Contents
Leishmaniasis is a tropical disease caused by protozoa of the genus Leishmania (L.), characterized by a variety of forms – from self-limiting cutaneous, mucocutaneous, and fatal organ disease.
Leishmaniasis — epidemiology
Leishmaniasis is a disease that affects over 12 million people in 88 countries around the world, including 72 developing countries. Annually, there are over 1 million new cases of cutaneous form and 500 cases. – visceral.
- Visceral leishmaniasis – is the second most common cause of death in the world due to parasitic diseases. The disease occurs in countries with tropical and subtropical climates, with the exception of Australia and Oceania. The geographical distribution is different for each form (Table 34.6).
- Cutaneous form – it is mainly observed in the Middle East, Central and East Asia, Africa and Central America.
- Mucocutaneous form – occurs mainly in Central America, less often in East Africa (Ethiopia, Sudan).
- Visceral form – is characteristic of the African continent, Central and Eastern Asia and Central America. So far, epidemics with the greatest dynamics and mortality have occurred in Sudan (1984-1994), Ethiopia (2005-2006), Kenya (2008), and also in Brazil (since 1999).
In Europe, cutaneous and visceral leishmaniasis is observed in the Mediterranean, incl. in Italy, Spain, Portugal, Greece and Turkey. In Poland, this disease is found sporadically as a disease imported from endemic areas.
The mechanism of infection with Leishmaniasis
Both humans, pets and wild animals can be considered a reservoir of leishmaniasis. The important sources of the disease are:
- rodents,
- horses,
- donkeys
- monkeys,
- sloths.
Parasites are transmitted by mosquitoes of the genus Phlebotomus and Lutzomyia. These insects with the common name “sand fly” are characterized by small size and high adaptability to changing climatic conditions.
Infection with leishmaniasis occurs as a result of pricking or crushing and rubbing the fly into the wound. One insect prick is enough to transmit the disease. The following are particularly exposed to the disease:
- people with weak immunity,
- malnourished people with comorbidities (HIV infection, patients after organ transplants),
- children,
- elder people.
Leishmaniasis is more common in men due to the greater risk of contracting infection in the field. In pregnant women, if ignored, the disease can lead to congenital leishmaniasis.
In recent years, the risk of contracting Leishmania has increased, for example among those infected with HIV, who are many times more susceptible to the disease. Infection with the parasite can accelerate the onset of AIDS. Leishmaniasis progresses more frequently in HIV-infected people, from subclinical to fully symptomatic – the exacerbation of the disease may occur even years after infection.
Existing HIV infection increases the risk of occurrence by more than XNUMX times active visceral leishmaniasis. The transmission of both pathogens is possible through the intravenous administration of psychoactive substances. In southern Europe, up to 70% of adult leishmaniasis cases are associated with HIV infection.
Leishmaniasis – causes of formation
Leishmaniasis is caused by over 20 species of protozoa of the genus Leishmania, which belongs to the group of flagellates. These protozoa are characterized by a large number of different species that make taxonomy difficult, and a specific occurrence in particular areas of the globe.
Their identification is based on biochemical and molecular methods. Cutaneous form is called, inter alia, by
- L. tropica,
- L. major,
- L. children,
- L. aethiopica.
Involvement of the skin and mucous membranes occurs due to infection with L. braziliensis, L. aethiopica, L. mexicana, while visceral leishmaniasis is caused by L. donovani, L. chagasi and L. infantum.
Leishmaniasis — pathogenesis
In the intestine of mosquitoes, Leishmania occurs in the extracellular, flagellated form of promastigote. When feeding on blood through a mosquito, the protozoan enters the human skin, and then with blood is transferred to the tissues.
Promastigotes are phagocytosed by macrophages, inside which they transform into intracellular non-flagellar forms – amastigote. As a result of intensive division of the parasite, the cell breaks down, the amastigote breaks out and further macrophages are infected, which causes the spread of the disease.
