Buruli ulcer A31.1

Cook 1897; Kleinschmidt 1935; McCallum 1948

Common tropical infectious disease caused by Mycobacterium ulcerans a"non-tuberculous mycobacterium" (NTM).

Mycobacterium ulcerans a non-tuberculous mycobacterium (NTM) that is the only mycobacterium that is obligately pathogenic. It grows in vitro at 30-35 °C. Infection remains confined to the (cool) skin (probably because of the limited temperature optimum). Unique among mycobacteria is the production of exotoxins(mycolactones) with immunosuppressive and necrotizing effects (this explains, among other things, the persistent and destructive course of the infection).

The disease is classified by WHO into three categories depending on the severity:

• Category I, when the patient has a small lesion with a size < 5 cm,
• Category II, when the patient has non-ulcerative or ulcerative plaques, edema, or a large lesion with a maximum diameter between 5 and 15 cm.
• Category III if he has disseminated or mixed forms, multiple lesions, or a large lesion with a diameter of > 15 cm (WHO 2017).

Since 1980, the detection rate of the disease has greatly increased. After tuberculosis and leprosy, Buruli ulcer is the third most common mycobacterial disease in immunocompetent individuals (Manry J 2020). The disease often occurs in remote areas where populations have limited access to health care.Buruli ulcer has been reported or suspected in 30 tropical countries worldwide, including Australia, with West Africa being the most severely affected region. Cases have also been reported in non-tropical areas. The number of reported cases in some West African countries is substantial: 5700 between 1989 and 2003 in Benin, with a Buruli ulcer detection rate of 21-5 per 100 000 in 1999 in the Zou region;717 000 between 1978 and 2003 in Côte d'Ivoire, where prevalence reaches 16% in some villages;8 in Ghana, a national survey in 1999 detected 5619 cases (overall a high national prevalence of 20-7 per 100 000, but 158-8 per 100 000 in the most affected districts) (Sizaire V et al. 2006).

High incidence and prevalence (up to 16% of the population) in endemic areas.

Affected regions: West and Central Africa, Australia, Papua New Guinea, Malaysia, Sri Lanka and South America.

Infection by M. ulcerans.

The route of transmission is unclear; contaminated soil, contaminated water, plants, insects (e.g., swimming bugs), aerosols, or human contact (disputed by some authors) are discussed.

Apparently, the main risk factor is contact with slow-moving water.

Apparently, the pathogens enter the host through micro-injuries. In an endemic case in Australia, mosquitoes were detected as vectors (Johnson PD et al. 2007). Furthermore, detection of M. ulcerans in clinically healthy koalas and oppossums was achieved in Australia.

HIV infection is not known to be a risk factor for Buruli ulcer; however, severe clinical forms of the disease have been described in HIV-positive patients.

All age groups can be affected. Major studies report an average age of 14.2 years (Abdoulaye S et al. 2014). Mostly, however, children aged less than 15 years are affected.

Leg or trunk, rarely face (see Fig. with infection of orm shell, case from Australia).

Incubation period: 2 to 14 weeks.

Infection usually begins as a painless subcutaneous nodule usually on the extensor sides of the lower extremity. Other preulcerative forms include cutaneous papules (more commonly observed in Australia than in other parts of the world), plaques (large, painless, and only slightly raised lesions), and inflammatory swellings (often heralding more severe forms of the disease). In general, however, patients do not show significant, systemic signs of infection!

After weeks to months, ulcer formation occurs with progressive growth in size. Untreated, ulcers can cover up to 15% of the body surface. Deeply undermined ulcer margins are typical. Extensive ulceration that may involve an entire limb is possible. Some patients develop bone (osteomyelitis) and joint lesions due to adjacent or hematogenous spread of M. ulcerans. Spontaneous remissions with scarring and corresponding loss of function may also occur.

Several factors may influence the clinical presentation of the disease, including the site of infection, the size of the inoculum, the type of carrier, the history of trauma, and also the host immune response. In an outbreak of BU in a small coastal town in southeastern Australia , the pathogen was detected in mosquitoes (predominantly Aedes camptorhynchus) (Johnson PD et al. 2007).

Note: M. ulcerans produces a toxin, mycolactone, which causes necrosis and ulceration through its cytotoxic and immunosuppressive properties.

Granulomatous dermatitis with Langhans giant cells. Acanthosis, hyperkeratosis.

Typical clinic with exorbitantly large ulcers.
The following methods are available for Buruli ulcer diagnosis:

Direct smear examination with Ziehl-Neelsen stain to detect acid-fast bacilli in a smear from a swab or biopsy.

Culture on Löwenstein-Jensen medium at 32 ºC (but this method is difficult, expensive, has low sensitivity).

Molecular biological detection by PCR.

The differential diagnosis includes pyogenic abscess in nodules, erysipelas in plaques. In endemic areas, any suspicious lesion should be treated as M. ulcerans infection until proven otherwise.

Early detection is important!

Surgery remains the treatment of choice. Although simple and effective in the early stages of the disease, treatment for advanced forms of the disease requires extensive excisions and long hospital stays.

Currently, no antibiotic treatment has been shown to be effective for all forms of M. ulcerans infection. Resistance determination of the pathogens is not possible due to restricted growth.

For deeper skin and soft tissue infections, surgical approach (debridement) is indicated, but only in combination with drug treatment (clarithromycin and RMP or RMP and streptomycin each for 8 weeks are recommended) (Griffith DE et al. 2007).

In addition, thermotherapy for local treatment is described as another new therapeutic approach.

In some BU patients, a so-called paradoxical reaction may occur after antibiotic treatment of M. ulcerans. PRs are characterized by intense inflammation in the lesions and worsening of the clinical condition after initial improvement (Dallmann-Sauer M et al. 2018).
WHO recommendation: rifampicin in combination with streptomycin (clarithromycin) + necessary surgical measures.

Experimental evidence of hyperthermia as a procedure.

Postoperative physiotherapy to prevent loss of function or contractures.

Development of major necrosis possible; mutilating contractures, possibly metastatic bone lesions; carcinomatous degeneration possible.

Although the disease has a low mortality rate, it has a tremendous socioeconomic impact on affected populations and is a public health problem in terms of morbidity, treatment, and functional disability.

Buruli ulcer is a district in Uganda. In the tropics, sufferers are often ostracized, which is why the disease is hidden for a long time under suitably long clothing and thus only diagnosed at a very advanced stage.

The disease has been largely ignored by many national health programs. Only recently has it been recognized as an emerging health problem, primarily because of its frequent disabling and stigmatizing complications.

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