The protective effect of BCG against Mycobacterium ulcerans disease: a controlled trial in an endemic area of Uganda

Abstract

In a BCG vaccination trial in an area of Uganda endemic for Mycobacterium ulcerans disease ("Buruli Ulcer"), 8,856 persons were examined for the disease in mid-1970 and tuberculin tested; BCG was given by intradermal injection to a random 50% of all those with negative, low or middle grade tuberculin reactions; Twelve months later the study group was re-examined for M. ulcerans lesions and, subsequently, new cases of the disease were detected, using a hospital registration system, to December 1974. One hundred and forty-nine patients with onset since July 1970 were thus ascertained and BCG was found to offer an overall protection of 47% against the disease, similar to that observed in a previous smaller trial by the Uganda Buruli Group (UBG, 1969). However, the protective effect was confined to those with tuberculin reactions of less than 4 mm before vaccination and was apparent only in the first year of the study. BCG offered no additional protection to those with previous M. ulcerans disease or an existing BCG scar at entry into the trial, although both these groups appeared to be protected against the disease, the protective effects being 88% and 82% respectively. An initial tuberculin reaction of 4 mm (or greater) offered some protection against the disease (37%). Lesions developing in the vaccinated group, or in those with initial tuberculin reactions of 4 mm or more, were smaller than those in unvaccinated persons. No relationship was found between the protective effect of BCG and either the prevalence of persons with evidence of previous M. ulcerans disease in different geographical areas, or the incidence of new cases in different areas during the first year of the study. A decline in the incidence was observed over the study period. The findings are consistent with BCG producing only short-lasting protection against M. ulcerans disease. However, long-lasting protection and a delay in onset of the disease in vaccinated persons, as suggested by the UBG in 1969, cannot be excluded on the basis of the data currently available from this trial.

Differential Production of Systemic and Intralesional Gamma Interferon and Interleukin-10 in Nodular and Ulcerative Forms of Buruli Disease

“…All these results taken together strongly favor the hypothesis that Ag85 is also a protective antigen in infection with M. ulcerans and that Ag85 could indeed be used in a vaccine against Buruli disease. The fact that several studies have demonstrated a protective role of BCG vaccination against Buruli disease is also in accordance with these findings (5,23,26).…”

Infection withMycobacterium ulceransInduces Persistent Inflammatory Responses in Mice

“…Indeed, there are several lines of evidence implicating CMI and delayed-type hypersensitivity responses in human M. ulcerans infections, favoring the possible existence of a phase of intracellularity of the pathogen, as follows. Studies with humans show that resistance to M. ulcerans is associated with the Th1 (24,25,26,55,76), while a shift to a Th2 phenotype is related to susceptibility (26), and point to a protective effect of BCG vaccination (46,53,54,63,66,73). Additionally, as BU disease progresses to healing, granuloma formation occurs (30,31,35,40,49,66,74), and the burulin skin test (65) tends to change from negative to positive (13,42).…”

Epidemiology of Infection by Nontuberculous Mycobacteria

“…Protection against M. ulcerans infection is provided by wearing long pants (335). Previous mycobacterial infection, evidenced by a tuberculin reaction of less than 4 mm, offers some protection against M. ulcerans disease (467). Protection is equivalent to that afforded by BCG vaccination (467).…”