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Buruli Ulcer Disease

Disease Details

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Description: Buruli ulcer disease is a chronic, debilitating skin and soft tissue infection caused by the bacterium Mycobacterium ulcerans, leading to the development of large ulcers.
Type: Buruli ulcer disease is a bacterial infection caused by *Mycobacterium ulcerans*. It is not genetically transmitted; transmission is typically environmental, potentially involving contact with contaminated water or soil.
Signs And Symptoms: The first sign of Buruli ulcer is a painless swollen bump on the arm or leg, often similar in appearance to an insect bite. Sometimes the swollen area instead appears as a patch of firm, raised skin about three centimeters across called a "plaque"; or a more widespread swelling under the skin.Over the course of a few weeks, the original swollen area expands to form an irregularly shaped patch of raised skin. After about four weeks, the affected skin sloughs off leaving a painless ulcer. Buruli ulcers typically have "undermined edges", the ulcer being a few centimeters wider underneath the skin than the wound itself.In some people, the ulcer may heal on its own or remain small but linger unhealed for years. In others, it continues to grow wider and sometimes deeper, with skin at the margin dying and sloughing off. Large ulcers may extend deep into underlying tissue, causing bone infection and exposing muscle, tendon, and bone to the air. When ulcers extend into muscles and tendons, parts of these tissues can be replaced by scar tissue, immobilizing the body part and resulting in permanent disability. Exposed ulcers can be infected by other bacteria, causing the wound to become red, painful, and foul smelling. Symptoms are typically limited to those caused by the wound; the disease rarely affects other parts of the body.Buruli ulcers can appear anywhere on the body, but are typically on the limbs. Ulcers are most common on the lower limbs (roughly 62% of ulcers globally) and upper limbs (24%), but can also be found on the trunk (9%), head or neck (3%), or genitals (less than 1%).The World Health Organization classifies Buruli ulcer into three categories depending on the severity of its symptoms. Category I describes a single small ulcer that is less than 5 centimetres (2.0 inches). Category II describes a larger ulcer, up to 15 centimetres (5.9 in), as well as plaques and broader swollen areas that have not yet opened into ulcers. Category III is for an ulcer larger than 15 centimeters, multiple ulcers, or ulcers that have spread to include particularly sensitive sites such as the eyes, bones, joints, or genitals.
Prognosis: Prognosis for Buruli ulcer disease:

