Leishmaniasis

Leishmaniasis - obligate vector-borne diseases, the causative agents of which are the protozoans of the genus Leishmania. The life cycle of the leishmania proceeds with the change of hosts and includes two morphological forms: amastigotic (no-fatty) and promastigous (flagellar). In amastigotic form, leishmania is parasitized in the cells (macrophages) of natural reservoirs (vertebrates) and humans; in promastigotnoy live in various parts of the digestive tract of mosquitoes, which serve as their carriers and in nutrient media.

The carriers of leishmanias are Diptera insects: the Old World - mosquitoes of the genus Phlebotomus, the New World - the genus Lutzomya. The main natural reservoirs are rodents and representatives of the dog family.

The area of distribution of leishmaniasis includes countries with hot and warm climates. Diseases of people are registered in 76 countries of Asia, Africa, Southern Europe, Central and South America. In many countries, leishmaniasis causes significant socio-economic damage. In Russia, local cases of leishmaniasis are currently absent, however, imported cases are recorded every year, among the infected - persons who have visited countries of near and far abroad, endemic for leishmaniasis. In this case, patients are identified among citizens of both foreign countries and the Russian Federation, returning from business or tourist trips to areas with subtropical or tropical climate.

There are three clinical forms of leishmaniasis: skin, skin-mucous and visceral. Skin leishmaniasis affects the skin; with skin and mucus - the skin and mucous membranes, mainly the upper respiratory tract, sometimes with the destruction of soft tissues and cartilage; with visceral leishmaniasis, the pathogen is localized in the liver, spleen, bone marrow and lymph nodes. In Russia, skin and visceral leishmaniasis are most often recorded.

[1], [2], [3], [4], [5], [6], [7],

The cycle of development of leishmania

The infectious process begins when promastigots penetrate the host's body with the saliva of mosquitoes, which bite the person's face or limbs. Parasites are absorbed by dermal macrophages and soon turn into amastigotes or micromastigots, multiplying by transverse division, which ultimately leads to the rupture of macrophages. This process continues for a long time, since the released amastigots are absorbed by new macrophages that accumulate in the lesion and proliferate here. Affected macrophages promote further dissemination of parasites. The subsequent development of the lesion depends on the individual characteristics of the parasite and the state of immune responses of the host organism. The situation is complicated by the fact that each strain of leishmania may contain several strains different from each other; nevertheless, usually each species or subspecies of leishmania causes a rather characteristic disease that belongs to one of the main groups.

The mosquito is infected with amastigotes of leishmania during bloodsucking on the infected vertebrate. In the intestine of the mosquito, the leishmania pass into the promastigotic stage, multiply by longitudinal division and develop within a week, turning into invasive forms that concentrate in the anterior parts of the intestine and in the mosquito's proboscis. The development of promastigot in mosquitoes occurs at temperatures above 15 ° C. With repeated bloodsucking of the transporter, the pro-mastigot enter the blood of the vertebrate host, are phagocytized by the cells of the RES and become amastigotes.

Mosquitoes are small Diptera insects, ranging in size from 1.2 to 3.7 mm. Distributed in all parts of the world in the tropical and subtropical zones, in the belt enclosed between 50 ° N. W. And 40 ° S. W. Mosquitoes live both in populated areas and in natural biotopes. In places, mosquitoes are produced by underground, garbage dumps and other places where decaying organic substances accumulate. In natural conditions, mosquitoes are buried in rodent burrows, bird nests, caves, tree hollows, etc.

The peculiarities of the spread of leishmanias and their circulation on the territory endemic in the leishmaniasis are closely related to the features of the ecology of their mosquito vectors. Thus, in the Old World, leishmaniasis is common in dry (arid) areas - deserts, semi-deserts and oases; In the New World - this (with rare exceptions) disease of the rainforest.

In the settlements of Central Asia, mosquitoes usually fly to a distance of only tens of meters from the sites of the otter; open areas spread to 1.5 km. In the northern part of its range mosquitoes have one generation and are active from June to August. In Central Asia, there are usually two generations with a maximum population in early June and early August. In tropical countries, mosquitoes are active for a year. Mosquitoes are twilight and nocturnal insects, within 2-3 weeks of their life females feed on blood and lay eggs 2-3 times.

Epidemiology of leishmaniasis

Leishmaniasis occupy one of the most important places in tropical pathology. According to the World Health Organization, leishmaniasis is spread in 88 countries of the world, in 32 countries diseases are subject to mandatory registration. According to expert estimates, the number of leishmaniasis patients in the world is 12 million people. Annually 2 million new cases occur. Approximately 350 million people live in leishmaniosis endemic areas and are at risk of infection.

