Buruli ulcer is an infectious dermatological disease caused by a lesion of the skin with one of the types of mycobacteria. It is mainly common in hot tropical countries with humid climates. Symptoms of this condition are ulcers with necrotic contents at the bottom, occurring mainly on the skin of the extensor surfaces of the knee and elbow joints. Diagnosis of Buruli ulcer is carried out by dermatological examination, examination of the patient’s anamnesis, bacteriological examination of the separated from ulcerative foci. The disease is treated with antibiotics, but their effectiveness may not be sufficient for a full recovery. Local treatment with antiseptic solutions is also used, in severe cases surgical removal of pathological foci is indicated.
A31.1 Cutaneous mycobacterial infection. Buruli ulcer
Buruli ulcer is an endemic dermatological disease belonging to the group of mycobacterioses of the skin, previously observed only in certain regions of Africa, but now common in more than 25 countries. The first descriptions of ulcers characteristic of this pathology date back to 1898, but its more serious study began only in 1948, when the Australian doctor P. Mccullam was able to isolate and cultivate the causative agent of the disease.
Buruli ulcer got its name in the 60s, when a real epidemic of this dermatological condition arose in the eponymous region of Uganda. To date, this disease occurs in a number of countries in Equatorial Africa, there are data on outbreaks of pathology in Southeast Asia and Australia, individual cases have been described in China. The spread of Buruli ulcer is facilitated by a warm and humid climate and a large number of reservoirs with stagnant water in the region. Infection occurs by contact, Mycobacteria can be transmitted from person to person through touching, using common objects, as well as through contact with contaminated water or soil.
Buruli ulcer is caused by Mycobacterium Mycobacterium ulcerans, this pathogen has both similarities and significant differences with other microorganisms from its group. Like other varieties of mycobacteria (for example, pathogens of tuberculosis and leprosy), Mycobacterium ulcerans is an acid-resistant microorganism with very slow development. The growth of noticeable colonies when sown on nutrient media takes 7-12 weeks.
Mycobacterium reservoirs in the wild have not been identified to date. It is assumed that it may be water from stagnant reservoirs, aquatic plants and some animals – in particular, the causative agent of Buruli ulcer was found on the wool of koalas and kangaroos in Australia. This uncertainty makes it difficult for epidemiologists to develop prevention and anti-epidemic measures in endemic regions. The explosive increase in the incidence of Buruli ulcer in the second half of the XX century is also inexplicable at the moment, when this pathology spread from several small foci in Africa to a huge territory from Uganda to Australia – it is believed that this was the result of increased migration flows and trade turnover between countries.
Long-term studies of Buruli ulcers have revealed the fact that for the development of this disease, it is often necessary to have a previous weakening of the body due to certain factors. These can be:
- chronic protein deficiency in the diet (fasting),
- infection with parasites (helminthiasis),
- debilitating diseases (for example, malaria).
This explains why Buruli ulcer is mainly common in poor developing countries with low levels of public health and social protection.
The causative agent of Buruli ulcer is not able to parasitize inside macrophages and other cells, like other mycobacteria, and unlike them secretes an active exotoxin (mycolactone), which has a cytolytic effect (especially against adipocytes – fat cells present in subcutaneous fat). There are indications that the toxin produced by Mycobacterium ulcerans has immunosuppressive properties, which facilitates infection and significantly complicates the course of the disease with multiple ulcerative foci.
Infection with the causative agent of Buruli ulcer occurs through the “entrance gate” – abrasions, cuts, insect bites and other injuries can be on the skin. Deep injuries reaching subcutaneous fat are especially dangerous, since Mycobacterium ulcerans has an affinity for lipid-rich tissues.
In the vast majority of cases, the development of Buruli ulcers occurs at the site of a previous skin injury, and – quite deep. At the same time, a painless infiltrate is formed at the site of a healing cut or abrasion, hard to the touch and located in the deep layers of the skin. Between the moment of infection and the development of the infiltrate, there is an asymptomatic incubation period lasting from several days to 7-10 weeks. The skin above the pathological formation in Buruli ulcer first becomes hyperpigmented, then cyanotic due to venous congestion. No subjective or general symptoms are determined at this stage of the disease.
6-15 days after the formation of the infiltrate, its central part softens, an ulcerative lesion forms with dense edges and necrotic masses at the bottom. With Buruli ulcer, these masses dry out quite quickly, forming a black scab. The size of the ulcerative defect can vary from a few millimeters to 3-4 centimeters, but the affected area also remains painless on palpation. As a rule, the lesion in Buruli ulcer is initially single, sometimes several ulcerative surfaces may occur that are separated from each other – this is due to infection of several skin areas at once. An important diagnostic sign of Buruli ulcer is the absence of any general reactions, including regional lymphadenitis – the lymph nodes are not enlarged and painless on palpation.
