniasis is caused by a protozoa parasite from over 20 Leishmania species and is transmitted by the bite of infected female phlebotomine sandflies. Over 90 sandfly species are known to transmit Leishmania parasites.
How is Leishmania parasite transmitted to animals?
Transmission of the Leishmania parasite to animals such as dogs or cats is no different from the transmission to humans. Infected female sand flies transmit the pathogen during blood feeding. Thus in veterinary medicine the prevention is directed to block the interaction between the blood feeding insect and the host by application of insecticides with repellent properties.
Some 70 animal species, including humans, are natural reservoir hosts of Leishmania parasites.
In many geographic areas where leishmaniasis is found in people infected animals such as rodents or dogs, along with sand flies, maintain the infection cycle.
In other parts of the world, infected people are needed to maintain the cycle. This type of transmission (human—sand fly—human) is called anthroponotic.
In areas with anthroponotic transmission, effective treatment of individual patients can help control the spread of the parasite.
How can the vector be controlled?
Vector control helps to reduce or interrupt transmission of disease by controlling sandflies, especially in domestic conditions. Control methods include insecticide spray, use of insecticide–treated nets, environmental management and personal protection.
Indoor residual spraying is a simple and cost effective method of controlling endophilic vectors and DDT (used in many Bayer products) remains the insecticide of choice for the control of leishmaniasis. However resistance to insecticide is likely to become more widespread in the population especially in those areas in which insecticides has been used for years.
In this context use of slow release emulsified suspension (SRES) may be the best substitute. Allethrin (coil) 0.1 and 1.6 per cent Prallethrin (liquid) (both used in many Bayer products) have been found to be effective repellents against Phlebotomus argentipes, the vector of Indian kalaazar. Insecticide impregnated bednets is another area which requires further research on priority basis for the control of leishmaniasis.
How can the sand fly vector be controlled in veterinary medicine?
Registered veterinary medicinal products are available to be applied to the animal prior to exposure to block the interaction between the sand fly vector and the treated host animal. There are many chemical classes that have insecticidal and acaricidal properties, however only one class, the synthetic pyrethroids are capable and therefore individual actives out of this class have been registered as veterinary medicinal products to be applied on animals.
What are the difficulties and challenges in combating Leishmaniasis?
Because transmission occurs in a complex biological system involving the human host, parasite, sandfly vector and in some causes an animal reservoir host fighting leishmaniasis requires a combination of intervention strategies.
- early diagnosis and effective case management reduces the prevalence of the disease and prevents disabilities and death
- early detection and prompt treatment of cases help to reduce transmission and to monitor the spread and burden of disease
- prompt data reporting is key to monitor and take action during epidemics and situations with high case fatality rates under treatment
- control of animal reservoir hosts is complex and should be tailored to the local situation
- mobilization and education of the community with effective behavioral change interventions must always use locally tailored communication strategies
- partnership and collaboration with various stakeholders and other vector-borne disease control programs is critical
Major risk factors:
-
Socioeconomic conditions
Poor housing and domestic sanitary conditions such as a lack of waste management or open sewerage may increase sandfly breeding and resting sites. Sandflies are attracted to crowded housing as these provide a good source of blood-meals. Human behavior, such as sleeping outside or on the ground, may increase risk.
- Malnutrition
Diets lacking protein-energy, iron, vitamin A and zinc increase the risk that an infection will progress to kala-azar.
- Population mobility
Epidemics of both cutaneous and visceral leishmaniasis are often associated with migration and the movement of non-immune people into areas with existing transmission cycles.
Occupational exposure as well as widespread deforestation remain important factors because people settling in areas that used to be forests may be moving near sandflies’ habitat. This can lead to a rapid increase in cases.
- Environmental changes
Environmental changes that can affect the incidence of leishmaniasis include urbanization, domestication of the transmission cycle and the incursion of agricultural farms and settlements into forested areas.
- Climate change
Leishmaniasis is climate-sensitive, and strongly affected by changes in rainfall, temperature and humidity. Global warming and land degradation together affect the epidemiology of leishmaniasis in a number of ways:- changes in temperature, rainfall and humidity can have strong effects on vectors and reservoir hosts by altering their distribution and influencing their survival and population sizes
- small fluctuations in temperature can have a profound effect on the developmental cycle of Leishmania promastigotes in sandflies, allowing transmission of the parasite in areas not previously endemic for the disease
- drought, famine and flood resulting from climate change can lead to massive displacement and migration of people to areas with transmission of Leishmania, and poor nutrition could compromise their immunity
What programs exist against Leishmaniasis?
The kala-azar elimination programs in South-East Asia are making sustained progress towards elimination, and cases are declining in the three major endemic countries: Bangladesh, India and Nepal.
Access to effective and safe anti-leishmanial medicines has significantly improved thanks to a WHO-negotiated price scheme and a medicine donation program through WHO.
