Buruli Ulcer: Symptoms, Treatments, Medications and Prevention

by topschoolsintheusa · Published October 2, 2024 · Updated September 14, 2024

Buruli ulcer is a chronic, debilitating skin disease caused by the bacterium Mycobacterium ulcerans. The infection leads to the development of large, destructive ulcers on the skin, often beginning as painless nodules or swellings before progressing to more severe lesions. Buruli ulcer primarily affects the skin but can also involve deeper tissues, including bones, leading to significant morbidity if left untreated. The disease is most common in tropical and subtropical regions, particularly in Africa, but cases have been reported in other parts of the world.

What is Buruli Ulcer?

The Causative Agent: Mycobacterium ulcerans

Mycobacterium ulcerans is a slow-growing bacterium that belongs to the same family as the bacteria responsible for tuberculosis (Mycobacterium tuberculosis) and leprosy (Mycobacterium leprae). However, unlike these other mycobacteria, M. ulcerans releases a unique toxin called mycolactone, which plays a key role in the disease process.

Mycolactone toxin: This toxin causes tissue damage by suppressing the immune response and destroying fat cells and skin tissue. As a result, the infection can progress without causing significant pain or inflammatory responses in its early stages.

Once M. ulcerans enters the skin, it can remain dormant for weeks or months before triggering an infection. The disease typically begins as a painless nodule or papule but can progress to form large ulcers, often with undermined edges. The ulcer can enlarge, damaging the skin and deeper tissues, and without treatment, it may lead to permanent disability.

Life Cycle and Pathogenesis of Mycobacterium ulcerans

The exact mode of transmission of M. ulcerans remains unclear, but it is believed to be associated with water sources and environmental exposure in endemic regions. Various studies suggest that aquatic environments, such as swamps, rivers, and ponds, may harbor the bacteria. Insects, such as aquatic bugs, have been implicated as potential vectors, though this has not been conclusively proven.

Once the bacterium infects the skin, the mycolactone toxin is released, causing tissue necrosis and immune suppression, allowing the bacteria to thrive in the skin and subcutaneous tissues without causing significant inflammation or pain in the early stages. As the disease progresses, ulcers form, which can enlarge and destroy surrounding tissues, including bones in severe cases.

Mode of Transmission

While the precise mode of transmission of Mycobacterium ulcerans remains uncertain, it is thought to be linked to environmental exposure. The following are potential factors contributing to the transmission:

Contact with contaminated water: Buruli ulcer is strongly associated with areas near slow-moving water bodies like swamps, rivers, and ponds. It is believed that the bacteria may be present in these water sources.
Insect vectors: Some research has suggested that aquatic insects may serve as vectors for the transmission of the bacteria. However, this hypothesis has not been conclusively proven.
Trauma to the skin: It is hypothesized that minor injuries or abrasions to the skin may allow the bacterium to enter and establish an infection.

Despite extensive research, there is no confirmed evidence of human-to-human transmission of Buruli ulcer.

Who is at Risk of Buruli Ulcer?

Although anyone can contract Buruli ulcer, certain populations and environmental factors increase the risk of infection.

Geographic Risk Factors

Buruli ulcer is most prevalent in tropical and subtropical regions, particularly in rural areas where access to healthcare and sanitation is limited. The disease occurs in over 33 countries, with the majority of cases reported in West and Central Africa.

Africa: The highest burden of Buruli ulcer is found in West Africa, particularly in countries such as Benin, Côte d’Ivoire, Ghana, and Togo. Central African countries, including Cameroon and the Democratic Republic of Congo, also report significant numbers of cases.
Australia: In Australia, particularly in the state of Victoria, Buruli ulcer (also known as Bairnsdale ulcer) is endemic in certain areas, though the disease is less common compared to Africa.
Other regions: Cases have also been reported in countries such as Papua New Guinea, Mexico, and Malaysia, though they are less frequent.

Occupational and Environmental Risk Factors

Certain occupations and environmental conditions can increase the risk of contracting Buruli ulcer.

1. Rural Populations in Endemic Areas

People living in rural, tropical, and subtropical regions near water sources are at higher risk for Buruli ulcer. The disease is often associated with agricultural work or activities that involve contact with contaminated soil and water, such as:

Farmers and fishermen working near slow-moving water sources like rivers, ponds, or swamps.
Children who play near or in water sources in endemic areas are also at heightened risk.