In the absence of treatment, complications of Buruli ulcers develop. Most often, a secondary bacterial infection is attached, usually of a purulent nature. Signs of this complication may be the appearance of throbbing pain in the area of ulceration of the skin, putrid odor and the presence of pus. Lymphadenitis occurs, a possible increase in temperature. In the absence of such a complication, daughter elements can form around the primary focus – as a rule, they are somewhat smaller, but also go through all stages of development from infiltration to ulcers. The lesions are separated from each other by strips of compacted skin, called “skin bridges” by dermatologists. In severe cases of Buruli ulcers, a combination of secondary infection and multiple lesions can threaten the patient’s life and become a reason for amputation of a limb.
Diagnosis of Buruli ulcer is based on the study of the anamnesis and the results of questioning the patient, examination by a specialist in the field of dermatology, microscopic and bacteriological examination of the separated from skin erosions.
- Dermatological examination. It reveals painless infiltrates (in the initial stages of the disease) or ulcers covered with dried black scab, predominant localization – hands (hands, forearms) and legs. There is always (with the exception of secondary infection) no reaction from the regional lymph nodes.
- Collecting anamnesis. When questioning the patient, in most cases it turns out that the development of the disease was preceded by a noticeable or deep injury to the skin. Often, in the same way, the source of infection can be detected – the presence of a similar pathology in relatives or friends, the development of symptoms after bathing in a stagnant freshwater reservoir, etc.
- Microscopy of the separable. For microscopic examination, they try to take the material at the edge of the ulcer – it forms a niche where the accumulation of dead skin tissues occurs. The most informative method of diagnosis is the staining of Cyll-Nielsen smears – at the same time Mycobacterium ulcerans are stained red. Mycobacteria, which are the causative agents of Buruli ulcers, are usually located in a smear singly, in pairs or in the form of long chains.
- Microbiological examination. Sowing samples on a nutrient medium (Levenstein-Jensen) and storing it at a temperature of 30-32 degrees after 7-12 weeks leads to the appearance of small colonies of pinkish color. Differentiation of Buruli ulcer pathogens from other mycobacteria is performed by the inability of Mycobacterium ulcerans to cleave urea and hydrogen peroxide and resistance to traditional anti–tuberculosis drugs – paraaminosalicylic acid (PASC), isoniazid.
- Molecular genetic diagnostics. In recent years, the polymerase chain reaction technique has been used to determine this disease, which makes it possible to identify the DNA of the pathogen – this method is considered the most accurate.
Therapy of Buruli ulcer is quite complicated due to the weak susceptibility of the pathogen to most antibacterial agents. Treatment should be comprehensive, including systemic and local therapy. An important role in therapy is played by an increase in the body’s resistance to infections – this is achieved by the appointment of immunostimulants, vitamin preparations, and proper nutrition of the patient.
- Antibiotic therapy. The first–line drug in the treatment of this disease is the antibiotic rifampicin, but its effectiveness differs greatly in different cases – from a rapid and long-lasting effect to almost complete immunity of mycobacteria. Antibiotics from other groups are even less effective in Buruli ulcer.
- Local treatment. It can be performed only in combination with systemic antibacterial therapy. Compresses are used from solutions of various antiseptics (for example, chlorhexidine), a good effect is achieved by applying bandages with a hypertonic solution – this has a good cleansing effect. The above measures not only facilitate the patient’s condition, but also are an active prevention of such a complication of Buruli ulcer as a secondary infection.
- Surgical treatment. It is recommended for prolonged absence of effect from conservative therapy or severe multiple skin lesions. It is performed by excision of areas affected by Buruli ulcer, removal of infiltrates and subsequent suturing of wounds or closure of defects by skin grafting.
Prognosis and prevention
The prognosis of Buruli ulcer is usually uncertain, since the severity of pathology symptoms depends on many factors – the size of the “entrance gate”, the body’s resistance to infection, the patient’s age, etc. With timely treatment, sometimes there is a fairly rapid healing of the ulcer with the formation of a scar, but in most cases, skin ulceration persists for many weeks. In especially severe cases (with multiple lesions of Buruli ulcer and secondary infection), toxic shock, gangrene of the extremities, sepsis may develop, which threatens the patient’s life.
Methods of prevention of this disease are only being developed, there have been attempts to use the vaccine in endemic areas. This gave temporary immunity against Buruli ulcer, but its duration was only 4-6 months. Currently, WHO continues to search for an effective vaccine, as well as the study of Mycobacterium ulcerans to reduce the incidence of this pathology.