The WHO's work on leishmaniasis control involves:
- supporting national leishmaniasis control programs to produce updated guidelines and make disease control plans
- raising awareness and advocacy on the global burden of leishmaniasis, and promoting equitable access to health services for disease prevention and case management
- developing evidence-based policy guidelines, strategies and standards for leishmaniasis prevention and control, and monitoring their implementation
- providing technical support to Member States to build sustainable, effective surveillance systems and epidemic preparedness and response systems
- strengthening collaboration and coordination among partners, stakeholders and other bodies
- monitoring the global leishmaniasis situation, trends, progress in the disease control, and financing
- providing diagnostic tests and antileishmanial medicines as last resort source
- promoting research on effective leishmaniasis control including in the areas of safe, effective and affordable medicines, as well as diagnostic tools and vaccines
- facilitating the dissemination of research findings
Drugs for Neglected Diseases initiative (DNDi) is a collaborative, patients’ needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected diseases.
DNDi aims to deliver:
- a safe, effective, low-cost and short-course, oral treatment for VL
- a new treatment for PKDL that is shorter and better tolerated than current options
- a new treatment regimen for patients co-infected with HIV and VL
- a safe, effective, and shorter-course treatment for CL
DNDi also pursues a shorter-term strategy, with the objective of improving therapies based on existing drugs, and overcome the barriers around affordability, treatment duration, burden on health systems and patients, and the risk of resistance. To this end, a number of clinical trials are currently underway or in the preparation phase:
- a Phase III clinical trial testing a new combination therapy for primary VL will be soon conducted in Ethiopia, Kenya, Sudan, and Uganda
- to address specific needs of patients living with post kala-azar dermal leishmaniasis (PKDL), two Phase II trials testing combination therapies are currently underway in India/Bangladesh and Sudan
- two PKDL infectivity studies are under preparation in Bangladesh and Sudan. The objective is to establish the infectivity of PKDL patients to sandflies, in order to determine if PKDL patients maintain inter-epidemic transmission of VL. If this is confirmed, early treatment of PKDL patients would be a critical element of any public health and elimination strateg
- the development of better treatment for HIV/VL is in progress, with promising results from a Phase III trial testing a combination therapy in Ethiopia
- and a Phase II clinical trial using a combination of therapeutic approaches (thermotherapy and oral treatment) is currently being conducted in Peru and Colombia
What is the Public Health contribution in Veterinary medicine?
As leishmaniasis is one of the NTDs and a very important zoonosis that impacts humans as well as animals, under the One Health scheme protection of animals, esp. dogs is important in sand fly and Leishmania endemic regions.
Not all Leishmania species, e.g. L. donovani are of importance in veterinary medicine. The interventions in canine medicine concentrate on endemic regions with L. infantum in the Mediterranean and L. chagasi in South America. In these endemic regions the protection of dogs with veterinary medicinal products containing synthetic pyrethroids such as permethrin (in spot on dermal formulation for dogs) or collars containing flumethrin registered for cats and dogs are capable to contribute to Leishmaniasis control.
What does Bayer contribute to the fight against Leishmaniasis?
Bayer’s Animal Health division is partnering with LeishVet, a scientific association founded by veterinarians from academic institutions of different countries focusing their research and clinical activity on leishmaniasis in veterinary medicine.
What is the societal burden of Leishmaniasis?
Scientists from the University of Manitoba, Manitoba, Canada wrote in an article on the
„Socioeconomic Impact of Leishmaniasis“:
Leishmaniasis affects mostly people living in the most impoverished parts of developing countries and places further economic stress on already strained meagre financial resources.
A 2006 study that looked at the economic impact of VL in Nepal found that the average VL treatment cost incurred by patients was greater than the annual household per capita income. Furthermore, the median cost per household diagnosed with more than one case of VL was USD 425, which is more than the median annual household income of USD 405. It was further found that direct costs, that is, costs that are directly related to treatment (such as consultation fees, payment for laboratory tests and drugs) accounted for 53% of the total costs while indirect costs were mainly as a result of loss of earnings because of illness.
It is important to note that 75% of the mean direct total health-care cost occurred even before the patient received treatment of VL. All affected household in the study depleted their savings to get treatment. Some other families in addition to using up their saving took high-interest loans or sold some of their livestock to pay for treatment.
Although health-care services are generally provided free in developing countries, affected household still incur a substantial amount of financial burden due to treatment of episodes of leishmaniasis.
A recent study in Nepal showed that indirect cost increased from 47% in 2006 to 53% in 2010. This may be because most affected individuals live in remote villages that are far away from the free government health-care facilities, which are usually located in the cities and urban centers.
