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Biomedical subjects

R J Rees

Publications and source records attributed to R J Rees.

At least 55 records · Page 3Linked to original sources

Induction of delayed-type hypersensitivity to Mycobacterium leprae in healthy individuals.

Delayed-type hypersensitivity (DTH) to a soluble Mycobacterium leprae skin test antigen (SML) was successfully induced in healthy volunteers following immunization with 2 X 10(8) killed armadillo-derived M. leprae. No better sensitization was obtained by a mixture of live BCG and killed M. leprae. The relative specificity of the DTH reaction to SML has been demonstrated in this study, since little cross-reactivity was observed to PPD, after immunization with BCG ro M, leprae alone, or combined. Moreover, armadillo-derived M. leprae readily induced a specific hypersensitivity with the time course DTH response associated with protective immunity suggesting that this bacterial preparation may be a candidate for an effective anti-leprosy vaccine.

Adolescent↗

Effect of purification steps on the immunogenicity of Mycobacterium leprae.

In studies aimed at the development of an antileprosy vaccine for use in man, Mycobacterium leprae suspensions were prepared from livers of experimentally infected armadillos. The 2 methods of purification in chief use, carried out after irradiation of the tissue with 2.5 megarads of gamma irradiation from 60Co, involved treatment with 0.1N NaOH for 2 h at room temperature, trypsin and chymotrypsin digestion for 24h at 37 degrees, and separation in a 2-phase liquid polymer (dextran:polyethylene glycol) system. All vaccines were autoclaved and injected intradermally in mice. Earlier studies have shown that heat inactivation does not interfere with the immunogenicity of M. leprae. Immunogenicity was measured by foot-pad enlargement (FPE) after challenge with heat-killed M. leprae suspensions or by protection against infectious foot-pad challenge. The results indicated that the irradiation and 2-phase separation did not decrease immunogenicity but the NaOH treatment and enzyme digestion did.

Animals↗

Rifampicin for lepromatous leprosy: nine years' experience.

Over 100 patients with lepromatous leprosy were treated with rifampicin in a series of pilot, uncontrolled, and controlled trials in 1968-77. The rapid bactericidal effect of rifampicin on Mycobacterium leprae was confirmed. Clinical improvement became apparent sometimes as early as 14 days after the start of treatment. Nevertheless, a few persisting viable M leprae were detected as long as five years after the start of treatment with rifampicin either by itself or in combination with the bacteriostatic drug thiambutosine. Treatment with rifampicin and dapsone for six months reduced the number of persisting leprosy bacteria more than treatment with dapsone alone. Although rifampicin proved more effective than dapsone, it is unlikely that used by itself if can significantly shorten the length of treatment in lepromatous leprosy. Therefore initial intensive combined treatment with two or more bactericidal drugs (including rifampicin) warrants further investigation in both untreated leprosy and lepromatous leprosy resistant to dapsone.

Animals↗

Formation of antibody against Mycobacterium leprae antigen 7 in armadillos.

A radioimmunoassay developed to measure antibody against Mycobacterium leprae antigen 7 in man was applied to the nine-banded armadillo (Dasypus novemcinctus). Normal armadillo sera had low but significant antibody activity in the test. Fourteen of 17 armadillos with systemic mycobacterial infection after inoculation with M. leprae showed increased antibody activity in the assay, and in some instances the activity was higher than in a pool of sera from patients with lepromatous leprosy. Crossed immunoelectrophoresis with armadillo serum in the intermediate gel revealed antibodies against five distinct antigenic components of M. leprae. Development of systemic mycobacterial infection after inoculation with M. leprae is thus associated with a distinct humoral immune response. The use of radioimmunosassay for selection of animals for inoculation and for following the development of the infection is discussed.

Animals↗

Lymphocyte response of leprosy patients to human-derived and purified armadillo-derived Mycobacterium leprae, BCG and PPD.

The lymphocyte transformation test was applied to compare in vitro lymphocyte responses of tuberculoid (high resistant) and lepromatous (low resistant) leprosy patients to purified Mycobacterium leprae derived from experimentally infected armadillos and crude M. leprae derived from man, as well as to bacille Calmette-Guérin (BCG) and purified protein derivative (PPD). It was found that the purification procedure using enzymic digestion did not affect the immunogenicity of armadillo-derived M. leprae as compared with the crude human-derived preparation, although 2.5-5-fold higher doses of the purified organisms were required to elicitate equivalent lymphocyte responses. The result indicated the suitability of purified armadillo-derived M. leprae as the standard antigen for lymphocytes transformation tests in leprosy. The cross-reactivity studies show a close relationship between PPD and BCG, but not between M. leprae and PPD or BCG.

Adolescent↗

Experimental lepromatous leprosy in the white-handed gibbon (Hylobatus lar): successful inoculation with leprosy bacilli of human origin.

Leprosy bacilli of human origin were inoculated into a white-handed gibbon by the i.v. and i.p. routes, and also locally into ears, testis and around an ulnar nerve. The animal was observed closely during a period of nearly 15 years and did not exhibit any clinical evidence of cutaneous or neurological disease. At death, a wide range of tissues was taken for bacterial counts and histological examination, and a disseminated and progressive infection was demonstrated. Acid-fast bacilli were found in many sites; their morphological appearance distribution in nerves, and pattern of multiplication in mouse foot-pads, and also the presence of anti-mycobacterial antibody in the serum and the absence of specific lymphocyte transformation were all in keeping with an infection by Mycobacterium leprae, at an early lepromatous stage. This is probably the first fully documented report of experimental lepromatous infection in a primate. The findings are discussed in relation to the long incubation period of le promatous leprosy and the difficulties of diagnosing the disease at an early stage in man.

Animals↗

Airborne infection with Mycobacterium leprae in mice.

Although the portal of entry and mode of spread of M. leprae in human leprosy are still uncertain, it is widely held that direct person-to-person skin contact is important. This assumption has ignored the fact that patients with highly bacilliferous leprosy have nasal as well as dermal infection and that, since M. leprae is shed predominantly from the nose, leprosy might be an airborne infection. The present study was designed to investigate this possibility with mice exposed to airborne infection with M. leprae. The conditions are described in which thymectomised-irradiated CBA strain mice exposed to M. leprae aerosols sustained an immediate lung retention of 1 X 10(5) bacteria. Fourteen to 24 months later, 33% (10 of 30) of the mice had countable numbers of acid-fast bacilli (greater than 2 X 10(4)) with the characteristics of M. leprae in one or more homogenates prepared from ears, foot pads, nose or lungs. Evidence is presented from the distribution of M. leprae that the infection had arisen from systemic spresd of bacilli initially entering the lungs rather than from multiplication of organisms locally retained there, or in the nose, at the time of airborne infection. The relevance of these results to the possible route of infection of leprosy in man is discussed.

Aerosols↗