2. Lack of Access to Clean Water and Sanitation

Communities with poor sanitation and limited access to clean water may be more susceptible to environmental exposure to M. ulcerans. Living near water sources that are potentially contaminated with the bacterium increases the likelihood of infection.

3. Trauma to the Skin

Individuals who sustain minor cuts, scrapes, or abrasions may be at greater risk if they are exposed to contaminated water or soil. Such injuries can provide an entry point for M. ulcerans.

4. People Visiting Endemic Areas

Travelers who visit endemic regions may also be at risk of contracting Buruli ulcer, particularly if they engage in activities that involve exposure to contaminated water or soil.

Symptoms of Buruli Ulcer

Buruli ulcer typically progresses through several stages, with each stage presenting distinct clinical features. The infection is often painless in the early stages, which can delay diagnosis and treatment.

1. Early Stage

The early stage of Buruli ulcer is characterized by the development of a painless nodule, papule, or plaque at the site of infection. At this stage, the skin may appear slightly swollen or firm to the touch, but there is usually no pain, itching, or significant discomfort.

Symptoms of Early-Stage Buruli Ulcer:

Painless nodule: The first sign of Buruli ulcer is typically a small, firm, painless lump (nodule) or swelling. This nodule may be red or slightly raised and can occur anywhere on the body, though it most commonly appears on the arms, legs, or face.
Papule or plaque: In some cases, the infection may begin as a papule (small, raised lesion) or plaque (flat, slightly elevated lesion).
Itching or mild discomfort: Although the nodule is typically painless, some individuals may experience mild itching or irritation.

2. Progressive Stage

As the infection progresses, the nodule or plaque enlarges and begins to ulcerate. This stage is marked by the breakdown of skin tissue, leading to the formation of a characteristic Buruli ulcer.

Symptoms of Progressive-Stage Buruli Ulcer:

Ulcer formation: The nodule or plaque gradually ulcerates, leading to an open wound with undermined edges (where the edges of the ulcer overhang). The ulcer can enlarge rapidly, sometimes reaching several centimeters in diameter.
Painless ulcer: Despite the significant tissue damage, the ulcer typically remains painless, likely due to the mycolactone toxin, which suppresses the immune response and reduces inflammation.
Discharge: The ulcer may discharge a serous (clear) or yellowish fluid. There is often little to no bleeding.
Foul odor: In some cases, the ulcer may emit a foul smell, particularly if secondary bacterial infection occurs.

3. Advanced Stage

If left untreated, Buruli ulcer can progress to more advanced stages, affecting deeper tissues such as muscles, tendons, and bones. In severe cases, the infection can lead to permanent disability.

Symptoms of Advanced-Stage Buruli Ulcer:

Large, extensive ulcers: The ulcers may continue to enlarge and coalesce, covering a large area of skin and subcutaneous tissue.
Bone involvement: In advanced cases, the infection can invade the bones, leading to osteomyelitis (bone infection) and causing pain, swelling, and deformity.
Contractures and deformities: As the infection progresses, it can cause scar tissue formation, leading to contractures (tightening of skin or muscles) and deformities, especially around joints.
Systemic symptoms: Although rare, systemic symptoms such as fever, fatigue, and malaise may occur in cases where secondary infection or widespread tissue damage is present.

Complications of Untreated Buruli Ulcer

If Buruli ulcer is not treated promptly, it can result in several serious complications, including:

Permanent disability: The destruction of skin, muscles, and bones can lead to severe physical deformities and disability, particularly if the ulcers are located near joints.
Amputation: In severe cases where the infection has caused extensive tissue destruction, amputation of the affected limb may be necessary.
Secondary bacterial infection: The open ulcers can become infected with other bacteria, leading to additional complications such as sepsis or gangrene.

Diagnosis of Buruli Ulcer

Diagnosing Buruli ulcer in its early stages is challenging, as the initial symptoms may resemble other skin conditions. A combination of clinical evaluation, laboratory tests, and imaging studies is often required to confirm the diagnosis and determine the extent of the infection.

