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(II ARY.), M.D. 

DELIVERED ON SEPTEMBER 20, 21, 22, 23 AND 24, 1915 



Copyright, 1916 , by 

Printed in the United States of America 


The importance of the etiologic relation of Focal Infection 
to Systemic Diseases has been a subject of study in the clinical 
material of Rush Medical College, in affiliation with the Uni¬ 
versity of Chicago and the Presbyterian Hospital for the past 
twelve or more years. 

As the study progressed, the attention and cooperation of 
clinicians and laboratory workers were aroused and developed 
into a scheme of “team work.” This esprit de corps eventually 
embraced the nursing staff and the patients. Real clinical re¬ 
search was made possible by this cooperative spirit. Living 
morbid tissues were obtained at surgical operations and also 
from other patients, who submitted voluntarily and in many 
instances requested the removal, when necessary under local or 
general gas anesthesia, of bits of infected tissue (muscle, 
capsule of joints, lymph nodes, erythematous nodes, fibrous 
nodes of tendons) of exudates and of the blood, for experimental 

Histologic and bacteriologic studies of this material were 
made. Animal inoculation was carried on and the lesions of 
the experimental animals were studied and compared with the 
morbid human tissues which were the source of the investi¬ 

Eventually the Memorial Institute for Infectious Diseases, 
the Otho S. A. Sprague Memorial Institute and the Pathological 
and Research Department of St. Luke’s Free Hospital of Chi¬ 
cago cooperated in the work. 

The conclusions based upon the researcli were not made until 
a critical survey of the work and the results were investigated 




by other qualified clinicians, pathologists and research workers. 

I may not name, because of want of space, all who have co¬ 
operated in the team work, which has made the research a 
practical success and has opened up a broad field for a more 
extended study along similar lines. To my clinical colleagues 
in the college and hospital I extend my grateful thanks. Pro¬ 
fessors L. Hektoen, E. R. LeCount and H. Gideon Wells have 
been of invaluable aid to all of us, with advice always helpful 
though sometimes critical. The members of the house staff 
have rendered invaluable help by a tireless and enthusiastic 
bedside and clinical laboratory service. Many of these 
internes have continued in the work as clinicians, patholo¬ 
gists and clinical bacteriologists. Drs. D. J. Davis, R. T. 
Woodyatt, H. K. Nicoll, W. E. Post, E. E. Irons, A. M. 
Moody, F. W. Gaarde, J. J. Moore, and George H. Coleman 
have done notable work in bacteriology, chemistry, and in 
experiments upon animals. 

The broad significance of the relation of focal infection to 
systemic disease has been made more definite by the brilliant 
work of Edward C. Rosenow, who joined the clinic in 1904. 

These lectures, therefore, represent the cooperative study of 
many workers. I have made free use of the results of the 
labors of all who have aided in the work and I am proud to be 
their spokesman. 

Frank Billings. 



I. A General Consideration of Focal Infection . . 1 

Site of Primary Foci—Etiology of Focal Infection— 
Susceptibility to Systemic and Local Diseases from the 
Focus of Infection—Greater Susceptibility to Systemic 
Disease from a Focal Infection Undoubtedly Occurs— 

The Diagnosis of the Focus of Infection—Mode of 
Dissemination of Bacteria and Toxic Products from 
the Focus of Infection—Focal Infection and Anaphy¬ 

II. The Streptococcus-pneumococcus Group. Trans- 
mutability of the Members Thereof. Patho¬ 
genicity and Specific Tissue Affinity of Trans¬ 
mutation Forms ............ 26 

Transmutation Within the Members of the Strepto¬ 
coccus-Pneumococcus Group. 

III. Acute Diseases Related to Focal Infection ... 48 

Acute Rheumatic Fever—Rheumatic Endocarditis, 
Myocarditis and Pericarditis—Chorea—Acute Sys¬ 
temic Gonococcus Infection—Malignant Endocardi¬ 
tis—Acute Nephritis—Acute Appendicitis—Cholecys¬ 
titis—Acute Gastric and Duodenal Ulcer—Acute Pan¬ 
creatitis—Erythema Nodosum Herpes—Spinal Mye¬ 
litis—Acute Osteomyelitis—Thyroiditis—Iridocyclitis. 

IV. Chronic Diseases Related to Focal Infection . . 107 

Chronic Infectious Arthritis—Chronic Infectious Ne¬ 
phritis—Chronic Cholecystitis—Chronic Peptic Ul¬ 
cer—Chronic Infectious Endocarditis. 

• • 




V. Treatment .127 

Focal Infection—Treatment of Resulting Acute and 
Chronic Systemic Diseases—Serum and Vaccine Ther¬ 

Bibliography .. A «... 159 


1. Strain 595 as a hemolytic streptococcus isolated from a 

case of scarlet fever.28 

2. Strain 595 as streptococcus viridans .29 

3. Strain 595 as a pneumococcus .29 

4. Strain of streptococcus from rheumatism.30 

5. The same strain as in Fig. 4 after it was transformed 

into a pneumococcus. 31 

6. Highly virulent pneumococcus. 31 

7. Same strain as in Fig. 6 after transformation into hem¬ 

olytic streptococcus.32 

8. Streptococcus^ nodular, valvular and mural endocarditis 

of dog.53 

9* Vegetative and ulcerative endocarditis of aortic valves 

and aorta of dog.60 

10. Section through vegetations on mitral valve shown in 

Fig. 9...61 

11. A glomerulus containing a hyaline thrombus .... 63 

12. Masses of fibrin in a glomerulus.64 

13. A glomerulus in which are masses of cocci filling a group 

of capillaries.65 

14. Marked hemorrhage of the appendix.67 

15. Hemorrhage and localized infection of mucous mem¬ 

brane .68 

16. Human appendicitis 12 hours after onset in young man 69 

17. Diplococci in peritoneal coat of appendix.70 

18. Hemorrhage necrosis and leukocytic infiltration ... 71 

19- Streptococci in lymph follicle shown in Fig. 18 . . . 72 

20. Streptococci and fusiform bacilli in human gangrenous 





21. Hemorrhage, necrosis and leukocytic infiltration of ap¬ 

pendix 24 hours after infection.73 

22. Streptococci and fusiform bacilli of appendix of rabbit 73 

23. Photomicrograph of 24-hour culture in ascites-dextrose- 

broth of a streptococcus. 74 

24. Hemorrhagic cholecystitis in dog.. 75 

25. Marked edema of gall-bladder in dog.. 76 

26. Streptococci in lymph space of edematous wall of gall¬ 

bladder shown in Fig. 25.77 

27. Photomicrograph of 24-hour ascites-dextrose-broth cul¬ 

ture of streptococcus from human ulcer.78 

28. Marked ulceration of stomach in guinea pig .... 79 

29. Photomicrograph 24-hour ascites-dextrose-broth culture 

of a streptococcus from blind abscess of jaw ... 79 

30. Ulcer of stomach of dog.. 80 

31. Capillary filled with diplococci in the apex of ulcer 

shown in Fig. 30.. . 80 

32. Section of wall of stomach of rabbit.81 

33. Streptococci at apex of wedge-shaped area shown in 

Fig. 32 .... 82 

34. Hemorrhagic pancreatitis in dog.83 

35. Section of pancreas in dog.. . 84 

36. Photomicrograph showing diplococci in area of round 

cell infiltration.85 

37- Subcutaneous tissues from erythema nodosum in man . 86 

38. Subcutaneous tissue from erythema nodosum in man . 87 

39. Smear from single colony in ascites-dextrose-agar . . 87 

40. Smear from blood of guinea pig.88 

41. Photograph showing circumscribed hemorrhages of the 

skin and symmetrical hemorrhages of the fascia of 
the inner aspect of the legs of a rabbit.89 

42. Section of skin of rabbit showing hemorrhage and leu¬ 

kocytic and round cell infiltration of subcutaneous 

43. A diplococcus in the area of infiltration shown in Fig. 42 91 



44. Section of the artery from the area of subcutaneous 

hemorrhage. 91 

45. Diplobacilli in the wall of artery shown in Fig. 44 . 92 

46. Photomicrograph of 24-hour culture in ascites-dextrose- 

broth of a streptococcus from the spinal fluid of a 

47. Herpes as seen on under surface of the skin over the 

lower right thoracic region of a rabbit.93 

48. Diplococci in the hemorrhagic spinal ganglion .... 94 

49. Herpes of the skin of the inner and upper aspect of 

right thigh of a rabbit.. . 95 

50. Thrombosis of a vein (a) and paravascular infiltration 

(b) of the posterior spinal root.96 

51. Diplococci in leukocytes within a thrombosed vein . . 97 

52. Diplococci in hemorrhagic and infiltrated area shown in 

Fig. 53...97 

53. Marked hemorrhage (a) and leukocytic infiltration (b) 

surrounding the lumbar nerve ..98 

54. Herpes of tongue, mucous membrane about teeth and 

lips of rabbit. 99 

55. Herpes of skin of left side of face of rabbit .... 100 

56. Hemorrhage (a) and round cell infiltration (b) of the 

gasserian ganglion of dog.101 

57. Section of iris and ciliary body of rabbit.104 

58. Photomicrograph of streptococci in area of infiltration 

shown in Fig. 57.105 

59. Localized hemorrhages (a) in the sclera near the limbus 

and at the attachment of the external rectus muscle 
of rabbit.106 

60. Diplococcus adjacent to area of hemorrhage in Fig. 59 . 106 

61. A typical subacute focal lesion in the cortex . . . . 114 

62. An interlobular vein surrounded by lymphocytes and 

plasma cells.115 

63. Cholecystitis and cholelithiasis in dog . . . . . . 117 



64. Streptococci and leukocytic infiltration in peritoneal 

coat in perforating ulcer of the stomach of man . 

65. Streptococci in peritoneal coat of ulcer of stomach in 


66. Streptococci and leukocytic infiltration in chronic ulcer 

of man. 

67- Chronic ulcer of duodenum of dog 13 weeks after a 
single intravenous injection of streptococcus from 
ulcer of the duodenum of man. 

68. Chronic ulcer of duodenum of dog 13 weeks after a 
single intravenous injection of streptococcus from 
human ulcer ... 











Permit me to express to you my sincere appreciation 
of the honor conferred upon me, by the Trustees and 
Faculty of Stanford University Medical School, to 
give the fifteenth course of the Lane Medical Lectures. 

I am complimented also by the fact that the group 
of workers with whom I am associated, has been en¬ 
gaged in the clinical and laboratory investigation of a 
subject about which you desire to hear. 

Systemic or general disease due to a local infection is 
a conception as old as medical knowledge. 

Long before the development of bacteriology there 
had been noted many examples of general disease aris¬ 
ing from trivial and serious accidental and surgical 
wounds. The general disease was, as a rule, character¬ 
ized by chills, fever, and general debility and was often 

The cause was thought to be contamination of the 
wound or focus with some substance which caused putre¬ 
faction. Hence the resulting general disease was called 
septic. The so-called laudable pus of an uneventful 

healing wound, when contaminated with putrefactive 




poison, which changed in color, fermented, acquired a 
bad odor, and, gaining entrance to the blood stream, 
caused pyemia or septicopyemia. Discussion as to the 
origin of the putrefactive agents brought forth many 
theories until the epoch-making discovery of Semmel- 
weis (1847) who traced the constant prevalence of child¬ 
bed fever in the Vienna lying-in hospital to contamina¬ 
tion of the genitalia of the woman in labor by the un¬ 
clean hands of students and physicians fresh from the 
dissecting rooms. Cadaveric poison, therefore, was 
proved to be a cause of childbed sepsis. Local infection 
followed by embolism, thrombosis and septicemia were 
recognized as successive stages which were observed in 
surgical and obstetrical sepsis. E. Ivlebs was probably 
the first to recognize that local and general sepsis were 
due to microorganisms which he termed microsporon 
septicum. But no material gain in practical results oc¬ 
curred until the deductions of Lister, based upon the 
brilliant researches of Pasteur, that wound infection was 
due to a virus animatum and the rational application by 
Lister of measures to prevent wound infection. Lister- 
ism—antiseptic surgery—was of rapid growth and in its 
evolutional form as applied today makes general sepsis 
in surgery and midwifery a criminal offense due to ig¬ 
norance, carelessness or faulty technic. 

But focal infection, which is the subject of these lec¬ 
tures, is broader in its application than is expressed in 
surgical sepsis. 

During the last decade a new interest has been 
aroused in the subject of focal infection as an etiologic 
factor of local and of general diseases. The wider dis- 



cussion of the subject made it appear as a new prin¬ 
ciple. The wider and broader interest in the subject 
has been brought about by a better knowledge of bac¬ 
teriology, of modes of infection, and by cooperative lab¬ 
oratory and clinical research. 


A focus of infection may be defined as a circum¬ 
scribed area of tissue infected with pathogenic micro¬ 
organisms. Foci of infection may be primary and sec¬ 
ondary. Primary foci usually are located in tissues 
communicating with a mucous or cutaneous surface. 
Secondary foci are the direct results of infection from 
other foci through contiguous tissues or at a distance 
through the blood stream or lymph channels. 


Primary foci of infection may be located anywhere 
in the body. Infection of the teeth and jaws, with the 
especial development of pyorrhea dentalis and alveolar 
abscess, infection of the faucial and nasopharyngeal 
tonsils and of the mastoid, the maxillary and other 
accessory sinuses are the most common forms of 
focal infection. Submucous and subcutaneous abscesses 
including the finger and toe nails are occasional foci. 
Chronic infection of the bronchi and bronchiectasis; 
chronic infection of the gastro-intestinal tract and aux¬ 
iliary organs of digestion, including cholecystitis, ap¬ 
pendicitis, intestinal ulcers and intestinal stasis due to 
morbid anatomical conditions; chronic infection of the 
genito-urinary tract, including metritis, salpingitis, 
vesiculitis seminalis, prostatitis, cystitis and pyelitis, are 
not uncommon forms. Infected lymph nodes, which are 



secondary to the primary foci named, become additional 
depots of local infection. The secondary lymph node 
infection may persist after the etiologic, distal, primary 
focus has been removed or has spontaneously disap¬ 
peared. Other secondary foci may appear in various 
tissues as a part of the general or local disease which 
results from a primary focus. As we shall see, systemic 
and local disease may occur through infection from a 
focal point by way of the blood stream. This mode of 
infection is often embolic in character. The tissues so 
infected may constitute new foci, which in part explains 
the chronicity of many local and general infections. 


Focal infection especially of the structures of the 
mouth and the upper air passages is a very prevalent 
condition. The incidence of infection of the mouth 
is enormous everywhere. In addition to the presence of 
innumerable saprophytes in the mouth and. pharynx, 
one may find in the saliva and pharyngeal mucus, strep¬ 
tococci and staphylococci, micrococcus catarrhalis, pneu¬ 
mococci, diphtheria and pseudodiphtheria bacilli, men¬ 
ingococci, tubercle bacilli and many other pathogenic 
bacteria. C. C. Bass (1) and others state that endameba 
buccalis was found in the mouths of 95 and even 100 
per cent, of all adults examined. The presence of these 
infectious microorganisms in the mouth and upper res¬ 
piratory tract indicates unhealthful surroundings and 
individual uncleanliness. The individual carrier infects 
others by contact and by other means. 



The character of local infection in various parts of the 
body is so important that separate consideration must 
be given to each kind. 

Pyorrhea Dentalis and Alveolar Abscess 

Pyorrhea dentalis and alveolar abscess (Rigg’s dis¬ 
ease) is a condition incident to all classes of adults. It 
is much less prevalent in the young. It is a disease 
which fundamentally involves the periosteum of the root 
and neck of the tooth (peridental membrane). It is the 
chief cause of the loss of the permanent teeth. It may be 
associated with caries of the crown, and, on the other 
hand, the crown may remain normal. The infection 
first attacks the edges of the gum, which may be macer¬ 
ated by decaying food particles between the teeth, or 
the gum may be injured in masticating hard substances, 
by toothpicks, and other traumatic agents. Ill health 
and poor general nutrition make the gums less resistant. 
The endameba buccalis and various pyogenic bacteria 
which gain admission to the edges of the gums cause 
retraction of the soft tissues and the exposed peridental 
membrane of the neck and root of the tooth become in¬ 
volved in sequence. This periosteum injured or de¬ 
stroyed, there follows softening and ulceration of the 
soft parts with the end result of acute or chronic alveo¬ 
lar abscess. 

Endameba has been known to be a parasite of the 
mouth for many years. Its relation to pyorrhea alveo- 
laris was first described by F. M. Barrett, (2) in col¬ 
laboration with Allen J. Smith in 1914. Without a 
knowledge of the work of Barrett and Smith, C. C. 



Bass and F. M. Johns (1) had recognized the relation 
of the parasite to pyorrhea and had begun experimental 
treatment with emetin. The endamebas may be found 
in the gum lesions and they are numerous in the deeper 
abscesses where they live on the dead tissues. Bass and 
other investigators believe that the endameba buccalis 
is the chief etiologic factor in the development of pyor¬ 
rhea alveolaris. 

From the pus and dead material of alveolar abscess 
and the infected pulp of the teeth, with a proper technic, 
cultures yield streptococci, chiefly streptococcus viridans 
and streptococcus hemolyticus, staphylococcus aureus 
and albus, fusiform bacilli and other less important bac¬ 
teria. Doubtless the endamebas play an important part 
in the occurrence of pyorrhea alveolaris and permit in¬ 
fection with the pyogenic bacteria. The bacteria pres¬ 
ent in the infected areas are the important factors, how¬ 
ever, in the causation of general infection from the 

Acute and Chronic Tonsillitis and Infection of 
Lymphoid Tissue in the Nasopharynx 

The faucial tonsils are frequently infected through 
contaminated air, infected food, especially milk, and by 
direct contact with infected individuals. Many children 
have large tonsils and overgrowth of other lymphoid 
structures of the pharynx which make a good soil for 
bacterial growth. Hypertrophy of the tonsils and ade¬ 
noid overgrowth in the nasopharynx interfere with res¬ 
piration, resulting in deformities of the bones of the face 
and thorax. Obstruction of the upper air passages pre- 



vents proper drainage from the nasal cavities and ac¬ 
cessory sinuses and leads to infection of the middle ear, 
the sinuses of the head and the mucous membrane cover¬ 
ing the turbinate bodies. In adult life small faucial ton¬ 
sils may look innocent because of a smooth covering of 
mucous membrane which seals over infected crypts or 
an actual abscess. So, too, the stumps of tonsils, the 
remains of tonsillotomy, may contain infected crypts 
sealed by the operative scar. 

Infected tonsils and adenoids may 
streptococcus mucosus, streptococcus viridans, strepto¬ 
coccus hemolysans, micrococcus catarrhalis, pneumococ¬ 
ci, bacillus mucosus capsulatus, grippe bacillus, diph¬ 
theria and pseudodiphtheria bacilli and other pathogenic 
microorganisms. The tonsils and surrounding lymph 
tissues may be a focus of tuberculosis from which lymph 
nodes of the neck and mediastinum may become in¬ 
fected. Smith and Barrett (3) found endameba buc- 
calis in the tonsils of five of seventeen patients. The 
presence of endamebas in the tonsils would probably 
favor deep pyogenic infection. 

Mastoiditis and Sinusitis of the Maxillary and Other 

Accessory Sinuses 

Mastoiditis as an extension of nasopharyngeal infec¬ 
tion through the eustachian tube and middle ear is a 
serious and frequent disease of the young and occasion¬ 
ally of adults. Members of the streptococcus-pneumo¬ 
coccus group are the usual infectious agents. Staphylo¬ 
cocci and influenza bacilli may be the invaders. The 
proximity of the mastoid cells to the venous sinuses of 

yield cultures of 



the skull makes this focus a frequent source of sinus 
thrombosis, bacteriemia and meningitis. 

Infection of the accessory sinuses is of frequent oc¬ 
currence during the changeable seasons. The most fre¬ 
quent bacterial causes are strains of streptococci, pneu¬ 
mococci, micrococcus catarrhalis and influenza bacilli— 
less frequently staphylococci. In chronic sinusitis, often 
unrecognized, various pyogenic bacteria occur with the 
occasional presence of colon bacilli, the bacillus welchii 
and various saprophytic organisms. Sinus infection is 
frequently chronic because of faulty drainage. When 
chronic it may present local symptoms only when a new 
“cold” is acquired. 

All infectious foci of the head may be associated with 
secondary infection of the lymph nodes of the neck and 
mediastinum. Ivretz (25) records six hundred autop¬ 
sies with especial reference to the infection of the cer¬ 
vical lymph nodes. In childhood, he says, the superfi¬ 
cial nodes of the anterior triangles are involved and soft, 
while in adults the deeper glands at the angle of the jaw 
and the region of the internal jugular vein are more 
often involved and are usually indurated. He stated 
that in 90 per cent, of the bodies examined the glands 
showed streptococcus infection and 10 per cent, yielded 
other bacteria. Ivretz believes that many children suffer 
from acute glandular fever, due to angina, and that the 
infectious microorganisms pass rapidly through the 
cervical lymph channels and glands with resulting severe 
bacteriemia and fever. H ence a fatal result obtains in 
virulent types of glandular fever in children. He states 
that in older people the filtration through the deeper 



cervical glands is slower. Consequently the virulence 
of the bacteria and the degree of bacteriemia may be 
less. The lymph node infection may disappear with 
the removal of the primary focus or may persist actively 
as new foci in the production of systemic disease or the 
infection of the nodes may become permanently latent. 

Chronic Bronchitis and Bronchiectasis 

Long standing bronchitis associated with emphysema, 
asthma, and bronchiectatic cavities presents a type of 
localized chronic infection which may be an etiologic fac¬ 
tor in systemic infection and trophometabolic changes 
in bones and joints probably due to toxic products ab¬ 
sorbed from the site of infection. The sputa in the 
conditions named yield cultures of many saprophytic 
bacteria as well as streptococci, staphylococci, pneumo¬ 
cocci, influenza bacilli, micrococcus catarrhalis, fusi¬ 
form anaerobes and other pathogenic bacteria. 

Focal I?ifection of the Gastro-intestinal Canal y Vermi- 
form AppendixGall-hladcler and Pancreas 

Auto-infection and auto-intoxication from the intes¬ 
tinal canal as a cause of disease is a popular idea with 
the medical profession. Stasis of the intestinal contents 
is alleged to be an important factor in the causation 
of auto-infection. Intestinal stasis may be due to habit¬ 
ual constipation, to partial obstruction of the intestines 
due to congenital defects, or to acquired morbid ana¬ 
tomical conditions which favor the presence of patho¬ 
genic bacteria with putrefactive changes, resulting, it is 
believed by many, in toxemia and systemic disease. An- 



emia, chronic arthritis, Bright’s disease, arteriosclerosis, 
and even local diseases like appendicitis, cholecystitis 
calculosa and peptic ulcer, are believed to be caused by 
stasis and putrefactive changes in the intestinal con¬ 
tents. This large focus of infection has been attacked 
in the attempt to remove the offending bacteria by intes¬ 
tinal antiseptics, colonic flushing, buttermilk and other 
lactic acid bacilli containing fluids and tablets and ca¬ 
thartic waters, and the surgeon has invaded the abdomen 
to correct the intestinal stasis by removing kinks, veils 
and other alleged deformities, and even by resecting the 
entire colon. 

There is doubtless some truth in the theory of in¬ 
testinal infection, but the pathogenic microorganisms in 
the intestinal canal, which remain there as infectious or¬ 
ganisms, gain entrance chiefly by swallowing infectious 
material from the mouth, throat and nose and also 
through infected food and drink, especially milk, for 
milk is very apt to contain streptococci which are viru¬ 
lent or may become so. Streptococci and other patho¬ 
genic bacteria probably infect the lymph tissue of the 
intestine or may pass into the lymph nodes of the mes¬ 
entery and set up active or passive infection. As we 
shall see later, streptococcal infection from a focus in 
the head may hematogenously cause appendicitis, chole¬ 
cystitis, peptic ulcer and pancreatitis. In addition to 
the immediate local damage, the bacteria in these tissues 
may form new foci from which proximal lymph nodes 
may become infected. From these new foci further ex¬ 
tension of the infection may take place through the 
lymph channels or the blood stream or through both. 



Appendicitis; is usually caused by a strain of the 
streptococcus group from a mouth or throat focus. The 
colon bacilli and other members of the intestinal bac¬ 
terial flora in the appendix may take on pathogenic 
qualities and cause a mixed infection. Often this mixed 
infection is fulminating and severe. Chronic types of 
appendicitis not only cause local distress and digestive 
disturbances, but may become a cause of infection of 
the mesenteric glands and through the lymph vessels 
and blood stream may infect the liver, bile tracts, and 
subdiaphragmatic tissues. Cholecystitis may also be 
caused by a streptococcus infection from a focus of the 
head. The infectious microorganism carried in the 
blood stream from the focus may lodge in the terminal 
blood vessels of the fundus of the gall-bladder. The 
inoculated blood vessel becomes wholly or partly oc¬ 
cluded by endothelial proliferation and leukocytic infil¬ 
tration, and blood containing the bacteria escapes into 
the wall of the bladder. Necrosis of the local tissues 
and rupture of the infected material into the gall-blad¬ 
der may occur. Acute severe cholecystitis may result. 
Less severe infection may result in a chronic cholecysti¬ 
tis and subsequent gall-stone formation. Typhoid and 
colon bacilli may cause cholecystitis or may be associated 
in a mixed infection of the organ. Cholecystitis may 
be a focus of systemic infection. 

The rectum, with its rich supply of hemorrhoidal 
veins, becomes a focus of infection, through ulcers, in¬ 
fected thrombi in veins and local abscesses. Infected 
thrombi from these points may produce acute circum¬ 
scribed hepatitis (abscess), and bacteriemia. 



Foci of Infection of the Genito-urinary Tract 

Immediately after childbirth, miscarriage or abortion, 
the endometrium is very susceptible to infection by any 
of the pyogenic microorganisms. The resulting focus 
is usually serious because of the tendency to the forma¬ 
tion of infected thrombi in the uterine sinuses. The 
bacteriemia which results is severe. At other times 
the endometrium is not a frequent site of focal infection. 

The fallopian tubes are very susceptible to infection 
with pyogenic bacteria, but most frequently the cause 
is the gonococcus with resulting obliterating salpingitis 
or abscess which may infect the peritoneum. Tubercu¬ 
lous salpingitis may cause tuberculous peritonitis. Fo¬ 
cal infection in the form of gonorrheal vaginitis is a 
common disease of defective girls and of girls in hospi¬ 
tals and public institutions. The condition is important 
because of the readiness with which it is conveyed from 
individual to individual by contact or through fomites. 
The condition usually remains a local one with conse¬ 
quent discomfort confined to the parts involved. Oc¬ 
casionally the peritoneum, joints and other tissues may 
become infected from the vaginal, uterine and tubal 

The seminal vesicles and testes are sites of focal in¬ 
fection with the gonococcus, tubercle bacillus and pyo¬ 
genic bacteria. 

Probably tuberculous infection of the genital ap¬ 
paratus is secondary to a focus elsewhere. Tuberculous 
infection of testes usually involves the seminal ducts and 
vesicles by extension through the lymph channels, blood 



stream or vas deferens. This focus may result in gen¬ 
eral tuberculosis or involve the urinary bladder and kid¬ 
ney by the blood stream or lymph canals. 

Gonorrheal vesiculitis may be acute or chronic and 
lead to gonorrheal arthritis, acute or chronic, or to gon¬ 
orrheal bacteriemia, and ulcerative endocarditis. Infec¬ 
tion of the seminal vesicles may be due to streptococci 
and staphylococci and cause systemic disease. The pros¬ 
tate gland may be infected with gonococci, streptococci, 
staphylococci, tubercle bacilli, colon bacilli and other 
less important bacteria. When infected and enlarged it 
is an important factor in infection of the bladder, ureters 
and kidneys, by causing urinary obstruction and cystitis. 
Cystitis may be due to pyogenic bacteria, tubercle ba¬ 
cilli, bacillus pyocyaneus, typhoid bacilli and other bac¬ 
teria. The colon bacillus is a very common inhabitant 
of the urinary tract and usually is apparently not harm¬ 
ful. In the presence of bladder stasis and in other types 
of cystitis (tuberculous, streptococcus, staphylococcus 
cystitis), the colon bacteria may take on pathogenic 
qualities as a mixed infection. Acute and chronic cysti¬ 
tis may be the source of infection of contiguous tissues 
and through the lymphatic vessels and lymph nodes of 
the base of the bladder and in the walls of the ureters, 
infection of the pelvis and parenchyma of the kidneys 
and perirenal tissues may occur as shown by S. Sugi- 
mura (4) and Carl Franke ( 5 ). The kidney and its 
pelvis, however, is usually infected hematogenously with 
pyogenic bacteria, typhoid, colon and tubercle bacilli and 
other microorganisms. Indeed cultures of the urine, 
with a proper technic, will yield characteristic bacteria, 



during the incidence of many infectious general and 
local diseases, as shown by George F. Dick and Gladys 
R. Dick (6). The kidney and renal pelvis may be 
the site of focal infection which may cause infection of 
the ureters and bladder through the urine contaminated 
with tubercle, colon, typhoid and pyocyaneus bacilli, 
pyogenic cocci, bacillus proteus and with other bac¬ 

Subcutaneous abscesses and abscesses about the nails 
are occasionally the source of systemic infection. Fur¬ 
uncles and carbuncles are well known sources of acute 
bacteriemia, especially in patients debilitated by ex¬ 
hausting diseases of which diabetes mellitus is an ex¬ 



The high percentage of incidence of localized infec¬ 
tion, especially about the head, has already been stated. 
The greater number of these individuals affected, both 
young and old, do not develop acute systemic disease 
therefrom. A majority of children suffer from chronic 
infection of the tonsils and nasopharyngeal lymphoid 
tissue with occasional acute exacerbations, while the in¬ 
cidence of acute rheumatic fever and endocarditis is 
relatively small in youth. Nevertheless, rheumatic 
fever and endocarditis are unquestionably the result of 
focal infection of the mouth and throat. 

