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Buruli Ulcer - Infection of Skin and Soft Tissue

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Buruli ulcer is a chronic infectious disease affecting the skin and soft tissue. Read this article to learn more about this debilitating condition.

Medically reviewed by

Dr. Dhepe Snehal Madhav

Published At March 7, 2023
Reviewed AtMarch 7, 2023

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:

  • Ulcer with undermined edges.

  • Clinically appearing as white cotton-wool-like.

  • The skin surrounding the lesion is usually thickened and dark in color.

WHO has categorized the disease into two stages:

  • Active - Characterized by non-ulcerative and ulcerative forms. The non-ulcerative variants include papules, nodules, plaques, and edema.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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:

  • Tropical phagedenic ulcers.

  • Chronic lower leg ulcers.

  • Diabetic ulcers.

  • Cutaneous leishmaniasis.

  • Initial nodular forms can be mistaken for boils, fungal infections, or lymph node tuberculosis.

  • Papular lesions may resemble an insect bite.

  • 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:

  • Prevent and reduce mosquito breeding sites.

  • Avoid mosquito bites by using insect repellent, using insect screens and mosquito nets, wearing long-sleeved clothes, and avoiding mosquito-prone areas.

  • Any new cuts and wounds should be dressed with topical antiseptics and appropriate dressing.

  • 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.

Frequently Asked Questions

1.

What Is the Clinical Appearance of a Buruli Ulcer?

Buruli ulcer frequently begins as a painless nodule, a large area of induration without any pain (plaque), or a widespread nodule, plaque, or edema on the face, arms, or legs. The ulcer may appear ‘fleshy’ or necrotic and can be shallow or deep with weakened edges. The skin around the affected area could be abnormally textured, thickened, or discolored. Without symptoms like fever and pain, the illness may advance. The nodule, plaque, or edema will erupt into an ulcer in four weeks if left untreated or occasionally even while receiving antibiotics. Deformities can sometimes result from affecting the bone.

2.

Does the Buruli Ulcer Spread Through Mosquitoes?

Mosquitoes may play a role in spreading Mycobacterium ulcerans, the bacteria that causes Buruli ulcers. However, the transmission is not solely dependent on mosquitoes. In areas where Buruli ulcer is common, cases are often found in specific locations, and nearby communities just a few kilometers away may not be affected. Aedes camptorhynchus mosquitoes, which are believed to be involved in the transmission, are found in both areas with and without Buruli ulcers. Additionally, various mosquito species can fly long distances, potentially carrying the bacteria outside of affected regions. This implies mosquitoes might not fully account for the M. ulcerans transmission model.

3.

Is There a Cure for Buruli Ulcer?

With the right care, Buruli ulcers are curable. An effective outcome depends on early detection and prompt treatment initiation. The standard course of treatment consists of administering a combination of antibiotics over a few weeks to several months, such as Rifampicin and Clarithromycin. Surgery might be required in some circumstances to remove dead tissue or reconstruct the injured area. Most Buruli ulcer cases can be cured with prompt and effective treatment.

4.

Which Individuals Are at Risk of Developing Buruli Ulcer?

Mycobacterium ulcerans, which causes Buruli ulcer (BU), is an ignored mycobacterial skin infection. Poor rural populations are primarily affected by this disease, particularly in places with poor sanitation and hygiene standards. Children under the age of 15 were more at risk for BU. If children aged three to four years old used unprotected water and lived in BU-endemic areas, their risk of contracting the disease increased.

5.

What Is the Recommended Approach for Managing Buruli Ulcer?

- The course of treatment includes both conventional medicine and antibiotics. The WHO (World Health Organization) publication on Buruli ulcers provides treatment recommendations for medical personnel. 
- According to a recent study, Rifampicin (10 mg/kg once daily) and Clarithromycin (7.5 mg/kg twice daily), should now be combined as the recommended treatment. 
- Surgery (primarily debridement and skin grafting) and other interventions, such as managing wounds and lymphoedema, are used to hasten healing and reduce hospital stays. In severe cases, physiotherapy is required to avoid disability.

6.

What Measures Can Be Taken to Prevent Buruli Ulcer?

The Buruli ulcer does not currently have any specific preventive measures in place. It is unknown how the infection is transmitted. Vaccination against Bacillus Calmette-Guerin (BCG) seems to offer only a minimal level of protection. However, the main way to prevent Buruli ulcers is by limiting exposure to the bacteria. The risk of infection can also be decreased by avoiding prolonged contact with potentially contaminated water bodies, wearing protective clothing when participating in outdoor activities, and promptly cleaning and covering any cuts or wounds.

7.

How Long Does the Treatment for Buruli Ulcer Last?

Typically, a course of treatment lasts between a few weeks and a few months. Early-stage ulcers might only need a short course of antibiotics, whereas more advanced or extensive ulcers might need a longer course. Antibiotics can be used to treat Buruli ulcers. As per some research studies, over 90 % of patients are cured after taking Rifampin for an 8-week period along with either Streptomycin or Clarithromycin.

8.

What Are the Commonly Prescribed Antibiotics for Buruli Ulcer?

Rifampicin and Clarithromycin are the two antibiotics that are frequently used to treat Buruli ulcers. The World Health Organization (WHO) advises using this combination because it has demonstrated strong efficacy in treating the illness. Mycobacterium ulcerans is inhibited from growing by the bactericidal medication Rifampicin, while the bacteriostatic medication Clarithromycin prevents the bacteria from proliferating. Together, the two antibiotics effectively eliminate the bacteria and treat the infection.

9.

In Which Regions of the Body Is Buruli Ulcer Commonly Found?

Buruli ulcers can appear anywhere on the body, but the lower limbs are where they are most frequently seen. Even though it happens less frequently, ulcers can also appear on the arms, trunk, or other parts of the body. Various factors, including the method of transmission and the degree of contact with the bacteria, can affect the distribution of the ulcers. Increased exposure to the environment or particular risk factors in those areas may be connected to the preference for the limbs.

10.

Is Buruli Ulcer Contagious?

After leprosy and tuberculosis, Buruli ulcer is the third most prevalent mycobacterial disease in immunocompetent hosts. It is considered an emerging infectious disease. Although the exact means by which the bacteria spread are not fully understood, it is thought that environmental factors and possible contact with contaminated water or soil are involved. Through skin breaks like cuts, abrasions, or insect bites, the bacteria can enter the body. However, unlike some other bacterial infections, person-to-person transmission of Buruli ulcers is uncommon, and the condition is not particularly contagious.

11.

What Is the Reason Behind the Lack of Pain in Buruli Ulcers?

The absence of pain during the early stages of Buruli ulcer is one of its distinguishing features. The toxin produced by the Mycobacterium ulcerans bacteria is thought to be the cause of this, though the exact cause is not yet known. As a result of the toxin's capacity to kill nerve endings, the affected area loses its ability to feel. This lack of pain can delay the detection and diagnosis of the ulcer, delaying the start of treatment and possibly causing the disease to progress more severely. According to the current research, mycolactone directly harms nerves and is the cause of the Buruli ulcer's lack of pain. 

12.

What Are the Treatment Options for Buruli Ulcer in Its Early Stages?

Rifampicin and Clarithromycin are the most common antibiotics used to treat early-stage Buruli ulcers. The antibiotics are taken orally for several weeks, and additional wound care procedures like routine cleaning, changing of the dressing, and shielding the ulcer from additional trauma may be added to the treatment. To stop the ulcer from spreading and reduce tissue damage, early detection and treatment are essential.

13.

How Long Does It Take for Symptoms to Appear After Contracting Buruli Ulcer?

According to variables like the host's immune response, the number of bacteria present, and other host-related factors, the exact time frame of the incubation period may differ. Some findings indicate that the incubation period for Buruli ulcers is approximately 4.8 months, ranging from two to nine months. This estimate aligns with a previous study conducted on patients who acquired their infections in a different geographic area. It suggests that the mode of transmission of the disease is likely similar across various endemic regions in Victoria.

14.

What Is the Vector Responsible for Buruli Ulcer Transmission?

According to a research hypothesis, mosquitoes play a role in the spread of Mycobacterium ulcerans. Mycobacterium ulcerans, which cause Buruli ulcers, are primarily linked to environmental factors and potential contact with contaminated soil or water. Research is ongoing to understand better the ecological reservoirs and transmission pathways of the bacteria in order to determine the precise mode of transmission to humans.
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Dr. Dhepe Snehal Madhav
Dr. Dhepe Snehal Madhav

Venereology

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