Leishmania

The pathogens belonging to the flagellates were discovered by Leishman and Donavan in 1903.

Protozoa(flagellates) of the class Mastigophora; Leishmania are flagellate-bearing protozoa that multiply in the blood in macrophages. Leishmania live obligately as intracellular parasites with host switching between insects and vertebrates. The pathogen and the clinical picture caused by leishmania are referred to asleishmaniasis orleishmaniosis after the first describer, William Boog Leishman.

Classification of pathogens:

• Leishmania donovani (Africa, Asia, Europe) - systemic/visceral
• Leishmania infantum (Mediterranean area) - systemic/visceral
• Leishmania chagasi (Central and South America) - systemic/visceral
• Leishmania amazonensis (South America) - systemic/visceral
• Leishmania tropica (Africa, Asia, Europe)-cutaneous
• Leishmania major (Africa, Asia, Europe)-cutaneous
• Leishmania aethopica (Africa, Asia, Europe) -cutaneous
• Leishmania mexicana (Central and South America) -cutaneous
• Leishmania peruviana (South America) -cutaneous
• Leishmania brasiliensis (Central and South America)-mucocutaneous
• Leishmania mexicana (mucocutaneous form) -mucocutaneous

The cases occurring in Germany are imported visceral leishmaniases mostly originating from the Mediterranean region. Exact figures on the frequency of leishmaniasis as a traveler's dermatosis are not available, but it is certainly one of the top 3 infectious diseases after travel.

Approximately one million cases of cutaneous leishmaniasis and 300,000 cases of visceral leishmaniasisare reportedeach year. The number of chronic leishmaniasis cases is estimated at 15-20 million. Leishmaniasis is a different type of disease that differs considerably in terms of its manifestation (cutaneous/mucocutaneous/systemic-visceral) and its geographical occurrence (v.Stebut 2015).

The disease is endemic in Mediterranean countries and is classically a childhood disease, L. infantum is the most common pathogen. Most cases worldwide occur in the Indian subcontinent, in the Indian states of Bihar, Uttar Pradesh, West Bengal and Jharkhand as well as in Bangladesh and Nepal. Here, visceral leishmaniasis is an anthroponosis caused by L. donovani. Other endemic areas in Asia are in Kashmir, Pakistan and northwest China. In southwest Asia, kala-azar is endemic in Iran, Iraq, Yemen and Oman. Sporadic cases are known from Afghanistan, Israel, Lebanon, Saudi Arabia and Syria. In East Africa, visceral leishmaniasis is also endemic as anthroponosis caused by L. donovani in Sudan, Ethiopia, Kenya and focally in Uganda. Sporadic occurrence of kala-azar (black skin) is known from Angola, Djibouti, Eritrea, Gambia, Guinea Bissau, Cameroon, Malawi, Niger, Senegal, Somalia, Chad and the Central African Republic. The disease also occurs as a zoonosis caused by L. chagasi/infantum in Brazil, particularly in north-eastern Brazil in the states of Alagoas, Ceara, Pernambuco and Bahia. Sporadic occurrences of kala-azar are also known from Argentina, Bolivia, Costa Rica, El Salvador, Guatemala, Honduras, Colombia, Mexico, Nicaragua and Venezuela as well as in the Caribbean from Martinique and Guadeloupe.

The cutaneous and mucosal leishmaniases of the New World: The various leishmaniases occurring in Central and South America have not yet been fully classified. 90% of all cases of mucosal leishmaniasis in the New World occur in Bolivia, Brazil and Peru (Desjeux et al. 2000). There are many different forms of the disease. These range from a harmless clinical picture with nodules and small ulcers to destructive lesions. Risk groups are travelers after stays in endemic areas, foreign citizens, migrants, asylum seekers, refugees from endemic areas; HIV-infected persons (opportunistic infection) and other patients with immunodeficiency.

Leishmania is transmitted from person to person by phlebotomes (sand flies) (anthroponosis) or from animals, such as dogs and small rodents, which serve as reservoirs, to humans (zoonosis). In isolated cases, the infection can also be transmitted vertically from asymptomatic carriers, i.e. pre- or perinatally from mother to child, or horizontally from blood and organ donors.

