J.M. Grange

Antibacterial properties of propolis (bee glue).

Propolis (bee glue) was found to have antibacterial activity against a range of commonly encountered cocci and Gram-positive rods, including the human tubercle bacillus, but only limited activity against Gram-negative bacilli. These findings confirm previous reports of antimicrobial properties of this material, possibly attributable to its high flavonoid content.

Zoonotic aspects of Mycobacterium bovis infection

The bovine tuberculosis eradication campaigns in many industrially developed countries have led to a huge reduction in the incidence of human tuberculosis caused by Mycobacterium bovis. Overt disease in man may, however, manifest decades after the initial infection and the occurrence of such disease raises several important questions. In particular, it is important to determine whether man-to-man transmission occurs, thereby rendering man a continuing reservoir of infection, and whether, if this is the case, man develops infectious forms of tuberculosis that enable M. bovis to be transmitted back to cattle. Epidemiological studies in South East England indicate that human tuberculosis due to M. bovis is rare and that the incidence is declining. In contrast to earlier days, the lung is now involved in many cases, raising the possibility of transmission of bacilli to other human beings and to cattle by the aerogenous route. No direct evidence of man-to-man transmission of overt disease was found but it is possible that inapparent primary pulmonary infections are occurring and these may proceed to overt post-primary disease in the future. The genito-urinary tract is now the most prevalent site of non-pulmonary lesions and there is firm evidence that this form of tuberculosis poses a hazard to cattle. Though uncommon, human tuberculosis due to M. bovis is still a public health problem of concern to both the medical and veterinary professions and there is a need to maintain careful bacteriological surveillance.

Impact of HIV infection on tuberculosis

Tuberculosis is increasing in prevalence in many countries and is now the leading infectious cause of death world wide, being responsible for three million deaths annually. Infection with HIV, likewise increasing in prevalence, has emerged as the most important predisposing factor for developing overt tuberculosis in people co-infected with Mycobacterium tuberculosis. Owing to the widespread geographical overlap of these two infections, it is estimated that in 1999, HIV related tuberculosis will reach one million cases and will cause 30% of the expected 2.5 million AIDS related deaths. Tuberculosis in HIV infected individuals may have unusual clinical features and can cause diagnostic difficulties. Despite the effectiveness of modern short course treatment, the mortality of HIV related tuberculosis during and after treatment remains high, and this may be due to other HIV related infections. The “cursed duet” of infection with both HIV andM tuberculosis is generating a threat to human health of unparalleled proportions which, if not taken seriously by health workers and decision makers, could become totally unmanageable.

The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies.

Proteins secreted by strains of Mycobacterium tuberculosis during short-term, zinc-sufficient batch culture were identified in order to define antigens likely to be relevant to the pathogenesis of human disease. [35S]Methionine-labelled proteins in supernatants of 4-7 d cultures were separated by PAGE under both denaturing and non-denaturing conditions, and the position of labelled material was determined. Secreted protein patterns of M. tuberculosis were quite similar to those of Bacillus Calmette-Guérin (BCG) but differed by the absence of the 46 kDa dimeric protein specific to BCG and by the presence in large amounts of a 23 kDa protein which, when denatured, gave 13 kDa subunits. This 13 kDa subunit protein constituted up to 20% of secreted proteins in classical strains of M. tuberculosis of phage type B but was not detected in phage type I strains from South India. This may be relevant to the different pathogenicity of these strains. Western blot analysis showed that antigens defined in supernatants of short-term (3 d) cultures of M. tuberculosis constituted a small subset of those seen in supernatants of organisms cultured for longer periods. One of the secreted proteins has the interesting property of binding to fibronectin. The available monoclonal antibodies and antisera have been used to identify lines on immunoblots corresponding to the secreted/released antigens of M. tuberculosis. The present findings suggest that there are major secreted antigens to which antibodies do not yet appear to have been produced experimentally.

The zoonotic importance of Mycobacterium bovis

The zoonotic importance of Mycobacterium bovis has been the subject of renewed interest in the wake of the increasing incidence of tuberculosis in the human population. This paper considers some of the conditions under which transmission of M. bovis from animals to humans occurs and reviews current information on the global distribution of the disease. The paper highlights the particular threat posed by this zoonotic disease in developing countries and lists the veterinary and human public health measures that need to be adopted if the disease is to be contained. The association of tuberculosis with malnutrition and poverty has long been recognized and the need to address these basic issues are as crucial as specific measures against the disease itself.

