Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity

doi:10.1016/S0140-6736(94)90748-X

The Lancet

Volume 344, Issue 8932, 5 November 1994, Pages 1245-1249

https://doi.org/10.1016/S0140-6736(94)90748-X Get rights and content

Abstract

Summary

There is a longstanding debate over the implications of natural and vaccine-induced delayed type hypertensivity for protective immunity to mycobacterial infections. The identification of correlates of vaccine-induced protective immunity should help explain the inconsistent behaviour of BCG vaccines in different populations and assist in efforts to devise improved vaccines.

More than 70000 subjects in Karonga District, northern Malawi were skin tested with soluble antigens of the tubercle and leprosy bacilli, and then followed up for five years for tuberculosis and leprosy incidence. Incidence rate ratios were calculated to compare subjects with different levels of prior skin test sensitivity, after controlling for the effects of age, sex and previous BCG vaccination. BCG vaccination protected against leprosy without persistent delayed-type hypersensitivity to tuberculin or to soluble antigens of the leprosy bacillus. In subjects who had not received BCG, hypersensitivity to tuberculin or to antigens of the leprosy bacillus was associated with strong protection against leprosy. In BCG-vaccinated and unvaccinated subjects, there was a J-shaped relation between hypersensitivity to tuberculin and subsequent rates of tuberculosis, with lowest rates associated with low grade sensitivity (induration 1-10 mm).

This study shows that delayed-type hypersensitivity to mycobacterial antigens has different implications for tuberculosis and leprosy: low-level hypersensitivity (probably attributable to environmental mycobacteria) is associated with protection, but persistent vaccine-associated hypersensitivity to mycobacterial antigens is not a correlate of vaccine-derived protection against mycobacterial diseases.

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Citation Excerpt :
BCG vaccination gives variable protection against leprosy in different study sites, ranging from 20% to 90%.18 Also environmental mycobacteria may confer some degree of protection against leprosy.19 M leprae is slow growing and the incubation period is long, 2 to 12 years, ranging from 1 to 20 and more years, with an estimated average of 5 years.17,20
Major gaps still exist in the knowledge about leprosy, particularly with regard to how it spreads. Leprosy epidemiology remains complicated due to the specific characteristics of Mycobacterium leprae. To describe epidemiologic trends for the 21st century, the first part of this paper gives an overview of the epidemiology of leprosy, followed by past trends and the present situation of new-case detection as a proxy of the incidence. The third part, regarding predicted epidemiologic trends for the 21st century, elaborates on the main topic of this paper. With limited diagnostic tools to detect infection with M leprae, other methods are necessary to estimate trends in incidence and transmission. A computer program has been developed for modeling the transmission and control of leprosy (SIMLEP). The effect of failure to sustain early case detection beyond 2005 on leprosy incidence and case detection is shown. Important unanswered questions are whether the incubation period is contagious and how rapid close contacts of leprosy patients are infected. As long as such key questions remain unanswered, it will be difficult to estimate the impact of control strategies on the transmission of M leprae on resulting disease incidence. In the meantime we can expect that the global new-case detection trends will stay more or less stable or only decrease slightly for many years to come. There is a need of new preventive interventions to change this situation and reduce the incidence of leprosy in the 21st century.
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ArticlesDelayed-type hypersensitivity, mycobacterial vaccines and protective immunity

Abstract

Tubercle

Lancet

Immunities in and to tuberculosis: implications for pathogenesis and vaccination

Immune mechanisms in the pathogenesis of pulmonary tuberculosis

Rev Infect Dis

Relation between delayed hypersensitivity and immunity in tuberculosis

Delayed hypersensitivity and its significance

Induction of delayed-type hypersensitivity in human volunteers immunized with a candidate leprosy vaccine consisting of killed mycobacterium leprae

Bull World Health Organ

Sensitization studies with potential leprosy vaccine preparations in Northern Malawi

Int J Lepr Other Mycobact Dis

Identification of an effective vaccine against tuberculosis

Am Rev Respir Dis

The Lepra Evaluation Project (LEP), an epidemiological study of leprosy in northern Malawi. I. Methods

Lepr Rev

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Delayed-type hypersensitivity, mycobacterial vaccines and protective immunity