A majority of civilized mankind, who are city dwell¬ 
ers, carry a latent tuberculous focus, usually infected 
lymph nodes of the mediastinum, mesentery or else- 



where in the body. A comparatively small number de¬ 
velop clinically recognizable tuberculosis. 

The marked prevalence of alveolar abscess is not 
associated with the frequent incidence of acute systemic 
infection. Probably the frequent relation of pyorrhea 
to rheumatic fever, heart disease, nephritis and other 
acute local and general infections has not been given 
the etiologic importance it deserves. Granting this fact 
one must still recognize the comparatively small inci¬ 
dence of acute systemic disease arising from alveolar 

The incidence of chronic gonorrheal infection of the 
prostate gland, seminal vesicles, vagina and fallopian 
tubes is very large as compared with the occurrence of 
gonorrheal arthritis, tenovaginitis, gonococcemia, and 
ulcerative endocarditis. 

The escape of a great majority of persons who harbor 
foci of infection from manifest clinical systemic disease, 
is the reason given by many thoughtful physicians for 
disbelief in the etiologic relation of foci of infection to 
systemic and local infection, especially of the chronic 

Based upon the present knowledge obtained by clini¬ 
cal and laboratory research and experiments upon the 
lower animals, there can be no doubt now of the etio¬ 
logic relation of localized infection to both acute and 
chronic systemic diseases, 
processes are sequential to primary acute diseases, etio- 
logically related to focal infection. Other chronic sys¬ 
temic diseases are primarily due to infection derived 
from focal infection. 

Many of the systemic chronic 



The relatively rare incidence of systemic disease as 
compared with the marked prevalence of focal infection 
may be answered, partially, at any rate, by well known 
facts concerning immunity both natural and acquired. 

The natural defenses of the body, due to the bacteri¬ 
cidal and antitoxic powers of the tissues, blood plasma 
arid cells, especially the phagocytes, protect the major¬ 
ity of us from the acute infectious diseases. All individ¬ 
uals do not possess an equal degree of natural immunity; 
some more readily succumb to the invading infectious 
agents. When the animal body is invaded with patho¬ 
genic bacteria the natural defenses are increased by 
their presence in the tissues and blood. The processes 
are: first, the phenomenon of positive chemotaxis with 
resulting leukocytosis and the accumulation of leu¬ 
kocytes in the areas of infection of the tissues by the 
formation of local exudates, liquid (purulent) and fi- 
brinoplastic, which may serve as walls of protection 
against further direct invasion; second, leukocytic 
phagocytosis with destruction of the invading bacteria; 
and third, the formation of protective antibodies in the 
blood and tissues. 

Similar protective processes may be induced in the 
body by the injection of non-lethal amounts of living 
or of dead pathogenic bacteria into a healthy man or 

It is not improbable that the bacteria of a focal infec¬ 
tion may excite the development of additional defenses 
in the host and prevent the evolution of a sequential 
systemic disease. 

Bacteria may diminish in virulency and pathogenicity 



and exist as harmless parasites of the skin, mucous 
membranes and. probably also as foci in the tissues 
(Ivolle and Wassermann (7)), for it is known that 
the reaction of the tissues is influenced by the virulence 
of the bacteria. A non-virulent streptococcus would be 
disposed of by the tissues with but little local or gen¬ 
eral reaction. 


Immunity both natural and acquired as described is 
not absolute. Pasteur found that the marked immu¬ 
nity of the chicken to anthrax could be overcome by 
lowering the body temperature by immersion of the 
fowl in cold water. It is known that physical and men- 
tal exhaustion, starvation, exposure to cold, debility 
from alcoholic dissipation, the misuse of narcotic drugs 
and exhausting general disease may reduce the natural 

Innumerable instances of the incidence of the sud¬ 
den onset of pneumonia, rheumatic fever, tonsillitis, 
sinusitis, nephritis, septicemia and other infectious proc¬ 
esses have been recorded after exposure to extreme cold. 
Undoubtedly the latent pathogenic bacteria usually 
present in the nose and throat may acquire coincidently 
with the exposure specific pathogenicity, and are able 
to invade the host because of the lowered resistance and 
because of added virulency. The acquisition of specific 
pathogenicity and tissue affinity by the members of the 
streptococcus-pneumococcus group will be fully con¬ 



Exhaustion and debility from physical and mental 
overwork, starvation, chronic disease and other condi¬ 
tions are important etiologic factors in the occurrence 
of acute and chronic systemic disease from focal in¬ 
fection. This is notably true of the chronic infectious 
arthritis and myositis. 

Many of the lesser ills of the body in the form of 
subjective soreness of the tissues, joints, muscles and 
nerves are possibly the result of slight infection from a 
focus in the mouth or throat or some other region of 
the body, especially in individuals with a lessened re¬ 
sistance. This is perhaps a vague hypothesis, but in¬ 
stances of the disappearance of these clinical phenomena 
with the institution of individual hygiene and removal 
of an existing focus of infection is suggestive of the 
truth of the statement. 


Usually a focus of infection is disregarded by the 
patient and physician unless it cause local discomfort. 
When a systemic disease occurs which present-day 
knowledge associates with a primary infectious focus, 
the site of the focus must be located. The character 
of the systemic disease may point to the most likely lo¬ 
cation of the primary portal of infection. The primary 
focus of acute rheumatic fever, endocarditis, chorea, 
myositis, glomerulonephritis, peptic ulcer, appendicitis 
and chronic deforming arthritis, as examples, is usually 
located in the head and usually in the form of alveolar 
abscesses, acute or chronic tonsillitis and sinusitis. One 
would look for the focus of gonorrheal arthritis in the 



genito-urinary tract. The failure to find a focus in the 
expected situation should indicate an extension of the 
field of examination until the primary infection shall 
have been found. In a superficial and hasty examina¬ 
tion the site of the focus of infection may escape detec¬ 
tion or the focus may be assumed to be in uninfected 
tissues and organs. Every patient should be carefully 
interrogated as to the past and present condition; a 
general examination should be made, including, if neces¬ 
sary, the services of specialists in diseases of the ear, 
nose and throat, the pelvic organs and the gastroin¬ 
testinal tract, and in all patients with evidence of pyor¬ 
rhea and sinusitis the service of the rontgenologist is 
demanded. Bacterial cultures made from the surface 
of the gums and tonsils, which will usually yield patho¬ 
logic types of bacteria, are not an index of focal infec¬ 
tion located in the dental alveoli or tonsils. In alveolar 
abscess, by scraping the accumulated “tartar” and exu¬ 
date from the exposed neck of the tooth and by penetrat¬ 
ing as deeply as possible into the infected alveolus, one 
may readily obtain material for microscopic examination 
which usually yields endameba bucealis and bacteria. 
Cultures of the feces may yield strains of streptococci 
and other bacteria not usually found in the intestinal 
flora. These bacteria may not be specifically pathogenic 
in the intestinal habitat and if free in the intestinal con¬ 
tents and not infecting the intestinal structures are 
quite likely not to be harmful to the host. Bacterio¬ 
logical examination including cultures should always 
be made of the sputa, urine, uterine, vaginal and 
urethral discharges and exudates obtained by massage 



of the prostate gland and seminal vesicles, for they 
often yield results of diagnostic importance. The na¬ 
ture of the general disease and its relation to a sup¬ 
posed focus may be made more evident by the coincident 
histologic and bacteriologic studies, both miscroscopic 
and cultural, of exudates of synovial cavities, and of 
excised lymph nodes proximal to the infected regions; 
bits of infected muscles; fibrous nodes on tendons and 
aponeuroses; the blood, and also of the exudate of the fo¬ 
cus; and by the inoculation of animals with strains of 
the dominant pathogenic bacteria so obtained, while the 
cultures are young. The discovery of the similarity of 
the pathogenic organisms in cultural characteristics, in 
the focus of infection and in the infected tissues, and the 
production of a similar infectious process in the inocu¬ 
lated animal from the tissues of which the infectious bac¬ 
teria are afterwards recovered, constitute reasonable 
proof of the etiologic relation of the focus of infection to 
the existing systemic infection. Many successful clinical 
and laboratory studies of this kind have been made with 
patients suffering with rheumatic fever, subacute or 
chronic infectious endocarditis, chronic infectious arth¬ 
ritis, appendicitis, peptic ulcer, cholecystitis, glomerulo¬ 
nephritis and other diseases. 


