![]() ![]() Gradually increasing subcutaneous doses of toxin were administered over a period of 2-3 months. The lethal volume was required to be below 0.1cc for the toxin to be of adequate strength (4).ġ0 The antiserum was usually produced in horses. This was the measurement of the volume of filtrate that would kill a guinea pig of 250g body weight within 5 days. The toxin could only be standardised by a biological assay. Typically, a virulent strain of bacillus was grown on a shallow layer of medium and, after 6-8 days, the formed toxin was obtained by filtration. Diphtheria Antitoxinĩ To produce an effective antitoxin, a potent toxin was required. According to most accounts the first clinical use of the antitoxin was in Berlin on Christmas Eve 1891, when von Behring administered it to a seriously ill girl who subsequently recovered (Fig. Consequently in 1890, von Behring and Kitasato were able to show that administration of very small amounts of diphtheria toxin to animals resulted in the presence in their plasma of a factor which, when mixed with the toxin, rendered it innocuous to animals (3).Ĩ The subsequent observation that this plasma, when actually administered to animals, could protect them from fatal doses of diphtheria toxin paved the way for the use of “diphtheria antitoxin” to treat diphtheric patients. This observation was very important, since studies on hog cholera in 1885 had demonstrated that administration to an animal of very small concentrations of a bacterial product could eventually produce immunity to that infection. Thus the systemic symptoms of the disease were due to the absorption of a toxin exuded during the growth of the bacilli on the mucous membrane. The filtered broth was also shown to be toxic for rabbits, dogs, cats and horses (2). Nevertheless, Loeffler’s report was somewhat reserved, since he was unable to explain the systemic symptoms of diphtheria.Ħ In both animals and man infected with the supposed causative organism there are severe systemic disturbances and even organ degeneration, but the bacillus could be found only in the local lesion.ħ The anomaly was resolved in 1888 by the observation by two of Pasteur’s colleagues, Roux and Yersin, that the broth used to grow the cultures of bacillus diphtheriae remained toxic for guinea pigs after the bacteria had been removed by filtration. ![]() When the cultures were inoculated onto injured mucous membranes of various animals, pseudomembranes developed, resembling those in patients. A year later Loeffler isolated and cultured the bacillus from 13 undisputed cases of diphtheria. The straight or slightly curved rods described by Klebs we know today were indeed Corynebacterium diphtheriae, although Klebs’study was purely morphological. Klebs in 1883 described a bacillus obtained from the pseudomembranes of diphtheria patients. Should the lesion occur in the laryngeal region, the airway may become occluded and intubation would therefore be necessary.ĥ The emergence of the germ theory triggered the start of the scientific investigation of the aetiology of diphtheria. It is a thick, leathery, bluish-white pseudomembrane composed of bacteria, dead cells and fibrin. The epidemics tended to be cyclical “often lasting for many years, and followed by intervals of quiescence” (1).Ĥ The primary lesion of the disease occurs in the upper respiratory tract. Add to this the demoralisation and sense of impotence caused by the lack of effective treatment, then one can appreciate how dispiriting the practice of medicine could be at that time.ģ Diphtheria was formally described by Bretonneau in 1826, although epidemics among children of “malignant sore throat destroying life by suffocation and sometimes leaving paralytic sequelae” had been described since earliest times. The melancholic effect of having to watch a succession of children die either from suffocation or, as the disease progressed, from paralysis and heart failure, was wretched enough. These treatments stemmed from basic research into causative agents and mechanisms of toxicity.Ģ A prime example is diphtheria. An inability, or unwillingness, to undertake this exercise largely explains the misrepresentation by some of the value of early treatments of infections. Yet this is the only way to appreciate the progress made in the treatment and prevention of infective disease. ![]() Diphtheria levies a toll of clinical incidence of 10% of all born with a mortality of 5 to immunisation reduces this to an incidence of 1% and zero mortality.ġ In the sanitary 1990s it is hard to envisage the experiences of physicians working in the fever hospitals a century ago. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |