Introduction:
Buruli ulcer is a chronic, incapacitating, neglected infectious skin disease caused by Mycobacterium ulcerans (M. ulcerans). It is an emerging infectious disease and is considered the third most common disease of mycobacterial origin, next to tuberculosis and leprosy. Extensive cases were found and described initially in the Buruli district of Uganda, from where it derived its name. It usually presents as an ulcer on the skin, which may progress into necrosis involving the skin, soft tissue, and bone. Delay in treatment could result in a functional disability that may be irreversible and permanent, subsequently causing emotional and psychological stress, decreased economic productivity, and unnecessary social stigma. However, since the 1998 initiative by WHO on this infectious condition, adequate awareness and efforts have been made to control and prevent this debilitating disease. Buruli ulcer is also known as Bairnsdale ulcer, Mossman ulcer, Searl ulcer, and Daintree ulcer.
Which Zones Are Buruli Ulcer Prevalent?
M. ulcerans is more prevalent in rural tropical regions with humid and moist environments. Most cases are reported in West Africa, particularly in Côte d'Ivoire, Ghana, and Bénin. A few cases have also been described in Mexico, South America, Papua New Guinea, and Australia. However, in Australia and Japan, the disease spread has also been noticed in moderate, nontropical environments. Globally reported cases in 2010 were roughly around 5000 cases which reduced to 1258 in 2020, which primarily could be due to the worldwide impact of Covid-19.
How Is Buruli Ulcer Transmitted?
The mode of transmission of Buruli ulcer remains debatable though the condition is associated with contaminated and stagnant water. Increasing cases have been observed during the rainy season and in regions related to environmental changes such as deforestation, hydraulic installations, or agricultural activities. Vectors such as Naucoris and Belostoma spp (water insects) and salt marsh mosquitoes have a potential role in the transmission of the disease. Possum poo from certain possum species has also been a known vector to transmit this disease. Skin trauma, though not proven, is also a suspected pathway for disease transmission. Though several animals have been confirmed as the carrier of the disease, zoonotic infection is, however, ruled out. Spread from humans to humans is also rare.
What Is the Mechanism of Disease Progression?
M.ulcerans is a slow-growing organism that thrives at an optimal temperature of 30 to 32 degrees Celcius, which is a little lower than the core body temperature. However, they are extremely sensitive to direct sunlight or temperatures above 37 degrees Celcius; hence they prefer to harbor a protective host. They gain entry into the human body via infected wounds or bites of water insects or marsh mosquitoes. Once inside the host body, the mycobacterium produces a soluble toxin known as mycolactone, which diffuses into the subcutaneous tissue. Mycolactone is a potent immunosuppressive and cytotoxic (causes cell death) agent that can cause extensive tissue damage without initiating an immune response. In addition, they inhibit certain protein metabolism in the host body, thus interfering with the body's coagulative, inflammatory, and immune responses.
What Are the Signs and Symptoms?
There is no racial or gender predilection associated with this disease. Buruli ulcer is known to affect any age group though the peak age group is children aged between 5 to 15 years. In Australia, it is more prevalent in the elderly age group (above 50 years). Buruli ulcer usually presents as a small painless swelling (initially, it resembles a lesion similar to a mosquito or a spider bite). Progressively the swelling may grow to form an induration (larger plaque) with a crusty, non-healing scab and may subsequently form an ulcer. It may affect the upper or lower limbs, face, or any other body part, though it primarily affects the lower limbs (55 percent). The disease usually progresses with no signs of infection, such as pain or fever. However, untreated cases may progress and result in deformity, functional disability, bone infection, or secondary infections. The disease has been classified based on its severity into the following three categories:
Category I – Single small lesion.
Category II – Non-ulcerative and ulcerative plaque and edematous types.
Category III – A disseminated disease with osteitis, osteomyelitis, and joint involvement.
How Is Buruli Ulcer Diagnosed?
Diagnosis, particularly in an endemic region, is effortlessly made by experienced health professionals. A detailed diagnostic workup is explained below:
1. Physical Examination – The characteristic features of Buruli ulcer as described by the World health Organisation (WHO) clinical case definition are:
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Ulcer with undermined edges.
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Clinically appearing as white cotton-wool-like.
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The skin surrounding the lesion is usually thickened and dark in color.
WHO has categorized the disease into two stages:
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Active - Characterized by non-ulcerative and ulcerative forms. The non-ulcerative variants include papules, nodules, plaques, and edema.
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Inactive - Previous infection with a prominent stellate scar with or without any sequelae.
2. Laboratory Tests – Laboratory tests such as histopathology, direct microscopy and culture, and polymerase chain reaction (PCR) can be used to identify the microorganism and confirm the presence of the disease.
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Direct Smear - Since M.ulcerans is an acid-fast bacillus (AFB), it can be easily identified by taking a direct smear from the ulcer base and staining it using the Ziehl-Neelsen technique which would reveal the mycobacterium under the microscope. It is easy to perform; results can be obtained swiftly and cost-effective; however, the sensitivity is low and is technique sensitive as it requires a trained histopathologist.
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PCR - PCR is a molecular analysis test that requires swabs, aspirates, or a biopsy sample. Though it is susceptible, it is expensive, can be conducted only in laboratories, and requires trained personnel.
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Culture - The microorganisms can be cultured using the exudate or the biopsy tissue sample. Though it is a confirmatory test, it is time-consuming as these organisms are slow growing and may take six to eight weeks to be isolated from the culture.
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Histopathology - A biopsy is considered only in establishing a differential diagnosis or if there is an unexpected response to the treatment. It is an invasive and expensive procedure and hence not recommended unless otherwise required.
3. Imaging Studies - Imaging studies such as X-ray, ultrasound, or computed tomography are advised if there is extensive ulceration or significant bone involvement indicating osteitis or osteomyelitis. It is also used to monitor the treatment response.
What Is the Differential Diagnosis?
The differential diagnosis includes:
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Tropical phagedenic ulcers.
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Chronic lower leg ulcers.
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Diabetic ulcers.
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Cutaneous leishmaniasis.
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Initial nodular forms can be mistaken for boils, fungal infections, or lymph node tuberculosis.
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Papular lesions may resemble an insect bite.
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Edematous Buruli ulcer may mimic cellulitis; however, the patient is febrile in cellulitis, and the lesions are painful.
How Is Buruli Ulcer Treated?
Antibiotics and supportive treatment are the mainstays in treating M.ulcerans. Several studies have shown that combination therapy of Rifampicin (10 mg/kg once daily) and Clarithromycin (7.5 mg/kg twice daily) or Rifampicin (10 mg/kg once daily) and Moxifloxacin (400 mg once daily) have proven successful in treating Buruli ulcer. Surgical interventions and debridement are required to remove dead skin and cover skin deformities. Physiotherapy and long-term rehabilitation may be required in patients with functional disabilities.
Can Buruli Ulcers Be Prevented?
Few tips to prevent infections:
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Prevent and reduce mosquito breeding sites.
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Avoid mosquito bites by using insect repellent, using insect screens and mosquito nets, wearing long-sleeved clothes, and avoiding mosquito-prone areas.
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Any new cuts and wounds should be dressed with topical antiseptics and appropriate dressing.
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BCG (bacillus calmette-guerin)vaccination offers limited protection.
Conclusion:
Buruli ulcer is an emerging and neglected infectious skin disease. Though it is not associated with high mortality rates, the extensive functional disability associated with this condition may have a massive physical and socioeconomic impact on the affected persons. Prompt diagnosis and early treatment can prevent complications and disabilities thereby reducing the social stigma and global burden.
