John Hayman
Parkville, Victoria, Australia

Five of the six patients in whom Mycobacterium ulcerans infection was first identified and described lived in the Bairnsdale district of southeastern Australia.¹ The mycobacterium was not initially named as such, but the progressive skin ulcer that it causes became known as the “Bairnsdale ulcer.” It was soon appreciated that this was not a disease confined to the Bairnsdale district, but one that occurred elsewhere in Australia, in Papua New Guinea (PNG), and in Africa.^2,3

The disease presents as a small skin papule, subcutaneous nodule, or plaque which later ulcerates.⁴ The mycobacterium produces a toxin named mycolactone, which, among other effects, causes necrosis of dermal and subcutaneous fat.⁵ The organism then proliferates in the lipid lakes derived from this necrotic tissue. Skin ulceration, with undermined skin edges, is secondary to this fat necrosis.

Characteristically, the condition is slowly progressive, with enlarging ulceration, scarring, and contracture. Even with extensive ulceration there is usually little pain and no systemic symptoms. However, a more severe form of the infection presents with acute swelling, pain, and fever, and may involve an entire limb.

The occurrence of infection in different geographical foci has led to a plethora of toponymic names, most of which have been discarded or are only used in the unfortunate locales.⁶ In northern Queensland, Australia, the disease is still known as the Daintree ulcer (to the chagrin of the Daintree tourist authorities); in New Guinea as the Kumusi ulcer; and confusingly, in the Ashanti region of Ghana, as the Kamasi ulcer. The most colorful name is “Sik belong wara Sepik,” relating to the focus along the Sepik River in northwest PNG. The name now generally accepted and applied by the World Health Organization is the Buruli ulcer, after the Buruli District, now known as the Nakasongola District in northwest Uganda. Mycobacterial skin ulcers were reported from this district in 1964, but were originally thought to be caused by a different species (Mycobacterium buruli).⁷

Albert Ruskin Cook (1896–1951) went to Uganda in 1896 as a medical missionary, sponsored by the Church Missionary Society (Fig 1). He established the Mengo Hospital in 1897, where he kept meticulous notes of the patients seen. One of these first patients was Luabila, who was suffering from “tubercular ulceration of the arms and legs,” which had been present for two years, together with bronchitis. This would appear to be the first hospital record of a patient with Mycobacterium ulcerans infection.

Even before this, one of the early explorers in Africa may have suffered from the disease. James Augustus Grant (1827–1892) (Fig 2), a captain in the Indian Army, accompanied John Hanning Speke (1827–1864) on his journey into East Africa in 1860, when Speke identified the source of the White Nile from Lake Victoria. In his book A Walk across Africa,⁸ Grant gives the following description of his illness, which broke out when they reached the native kingdom of Karague, on the western side of the lake in December 1861:

The following account of my own ailments I give, not with a wish to parade them, but in order to convey information: Having had fevers twice a month, in December my usual complaint assumed a new form. The right leg, from above the knee, became deformed with inflammation, and remained for a month in this unaccountable state, giving intense pain, which was relieved temporarily by a deep incision and copious discharge. For three months abscesses formed, and other incisions were made; my strength was prostrated; the knee stiff and alarmingly bent, and walking was impracticable. Many cures were attempted by the natives, who all sympathized with me in my sufferings, which they saw were scarcely endurable; but I had great faith – was all along cheerful and happy, except at the crises of this helpless state, when I felt it would have been preferable to be nearer home. The disease ran its course, and daily, to bring out the accumulated discharge, I stripped my leg like a leech. Bombay (an interpreter) had heard of a poultice made of cow-dung, salt, and mud from the lake; this was placed on hot, but merely produced the effect of a tight bandage. Baraka (another interpreter) was certain a serpent had spat upon my leg- “it could not have been a bite”. Dr. M’nanagee, the sultan’s brother, knew the disease perfectly; he could send me a cure for it and a mild gentle peasant of the Wanyambo race came with his wife, a young pleasing like person, to attend me. With the soft touch of a woman he examined the limb, made cuts over the skin with a penknife, ordered all lookers-on outside the hut, when his wife produced a scroll of plaintain-leaf, in which was a black paste. This was moistened from the mouth and rubbed into the bleeding cuts, making them smart; afterwards a small piece of lava was dangled against my leg and tied as a charm round the ankle. …. . These cures had no apparent effect, but the disease did improve. By the fifth month the complaint had exhausted itself; at last I was able to be out of the hut inhaling the sweet air, and once more permitted to behold the works of God’s creation in the beautiful lake and hills below me.

Grant’s illness prevented him from being with Speke when Speke became the first white man to see the outpouring of the White Nile from Lake Victoria. The print, taken from his book, shows Grant being carried on a wicker stretcher, leaving Karague. The illness was consistent with Mycobacterium ulcerans infection for the following reasons:

1. The explorers passed through an area where the disease has since been known to occur.
2. The history of the lesion, with a prodromal fever, swelling, followed by ulceration and a copious discharge would seem typical of the severe edematous form of the disease, as occurs in Uganda. It was recognized by the local inhabitants who had a treatment for it, similar to traditional remedies that may still be in use (Lunn HF, personal communication).
3. Gradual healing after six months, leaving residual scarring and contractures, is characteristic of the more severe form of the illness.

Mycobacterium ulcerans infection, the third mycobacterial infection known to cause serious illness in humans, is of relatively recent recognition and description. As a disease, at least in Africa, it has clearly existed for many years. Why it should appear and be characterized from the southeast corner of mainland Australia remains unexplained.

References

1. MacCallum P, Tolhurst JC, Buckle G, Sissons HA. “A new mycobacterial infection in man.” J Pathol Bacteriol 1948;60(1):93-122. PMID: 18876541.
2. Radford AJ. “Mycobacterium ulcerans in Australia.” Aust N Z J Med 1975;5(2):162-9. doi: 10.1111/j.1445-5994.1975.tb03649.x.
3. Radford AJ. “Mycobacterium ulcerans infections in Papua New Guinea.” Papua New Guinea Med J 1974; 17: 145-9.
4. Hayman J. “Clinical features of Mycobacterium ulcerans infection.” Aust J Derm 1985; 26: 67-73. doi.org/10.1111/j.1440-0960.1985.tb01819.x.
5. George KM, Chatterjee D, Gunawardana G, Welty D, Hayman J, Lee R, Small PL. “Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence.” Science 1999 Feb 5;283(5403):854-7. doi: 10.1126/science.283.5403.854.
6. Radford AJ. “What’s in a name? Ulcerans disease: infections due to Mycobacterium ulcerans.” Trans R Soc Trop Med Hyg 2009;103(10):979-80. doi: 10.1016/j.trstmh.2008.12.009.
7. Clancey JK. “Mycobacterial skin ulcers in Uganda: description of a new mycobacterium (Mycobacterium Buruli).” J Pathol Bacteriol 1964;88:175-87. doi: 10.1002/path.1700880123.
8. Grant, James Augustus. A Walk Across Africa. W. Blackwood and Sons, 1864. doi: https://doi.org/10.5962/bhl.title.104693.