II cmatogenous 

Systemic infection and intoxication from a primary 
focus is usually hematogenous. The bacteria may be 
compared with emboli loosened from the place of origin 



and carried in the blood stream to the smallest and 
often terminal blood vessels. If virulent and endowed 
with specific elective pathogenic affinity for the tissues 
in which they will lodge, and if in sufficient number , the 
invading bacteria will excite characteristic reactions in 
the infected tissues and a sequential train of morbid 
anatomical lesions. The evolution of the anatomical 
lesions and the clinical phenomena aroused thereby are 
dependent on the type and virulence of the bacteria, 
the character of the tissue and the function of the organ 
involved. The specific tissue reaction consists of a local 
inflammation with endothelial proliferation of the lining 
of the blood vessel with or without thrombosis; blocking 
of the blood vessels; hemorrhage into the immediate tis¬ 
sue ; positive chemotaxis with resulting multiplication of 
the leukocytes and plasma cells in the infected area, or 
fibrinoplastic exudate with local connective tissue over¬ 


The infectious microorganisms may also pass from 
the focus to other tissues through the lymph channels 
and lymph nodes. This may occur from the primary fo¬ 
cus coincidentally with hematogenous systemic infection. 
Primary focal infection of the tonsils, nasopharyngeal 
tissue, the accessory sinuses and the mastoid cells is not 
infrequently associated with secondary infection of the 
lymphatic vessels and lymph nodes of the neck, some¬ 
times extending to the mediastinal lymph nodes. The 
lymph nodes which drain areas of tissues which have 
been infected hematogenously from a primary focus 
may become infected and enlarged from the systemi- 



cally infected areas as in infected joints, cholecystitis, 
appendicitis and infection about the pelvic organs. 

The tissue reaction which occurs in infected lymph 
nodes varies in intensity with the virulencv and char¬ 
acter of the invading bacteria. Thus a varying degree 
of inflammation results in proliferation of the lymphoid 
cells with swelling and tenderness of the nodes. These 
secondary foci may continue as active depots of supply 
of bacterial infection to other tissues. If the invading 
bacteria of the lymph node are pyogenic and virulent, 
positive chemotaxis will result in the invasion of the 
infected gland with leukocytes and a circumscribed ab¬ 
scess may result. Lymph node infection with necrotic 
changes may rupture into or may cause infectious 
thrombophlebitis in a contiguous vessel and bacteriemia 
may result. In other instances the infection in the 
lymph node may be a protection by holding the invad¬ 
ing organisms in a tissue environment which renders 
them latent and for the time harmless to the patient. 


Systematic intoxication from a focus of infection is 
characteristic of the exotoxic bacteria. Diphtheria and 
tetanus are two examples of infectious disease in which 
the morbid tissue reactions are caused by soluble toxins 
excreted by the specific microorganisms in a focal area. 

It has been assumed that focal infection due to micro¬ 
organisms which produce endotoxins may cause sys¬ 
temic disturbances by dissemination of toxic substances 
from the focus. It is suggested that the toxic material 
may be formed by biochemical reactions excited by the 



microorganisms and the tissues and cellular exudate of 
the focus; also that autolysis of the dead microorgan¬ 
isms of the focus sets free the endotoxin. Hence it is 
said that morbid processes of a degenerative and meta¬ 
bolic character which may occur in many organs and in 
varying degrees of severity, are caused by toxins and 
toxic substances elaborated in a focus of infection. 

Semmelweis, Ivlebs, Virchow, Pasteur, Lister and 
others proved long ago that virulent microorganisms 
are the cause of infectious disease. Modern bacteriology 
and clinical research are adding day by day incontestable 
proof that bacterial invasion and infection of tissue is 
the fundamental cause of many of the systemic diseases, 
which have been classed as toxic, metabolic or nutri¬ 
tional. A sequence of the fundamental and primary 
infection of tissue may create a morbid anatomy, dis¬ 
turbed function, malnutrition and in consequence sec¬ 
ondary metabolic and degenerative changes. The endo¬ 
toxin of the invading bacteria is set free in the blood and 
tissues and is a factor in the cellular reaction expressed 
in general infection by chill, fever, disturbed functions 
and altered metabolism and in local infection by cellular 
reaction and symptoms varying with the character of 
the invading bacteria, the anatomical lesions and dis¬ 
turbance of function of the tissue and organ involved. 


Focal infection may be the cause of the condition 
known as anaphylaxis. The bacterial protein of the 
pathogenic microorganism of the focus may sensitize 
the body cells. 



If a foreign protein gains entrance to the body par- 
enterally, via the blood stream or the lymphatics, the 
animal body always responds to the parenteral intro¬ 
duction of the foreign protein by the production of 
specific antibodies to that foreign albumen. The forma¬ 
tion of the specific antibodies requires a certain period 
of time. After this interval a second introduction of 
the same protein, again by a parenteral route, results 
in a union of the newly formed antibody with the anti¬ 
gen (foreign protein), which may excite physical phe¬ 
nomena of an explosive character. These phenom¬ 
ena, the so-called anaphylactic shock, differ materially 
with various species of animals and with man. In man 
the typical phenomena may consist of bronchial spasm, 
urticaria, vasodilatation and fall of blood pressure, eosin- 
ophilia, physical weakness and arthropathy. In some 
individuals, urticaria or bronchial asthma may be the 
only expression of anaphylaxis. 

Anaphylaxis has been studied as serum disease by 
Rosenau and Anderson (44), Park (47) and others. 
Von Pirquet (43), Weil (42), Meltzer (52) and 
Vaughan (45) have shown the relation of anaphylaxis 
to the symptom expression of infectious disease and to 
bronchial asthma. Theobald Smith (39), Auer and 
Lewis (46), Jobling, Petersen and Eggstein (53) and 
many others have reported the result of extensive re¬ 
search upon laboratory animals in the production of 
immunity and of anaphylaxis. 

The relation of anaphylaxis to bronchial asthma, 
many dermatological lesions, gastro-intestinal symp¬ 
toms, cardiovascular disturbance, especially arterial 



hypotension and other morbid conditions, of man, has 
not received the attention which its importance de¬ 
mands. Definite clinical evidence has been established 
of the etiologic relation of confined focal infection to 
anaphylaxis, in the form of bronchial asthma and other 
morbid conditions. The subject is not well understood, 
but is so important that it demands the cooperative re¬ 
search of the immunologist and clinician. 




Recent coordinate research in clinical medicine and 
bacteriology, fortified by animal experimentation, has 
made more evident the etiologic relation of focal infec¬ 
tion to systemic disease. 

The main and fundamental principles which have 
been proved are: 

1. The apparent confirmation of the transmutability 
of the members of the streptococcus-pneumococcus 
group in variations of morphology, cultural character¬ 
istics, biological reactions and also of general and spe¬ 
cial pathogenicity. 

2. The acquisition of pathogenic elective tissue af¬ 
finity by bacteria in foci of infection in culture media 
and serial animal passage. 

In a clinical and bacteriological study of chronic in¬ 
fectious endocarditis Rosenow (8) and Billings (9) 
confirmed the report of Schottmiiller (10) in the isola¬ 
tion from the blood during life of the patient of a pure 

culture of streptococcus viridans. Schottmiiller (10) 



isolated a streptococcus from patients with chronic in¬ 
fectious endocarditis, which grew fine colonies on blood 
agar plates, was non-hemolyzing, but produced a 
greenish halo around the colonies. In consequence it 
was named streptococcus viridans and because of its low 
pathogenicity for animals it was also called strepto¬ 
coccus mitior. The streptococcus viridans, isolated from 
the blood of our eleven patients, was cultivated in vari¬ 
ous media and animals were inoculated with successive 
strains. The behavior of the strains obtained from all 
patients was the same. The end result was a pneumo¬ 
coccus of specific pathogenicity for animals in the pro¬ 
duction of pneumococcemia and pneumonia. 

In consequence of these results the bacteriological 
diagnosis of our series of observed patients was chronic 
pneumococcus endocarditis. Rosenow soon recognized 
the fact that the bacteria studied were typical pneumo¬ 
cocci and that transmutation of the original pure cul¬ 
ture of streptococcus viridans had occurred in form, 
culture characteristics and in general and special patho¬ 
genic virulence for animals. 

Since that time Rosenow (8) has apparently con¬ 
firmed the transmutability of the members of the strep¬ 
tococcus group and that the property of trans¬ 
mutation is reversible within the members of this fam¬ 
ily. He says: “From this study the apparent po¬ 
sition of the various members of the streptococcus 
group may be illustrated by the position of the fingers 
in a partially flexed hand, in which the hemolytic 
streptococcus occupies the position of the little finger, 
the pneumococcus the place of the index finger (the op- 



posite extreme), streptococcus viridans (representing 
the group of more or less saprophytic, non-hemolyzing 
streptococci) the middle finger, the streptococci from 
rheumatism the ring finger, and streptococcus mucosus, 
having some of the properties of both pneumococci and 
streptococci, the thumb. In this grouping there is in 
general an increase in parasitism and virulence as we 

Fig. 1. —Strain 595 as a Hemolytic Streptococcus Isolated from a Case 
of Scarlet Fever. Smear from 24 hour culture in ascites-dextrose- 
broth. Gram stain. 

approach the thumb (streptococcus mucosus).” Rose- 
now has arrived at this conclusion by working with 
strains of streptococci and pneumococci obtained from 
various sources: Strains of hemolytic streptococci iso¬ 
lated from patients suffering from erysipelas, puerperal 
sepsis, scarlatina, acute tonsillitis and acute polyar¬ 
thritis; from cow’s milk and other sources; strains of 
streptococcus viridans isolated from tonsils, alveolar 
abscesses, the blood, from other tissues and cow’s milk; 
streptococcus mucosus from sputa, tonsils and else- 



Fig. 2 .— Strain 595 as Streptococcus Viridans. Smear from 24 hour cul¬ 
ture in ascites-dextrose-broth. Gram stain. 

where and pneumococci isolated from sputa, the blood 
during life and post mortem, the exudate of empyema, 
from hepatized lung and also Cole’s (11) strains I and 

Fig. 3.—Strain 595 as a Pneumococcus. Smear from 24 hour culture 
in ascites-dextrose-broth. Capsule stain. 



II. These have been successfully made to assume the 
varying types as to form, cultural characteristics, bio¬ 
logic reactions and special and general pathogenic viru¬ 
lence of the group. 