Protozoa have an affinity for cells of the immune system, mainly:
- spleen
- liver,
- bone marrow
causing damage to these organs. Numerous granulomas appear around the infected cells, and in the spleen there is parenchymal atrophy and its fibrosis, in the liver – fibrosis with steatosis, in the intestines – mucosal ulcerations, and pancytopenia is the consequence of bone marrow damage.
A characteristic feature of leishmaniasis are deep immune disorders. In cutaneous forms of leishmaniasis, an active Th1 response is observed, with increased production of IL-2, IFN-alpha and IL-12, often leading to self-healing. On the other hand, in visceral leishmaniasis the Th2-type responses predominate, with the immune system anergy in relation to the parasite.
What is leishmaniasis like?
The hatching period of leishmaniasis is long, it can last from several weeks to several months, and its course depends on the form.
- Cutaneous leishmaniasis is usually a self-limiting disease, with skin lesions healing within 2-10 months. It can be limited, disseminated, recurrent and after visceral leishmaniasis (so-called post-kala-azar dermal leishmaniasis).
- Leishmaniasis of the skin and mucous membranes may appear long after the primary skin lesion has healed and lead to significant damage to the tissues of the nose, mouth and larynx, causing disfigurement (“white leprosy”).
- Visceral leishmaniasis is the most dangerous form of the disease – it causes damage to the parenchymal organs and bone marrow. Mortality in this form, in untreated cases, is very high and reaches 95%.
Symptoms of leishmaniasis
1. Skin leishmaniasis (Aleppo ulcer) – skin lesions appear, usually painless, occurring several weeks after a bite of a fly. They are characterized by great morphological diversity, often compared with leprosy. The disease usually does not cause systemic symptoms and its lesions are most often located on exposed parts of the body (face, limbs).
Initially, a red lump up to 2 cm in diameter appears. Within a few weeks, the lesion darkens and transforms into a typical ulcer with raised edges and central necrosis. The ulcer may be associated with a serous exudate (“wet ulcer”) or with necrosis and crusting (“dry ulcer”). There is an enlargement of the surrounding lymph nodes and subcutaneous nodules, as well as satellite changes. After a few months of cutaneous leishmaniasis, the ulcer heals itself, leaving scars and discoloration of the skin. In people with lowered immunity, the disease may be disseminated, with numerous papules, ulcers and subcutaneous nodules.
2. Leishmaniasis of the skin and mucous membranes
Initially, single or disseminated skin ulcers are observed. At various times after their resolution, even many years later, changes in the mucous membranes develop. The mechanism of the parasite’s migration from the skin to the upper respiratory tract is unknown, but the first symptoms may include:
- stuffy nose
- bleeding.
As leishmaniasis progresses, the mucosal lesions become painful and ulcerate and destroy the soft tissues and cartilages of the nasal septum, palate and lips, which can lead to a significant degree of disfigurement and disability.
3. Visceral leishmaniasis (kala-azar, dum-dum fever)
An important feature of visceral leishmaniasis is damage to:
- parenchymal organs,
- intestines,
- marrow.
The disease may be asymptomatic for a long time, but in some patients it is electrifying. Development is often long-term and tricky. The name kala-azar (black fever) comes from the typical hyperpigmentation of the skin.
In patients with cutaneous leishmaniasis, the following is observed:
- long-lasting fever up to 40 ° C, with a continuous or intermittent path,
- weakness,
- wasting the body,
- diarrhea.
Physical examination reveals moderate hepatomegaly, marked splenomegaly, and lymphadenopathy. The long-lasting disease process and multi-organ damage usually lead to edema, ascites and hemorrhagic diathesis. In laboratory studies it reveals itself: leukopenia, anemia, thrombocytopenia, hypoalbuminemia and hypergammaglobulinemia. Visceral leishmaniasis is often accompanied by secondary bacterial infections of the lungs and gastrointestinal tract, sepsis and tuberculosis, which are the most common causes of death.
How do we diagnose leishmaniasis?
In leishmaniasis of the skin and mucous membranes, the diagnosis is based on direct microbiological examination scrapings or sections taken from the edge of the ulcer. In over 70% of cases, it is possible to visualize the protozoan with staining by the Giemsa method or histological examination. Breeding is difficult due to problems associated with the isolation of the parasite. May be helpful intradermal test result (Montenegro test)with the use of killed parasite flagellates – it is positive 2-3 months after the appearance of skin lesions.
They have been available since the 90s rapid serological tests, incl. direct agglutination using recombinant Leishmania antigens (e.g. rK39, rKE16).
Important! Currently, these tests (including Kalazar DetectTM, DiaMed-IT LEISH) are the basic diagnostic method of visceral leishmaniasis in field conditions. The main advantage is their storage stability at temperatures up to 30 ° C and high specificity (> 90%), while the sensitivity may differ from one geographical area to another (66-97%).
The confirmation of leishmaniasis infection is visualization of the protozoan in study of biopsies from the bone marrow, spleen, liver and lymph nodes. In turn, the examination of the biopsy material obtained from the spleen is of greatest value, however, this procedure is potentially associated with serious complications.
It is possible to cultivate the parasite in NNN medium or with the addition of fetal calf serum, and the cultivation time is from 1 to 3 weeks. In the diagnosis of leishmanosis, enzyme immunoassays (ELISA) and western blots are also used. PCR is an examination of high sensitivity (> 90%) and specificity (~ 100%).
Leishmaniasis – treatment of the disease
The high species diversity of Leishmania protozoa, as well as the presence of resistance to the preparations used, make treatment difficult.
Most cases of skin leishmaniasis do not require systemic treatment, but it is necessary in L. braziliensis infections, lymph node involvement and multiple lesions.
Mucosal and visceral leishmaniasis should be treated parenterally. For over 50 years, they have been the drugs of choice 5-valent antimony compounds (Pentostam). Treatment is long-term (20-40 days) and may require several cycles. Efficiency of administration of 1-3 cycles is estimated at 90-97%. Leishmaniasis resistance to this treatment is increasing, especially in India.
The importance is growing liposomal form of amphotericin B (drug of choice in visceral leishmaniasis in the USA) used for 1 to 5 days IV. Its effectiveness is high, also in single administration (up to 96%). Due to the high cost, this drug is available in African countries only under the early access programs organized by WHO and Gilead.
In recent years, an oral preparation with high activity has been introduced in the treatment of leishmaniasis – Miltefosine (efficacy 82-95%), however, further studies are necessary to confirm the usefulness of this drug in monotherapy, due to the resistance described in laboratory conditions.
Second-line drugs are:
- pentamidyna,
- paromomycyna,
- ketoconazole.
There are currently studies on the efficacy and safety of combination therapies (amphotericin B, miltefosin and paromomycin). In patients with visceral leishmaniasis, it is important to treat malnutrition and concomitant bacterial superinfections, as well as concomitant diseases (e.g. tuberculosis and HIV infection).
How can leishmaniasis be prevented?
Strategies for reducing the incidence of leishmaniasis include:
- liquidation of reservoirs and the fight against the carrier,
- early diagnosis and initiation of treatment as soon as possible,
- reducing the population of mosquitoes with home insecticides,
- personal protection, which consists in wearing long clothes, using repellants and mosquito nets coated with insecticides.
So far, no vaccine against leishmaniasis has been developed. Clinical trials are underway to test the safety of the second generation vaccine containing recombinant L. donovani antigen (LEISH-F1 antigen).
What’s the prognosis?
In skin leishmaniasis, the prognosis is favorable – lesions heal spontaneously in 90% of cases. In contrast, disseminated leishmaniasis of the skin and mucous membranes often causes permanent disfigurement and is associated with a high risk of life-threatening bacterial superinfections. In turn, visceral leishmaniasis is a progressive disease, if untreated it leads to death in over 95% of patients. The effectiveness of the correct treatment is high.
Literature
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Source: J. Cianciara, J. Juszczyk, Infectious and parasitic diseases; Czelej Publishing House