220 INFECTION AND RESISTANCE 



nated by the patient's serum, thus discovering the dysentery bacillus 

 which bears his name. 



Within a few months after the publication of Gruber and Dur- 

 ham's work, Widal and, apparently independently of him, Griin- 

 baum, 6 by a process of reasoning the converse of that detailed above, 

 applied the reaction to the diagnosis of infectious disease. 



It is obvious that a human being or an animal infected with a 

 given variety of bacteria may develop agglutinating properties 

 against these bacteria. It is of great value, therefore, to determine 

 the agglutinating power of the serum of a patient for the bacteria 

 which are known to cause the disease suspected in the particular case 

 in which a diagnosis is desired. This method has become a routine 

 measure in the early diagnosis of typhoid fever under the name of 

 "Widal" or "Gruber-Widal" reaction and, since the quantities of 

 serum which can easily be obtained from a patient are usually small, 

 it is convenient to carry out the reaction by the microscopic method. 

 This consists in mixing serum and bacterial emulsion in hang-drop 

 preparations and observing them with the microscope. An excellent 

 method, also, is the so-called Proescher 7 method in which serum and 

 bacterial emulsion are mixed in small watch-glasses or salt cellars. 

 Proescher used this method extensively in the study of staphylococcus 

 agglutinations. The mixtures in the salt cellars were set away at 

 37 C. for two hours, and then observed with a magnification of 60 

 to 70 diameters. 



Close observation of the occurrence under the higher power of a 

 microscope shows that the bacteria, if motile, lose their motility, if 

 non-motile the Brownian motion is arrested. They are then rapidly 

 gathered in small clumps, isolated individuals between these clumps 

 being gradually drawn into them, until finally the fluid between the 

 masses is entirely clear. This complete clearing, of course, happens 

 only when there is not an excess of bacteria, for, like other serum re- 

 actions, this phenomenon is a quantitative one in which definite pro- 

 portions must be maintained. 



Clinically the most frequent use of the agglutination reaction is 

 in the diagnosis of typhoid fever. The technique used for this test 

 is, in the large majority of cases, the microscopic hang-drop method. 

 In Germany the Proescher method is sometimes used, and the micro- 

 scopic method with dead organisms, as first introduced by Ficker, is 

 also not uncommon at the present day. 



Since the serum of normal human beings very often contains 

 moderate agglutinating powers for the typhoid bacillus, the diag- 

 nostic value of the reaction in this disease depends upon the elimina- 

 tion of this error by sufficient dilution. If dilutions of the serum of 

 from 1-40 to 1-60 are used diagnostic errors on this point are 



6 Griinbaum. Lancet, 1896, Vol. 2. 



7 Proescher. Centralbl f. Bakt., Vol. 34, 1903. 



