Cases and Conditions / Buruli Ulcer / Research

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In 1998 the World Health Organisation drew attention to the severity of this disease as an emerging public health problem and expressed concern about its many poorly understood features

Buruli ulcer, a disease caused by Mycobacterium ulcerans is an important cause of human suffering. The causative organism is from the family of bacteria which causes tuberculosis and leprosy. It destroys skin, underlying tissues and causes deformities. Lesions occur mainly in the limbs but also in the trunk and the eyes.

Buruli ulcer is one of the three most common mycobacterial infections in healthy people along with tuberculosis and leprosy. It is the most poorly understood of these three diseases. Most patients are children who live in rural areas near rivers or wetlands. Little is known about the mode of transmission to human beings.

Prevalence
Buruli ulcer is found in marshy parts of the tropical and sub-tropical regions of the world but most commonly in West Africa . All countries along the Gulf of Guinea are now affected. In Ghana 1,000 new cases are reported annually with up to 22 per cent of villagers affected in some areas. There is evidence of huge under-reporting of the disease.

Symptoms
The disease often starts as a painless swelling in the skin. A nodule develops beneath the skin's surface teeming with mycobacteria. Unlike other mycobacteria, M. ulcerans produces a toxin, which destroys tissue and suppresses the body's immune system. Massive
areas of skin and sometimes bone are destroyed causing gross deformities. When lesions heal, scarring may cause restricted movement of limbs and other permanent disabilities. One important feature of Buruli ulcer is the initial minimally painful nature of the disease which may partly explain why those affected do not seek prompt treatment.

Treatment
Unlike TB there is no known treatment for Buruli ulcer apart from surgery to remove the lesion followed by skin grafting if necessary. This is both costly and dangerous, leading to the loss of large amount of tissues/or permanent disability. Early detection and surgical removal of small lesions could prevent many of its devastating consequences.

Prevention
Presently there is no known biomedical intervention to help control Buruli ulcer.

Social and economic implications
Access to health services is restricted in endemic areas. Patients often seek treatment late causing frequent and severe complications and prolonging costly hospitalization. In some areas, about 20%-25% of people with healed lesions are disabled. With an increasing number of cases, and associated complications, the long-term economic and social impact of Buruli ulcer on rural populations will be substantial.

RESEARCH PROPOSAL

AIMS:

TO ESTABLISH A ROBUST TYPING SYSTEM FOR M.ULCERANS
Using Ref strains from ATCC and NCTC, and clinical isolates from Ghana compare existing and newer molecular methods. Establish the best (may be a combination) of methods that provides reliable and robust typing of the isolates. This to establish mode of transmission -> break the chain: elucidation of environmental sources -> eradications: correlation of particular strains with disease severity.

INVESTIGATE THE EPIDEMIOLOGY OF BURULI ULCER
Once a robust typing method is established, use the method to investigate the epidemiology of Buruli ulcer. Correlate the lab-based typing data with the local network of cases. The ultimate aim would be to implement evidence-based control interventions to halt the spread of Buruli ulcer. This arm of the study would also investigate potential environmental / insect vector sources of M. ulcerans.

INVITRO ANTIBIOTIC SUSCEPTIBILITY/SENSITIVITY TESTING OF M.ULCERANS
Using the collections of clinical, environmental and reference strains of M.ulcerans test against established and newer antimicrobial agents e.g. linezolid, new generation of fluoruquinolones both singly and in synergistic combination testing. The implementation of this invitro data would help in the design of future clinical trials of these antimicrobial agents.

PROGRESS
A reconnaissance mission to Ghana in Oct 2005 established that sampling procedures and facilities for tissue culturing are satisfactory and that the institutions involved approved of, and were enthusiastic about participating in, the research. The Action Plan and timetable have been decided. Protocols will be finalised in Ghana in 2006. Funding is now required.