The technic which Rosenow pursues consists of the 
use of the ordinary solid and liquid culture media in 
which the oxygen content is increased and decreased, 

Fig. 4.—Strain of Streptococcus from Rheumatism Which Produced 
Slight Hemolysis on Blood Agar and Myositis in Animals. Smear 
from blood agar slant. Capsule stain. 

the use of hypotonic and hypertonic media, cultures 
made in symbiosis with bacillus subtilis as the occasion 
may indicate and of serial animal inoculation. Haessli 
(12) produced transmutation of a non-color-forming 
strain of streptococcus fecalis, by passing it several times 
through horse serum, when it finally became strongly 
hemolytic and had acquired all the pathogenic charac¬ 
teristics of streptococcus erysipelas. By the same 
method streptococcus viridans first lost its greenish 

Fig. 5 . —The Same Strain as in Fig. 4 After It Was Transformed Into 
a Pneumococcus. Smear from blood agar slant. Capsule stain. 

Fig. 6. —Highly Virulent Pneumococcus. Type 1. Originally Isolated 
by Neufeld. Smear from surface and water of condensation of blood 
agar slant. Capsule stain. 




color producing quality, finally became hemolytic and 
a strain of streptococcus mucosus became hemolytic. 
Haessli finally states that his experiments confirm the 
clinical differentiation of streptococci as demonstrated 
by Schottmiiller. Schottmiiller (10) probably recog¬ 
nized the transmutability of members of the streptococ¬ 
cus group pathogenic for man which he classified as 

Fig. 7.—The Same Strain as in Fig. 6 After Transformation Into Hemo¬ 
lytic Streptococcus. Smear from surface and water of condensation 
of blood agar slant. Capsule stain. 

streptococcus longus (hemolysans), streptococcus mitior 
(viridans) and streptococcus mucosus. Schottmiiller 
(10) also described strains of streptococcus mucosus, 
which possessed all the characteristics of strains first iso¬ 
lated from patients with parametritis in 1896, obtained 
in pure culture from the blood and hepatized lung of five 
patients with clinical lobar pneumonia. The strains de¬ 
scribed occurred as diplococci with capsule in chains of 
ten to fourteen pairs. Evidently he did not recognize 
the pneumococcus as a member of the group and espe- 


cially its close relation to the streptococcus mucosus. 
Transmutation within the members of other groups of 
pathogenic bacteria probably occurs. The members of 
the colon-typhoid group shade into one another in 
form, motility, cultural characteristics and in degrees of 
pathogenicity from nil to exalted virulence. 

Virulence and Elective Pathogenic Tissue Affinity 

The varying virulence of facultative pathogenic bac¬ 
teria has been long recognized. Environment seems to 
play an important role. This seems especially true of 
living tissue environment. Not only may there be a 
variation in general virulence, but apparently a special 
pathogenic virulence for certain tissues may be acquired. 
In this connection we may note the recent epidemics of 
septic tonsillitis, frequently associated with fatal bac- 
teriemia, due to milk infected with streptococci from 
human carriers. The acquirement of a selective specific 
tissue affinity by a strain of streptococci has been noted 
by Forssner (13). By culture in kidney and kidney 
extract the ordinary streptococcus pyogenes (hemoly- 
sans), which had no pathogenic elective affinity for the 
kidney, was converted into a strain, which injected in¬ 
travenously into animals constantly produced outspoken 
anatomical lesions of the kidney. This Forssner be¬ 
lieves is positive proof that the bacteria of a local in¬ 
fection may attain a specific pathogenic and elective 
tissue affinity. 

By making continued cultures in bouillon, for a long 
time these specific kidney strains assumed a general 
virulence. Again grown on kidney and kidney extract, 



the specific kidney pathogenicity was regained and 
maintained through numberless generations. This spe¬ 
cific kidney pathogenicity was lost after a few genera¬ 
tions in continued bouillon cultures. The general viru¬ 
lence was also finally lost. 

Poynton and Paine (14) in a discussion of the re¬ 
lation of malignant to rheumatic endocarditis state that 
the diplococcus isolated from patients with acute rheu¬ 
matism caused acute non-suppurative arthritis and sim¬ 
ple rheumatic endocarditis in rabbits. In culture after 
a few months the same strain of diplococci caused ma¬ 
lignant endocarditis in the inoculated animal. They 
could not recover the diplococcus from the nodular vege¬ 
tations in rheumatic endocarditis, but succeeded in ob¬ 
taining pure cultures of a smaller diplococcus from the 
large vegetations and contained thrombi of malignant 
endocarditis. They concluded that the diplococcus 
rheumaticus was capable of producing not only arthritis 
and rheumatic endocarditis but also malignant endo¬ 
carditis. Rationally we may interpret their observa¬ 
tions and results as a transmutation of the diplococcus 
rheumaticus in virulency and in specific pathogenicity. 
Our clinical observations and Rosenow’s experiments 
seem to show that the members of the streptococcus- 
pneumococcus group may acquire specific pathogenic 
elective affinity for certain tissues in the primary focus 
and also in the tissues. 

Clinical examples have been observed of acute ap¬ 
pendicitis; cholecystitis; acute gastric and duodenal 
ulcer; acute and subacute glomerulonephritis; rheumat¬ 
ic fever; erythema nodosum; herpes zoster; malignant 


endocarditis; simple endocarditis; myocarditis and other 
acute and chronic systemic diseases, associated with co¬ 
incident focal infection of the tonsils, accessory sinuses, 
dental alveoli, the skin and its appendages, the fallopian 
tubes, the prostate and seminal vesicles and other foci. 
Dominant pathogenic bacteria have been isolated from 
tissues and exudates of patients at surgical operation; 
by blood culture; from the urine; from joint exudates 
and pieces of tissue (muscular, lymphoid, joint capsules 
and fibrous nodes), removed with the consent and often 
at the request of patients. These cultures have been 
intravenously injected into laboratory animals and at 
the same time cultures of bacteria isolated from the 
primary foci of the patients have been likewise used 
to inoculate other animals. 

The evidences of the specific elective tissue affinity of 
the pathogenic streptococci from the various tissues and 
likewise of the primary foci is very marked. This is 
significantly expressed in the following table prepared 
by Rosenow (8) from an enormous number of animal 

The principles of localized infection in man and ani¬ 
mals are so important that the technic of the experi¬ 
ments and the interpretation of the table by Rosenow 
are quoted very fully here. 


The streptococci were usually grown from sixteen to twenty- 
four hours at 37° C. in tall columns of ascites (10 per cent.) 
dextrose (0.2 per cent.) broth (0.6 to 0.8 -f-) to which 
sterile tissue (guinea-pig kidney or heart muscle) was often 
added; the sterility of the ascites fluid and broth containing 






























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the tissue was always proved beforehand. After incubation 
smears were made, the cultures were centrifuged in the con¬ 
tainers in which they were cultivated, 1 the supernatant fluid 
was decanted and the sediment suspended in sodium chlorid 
solution so that 1 c.c. of the suspension contained the growth 
from 15 c.c. of broth. The doses for rabbits (ear vein) were 
usually from 0.5 to 3 c.c., and for dogs (leg vein) from 1 to 
5 c.c. of this suspension. The injections were made quite 
rapidly through a rather fine needle (22 gauge), usually within 
an hour after the suspension was made. Blood agar plate cul¬ 
tures were made at the time the suspensions were injected to 
study the character of the organisms, to test their viability and 
to save them for further study. This is an important precau¬ 
tion because negative results have at times proved to be due to 
early death of the recently isolated organisms in the broth 
cultures. In the accompanying table, “when isolated” indi¬ 
cates the first or second and, occasionally, the third or fourth 
cultures, or the first culture after one animal passage. “Later” 
indicates that the strains were cultivated for a week or longer. 
“After animal passage” indicates usually from the second to 
the sixth animal passage. 

The strains tested from appendicitis, ulcer of the stomach, 
cholecystitis, rheumatic fever, erythema nodosum, myositis and 
endocarditis include strains isolated from the characteristic 
lesions as well as from the apparent atrium of infection. Those 
from herpes zoster were from the tonsils and spinal fluid, and 
those from epidemic parotitis were obtained by catheterizing 
Steno’s duct and from the tonsils. The strains from miscel¬ 
laneous sources were usually from tonsils approaching the 
normal condition; and the laboratory strains were streptococci 
or pneumococci cultivated on artificial mediums for a long time 
and had lost all apparent virulence. The figures in the lowest 
line of the table represent the average percentage incidence 

1 The common 8-ounce nursing bottle is used both as a culture 
flask and centrifugal tube, and serves the purpose admirably. 



of lesions in individual organs following injection of various 
strains of streptococci except those from the specific disease. 
Thus the first figure indicates that 5 per cent, of the animals, 
injected with the various strains except those from appendi¬ 
citis, showed lesions in the appendix. 

Care was exercised to obtain growths from the depths of the 
supposed primary focus with as little contamination from the 
surface as possible, the cultures being made from the material 
expressed from the tonsils or from emulsion of extirpated 
tonsils after thorough washing in sodium chlorid solution. The 
material from the depths of pyorrheal pockets was obtained 
by means of a pipet. 