The prognosis of Buruli ulcer disease varies based on the stage at diagnosis and the promptness of treatment. Early diagnosis and treatment, typically with a combination of antibiotics and wound care, lead to a favorable outcome with a high rate of cure and minimal complications. If left untreated, the disease can cause severe skin and soft tissue destruction, potentially resulting in permanent disfigurement, functional impairments, and disability. Surgical intervention may be necessary for advanced cases to remove necrotic tissue and perform skin grafting. Early treatment significantly improves the prognosis and reduces long-term consequences.
Onset: Buruli ulcer disease, caused by the bacterium Mycobacterium ulcerans, typically starts as a painless, well-defined nodule or papule. Over a period of weeks to months, it can progress to a large ulcerated lesion. The onset is generally gradual, and early symptoms may be mistaken for other skin conditions.
Prevalence: The prevalence of Buruli ulcer disease, caused by the bacterium *Mycobacterium ulcerans*, is not well-documented on a global scale, leading to a lack of precise prevalence figures. The disease is most commonly reported in tropical and subtropical regions, particularly in West and Central Africa, with hotspots in countries such as Ghana, Côte d'Ivoire, and Benin. Cases have also been reported in Australia, Southeast Asia, and the Americas. Prevalence rates can vary significantly based on local environmental conditions and exposure, with many cases occurring in rural areas near stagnant or slow-moving bodies of water.
Epidemiology: Buruli ulcer is relatively rare, with 2,713 cases reported to the World Health Organization in 2018. Most countries do not report data on Buruli ulcer to the World Health Organization, and the extent of its spread is unknown. In many endemic countries, health systems likely do not record each case due to insufficient reach and resources, and so the reported numbers probably underestimate the true prevalence of the disease.Buruli ulcer is concentrated in West Africa and coastal Australia, with occasional cases in Japan, Papua New Guinea and the Americas. In West Africa, the disease is predominantly reported from remote, rural communities in Benin, Côte d'Ivoire, Cameroon, and Ghana. Other countries in the region also have Buruli ulcer to some degree; a 2019 systematic review of prevalence studies found a clear consensus that it is present in the Democratic Republic of the Congo, Gabon, Liberia, Nigeria, Togo, and South Sudan, as well as "strong" or "very strong" evidence of the disease in the Republic of the Congo, Sierra Leone, the Central African Republic, Guinea, and Uganda. Buruli ulcer is regularly reported from Australia, where it occurs in coastal clusters—two in Queensland (near Rockhampton and north of Cairns) and two in Victoria (near Bairnsdale and Melbourne). It is more rarely reported from Japan, Papua New Guinea, and the Americas. Japan reports a few locally acquired cases per year scattered across the main island, Honshu. Papua New Guinea sporadically reports cases to the World Health Organization, typically less than a dozen per year. In the Americas, most Buruli ulcer is reported from French Guiana, with few cases described in surrounding countries. A 2019 review found "strong" evidence for the presence of Buruli ulcer in French Guiana and Peru, and "moderate" evidence in Brazil, Mexico and Suriname.Within affected countries, Buruli ulcer tends to occur in rural areas near slow-moving or stagnant water. In particular, the disease tends to appear near water that has experienced human intervention, such as the building of dams or irrigation systems, flooding, or deforestation. Within endemic communities, few characteristics predict who will acquire Buruli ulcer. Males and females are equally likely to be infected. Ulcers can appear in people of all ages, although infections are most common among children between 5 and 15 years in West Africa, and adults over 40 in Australia and Japan.
Intractability: Buruli ulcer disease, caused by Mycobacterium ulcerans, can be challenging to treat, but it is not considered intractable. Early detection and appropriate antibiotic treatment, often accompanied by wound care and sometimes surgery, typically lead to good outcomes. Delayed treatment can result in more severe disease and complications.
Disease Severity: Buruli ulcer disease severity can vary significantly. It ranges from small, solitary nodules or plaques to extensive ulcers which can lead to severe disfigurement and disability if left untreated. Early diagnosis and prompt treatment are crucial to prevent advanced stages and minimize long-term effects. The disease is caused by infection with the bacterium *Mycobacterium ulcerans*.
Healthcare Professionals: Disease Ontology ID - DOID:0050456
Pathophysiology: Buruli ulcer disease is caused by Mycobacterium ulcerans, a pathogen that produces mycolactone, a toxin responsible for tissue damage and immune suppression. The disease typically starts as a painless nodule, which can progress to large ulcers if untreated. Mycolactone's cytotoxic effects lead to necrosis of skin, fat, and sometimes deeper structures, resulting in extensive tissue damage and, potentially, significant disfigurement and disability.
Carrier Status: Buruli ulcer disease is caused by the bacterium *Mycobacterium ulcerans*. The exact mode of transmission is not fully understood, but it is believed to involve environmental factors such as contact with contaminated water or soil. There is no known human carrier state for Buruli ulcer disease.
Mechanism: Buruli ulcer disease is caused by the bacterium *Mycobacterium ulcerans*. The primary mechanism involves the production of a toxin called mycolactone.

Molecular Mechanisms:
1. **Mycolactone Production**: *Mycobacterium ulcerans* produces mycolactone, a polyketide-derived macrolide, which is crucial for the bacterium's virulence.
2. **Cytotoxic Effects**: Mycolactone induces apoptosis (programmed cell death) in host cells and disrupts the immune response by inhibiting the production of pro-inflammatory cytokines.
3. **Immunosuppression**: Mycolactone suppresses the function of immune cells, including macrophages and dendritic cells, impairing the host's ability to mount an effective immune response.
4. **Tissue Necrosis**: The cytotoxic effects lead to extensive tissue damage and necrosis, resulting in the characteristic ulcerative lesions of the disease.