1. Clinical Evaluation

The initial diagnosis of Buruli ulcer is often based on the characteristic clinical presentation, including:

The presence of a painless nodule, papule, or ulcer with undermined edges.
A history of exposure to water sources in endemic regions.
The absence of pain or significant inflammation, which is unusual for other types of ulcers or skin infections.

However, clinical evaluation alone is not sufficient to confirm the diagnosis, and laboratory testing is required to identify Mycobacterium ulcerans.

2. Laboratory Tests

Several laboratory tests can be used to confirm the diagnosis of Buruli ulcer and identify the causative organism.

1. Polymerase Chain Reaction (PCR)

PCR is the most sensitive and specific test for diagnosing Buruli ulcer. It detects the DNA of Mycobacterium ulcerans in samples taken from the ulcer, such as a swab or biopsy. PCR is the gold standard for diagnosis and is widely used in endemic regions.

Sample collection: A swab of the ulcer exudate or a small biopsy of the lesion is collected and sent to the laboratory for PCR testing.
Results: PCR can confirm the presence of M. ulcerans and is highly accurate, even in early-stage disease.

2. Microscopy

Microscopy is used to examine tissue samples or swabs for the presence of acid-fast bacilli (AFB), which are characteristic of mycobacterial infections. The sample is stained using Ziehl-Neelsen stain to visualize the bacteria under a microscope.

Limitations: Microscopy is less sensitive than PCR and may not detect M. ulcerans in early-stage disease, but it is useful in areas where PCR is not available.

3. Culture

Culture of M. ulcerans from tissue samples can be used to confirm the diagnosis, but it is not commonly performed because the bacteria grow very slowly, often taking several weeks to produce visible colonies. PCR is preferred due to its speed and accuracy.

4. Histopathology

A biopsy of the ulcer can be examined for histopathological changes, such as necrosis, granulomas, and acid-fast bacilli. Histopathology can help distinguish Buruli ulcer from other skin conditions and confirm the presence of M. ulcerans.

3. Imaging Studies

In cases where the infection has spread to deeper tissues, imaging studies may be necessary to assess the extent of the damage.

1. X-rays

X-rays can be used to evaluate bone involvement in advanced cases of Buruli ulcer. If the infection has spread to the bones, X-rays may show signs of osteomyelitis or bone destruction.

2. Ultrasound

Ultrasound is a non-invasive imaging technique that can help assess the depth of the ulcer and determine whether deeper tissues, such as muscles and tendons, are involved.

3. Magnetic Resonance Imaging (MRI)

MRI is sometimes used to provide detailed images of the soft tissues and bones in cases where the infection has spread beyond the skin. MRI can help determine the extent of tissue destruction and guide surgical intervention if necessary.

Treatments for Buruli Ulcer

The treatment of Buruli ulcer requires a combination of antibiotic therapy and, in some cases, surgical intervention. Early diagnosis and treatment are essential to prevent complications, minimize tissue damage, and improve outcomes.

Antibiotic Treatment

Antibiotic therapy is the cornerstone of Buruli ulcer treatment. The WHO recommends a combination of antibiotics to effectively treat the infection and prevent its spread.

1. Rifampicin and Clarithromycin

Rifampicin and clarithromycin are the two most commonly used antibiotics for treating Buruli ulcer. The combination of these drugs has been shown to be highly effective in killing Mycobacterium ulcerans and stopping the progression of the disease.

Dosage: Rifampicin (10 mg/kg) is taken orally once daily, while clarithromycin (500 mg) is taken orally twice daily. The standard course of treatment lasts for 8 weeks.
Side effects: Common side effects of rifampicin include orange discoloration of urine, nausea, and hepatotoxicity. Clarithromycin can cause gastrointestinal upset and, in rare cases, liver toxicity.

2. Rifampicin and Streptomycin

In some cases, rifampicin may be combined with an injectable antibiotic, such as streptomycin, to treat more advanced cases of Buruli ulcer.

Dosage: Streptomycin (15 mg/kg) is given as an intramuscular injection once daily, in combination with oral rifampicin. Treatment typically lasts for 8 weeks.
Side effects: Streptomycin can cause ototoxicity (hearing loss) and kidney damage, so it is usually reserved for more severe cases.

Surgical Treatment

Surgical intervention may be necessary in cases where the ulcer is large, involves deeper tissues, or has caused significant damage. Surgery is often combined with antibiotic therapy to remove necrotic tissue and facilitate wound healing.

