Elsevier

The Lancet

Volume 354, Issue 9183, 18 September 1999, Pages 1013-1018
The Lancet

Seminar
Mycobacterium ulcerans infection

https://doi.org/10.1016/S0140-6736(99)01156-3Get rights and content

Summary

After tuberculosis and leprosy, Buruli-ulcer disease(caused by infection with Mycobacterium ulcerans)is the third most common mycobacterial disease in immunocompetent people. Countries in which the disease is endemic have been indentified, predominantly in areas of tropical rain forest; the emergence of Buruli-ulcer disease in West African countries over the past decade has been dramatic. Current evidence suggests that the infection is transmitted through abraded skin or mild traumatic injuries after contact with contaminated water, soil or vegetation; there is one unconfirmed preliminary report on possible transmission by insects. The clinical picture ranges from a painless nodule to large, underminded ulcerative lesions that heal spontaneously but slowly. Most patients are children. The disease is accompanied by remarkably few systemic symptoms, but occasionally secondary infections resulting in sepsis or tetanus cause severe systemic disease and death. Extensive scarring can lead to contractures of the limbs, blindness, and other adverse sequelae, which impose a substantial health and economic burden. Treatment is still primarily surgical, and includes excision, skin grafting, or both. Although BCG has a mild but significant protective effect, new vaccine developments directed at the toxins produced by M ulcerans are warranted. In West Africa, affected populations are underprivileged, and the economic burden imposed by Buruli-ulcer disease is daunting. Combined efforts to improve treatment, prevention, control, and research strategies (overseen by the WHO and funded by international relief agencies) are urgently needed.

Section snippets

Bacteriology

M ulcerans belongs to the large group of environmental mycobacteria. It is a slowly growing acid-fast and alcohol-fast microorganism that is best cultured in egg-yolk-enriched Löwenstein-Jensen medium at 32°C (pH 5·4–7·4, pO2<2·5 kPa). Attempts to culture the microrganism from clinical specimens fail in over half of all cases. Standard techniques require much time for isolation and identification. If carbon-14 is added to the culture medium, a radiometric assay (BACTEC system) may detect growth

Epidemiology and transmission

Most researchers believe that M ulcerans infection is acquired from the natural environment, and that small, penetrating injuries transmit the bacterium to the subcutaneous fat of exposed parts of the body.3 Patients may have forgotten such injuries by the time they develop overt disease. Children outnumber adults in almost all reported large case series, and this fact may partly explain why many affected individuals have no recollection of any previous injury.

Support for the theory that M

Clinical features

In most African patients with Buruli-ulcer disease, the subcutaneous tissue is the primary focus of infection (figure 2). A firm, non-tender nodule indicates the first stage of disease, but preulcerative lesions also include plaques, which consist of larger areas of indurated skin, and oedema (figure 3). In the second stage, ulceration takes place (figure 4). Coalescent necrosis of the subcutaneous fat with vascular occlusion results in sloughing and secondary ulceration of the overlying skin,

Diagnosis

In endemic areas, the clinical diagnosis of ulcerating lesions is straightforward. The painless ulcer with undermined edges, with a necrotic slough can be recognised easily (figure 4). Most lesions are on the limbs, although they may also be present on the trunk or face; facial lesions may be mistaken for cancrum oris (noma). Patients with Buruli ulcer have no clinically detectable lymphadenitis, and have no systemic symptoms such as fever or malaise, which would suggest staphylococcal or

Surgery

Early excision of small preulcerative lesions (papules and nodules) is curative. After excision, the skin can be closed. Extensive preulcerative lesions (plaques and oedema) require surgery also, but effective surgical treatment can be delayed because of diagnostic uncertainty. Necrotic ulcers are easily recognised and should be excised. All necrotic tissue should be carefully removed, with excision extending into healthy tissue, so as to prevent persistent subcutaneous infection from residual

Prevention

BCG vaccination had an incomplete but significant protective effect against Buruli ulcer in two controlled clinical trials in Uganda.25, 26 The potential role of other available mycobacterial vaccines in the prevention of M ulcerans infection is unknown. M vaccae, an environmental mycobacterium, seems to induce a protective cell-mediated immune response, switching the immune system from a predominantly Th-2-like immune response into a Th-1 immune response pattern in mice.27 The first studies in

Yamoussoukro meeting

The first International Conference on Buruli Ulcer Control and Research was held during July 6–8, 1998, in Yamoussoukro, Cote d'lvoire. The primary objectives of the conference were to raise awareness of the importance of the disease, and to increase recognition of M ulcerans infection. Representatives from Benin, Ghana, Togo, and Cote d'lvoire reported substantial increases in numbers of patients,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 and emphasised the

Conclusions

50 years after its first description in the medical literature,1 and 100 years after Cook first observed Buruli ulcer in Uganda,5 the time is right for action to alleviate and control the suffering inflicted by this disease. A strong combined effort, both by the International M ulcerans Study Team, and by sponsor organisations, is needed to find answers to basic scientific questions. Modern molecular tools can be used to confirm modes of transmission, and contaminated reservoirs should be

References (31)

  • PJ Mitchell et al.

    Epidemiology of Mycobacterium ulcerans infection in koalas (Phascolarctos cinereus) on Raymond Island, southeastern Australia

    J Wildl Dis

    (1987)
  • JC Palomino et al.

    Effects of decontamination methods and culture conditions on viability of Mycobacterium ulcerans in the BACTEC system

    J Clin Microbiol

    (1998)
  • F Portaels et al.

    Direct detection and identification of Mycobacterium ulcerans in clinical specimens by PCR and oligonucleotide-specific capture plate hybridization

    J Clin Microbiol

    (1997)
  • BC Ross et al.

    Detection of Mycobacterium ulcerans in environmental samples during an outbreak of ulcerative disease

    Appl Environ Microbiol

    (1997)
  • HF Lunn et al.

    Buruli (mycobacterial) ulceration in Uganda: a new focus of Buruli ulcer in Madi district, Uganda

    East Afr Med J

    (1965)
  • Cited by (0)

    View full text