Monday, February 08, 2010

Good News for Buruli Ulcer

I first saw cases of Buruli Ulcer in Agogo Hospital, in Ashanti Region, in Ghana. I was shaken by what I saw.
Buruli Ulcer is a serious skin disease afflicting poor, rural people, notably children and teenagers. It occurs in wet tropical regions; in West Africa, Uganda, East Africa, South-East Asia, New Guinea, Australia, and Central and South America. Its prevalence seems to be increasing in most areas.
Pictures of the disease can be found here - beware, they are distressing.

Death from Buruli Ulcer is uncommon. Ulcers may become huge, but are usually painless and not smelly. Most cases eventually heal, but after months of activity, and leaving extensive scarring with deformity, contractions, and disability. Buruli Ulcer on the face may threaten eyes, mouth or ears; on the lower trunk the genitals are at risk; and an ulcer crossing a joint may leave a limb or hand useless.

Buruli Ulcer is caused by infection by Mycobacterium ulcerans. This is a bacterium related to the Mycobacteria causing tuberculosis and leprosy.
It is likely that M. ulcerans comes from stagnant water or mud. Skin is contaminated, and the bacteria are inoculated by thorn stabs, insect bites or other trauma. This may explain a curious excess of right-sided disease - inoculation occurring while people are working or pushing forward through vegetation.
But the mode of transmission is not established.

Inoculated M. ulcerans multiply in the panniculus adiposus - the layer of fat which underlies the skin. Destruction of fat cells undermines the skin, which breaks down to expose the fascia - the fibrous sheath covering the underlying muscle, bone and other tissues.
The initial lesion is an itchy lump under the skin. In many cases this heals without ulcerating. As in other mycobacterial diseases, most infected people mount a successful immune defence and contain the disease.
But immunity fails in a minority, for reasons not well understood, and serious progressive disease may ensue. The lump becomes a plaque, the plaque becomes an ulcer, and the ulcer grows. At any point immunity may pick up, and healing begin, but great damage can be done before this happens.

For many years the only treatment was dressings and surgery: excision of smaller ulcers, otherwise removal of as much diseased tissue as possible, and maybe skin grafting. A need for skin grafting is always bad news; in a rural hospital in hot, humid areas it is difficult at best, and often impossible.

Now there is good news, published in The Lancet. Buruli Ulcer responds to treatment with rifampicin and streptomycin, and rifampicin and clarithromycin. Streptomycin has to be given by injection; rifampicin and clarithromycin are given orally.
The new work is a controlled trial, completed with commendable thoroughness in difficult circumstances. It shows that an effective protocol is streptomycin and rifampicin for one month, then rifampicin and clarithromycin for a second month. This reduces the need for injections.
Healing occurred in more than 90% of patients, but still needed months of observation and dressing after the drug course was completed.
Obviously best results come with early diagnosis, prompt prescription, and persistent follow-up.
And big neglected ulcers will still need surgery, if possible.

But at last there is progress in management of this dreadful disease, and hope for the thousands of poor people afflicted by it every year. Let the message be spread through the villages: if you get an ulcer, don't delay; come to the hospital for treatment.
And I hope WHO, governments or charities will fund drug provision without question.

Willemien Nienhuis, her colleagues, and the project leader, Tjip van der Werf merit congratulation and recognition for their important achievement.
My small contribution is to award them the Kataphusin Prize for the most important contribution to the management of neglected diseases in the past year.