1. Debridement

Surgical debridement involves the removal of dead or infected tissue from the ulcer. This helps reduce the bacterial load and promotes the healing of healthy tissue.

2. Skin Grafting

In cases where the ulcer has caused extensive skin loss, skin grafting may be performed to cover the wound and promote healing. This involves taking healthy skin from another part of the body and transplanting it to the affected area.

3. Amputation

In rare cases of advanced disease, where the infection has spread to the bones and caused significant damage, amputation of the affected limb may be necessary to prevent the spread of the infection and save the patient’s life.

Wound Care and Rehabilitation

In addition to antibiotic and surgical treatment, wound care and rehabilitation play an important role in the recovery process.

Wound dressing: Proper wound care, including regular dressing changes and cleaning of the ulcer, is essential to prevent secondary infection and promote healing.
Physical therapy: Physical therapy may be needed to restore mobility and function in cases where the ulcer has affected muscles or joints. Exercises and rehabilitation can help prevent contractures and deformities.

Most Common Medications for Buruli Ulcer

The most commonly prescribed medications for treating Buruli ulcer include:

1. Rifampicin

Rifampicin is the first-line antibiotic for treating Buruli ulcer. It is effective against Mycobacterium ulcerans and is used in combination with other antibiotics for a duration of 8 weeks.

2. Clarithromycin

Clarithromycin is often used in combination with rifampicin to treat Buruli ulcer. It is an oral antibiotic that helps stop the progression of the disease.

3. Streptomycin

Streptomycin is an injectable antibiotic used in combination with rifampicin for more severe cases of Buruli ulcer. It is typically given as a daily injection for 8 weeks.

4. Moxifloxacin

Moxifloxacin is a newer antibiotic that may be used as an alternative to clarithromycin in some cases. It is effective against M. ulcerans and can be used in combination with rifampicin.

Where is Buruli Ulcer Most Prevalent?

Buruli ulcer is most commonly found in tropical and subtropical regions, particularly in West and Central Africa. However, the disease has been reported in over 33 countries worldwide.

1. West Africa

West Africa is the most heavily affected region, with countries such as Benin, Côte d’Ivoire, Ghana, and Togo reporting the highest number of cases. The disease is particularly common in rural areas near water sources, such as rivers and swamps.

2. Central Africa

Central African countries, including Cameroon and the Democratic Republic of Congo, also report significant numbers of Buruli ulcer cases. The disease is often found in regions with poor sanitation and limited access to healthcare.

3. Australia

In Australia, Buruli ulcer (known as Bairnsdale ulcer) is endemic in certain regions, particularly in the state of Victoria. Cases are reported primarily in coastal areas and are associated with exposure to contaminated soil or water.

4. Other Countries

Buruli ulcer has been reported in several other countries, including Papua New Guinea, Mexico, Malaysia, and French Guiana, though the disease is less common in these regions.

Prevention of Buruli Ulcer

Preventing Buruli ulcer involves reducing exposure to Mycobacterium ulcerans in endemic areas and promoting early diagnosis and treatment to prevent complications.

1. Avoiding Contact with Contaminated Water

Since Buruli ulcer is associated with exposure to contaminated water sources, individuals living in or visiting endemic areas should take steps to avoid contact with slow-moving or stagnant water. This includes:

Avoiding wading or swimming in rivers, ponds, or swamps in endemic regions.
Wearing protective clothing, such as long sleeves and pants, when near water sources.

2. Wearing Protective Clothing

Individuals in endemic areas should wear protective clothing to minimize the risk of skin injuries that could serve as entry points for the bacterium. This includes wearing long sleeves, pants, and sturdy footwear when working outdoors.

3. Prompt Treatment of Skin Injuries

Treating minor cuts and abrasions promptly can help reduce the risk of infection. Keeping wounds clean and covered can prevent M. ulcerans from entering the skin.

4. Public Health Education

Raising awareness about Buruli ulcer and promoting early diagnosis and treatment are key to reducing the burden of the disease. Public health campaigns in endemic areas should focus on:

Educating communities about the symptoms of Buruli ulcer and the importance of seeking early medical care.
Training healthcare workers to recognize and diagnose the disease in its early stages.