Mycobacterium marinum infections in man

Mycobacterium marinum , formerly known as ‘Mycobacterium balnei’, is a free-living organism which causes disease in fish and occasionally in man. When such infections occur in man they are usually associated with some aquatic activity, e.g. swimming, fishing, boating and keeping tropical fish. For this reason, the organism has been called a ‘leisure-time pathogen’ by Feldman, Long & David (1974) and the disease a ‘hobby hazard’ by Heineman, Spitzer & Pianphongsant (1972).

Clinically Significant Drug Interactions with Antituberculosis Agents

SummaryStandard short-course regimens for tuberculosis are used worldwide with very few problems. Unfortunately, the emergence of multiple drug-resistant tuberculosis in many parts of the world is leading to a diversification of drug regimens and to the use of drugs that are more toxic per se and more likely to interact with others. In addition, the treatment of HIV/AIDS patients with tuberculosis or disease due to Mycobacterium avium-intracellulare complex (MAC) infection with new drugs and multidrug regimens has added to the problem of drug interactions, especially as such patients may often be receiving concomitant treatment for a range of bacterial, fungal and viral infections.In general, there are very few clinically significant interactions between the first-line antituberculosis drugs themselves, although problems of bioavailability, notably of rifampicin (rifampin), have been encountered in the manufacture of combination tablets.Of the first-line drugs used to treat tuberculosis, i.e. rifampicin, isoniazid and pyrazinamide, rifampicin is particularly likely to cause clinically significant drug interactions as it is a potent inducer of the cytochrome P450 enzyme group, which is involved in the metabolism of many drugs, in particular oral contraceptives, corticosteroids, oral anticoagulants and cyclosporin. The use of quinolones to treat multiple drug-resistant tuberculosis and AIDS-related MAC disease raises further problems of drug interactions as, in contrast to rifampicin, these drugs inhibit some cytochrome isoenzymes, leading to reduced metabolism of certain drugs.

A study of vitamin D levels in Indonesian patients with untreated pulmonary tuberculosis

The levels of serum vitamin D, measured as 25-hydroxycholecalciferol (25-OHD3), among 40 Indonesian patients with pulmonary tuberculosis and 38 healthy controls were very similar. In both groups the distribution of the serum 25-OHD3 levels were bimodal with about a quarter of the individuals belonging to the group with higher levels. There was a tendency for controls in this group to be tuberculin negative and for patients in this group to have less extensive active pulmonary disease. Although it is uncertain whether such associations result from a direct effect of vitamin D on protective immune reactions, the use of this vitamin as an adjunct to antituberculosis therapy merits consideration.

Enzyme-linked immunosorbent assay (ELISA): a study of antibodies to Mycobacterium tuberculosis in the IgG, IgA and IgM classes in tuberculosis, sarcoidosis and Crohn's disease.

Enzyme-linked immunosorbent assay (ELISA) has been used to study the levels of antibody binding to the soluble antigens of Mycobacterium tuberculosis (BCG) in the IgG, IgM and IgA classes in sera from patients with tuberculosis, sarcoidosis and Crohns disease. Of the patients with tuberculosis, 75% had significantly elevated levels of anti-M. tuberculosis antibodies in the IgG class. The levels of antibodies in the IgM and IgA classes were much less discriminative. Many of the patients with sarcoidosis and Crohns disease had significantly elevated levels of antimycobacterial antibodies, principally in the IgM and IgA classes. These elevated levels of antibody were not related to the total levels of the immunoglobulin classes. For the purpose of serodiagnosis, an estimation of the antimycobacterial antibodies in the IgG class gives the most discriminative results.

Activity of bromhexine and ambroxol, semi-synthetic derivatives of vasicine from the Indian shrub Adhatoda vasica, against Mycobacterium tuberculosis in vitro.

The benzylamines, bromhexine and ambroxol, widely used as mucolytics, have a pH-dependent growth-inhibitory effect on Mycobacterium tuberculosis. As these compounds are concentrated in macrophages, they might exert a clinically useful effect on intracellular tubercle bacilli. This, combined with indirect effects including enhancement of lysozyme levels in bronchial secretions and levels of rifampicin in lung tissue and sputum, and possibly clearance of bacilli-laden mucus from cavities and bronchi, suggests a potentially useful adjunctive function for these agents in the therapy of tuberculosis, and adds credibility to early reports of the beneficial effect of benzylamines in this disease.