Buruli ulcer, one of the most neglected diseases in the world

Buruli ulcer is an NTD that affects the skin, soft tissues and bones, and mainly attacks people from rural environments and impoverished contexts, where access to health services is limited. The treatment recommended by the World Health Organization (WHO) requires eight weeks of two antibiotics (rifampicin and clarithromycin), administered daily. Besides, A lot of care is needed to heal the ulcers caused by the disease on the skin. and prevent affected people from needing skin grafts and surgery. If the disease is not treated, it can cause disability and even death. With proper treatment and follow-up, healing can take up to a year.

Based on previous work by the research group, it has been observed in in vitro tests that beta-lactams (a family of antibiotics) increase the activity of rifampicin and clarithromycin. Consequently, The objective of this project is to evaluate whether treatment could be reduced from eight to four weeks by co-administering amoxicillin/clavulanic acid with current therapy.

For that, A phase II clinical trial has been initiated in three Buruli ulcer diagnosis and treatment centers in Benin, in the towns of Pobè, Lalo and Allada. Patients are divided according to the severity of the injury and randomly assigned to two different treatments: rifampicin plus clarithromycin for eight weeks; and rifampin, clarithromycin plus amoxicillin/clavulanic acid for four weeks. At the end, the percentage of patients in each group whose lesion has healed, without recurrence and without needing surgery at 12 months after starting treatment will be compared.

What is Buruli ulcer?

Buruli ulcer is a chronic and debilitating infection caused by an environmental mycobacteria, Mycobacterium ulcerans, which belongs to the same family of bacteria that cause tuberculosis or leprosy. More than 30 countries – especially in West and Central Africa – have reported this disease. To date, its mode of transmission is unknown, but it is related to areas with stagnant and unhealthy water. The greatest burden falls on children under 15 years of age in sub-Saharan Africa. It is a disease that affects the most impoverished communities and, if left untreated, can lead to permanent disability., with the psychosocial and socioeconomic implications that this entails. Most cases continue to be detected in advanced stages of the disease; The need for hospitalization for treatment and care of wounds has a great impact at home.

How do projects like this impact?

A positive result from this trial would provide the basis for implementing a new treatment in Buruli ulcer endemic countries, which could guide a change in WHO policy and practice. A shorter, highly effective and totally oral treatment would reduce both the duration of treatment and the healing time of all types of injuries. Furthermore, this would have an impact on expenses related to hospitalization (fewer days), indirect costs (loss of income and family costs to support the patient) and barriers to access to therapy (easier and shorter therapy).

This project has a transversal approach due to the participation of affected communities, awareness campaigns and training activities. Skin NTDs are co-endemic in many countries and communities. They have common clinical manifestations and diagnoses and it is known that the number of reported cases is below reality. Information, education and communication campaigns, as well as active case finding, have been intensified during the study period, increasing the possibility of detecting and treating skin infections. This trial could also provide enlightening information on strategies to shorten treatments for other infections caused by mycobacteria such as tuberculosis, leprosy and others caused by nontuberculous mycobacteria that have rifampicin as a central component of their treatment.

How can progress be made in controlling this disease?

In recent years, the number of Buruli ulcer cases reported in endemic African countries has decreased. However, The covid-19 pandemic has emphasized inequality and caused a setback in the control of Neglected Tropical Diseases (ETD).

The objective of controlling this disease is to minimize the suffering, disabilities and socioeconomic burden of people who suffer from it. YesPrevention and mode of transmission remain unknown and therefore early diagnosis and treatment are crucial. Furthermore, the integration approach to NTDs and the adoption of multisectoral measures within and outside the health sector are necessary for their control. It is important to mobilize resources and carry out projects like this, with a transversal approach and made up of multidisciplinary actors, to advance in the control of a disease as complex as Buruli ulcer.

Santiago Ramón-García ARAID researcher at the University of Zaragoza Emma Sáez-López Unizar Researcher

Source: Heraldo de Aragón