The combination of these molecular mechanisms contributes to the chronic, necrotizing skin infection seen in Buruli ulcer disease.
Treatment: Buruli ulcer is treated through a combination of antibiotics to kill the bacteria, and wound care or surgery to support the healing of the ulcer. The most widely used antibiotic regimen is once daily oral rifampicin plus twice daily oral clarithromycin, recommended by the World Health Organization. Several other antibiotics are sometimes used in combination with rifampicin, namely ciprofloxacin, moxifloxacin, ethambutol, amikacin, azithromycin, and levofloxacin. A 2018 Cochrane review suggested that the many antibiotic combinations being used are effective treatments, but there is insufficient evidence to determine if any combination is the most effective. Approximately 1 in 5 people with Buruli ulcer experience a temporary worsening of symptoms 3 to 12 weeks after they begin taking antibiotics. This syndrome, called a paradoxical reaction, is more common in those with larger ulcers and ulcers on the trunk, and occurs more frequently in adults than in children. The paradoxical reaction in Buruli ulcer is thought to be due to the immune system responding to the wound as bacteria die and the immune-suppressing mycolactone dissipates.Small or medium-sized ulcers (WHO categories I and II) typically heal within six months of antibiotic treatment, whereas larger ulcers can take over two years to fully heal. Given the long healing times, wound care is a major part of treating Buruli ulcer. The World Health Organization recommends standard wound care practices: covering the ulcer to keep it moist and protected from further damage; regularly changing wound dressings to keep the ulcer clean, removing excess fluid, and helping prevent infection. Treatment sometimes includes surgery to speed healing by removing necrotic ulcer tissue, grafting healthy skin over the wound, or removing scar tissue that can deform muscles and joints. Specialized wound dressings developed for non-infectious causes of ulcer are occasionally used for treating Buruli ulcer, but can be prohibitively expensive in low-resource settings.
Compassionate Use Treatment: Buruli ulcer disease, caused by the bacterium *Mycobacterium ulcerans*, is primarily treated with antibiotics. However, for cases that do not respond well to standard treatments, compassionate use or experimental treatments may be considered.

1. **Compassionate Use Treatment:**
- **Rifampicin and Clarithromycin:** Primarily part of the standard treatment, but they can be continued for compassionate use in severe or resistant cases.
- **Adjunctive Hyperbaric Oxygen Therapy (HBOT):** Used in some cases to enhance wound healing by increasing oxygen supply to the affected tissues.

2. **Off-label or Experimental Treatments:**
- **Heat Therapy:** Some studies suggest applying heat to the ulcer can inhibit bacterial growth, though this is not widely adopted yet.
- **Antimicrobial Peptides:** Experimental use of peptides like LL-37, which have shown some efficacy in preclinical studies.
- **Topical Ointments:** Experimental topical treatments containing antibiotics or antimicrobial agents like silver sulfadiazine.

Patients considering these treatments should consult healthcare professionals specializing in infectious diseases to evaluate the suitability and potential risks.
Lifestyle Recommendations: Buruli ulcer is a chronic, debilitating disease caused by the bacterium Mycobacterium ulcerans. Lifestyle recommendations for those at risk of or diagnosed with Buruli ulcer include:

1. **Early Detection**:
- Regularly check for any painless swelling or nodules on the skin, especially after spending time in endemic areas (e.g., near wetlands and slow-moving water bodies).

2. **Wound Care**:
- Keep any skin lesions clean and covered.
- Consult healthcare professionals promptly if a suspicious ulcer or nodule appears.

3. **Prevention Practices**:
- Avoid direct contact with stagnant water where possible.
- Use protective clothing (long sleeves and pants) and insect repellent to reduce the risk of insect bites that might contribute to transmission.

4. **Health Education**:
- Participate in community awareness programs about the disease and its early symptoms.
- Encourage timely medical consultation within your community if symptoms are observed.

5. **Hygiene**:
- Maintain good personal hygiene to prevent secondary infections if you have any ulcers or open wounds.

Following these recommendations is vital for managing and preventing Buruli ulcer disease.
Medication: For Buruli ulcer disease, the primary treatment involves antibiotics. The World Health Organization (WHO) recommends a combination of rifampicin and clarithromycin. Additionally, wound care, including surgical interventions if necessary, supports the healing process.
Repurposable Drugs: For Buruli ulcer disease, repurposable drugs include rifampicin and streptomycin, which are typically used in combination as the standard treatment. Clarithromycin is another antibiotic that has been investigated for potential use in treating Buruli ulcer.
Metabolites: Buruli ulcer disease, caused by *Mycobacterium ulcerans*, produces a toxin called mycolactone, which is a key virulence factor. Mycolactone affects cellular metabolism and immune response, leading to tissue necrosis and immunosuppression. The impact on metabolites can include altered lipid metabolism and immune signaling pathways, although specific metabolite concentrations in infected patients are still under research.
Nutraceuticals: There is no established use of nutraceuticals for the treatment or prevention of Buruli ulcer disease. Nutraceutical approaches are not a primary or widely recognized treatment modality for this condition.
Peptides: Buruli ulcer disease is a debilitating skin infection caused by the bacterium *Mycobacterium ulcerans*. Peptides might play a role in potential treatments or vaccine development as they can be designed to target specific bacterial components. However, the research on peptide-based therapies for Buruli ulcer is ongoing and not yet definitive. The application of nanotechnology (nan) in this context could include the use of nanoparticles for targeted drug delivery, enhancing the effectiveness of existing treatments with fewer side effects. More research is needed to fully explore and validate these advanced therapeutic approaches.