Leishmaniasis is included in the WHO Special Program for the Study and Control of Tropical Diseases. In some developing countries, leishmaniasis can act as a deterrent to the economic development of a particular area.

There are several types of leishmania, pathogenic to humans, which are similar in their morphology, but differ in antigenic, molecular-biological and biochemical characteristics, as well as in the clinical picture and epidemiology of the diseases caused by them.

There are three main groups of leishmaniasis:

1. Cutaneous leishmaniasis.
2. Skin and slimy American leishmaniasis.
3. Visceral leishmaniasis.

However, this division can not be considered absolute: in some cases, the causative agents of visceral forms of the disease can cause skin lesions, and the causative agents of cutaneous forms - lesions of internal organs.

Cutaneous leishmaniasis was first described by the English physician Rososke (1745). The clinical picture of the disease was covered in the writings of the Russel brothers (1756), Russian military doctors NA. Arendt (1862) and L.L. Reidenreich ("The Penny's Ulcer", 1888).

A major event was the discovery of the causative agent of cutaneous leishmaniasis by the Russian military physician P. F. Borovsky (1898). This causative agent was also discovered by the American physician JH Wright (1903). In the 1990-1903 gg. WB Leishman and S. Donovan found in the spleen of patients with Indian leishmaniasis the causative agent of visceral leishmaniasis, which was described by A. Laveran and F. Mesnil (1903) under the name L. Donovani, and the causative agent of cutaneous leishmaniasis was named L. Tropica in 1909.

Only with cutaneous leishmaniasis, the disease can result in the development of intense sterile immunity and resistance (resistance) to re-invasion. But even with this disease, parasites can sometimes persist (persist for a long time) in the body of the patient. For example, L. Brasiliense can spread and affect the nasopharynx many years after the initial disease. L. Tropica can cause chronic recurrent lesions, and in some patients with a burdened premorbid background, when invading L. Mexicana or L. Aethiopica, an anergic form of the disease known as "diffuse cutaneous leishmaniasis" may develop. Immunity to re-invasion in the presence of current invasion is denoted by the term preunition (a synonym for non-sterile immunity).

Cutaneous leishmaniasis is characterized by skin lesions, which are called leishmaniasis. Due to the multiplication of leishmanias at the site of their introduction by mosquitoes, specific granulomas arise consisting of plasma cells, neutrophils, and lymphoid elements. The vessels in and around the infiltrate are enlarged, swelling and proliferation of their epithelium are noted. The process of leishmanioma development consists of three stages: a tubercle, a manifestation and scarring. Perhaps the spread of infection through the lymphatic vessels and the development of lymphangitis and lymphadenitis.

There are anthroponous and zoonotic cutaneous leishmaniasis.

Features of two types of leishmaniasis

Characteristics of infection	Type of infection
	Urinary cutaneous leishmaniasis	Rural skin leishmaniasis
	Synonyms
	Anthroponous Ashkhabad ulcer, a yearling, a late ulcer form ("dry"),	Zoonotic pendin ulcer, murghab ulcer, acute necrotizing form, desert type ("wet"),
The incubation period	Long-term: 2-3-6 months, often 1-2 years and more	Short: usually 1-2-4 weeks, sometimes up to 3 months
Initial phenomena	Small papula-tubercle of corporal or brown color	Significant inflammatory, often furuncle-like infiltrate
Process development	Slow	Fast
Time of onset of ulceration	In 3-6 months and more	After 1-2-3 weeks
Lymphangites	Rare	Frequent
Semiglossal tubercles	Relatively rare
Localization	On the face more often than on the lower limbs	On the lower extremities more often than on the face
The duration of the process before epithelization	Year and more	2-6 months
Seasonality	2-6 months	Primary diseases occur in the summer-autumn months (June-October)
Epidemiological outbreaks	Seldom observed	Develop often
Sources of infection	Man (anthroponosis)	Wild rodents of the desert (zoonosis)
Place of distribution	Mostly in cities (Typus urbanus)	In rural settlements, on the outskirts of cities and in desert areas
Number of parasites in granules	A lot of	Few
Virulence for white mice	Small	Large
Cross immunity	To date, data have been accumulated that indicate the presence of cross immunity between pathogens of two types of cutaneous leishmaniasis
Causative agent	Leishmania tropica minor	L. Tropica major
Skin test	From the 6th month after the onset of the disease	From the 2nd month
Primary carrier	Ph. Sergenti	Ph. Papatasi

[8], [9], [10], [11], [12], [13], [14],

What causes leishmaniasis?

