AGGLUTINATION OF TREPONEMA PALLIDUM IN HUMAN SYPHILIS
Authors: Kolmer John A. , Broadwell Stuart , Matsunami Toitsu 
Published: June 2004

The results observed with this strain of Treponema pallidum may be stated as follows:
1. Normal human serum did not agglutinate this culture of Treponema pallidum in dilutions of 1:5 or higher; equal parts of treponema culture and normal serum (dilution 1:2) resulted in agglutination in about 50 per cent of the sera. With the strain of Treponema pallidum used in this study specific agglutination was not considered as having occurred unless observed in dilutions of 1:5 or higher.
2. The agglutinating power of the sera of non-syphilitic persons suffering with various infections was not higher than that of normal sera.
3. Traces of specific agglutinin for this culture of Treponema pallidum were found in the sera of persons late in the primary stage of syphilis.
4. In the secondary stage of syphilis about 58 per cent of sera showed the presence of a demonstrable amount of agglutinin in dilutions of 1:5 and higher; in no instance, however, was agglutination in evidence in dilutions higher than 1:20.
5. In tertiary and latent syphilis, mostly infections of the central nervous system, agglutination in dilutions of 1:5 and higher was found with about 84 per cent of sera. The highest concentration of pallida agglutinin in the blood serum was found in the later stages of syphilis.
6. The formation of agglutinin for culture Treponema pallidum in human syphilis is probably tardy and does not reach a state of high concentration.
7. There was no direct relation between the presence of the Wassermann antibody and agglutinin for this strain in the sera of syphilitics. The former appears in the body fluids earlier and is probably in higher concentration in all stages of syphilis; while agglutination is most likely to occur with Wassermann positive sera, it may be occasionally observed with sera yielding negative Wassermann reactions. Likewise strongly Wassermann positive sera may not contain demonstrable amounts of agglutinin.
8. It is probable that different strains of pallida vary in susceptibility to agglutination. For example, in the first investigation on agglutinins for Treponema pallidum by Kolmer, the sera of syphilitics in different stages of the disease did not cause agglutination of one of Noguchi's strains in dilutions of 1:20 and higher, whereas the strain used in the present study was frequently agglutinated in this dilution by sera from a similar group of patients. As shown by Zinsser, Hopkins, and McBurney, virulent pallida from human lesions resist agglutination to a remarkable degree.
9. While further studies are necessary to establish the practical value of agglutination in the diagnosis of human syphilis, we believe that with a suitable culture or cultures well marked agglutination of Treponema pallidum in dilutions of 1:5, or better 1:10 and higher, indicates pallida infection and may prove of value in the diagnosis of isolated cases, particularly in the later stages. Investigations bearing upon the relation of agglutinins for culture pallida to immunity in syphilis will be given in a separate communication (16).