Buruli ulcer: causes, symptoms, diagnosis, treatment

The nosological independence of Buruli ulcer due to its fairly typical clinical and epidemiological features is recognized by most authors. Buruli ulcer was named in the 1960s, when a large number of its observations were first described as a local epidemic in Uganda in the Buruli province. Currently, numerous cases of Buruli ulcer are observed mainly in West Africa (Benin, Côte d'Ivoire, Ghana, Guinea, Liberia, Togo), French Guiana, Papua New Guinea and Australia.

The disease is much less frequently described in the countries of Southeast Asia, and isolated cases have been noted in China. Buruli ulcer has been registered in 27 countries worldwide, primarily in damp marshy areas with stagnant water. According to the National Health Service of Ghana, the incidence of Buruli ulcer in this country is 3.2 cases per 1000 population, and in some rural areas of Côte d'Ivoire, 16% of residents suffer from this disease. According to WHO experts, Buruli ulcer is the third most common mycobacteriosis after leprosy and tuberculosis.

Causes of Buruli Ulcer

The etiologic factor of ulcerative skin lesions in Buruli ulcer is Mycobacterium ulcerans. Mycobacterium ulcerans is an acid-resistant mycobacterium that grows on the Lowenstein-Jensen medium at a temperature of 30-32 °C, with reduced partial pressure of oxygen - for 6-8 weeks.

Unlike other mycobacteria, Mycobacterium ulcerans produces a toxin, which is a macrolide derivative called mycolactone by its chemical structure. The toxin has an affinity for fat cells, has a cytotoxic effect, promoting the development of necrotic processes, and an immunosuppressive effect, since the sensitivity of skin tests decreases in the necrotic phase of the disease. Unlike other mycobacteria, which are facultative intracellular parasites and are located inside phagocytes, Mycobacterium ulcerans forms extracellular colonies.

As with other human mycobacterioses, the mechanisms of pathogenesis of this disease are closely related to the features of the immune response of a particular organism, the duration of contact with the source of infection and numerous endogenous and exogenous factors. A distinctive feature of M. ulcerans is the ability to produce the toxin mycolactone, which explains the deep nature of ulcerative lesions. The entry points for the pathogen are most often banal skin lesions (scratches, abrasions, schools, insect bites, crushed tissue, etc.), i.e. what is commonly called microtrauma. Apparently, such aggravating diseases as malaria, helminthiasis, hypovitaminosis, drug addiction, etc. are also important. Children and adolescents under 15 are most susceptible to the occurrence and severe course of Buruli ulcer, somewhat less often - adults and the elderly.

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Symptoms of Buruli Ulcer

Symptoms of Buruli ulcer most often begin with the appearance of a dense to the touch painless subacute inflammatory infiltrate (tubercle, papule) at the site of, as a rule, previous skin trauma, most often in the area of the shins, thighs, forearms and less often in other areas of the body. As it matures through the stage of central softening, the tubercle transforms into a painless ulcer, which occurs without treatment in the vast majority of cases. Much less often (10%), the tubercle disintegrates without opening in the direction of the underlying tissues, up to bone damage and the development of osteomyelitis. Very typical symptoms of Buruli ulcer are more pronounced hyperpigmentation of the skin in the area of the palpable infiltrate, which is caused not so much by a local disorder of the melanogenesis function as by a stagnant-cyanotic tint and partly by the development of hemosiderosis. At the stage of infiltrate formation, general symptoms are usually absent; patients may only feel a feeling of tension in the affected area.

In a week or two (less often earlier), as a result of central softening, decay and opening of the lesion, one, sometimes several ulcers are formed, the typical signs of which are a noticeable depth, right down to the subcutaneous fatty tissue, an uneven bottom covered with foul-smelling purulent-necrotic masses, sharply undermined edges and compaction at the base of the ulcer. The reaction of regional lymph nodes and especially the phenomena of periadenitis and lymphangitis are extremely rare and occur only in cases of layering of secondary pyogenic flora.

The dynamics of the development of the Buruli ulcer is characterized by peripheral growth and sometimes a migratory nature. As the ulcer defect tends to scar on one side, it continues to develop in the other direction. Sometimes, as a result of inoculation, small, "daughter" lesions may form near the main, "mother" ulcer, and their course becomes more torpid, they often connect along the surface or in depth, forming fistulous passages and bridges.

The process in many cases lasts from 2 months to six months or more and sometimes, even without treatment, ends with complete scarring of ulcerative defects and deep tissue damage with rough constricting and deforming scars, subsequently limiting the range of motion in the affected limb.

Diagnosis of Buruli ulcer

Diagnosis of Buruli ulcer is based in most cases on the typical clinical picture.

Laboratory diagnostics of Buruli ulcer are performed microscopically (Ziehl-Neelsen staining), bacteriologically and PCR. The material for the study is necrotic tissue. Isolation of a pure culture is carried out by direct sowing of the test material on the Lowenstein-Jensen medium or by preliminary infection of mice in the paw pads or subcutaneously in the tail with subsequent transfer of inflamed tissues to the Lowenstein-Jensen medium. Grown colonies are identified from other types of mycobacteria by the inability to grow at 37 C, the absence of catalase and urease, the inability to reduce nitrate, resistance to isoniazid, PAS and ethambutol. When identifying, it is necessary to take into account the differences observed between Mycobacterium ulcerans isolated from different geographical sources. PCR identification can be carried out both directly from clinical material and from the grown culture.

Differential diagnosis of Buruli ulcer in tropical conditions is necessary with tropical ulcer, leishmaniasis, tuberculosis of the skin, noma and other ulcerative processes.

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Treatment of Buruli ulcer

Treatment of Buruli ulcer at the stage of infiltration before ulceration consists of prescribing antibiotics, primarily rifampicin, as the most effective against all mycobacterioses. When the ulcer has formed, the method of choice is surgical excision of defects with subsequent possible plastic surgery. Various disinfectants and cleansers are applied externally to ulcer defects in the form of dressings. Excision of necrotic lesions is performed; in advanced cases, amputation of the affected limb may be required. The earlier treatment of Buruli ulcer is started, the faster scarring occurs and with fewer disabling consequences.

How is Buruli ulcer prevented?

There is no specific prophylaxis for Buruli ulcer. However, it is believed that repeated BCG can provide a protective effect of 30-40%. In the main endemic countries, special educational programs are being implemented among the population under the auspices of WHO, aimed at eliminating environmental factors that increase the risk of infection with Buruli ulcer.