Pathogens of cutaneous leishmaniasis are described by Cunigam (Cuningham, 1884) and Firth (1891). In 1898, P.F. Borovsky determined that these organisms belong to the simplest. In 1900, Wright observed similar parasites in the patient's spleen with visceral leishmaniasis and in 1903 published for the first time an accurate description of these parasites and drawings.

In 1974, Jadin reported the presence of a small bundle in the intracellular forms of some leishmania (L. Tropica, L. Donovani, L. Brasiliensis), detected on a microelectronogram. In this connection, along with the terms "amastigot", the term "micromastigoth" also appears, denoting the same stage of the life cycle of leishmania.

In the body of warm-blooded amastigots and micromastigots of leishmania are found in the protoplasm of cells of the reticuloendothelial system, capable of phagocytosis. They have the form of small oval or round bodies in the size from 2 to 5 microns.

Protoplasm is colored according to Romanovsky-Giemsa in a grayish-blue color. In the central part or on the side there is an oval core, which is painted red or red-violet. Near the nucleus there is a kinetoplast (a round grain or a short stick lying excctrically and dyeing more intensively than the core into a dark purple color). The presence of nucleus and kinetoplast is the main feature that makes it possible to distinguish leishmanias from other formations (platelets, histoplasm, yeast cells, etc.).

Promastigoty leishmanii have an elongated fusiform form; their length is 10-20 microns, width 3-5 microns. The core, protoplasm and kinoplasm are stained in the same gon, kach and amastigot. In cultures, promastigots are often collected in bundles in the form of rosettes, with flagella facing the center (agglomeration phenomenon).

How to prevent leishmaniasis?

In the endemic areas, the prevention of leishmaniasis is carried out differentially depending on the form of the disease in several directions. For anthroponoses (kala-azar, ACL), the main prevention measures are: the identification and treatment of patients, the fight against mosquitoes in populated areas. Significantly more complex and time-consuming prevention of visceral leishmaniasis and ZCL, in which the reservoirs of pathogens and sources of human infection are mostly wild animals. Preventive measures in the centers of visceral leishmaniasis include: active detection and treatment of patients, detection and destruction of sick dogs in populated areas (possible treatment of valuable species), limiting the number of wild, predatory animals (foxes, jackals, etc.). In the vicinity of settlements, mosquitoes. Activities in the ZKL foci, along with the identification and treatment of patients, are aimed at eliminating the main reservoir of the pathogen in nature - various species of rodents and fighting with burrowing mosquitoes.

In addition, prophylactic vaccinations with live virulent L. Major cultures are used to protect the population in the outbreaks of ACL and ZCL.

A very effective measure of leishmaniasis prophylaxis is protection from mosquitoes attack. To do this, in the evening, just before sunset and throughout the night, it is advisable to use special mosquito repellent substances - repellents, as well as a canopy of fine mesh.

Citizens of Ukraine traveling abroad can become infected with leishmaniasis when they visit the active season of transmission of infection (May-September) of the countries of the near abroad: Azerbaijan (HL), Armenia (HL), Georgia (HL), South Kazakhstan (HL, ZKL), Kyrgyzstan (HL), Tajikistan (HL, ZKL), Turkmenistan (ZKL, HL), Uzbekistan (ZKL, VL). Endemic to visceral leishmaniasis should be considered and Crimea, where in the past single cases of visceral leishmaniasis were recorded.

Out of the far-abroad countries, India is the most dangerous with regard to kala-azar, where tens of thousands of cases of this disease are annually recorded. Visceral leishmaniasis most often can be infected in the Middle, Middle East and the Mediterranean. Cutaneous leishmaniasis is dangerous for people traveling to countries in the Middle, Middle East and North Africa. In the countries of Central and South America, along with visceral there are foci of cutaneous mucous leishmaniasis.

The main measure of prevention for citizens, even for a short time traveling to these regions, is protection from the attack of mosquitoes. In addition, to prevent ZCL, vaccination with live culture and chemoprophylaxis with pyrimethamine can be recommended. It should be noted that vaccinations are contraindicated in children under 1 year old, with skin or chronic diseases (tuberculosis, diabetes mellitus, etc.) and people who had previously had skin leishmaniasis, and pyrimethamine is contraindicated in diseases of the hematopoietic organs, kidneys and pregnancy.