For the study of pathogenicity of the cultures, dogs and rab¬ 
bits were chiefly used, being killed with chloroform at the de¬ 
sired time, usually in from twenty-four to forty-eight hours. 
Post mortem examinations were always made as soon after 
death as possible. A thorough inspection in a bright light with 
the unaided eye or with the aid of a hand lens was made for 
focal lesions. The exact character of the lesions and the pres¬ 
ence of the streptococci in each of the various diseases have 
been determined by microscopic study of sections. Cloudy 
swelling is not included in the results given in the table. Hemor¬ 
rhage, localized necrosis, exudation and infiltration were the 
usual lesions. Thus, in case of the joints, hemorrhage about the 
joint or turbidity of fluid, as determined with a pipet, or both, 
were considered as evidence of arthritis. Hemorrhages in the 
pericardium and turbidity of pericardial fluid, due to leu¬ 
kocytes, were considered as evidence of pericarditis. The post 
mortem study of animals often symptomless is essential to ob¬ 
tain accurate knowledge of the pathogenicity of a culture, and 
must supplant the older method of merely finding out whether 
a culture produces death or not, a method still too much in 
vogue. The table includes data only from those animals in 
which the post mortem was comprehensive, and does not in¬ 
clude some of the earlier experiments, especially on endocardi- 


tis. Increase in mortality rate, earlier death and greater de¬ 
gree and distribution of lesions following standard dosage were 
considered as proof of high virulence. Changes in the spleen 
and liver were so rare following injection of the strains as 
isolated, except those from cholecystitis, that they are not 
included in the table. Acute splenitis and such changes in the 
liver as focal necrosis, parenchymatous and bile duct hemor¬ 
rhages and acute degeneration with marked acidity occurred, 
however, after the strains had acquired greater virulence from 
animal passage. In the earlier experiments not sufficient at¬ 
tention was paid to the occurrence of lesions in the thyroid, 
thymus, suprarenals and lymphatic glands. Later a closer 
search for lesions in these structures was made, especially after 
it was found that lesions in the thyroid followed intravenous 
injection of bacteria isolated from goiter. It must be said, too, 
that strains of streptococci from rheumatic fever, myositis and 
cholecystitis produce hemorrhages in the thyroid quite com¬ 
monly, while those from other sources rarely produce them. 


A study of the table shows that streptococci from the various 
diseases often have a most striking affinity or tropism for the 
organs or tissues from which they are isolated. Thus, fourteen 
strains from appendicitis produced lesions in the appendix in 
68 per cent, of the sixty-eight rabbits injected, which is in 
marked contrast to an average of only 5 per cent, (given in 
lowest line of table) of lesions in the appendix in the animals 
injected with the strains as isolated from sources other than 
appendicitis. Eighteen strains from ulcer of the stomach or 
duodenum produced hemorrhages in 60 per cent, and ulcer of 
the stomach or duodenum in 60 per cent., a combined total of 
74 per cent, of the 103 animals injected, in contrast to an aver¬ 
age of SO per cent, hemorrhages and 9 per cent, ulcer following 
injection of other strains. Twelve strains from cholecystitis 
produced lesions in the gall-bladder in 80 per cent, of the forty- 



one animals injected, in contrast to an average incidence of le¬ 
sions here of only 11 per cent, with the other strains. Twenty- 
four strains from rheumatic fever produced arthritis in 66 per 
cent., endocarditis in 46 per cent., pericarditis in 27 per cent., 
and myocarditis in 44 per cent, of the seventy-one animals in¬ 
jected, in contrast to an average of arthritis in 27 per cent., 
endocardial lesions in 14 per cent., pericarditis in 2 per cent, 
and myocarditis in 10 per cent, of the animals injected with 
strains from sources other than rheumatic fever. Six strains 
from erythema nodosum produced lesions of the skin in 90 per 
cent, of twenty animals injected, in contrast to an average of 
2 per cent, in the animals injected with the strains from sources 
other than erythema nodosum and herpes zoster. Eleven strains 
from herpes zoster produced herpetiform lesions of the skin, 
lips, tongue or conjunctivae in 77 per cent, of the sixty-one 
animals injected, in contrast to the average of only 1 per 
cent, of what seemed to be herpes of the skin with the other 
strains. Nine strains of streptococcal organisms from epidemic 
parotitis produced lesions in one or both parotid glands in 73 
per cent, of the nineteen animals injected intravenously, in con¬ 
trast to no instance of lesions here with the other strains. Three 
strains from cases of true myositis produced myositis in 75 per 
cent, and myocarditis (chiefly of the right ventricle) in 35 per 
cent, of the forty animals injected, in contrast to an average 
of myositis of 12 per cent, and myocarditis of 10 per cent, 
following injection of strains from sources other than myositis 
or rheumatic fever and eight strains of streptococcus viridans 
from chronic septic endocarditis produced lesions in the endo¬ 
cardium in 84 per cent, of the forty-four animals injected, in 
contrast to an average of 15 per cent, with the strains other 
than those from endocarditis. The results following injection 
of the miscellaneous strains (usually the first culture from ton¬ 
sils) and the laboratory strains serve as a basis of comparison 
with those following injection of the strains from the various 
diseases, and correspond roughly with the total average inci- 


dence of lesions in the various organs as given in the lowest line 
of the table. 

While the incidence of lesions in the organs following injec¬ 
tion of the strains isolated from such organs is high, as shown 
by these figures, the appearances at the necropsy are even more 
significant. In many instances in which the animals survive the 
injection for some time, no other focal lesions could be found 
except those in the organ in question; and when the animal 
died early, these lesions were the marked feature and the asso¬ 
ciated ones were relatively insignificant. Frequently the injec¬ 
tion of a very small dose was sufficient to prove the elective 
localization. This elective property was shown not only by 
the cultures from tissues and foci but also by the bacteria con¬ 
tained in the foci, directly injected in other animals. 

In many cases of both acute and chronic diseases the ap¬ 
parent atrium of infection was found to harbor streptococci 
having elective affinity; in the former usually only at the time 
of the attack, in the latter in some instances for months. The 
elective affinity, however, was less marked in the strains isolated 
from the supposed focus than in the strains isolated from the 
lesions in the various organs. The rather wide range of lesions, 
as indicated in the table, following the injection of the strains 
from herpes zoster and parotitis is due to the fact that often 
primary mixed cultures from tonsils and pyorrheal pockets 
were injected. 

Attempts to find a method which would preserve the original 
tropic property, while only partially successful, have shown 
that it may be preserved for some weeks in the deeper colonies 
of the original shake cultures and for as long as seven months by 
keeping the suspensions containing sterile tissue in the ice chest, 
thus maintaining the bacteria in a condition of latent life. 

The localization of the strains from appendicitis, ulcer of 
the stomach and cholecystitis as isolated, after cultivation and 
after animal passage, is of particular interest. It should be 
stated here, however, that these strains resemble one another 



very closely indeed in cultural and other respects. Those from 
appendicitis are the least virulent, those from ulcer occupy 
a middle position and those from cholecystitis are the most 
virulent. The virulence seems to be one of the factors that 
determine their place of survival after intravenous injection. 
Now if the localization is dependent to a certain extent on 
virulence, then the occurrence of ulcer and cholecystitis should 
become greater as the strains from the appendix are passed 
through animals, and appendicitis should occur oftener after 
the strains from ulcer and cholecystitis lose virulence from 
cultivation on artificial mediums. This is found actually to 
be the case (see figures in table). In this connection other 
facts should be mentioned. None of the strains from appen¬ 
dicitis produced pancreatitis. The strains from ulcer and 
cholecystitis as isolated (mostly those from acute cases) pro¬ 
duced pancreatitis in 3 per cent, and 5 per cent., respectively, 
of the animals injected. After animal passage, pancreatitis 
occurred in 15 and 19 per cent, respectively, while after culti¬ 
vation on artificial mediums pancreatitis in no case was ob¬ 

Lesions in the intestines, exclusive of the duodenum, were 
more common with the strains from cholecystitis and rheuma¬ 
tism than with those from appendicitis, and all the strains pro¬ 
duced intestinal lesions (chiefly of the mucous membrane and 
lymphoid structures) quite commonly after they had been 
passed through animals, whereas, after cultivation for a time, 
no noteworthy lesions were found in the intestinal tract. 

The streptococci studied from parotitis resemble the organ¬ 
ism described by Herb 1 and, like hers, produced the char¬ 
acteristic picture of mumps in dogs when injected into Steno’s 
duct. Intravenous injection of these organisms produced 
marked edema and hemorrhage in and surrounding the parotid. 
The affinity was so great that the streptococci were found in 

1 Herb, Isabella C.: Experimental Parotitis, Arch. Int, Med., 
September, 1909, p* 201, 


pure culture in the enlarged parotid in three of five full-time 
puppies removed from the uterus of a dog which was chloro¬ 
formed during a marked parotitis following injection into 
Steno’s duct. Antigens prepared from a number of these strains 
were found to bind specifically complement in serum from paro¬ 
titis (Howell). 

Lesions in the skeletal muscles occurred in 75 per cent, of 
the animals injected. The number of lesions in the muscles and 
myocardium in the animals injected with strains from myositis 
was often in proportion to the quantity injected, and occurred 
mostly in the tendinous portion and in the right ventricle. 

Lesions in the kidney were especially common after injec¬ 
tions of streptococci from rheumatic fever (39 per cent.) and 
from endocarditis (20 per cent.). These occurred chiefly in the 
medullary portion in the former and in the glomeruli in the 

Lesions in the lung, consisting usually of hemorrhages and 
edema, were rare following injection of the strains when iso¬ 
lated and after they were cultivated on artificial mediums but, 
just as was found previously, they occurred oftener after the 
virulence was increased by animal passage. 

That the streptococci are the underlying cause of the dis¬ 
eases from the lesions of which they were isolated is indicated 
further by the fact that they have elective affinity for the 
corresponding structures in animals. Moreover, the fact that 
the same streptococcus may be made to localize in different or¬ 
gans is in consonance with the knowledge that streptococci may 
cause diseases with different symptomatology. The possibility, 
however, that they are secondary invaders to some ultramicro- 
scopic, filterable organism has to be considered. Filtrates of 
the streptococcal cultures from various diseases were injected 
in the organs from which the strains were isolated; the lesions, 
however, were not due to living organisms because the broth 
which was inoculated and incubated with the tissues failed to 
produce any lesions. The results, while inconclusive, may be 



said to indicate that streptococci produce substances which 
cause injury specifically in the tissues from which the strains 
are isolated. 


