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Although Mycobacterium ulcerans elicits extensive necrosis of human skin and subcutaneous tissue, the specific cause of the necrosis has never been elucidated. In an attempt to define a toxic substance, 18 strains of M. ulcerans were inoculated into mice, and the progress of each infection was observed and compared with infections of other mycobacteria, including M. cheloni, M. marinum, and M. bovis. Culture filtrates and viable organisms of each of these mycobacteria were inoculated onto tissue culture cells. Inoculation of mouse footpads with M. ulcerans resulted in progressive infections, leading to ulceration and eventual death. Strains of M. cheloni, M. marinum, and M. bovis did not produce progressive infections in the mice. Culture filtrates of M. ulcerans produced severe cytopathogenic effects on tissue cells, but washed, viable organisms of the same strains had no cytopathogenic effect. Culture filtrates and viable organisms of M. cheloni, M. marinum, and M. bovis did not produce a cytopathogenic effect on the tissue cells. Viable organisms of selected strains of M. ulcerans and the culture filtrates of the same strains were inoculated into guinea pig skin. The culture filtrates and the viable organisms both caused focal necrosis and focal inflammation, changes that resemble those in the naturally occurring infection in man. Preliminary purification of the culture filtrate by ultrafiltration indicates that the toxic fraction has a molecular weight of approximately 100,000, and temperature studies indicate that the toxic fraction is heat labile.

In Zaire, we studied 180 patients with Mycobacterium ulcerans infections and found 14 with a history of antecedent trauma at the site of the lesion (e.g., gunshot and land mine injuries, penetrating wood splinters, and scorpion stings). Two patients developed lesions following hypodermic injections. We believe that trauma is an important mode of transmitting M. ulcerans infections, or of introducing the etiologic agent into the dermis of subcutaneous tissue from superficially contaminated skin.

Eight patients from Zaire with Mycobacterium ulcerans infection were treated by the local application of heat to maintain a temperature of approximately 40 degrees C in the ulcerated area. All lesions healed without surgical intervention and without local recurrences during follow-up periods of up to 22 months. This study shows that local heat promotes healing of M. ulcerans lesions. We postulate that the mechanism is primarily by direct inhibition of multiplication of M. ulcerans. Other possible contributory effects are discussed.

Seeking to determine whether there is a relationship in New Guineans between hepatic sinusoidal infiltration and splenomegaly on the one hand and malaria on the other, the authors studied 24 adults from a village protected from malaria for 5 years by 6-monthly DDT spraying and 34 adults from an unprotected village with hyperendemic malaria.It was found that clinical splenomegaly tended to be associated with greater hepatic sinusoidal infiltration among persons from the malarious village and that higher malaria antibody titres were more common in patients with splenomegaly in this village. In adults in the protected village the prevalence of malaria parasitaemia was much lower than in the malarious village and the sinusoidal infiltrates were also diminished.No associations between parasitaemia, malaria antibody titre, and hepatic sinusoidal infiltration could be demonstrated in the malarious village. The implications of these findings are discussed and the question of malaria being responsible for the marked splenomegaly encountered in tropical practice is discussed.

Microfilariae of O. volvulus were recovered from the urine of 11% of the residents of a village in the Republic of Chad where onchocerciasis was holoendemic. A follow-up study of the same population 3 years after the original investigation revealed that microfilaruria was still present and that living microfilariae of O. volvulus could be recovered from small urine samples obtained by high catherization of the ureters. Radiological changes consistent with chronic pyelitis were found in 4 out of 14 persons with microfilaruria who were examined by retrograde pyelography. The recovery of microfilariae in the urine was associated with the intensity of the infection, as determined by counts of microfilariae in skin snips and the number of onchocercomata. A systematic comparison for differences between onchocerciasis patients with and without microfilaruria revealed that the microfilaruria patients had a low weight: height ratio, deficient antibody responses in indirect haemagglutination tests with O. volvulus antigen, elevated serum aminotransferase levels, and reduced systolic blood pressure.