Because leishmaniasis is primarily more common in rural areas and villages, many of the affected individuals patronize the more expensive and often inadequate private health-care facilities located in these villages. The mechanism of financing out-of-pocket payments plays an important role in the economic impact on the households especially in developing countries where this is done through borrowing from informal sources of financing.
The average cost of treatment of an episode of VL was shown to be 17.5% while the average total cost (for the entire duration of illness) was 44% of the average household income.
In a similar study in India, the estimated annual overall household expenditure was USD 1,312, which is higher than the average household assets of USD 1,273.
In this study, VL treatment represented 11% of the total household expenditure. Also, the economic impact of VL was equal to 13% of total household assets, and in the most vulnerable population, this was equivalent to 72%.
Similar findings were reported by a recent study in Nepal. Despite the provision of free medications by the government, the cost of treating one episode of VL was USD 165 and the economic burden, which includes direct and indirect cost, was estimated at 11% of annual household income or 57% of median per capita income.
Catastrophic payment is a measure of the cost of health-care services in excess of a given threshold (5–25%) that diverts consumption from basic needs or cause households to resort to using their savings.
According to Adhikari and others,10 93% and 31% of affected households spent at least 5% and 15%, respectively, of their income on VL treatment.
In another study, 51% of households exceeded catastrophic threshold of 10% of the annual household income
It is interesting to note that without the provision of free drugs, the catastrophic index would have increased from 51–74%.
How did the history of the disease proceed?
Leishmaniasis is named after the Scottish pathologist William Boog Leishman:
- in 1900 Leishman discovered ovoid bodies in smears taken post-mortem from the spleen of a soldier who died from emaciation and splenomegaly while stationed at Dum Dum, a town near Calcutta
- in 1903 he published his findings assuming that the illness which he termed ‘Dum-dum fever’ was a form of trypanosomiasis
- in the same year the American pathologist James Homer Wright published a detailed description of L. tropica and named the parasite Helcosoma i 9 tropicum
- in 1904 the scientists involved in the discussion on Leishman´s findings agreed that the ovoid bodies were a novel protozoan organism, that the clinical picture of the cases resembled that of kala-azar and the term Leishmania donovani was generally adopted
- in 1906, the German physician and zoologist Max Lühe changed the name into Leishmania tropica
- in 1908 the related VL causing species Leishmania infantum was first described by the French bacteriologist Charles Jules Henry Nicolle in children in Tunisi
- in the same year, together with his colleague Charles Comte), he found out that dogs are important reservoir hosts for VL
- in 1909 New World leishmanial parasites were first described independently by the Brazilian doctor Adolpho Carlos Lindenberg and the Italian physician Antonio Carini together with his Brazilian colleague Ulysses de Freitas Paranhos.
- in 1911 the Italian physician and bacteriologist Alfonso Splendore found the parasite in mucocutenous lesions of espundia patients (Initially it was thought that the New World parasites were identical with L. tropica)
- in the same year the Brazilian clinician and scientist Gaspar de Oliveira Vianna studying leishmanial specimens concluded that the parasite was different from L. tropica, a decision he based on apparent morphological differences and named the new species by a lapsus calami Leishmania brazilienses, which was corrected to Leishmania braziliensis by Vianna’s colleague Alfredo Augusto da Matta in 1916
- in 1914, the Russian physicians Wassily Larionovich Yakimoff and Nathan Isaakovich Schokhor suggested that L. tropica should be divided into the two subspecies L. tropica minor and L. tropica major based on the size of the parasites found in skin lesions, which became the standard for the next 60 years
- meanwhile L. t. minor was found to cause dry nodular lesions and to occur in urban environments while L. t. major was discovered to produce wet ulcerating lesions and to appear in rural regions
- in 1973 based on these differences, Bray et al. proposed to classify the two subspecies as L. tropica and L. major, respectively.
In the same publication they reported the discovery of a new Leishmania species causing a different form of CL in Ethiopia which they named L. aethiopica.
Although L. peruvianna was already described in 1913, all other New World Leishmania species causing LCL and MCL were characterised much later: L. mexicana in 1953, L. guyanensis in 1954, L. amazonensis and L. panamensis in 1972, L. venezuelensis in 1980, L. lainsoni in 1987, L. naffi and L. shawi in 1989, L. lindenbergi in 2002 and L. waltoni in 2015.
VL was first recorded in Latin America in the 1930s.
The species L. martiniquensis was first isolated in 1995, its taxonomical position established in 2002 and named in 2014.
Although sand flies were suspected early on to be the vectors for transmission of Leishmania parasites, it was not until 1921 that this was proven. The actual mode of transmission through the bite of the sand fly was finally demonstrated in 1941. One year later, it was also conclusively proven that sand flies are the vector of kala-azar. Meanwhile 42 Phlebotomus species and 56 Lutzomyia species have been implicated in the transmission of leishmaniasis in the Old and New World, respectively.