5 77 
1908-9.] The Pathogenesis of Micrococcus melitensis. 
form of M. melitensis septicaemia in man, in which, though the blood and 
tissues contain the micrococcus, no pyrexia is produced — and probably man. 
But although specific bacteriolysin is absent from the serum of the 
inoculated animal, specific agglutinin is readily formed, and this aspect of 
resistance to the M. melitensis and its products has been exhaustively 
studied by many observers, particularly by Durham and myself. 
Agglutination React ion . — Since the “ serum reaction ” test of Gruber 
and Durham was applied to the diagnosis of M. melitensis septicaemia by 
Wright in 1897 this method has been extensively employed ; and it has been 
shown that the specific agglutinin may be present in the blood of infected 
animals, including man, from the fifth day onwards (Aldridge, Bassett-Smith, 
Gilmour) — exceptionally it is present on the first day, sometimes its appear- 
ance is delayed until weeks after the disease is well established. Usually it 
is present in large amount, giving to the serum a titre of 1 : 100 or 1 : 1000 
even during the first week of the disease, whilst subsequently sera reacting 
in much higher dilutions, even up to 1 : 500,000, have been observed. 
Moreover, it must be noted that in man the agglutinins persist in the 
blood long after recovery, and the serum may react in dilutions of 1:50 
and 1 : 100 for from three to seven or even ten years after naturally 
acquired infection. 
Finally, sera from healthy animals and from those suffering from 
infections other than those due to micrococcus melitensis never yield a 
complete reaction when tested in dilutions of 1 : 10 (Birt and Lamb), 
or a partial reaction when tested in dilutions of 1 : 20. 
Specific agglutinins are elaborated in response to injections of the dead 
bodies of M. melitensis as well as to living cultivations. 
Experiments have so far failed to confer active immunity upon any of 
the ordinary laboratory animals. After long-continued treatment of rodents 
by repeatedly injecting suitable doses of killed cultures in the attempt to 
produce some degree of immunity and the establishment and maintenance 
of a high agglutinin content of the blood serum, the introduction of even 
comparatively small amounts of living virulent cultures almost invariably 
caused the death of the animal. 
Animal. 
Weight 
in 
Grams. 
Period of 
Treatment. 
Titre of 
Serum. 
Dose of 
Living 
Cultivation. 
Method of 
Inoculation. 
Result. 
Rabbit 8 
3000 
7 months 
1 : 1500 
1 loop 
Intracerebral 
t in 10 days 
Rabbit 25 
2500 
7 „ 
1 : 5000 
o-oi „ 
t in 60 „ 
Rabbit 73 
2800 
7 „ 
1 : 4000 
o-oooi 
Subcutaneous 
Recovery 
Guinea-pig 50 
600 
4 „ 
1 : 5000 
1-0 
Intracerebral 
t in 3 days 
vol. xxix. 37 