The vector: Sandflies live mainly in warm, southern regions. However, there are also permanent occurrences north of the Alps. Sandflies live for about 40 days and are so-called "pool" suckers, as they scratch the skin with their broad mouthparts and then suck up the blood that accumulates. Compared to the local mosquitoes, they are very small (0.2 cm) and can overcome mosquito repellent nets with normal mesh size. Sandflies are mainly nocturnal, avoid wind and can only travel short distances. When enlarged, sandflies are easily distinguished from other mosquito species because of their characteristically large eyes . Transmission occurs from the salivary gland of female sandflies during the bite. Within minutes, the flagellated promastigote life form of the parasite is taken up by skin resident macrophages/histiocytes in the dermis. In these, the pathogens transform into the obligate intracellular life form, the amastigote form. These amastigote parasites are highly specialized and well adapted to survive in the phagolysosome of the cell.

Life cycle of Leishmania parasites: Within host phagocytes (especially macrophages and neutrophilic granulocytes), the parasites multiply until they are released and can infect other cells. Due to an accumulation of inflammatory cells (macrophages, neutrophilic granulocytes, dendritic cells, T cells), the characteristic granuloma with epithelioid cells and plasma cells is formed after a few weeks.

The life cycle of the pathogen is complete when a sandfly again ingests amastigote Leishmania during the act of sucking, which then transforms again to the promastigote form in the mosquito's intestine. The end result is promastigote forms that collect in the mosquito's proboscis, clogging it and interfering with feeding. The mosquito thus placed in a starvation situation will repeatedly attempt to bite, transmitting the pathogens to mammals such as humans. Crushing the insects on the skin also releases the pathogens, which can enter the organism via microlesions.

Humans are considered to be false hosts in leishmaniasis; small rodents, dogs and, more rarely, horses are predominantly infected. For this reason, the disease is less known in human medicine in Germany than in veterinary medicine.

The cutaneous form is with 90 % the most frequent form of progression. Predilection sites are all uncovered body parts (face, neck, arms, legs). After two to ten years, there is severe tissue destruction, starting at the nasal septum with possible perforation, destruction, superinfection and obstruction in the course. Finally, a typical dark pigmentation of the skin develops (Hindi: Kala-Azar = black skin).

Leishmania/HIV co-infection: Leishmania/HIV co-infection is a serious disease. It is spreading rapidly. Many people infected with Leishmania do not develop the disease. However, immunosuppressed people (e.g. HIV infection, after organ transplantation, autoimmune diseases) quickly develop a full clinical picture of visceral leishmaniasis. HIV increases the rate of spread of VL in endemic areas by up to 100-1000 fold. This combination produces a cumulative deficiency in the immune response as the parasites Leishmania and HIV destroy the same cells.

Leishmaniasis can be transmitted directly from person to person, by sharing needles especially among intravenous drug abusers. This population has the highest risk of co-infection. Cases of co-infection in Leishmania/HIV have been reported in various parts of the world.

The gold standard of diagnosis in cutaneous leishmaniasis is the taking of a biopsy. Within the histiocytes (preferentially in the vicinity of the epidermis) intracellular amastigotes of Leishmania can be seen, which are indicative for further diagnostics. In case of suspicion, it is recommended to perform step sections of the fixed tissue with detection of Leishmania-specific nucleic acid by PCR.

In the visceral form, detection is carried out in stained blood smears (Giemsa stain). Detection from organ biopsy specimens (bone marrow, liver, spleen) is also possible.

Serological detection is usually unnecessary. Serological findings should always be confirmed by direct pathogen detection.

When travelling to risk areas, it is advisable to ensure good protection against mosquito bites. Clothing should cover as much skin as possible. Repellents to apply also keep the annoying bloodsuckers away. Fine-meshed mosquito nets attached to doors and windows and over the bed are another way to prevent mosquito bites.

Otherwise see therapy for the individual clinical pictures

1. Desjeux, P (2001). Worldwide increasing risk factors for leishmaniasis. Medical Microbiology and Immunology 190: 77-79.
2. Hof H et al. (2019) Hof H et al. (2019) Leishmaniasis In: Hof H, Schlüter D, Dörries R, eds Duale Reihe Medizinische Mikrobiologie. 7th, completely revised and expanded edition. Stuttgart: Thieme pp 552-544.
3. Ritmeijer K H et al. (2011) Limited effectiveness of high-dose liposomal amphotericin B (AmBisome) for treatment of visceral leishmaniasis in an Ethiopian population with high HIV prevalence. Clin Inf Dis 53:e152-158
4. Schraner C et al. (2005) Successful treatment with miltefosine of disseminated cutaneous leishmaniasis in a severely immunocompromised patient infected with HIV-1". Clin Infect Dis 40:e120-4.
5. S1 Guideline 042/004: Diagnosis and treatment of visceral leishmaniasis current status: 11/2016.
6. v. Stenbut (2015) Leishmaniasis JDDG 13: 191-201