Although the circulation is an important factor in determin¬ 
ing localization, the tissues themselves play an even more im¬ 
portant role. The question whether the lesions in the organ 
for which a particular strain appears to have elective affinity 
are due to the lodgment of a larger number of bacteria here 
than in the other organs, or whether the bacteria lodged in 
equal numbers in the various organs but survive only in the 
one showing lesions, is now under study. The evidence already 
obtained, however, points strongly to the former mechanism. 
It appears that the cells of the tissues for which a given strain 
shows elective affinity take the bacteria out of the circula¬ 
tion as if by a magnet—adsorption. 

This remarkable tropic condition tends to disappear quite 
promptly both on cultivating the streptococci on artificial me¬ 
diums and on passing them successively through animals, and 
this may occur without demonstrable changes in morphology, 
grouping or character of chain formation. I have previously 
shown that the ability of streptococcus viridans and staphylo¬ 
cocci to produce lesions in the endocardium is due partly to 
physical clumping. A careful study of smears of the suspensions 
injected in these experiments revealed no constant relation 
between localization and clumping or size of the bacteria. 

Individual variations in resistance to infection were found 
in the injected animals. The effects of these conditions in the 
host as determining factors in localization are important; they 
are probably expressions of differences in metabolism, oxidation 
rates, etc., which influence the soil for bacteria. The tendency 
of virulent bacteria, temporarily or permanently, to render this 
soil less favorable for their growth is well established. There 
is some evidence, on the other hand, which goes to show that 
certain bacteria of very low virulence (commonly found in 


chronic foci of infection) tend actually to make this soil more 
favorable. But it must be considered that differences in the 
host may afford the peculiar type of reaction, or that the 
individual harbors a particular form of focus of infection which 
is favorable for bacteria to acquire elective properties. The 
following- facts support the latter view: (1) the common occur¬ 
rence of certain non-contagious diseases, such as herpes 
zoster, ulcer of the stomach, etc., during definite age periods; 
(£) the fact that foci of infection afford opportunity for 
bacteria to grow under varying grades of oxygen pressure and 
in mixed culture, both of which have been shown to cause 
changes in virulence and other properties of bacteria, in¬ 
cluding the streptococcus group; (3) the occurrence of sys¬ 
temic infections such as rheumatic fever, appendicitis, ulcer of 
the stomach, etc., usually after the acute symptoms in follicu¬ 
lar tonsillitis (hemolytic streptococci) have subsided, and (4) 
the finding in the focus and involved tissues at the time of the 
systemic infection, streptococci having elective affinity for these 
structures in animals. 

Since different bacteria may acquire simultaneously affinity 
for the same tissue, diseases which resemble each other more or 
less closely, such as the different forms of arthritis, may be due 
to bacteria of different species each having elective affinity for 
the particular structures involved. 

The figures in the lowest line of the table represent the results 
of numerous experiments (833) with streptococci (£20) from 
a wide range of sources, and may therefore be regarded as an 
index of the liability of the various organs to infection. Thus, 
joint lesions occurred more often (£7 per cent.) than lesions in 
other organs, corresponding to the frequent occurrence of spon¬ 
taneous arthritis in man and animals. The occurrence of le¬ 
sions in the stomach (£0 per cent.), valves of the heart (14 per 
per cent.), myocardium (1£ per cent.) and skeletal muscles (1£ 
per cent.) correspond in a general way to the occurrence of 
infection in these organs in man. The very infrequent involve- 



ment of the skin, tongue and the parotid in the animals is in 
keeping with the rarity of embolic infections in these struc¬ 
tures. The character of the lesions and their occurrence simul¬ 
taneously in the joints, heart, muscles and kidneys, and the 
development of chorea (7 per cent, mostly in young rabbits) 
following injection of the streptococci from rheumatic fever, 
parallels quite closely the phenomena of rheumatic infection 
as observed in man. The strains from erythema nodosum re¬ 
semble those from rheumatic fever, producing a relatively high 
incidence of arthritis, pericarditis and myositis, a fact which 
supports the view held by clinical observers, that the causative 
agents of rheumatic fever and erythema nodosum must be 

The tendency to localize electively within a limited range, 
“monotropism,” is most highly developed in the relatively non- 
virulent strains isolated from chronic lesions. In the more 
virulent strains from acute lesions and after animal passage, this 
tendency is less highly developed, the lesions occurring over a 
wider range, “polytropism.” Since the bacteria which have 
grown in a given tissue acquire greater affinity for this tissue, 
the likelihood of these bacteria to involve other structures is rel¬ 
atively slight; hence the secondary focus, a cholecystitis, for 
example, would appear to be less important as a distributer of 
bacteria than the primary focus; if, however, the secondary 
focus happens to be in a joint, of which there are many, it may 
play an important role in causing extension to uninvolved joints 
and in preventing recovery. 

The great importance of the enormous and pains¬ 
taking experiments and the rational deductions made 
by Rosenow must be apparent to clinicians, bacteriolo¬ 
gists and pathologists. 

The practical application of the principles involved 
may serve to lessen the incidence of and the recru- 


descence of many local inflammatory organic diseases, 
notably appendicitis, nicer of the stomach and duo¬ 
denum, cholecystitis, glomerulonephritis, acute and 
chronic arthritis and other abnormal conditions, by the 
removal of the primary focal cause. 



We have considered the causes, character and diag¬ 
nosis of focal infection; the mode of systemic infec¬ 
tion from the focus; the important fact of transmuta¬ 
tion within the members of the streptococcus-pneumo¬ 
coccus group, with coincident variations of specific path¬ 
ogenicity and virulency and the acquirement of 
pathogenic elective tissue affinity by bacteria in culture 
media, in serial animal passage and in the foci of in¬ 

We may now understandingly consider some of the 
systemic infections which are etiologically related to 
focal infection. 


It is not necessary to consider the controversies which 
have taken place concerning the bacterial cause of rheu¬ 
matic fever. There is now no doubt that the diplococcus 
also called by other observers micrococcus rheumaticus 
and streptococcus rheumaticus, isolated from the blood 
and joint fluids, throat and endocardial nodes of patients 
suffering from rheumatic fever by Poynton and Paine 
(14) confirmed hv Beattie (15), Walker and Ryffiel 
(16) and finally and conclusively by Rosenow (8), is 

the true infectious cause of the disease. 




With a knowledge of the possibility of transmutation 
in form, cultural characteristics and coincident varia¬ 
tion in specific pathogenicity, virulency and tissue af¬ 
finity, we may now understand the conflicting results 
of animal inoculation with undifferentiated strains of 
streptococci as reported by many workers. It is a well 
known fact that virulent strains of streptococci, when 
injected intravenously into animals, may produce acute 
arthritis, usually with such violent tissue reaction that 
suppuration occurs. But the streptococcus rheumati- 
cus never produces suppuration. Doubt of its etiologic 
relation to acute rheumatism also arose from the fact 
that it was not usually found by cultural methods in 
the joint exudate and circulating blood of patients. 
But Rosenow (8) has found that with an improved 
technic it may be always found, at the proper stage 
of the disease, in the joint exudate, joint capsule, cir¬ 
culating blood, tonsil, alveolar abscess or other focus. 

Rosenow’s studies of cultures from the joint exudate 
of patients with acute rheumatism yielded three strains. 
From five patients without muscular involvement, on 
blood agar the colonies were green and grew in long 
chains, longer than streptococcus viridans. Injected 
intravenously into animals they developed acute non¬ 
destructive arthritis, myositis, marked myocarditis with 
endocarditis and occasionally pericarditis. From six 
patients with acute rheumatic fever involving the joints 
and muscles the isolated microorganisms produced slight 
hazy hemolysis on blood agar, and grew as diplococci in 
the short chains. Injected intravenously the inoculated 
animals developed non-destructive, acute arthritis, 



myositis, severe myocarditis, endocarditis and occasion¬ 
ally pericarditis. From three patients with acute rheu¬ 
matism the joint exudate yielded small gray colonies 
on blood agar. They grew in clumps of small micro¬ 
cocci and diplococci and occasionally in short chains. 
Animals injected intravenously developed a character¬ 
istic arthritis with endocarditis and pericarditis, but no 
myositis or myocarditis. 

The three types of cocci found by Rosenow explains 
the variations in name given by Poynton, Paine, Walker 
and Beattie, i. e.: diplococcus, streptococcus and micro¬ 
coccus rheumaticus. 

The virulence of all the strains is low. All are very 
sensitive to oxygen pressure in culture and all multiply 
at low temperature. The three strains are transmut- 
able. All produce excessive acidity in dextrose broth. 
Walker and Ryffel (16) found formic acid in the cul¬ 
tures of the strains with which they worked. 

Exposure of the inoculated animal to low tempera¬ 
ture intensifies the disease, presumably by lowering 
phagocytosis and by vasocontraction. Rosenow also 
noted in some injected animals the development of iritis 
by hematogenous infection. Some inoculated animals 
also developed appendicitis, colitis, mesenteric lympha¬ 
denitis and diarrhea. Poynton and Paine (14) also 
have noted the occurrence of obscure infection of intes¬ 
tines and appendix of animals intravenously inoculated 
with the diplococcus rheumaticus. The intestinal lesions 
produced in animals and the fact that the stool of a pa¬ 
tient with rheumatic fever may yield cultures of strepto¬ 
coccus rheumaticus indicate that the intestinal tract and 



mesenteric lymph nodes may be a secondary and pos¬ 
sibly a primary focus of rheumatic fever. 

Rosenow has shown that cultures kept for one to 
eight months lose the power to grow at a low tempera¬ 
ture, the sensitiveness to oxygen tension, the production 
of excessive acid in dextrose broth and at the same time 
lose the specific pathogenic affinity for joint, muscle, 
myocardium, endocardium and pericardium. By serial 
animal passage the streptococcus rheumaticus and espe¬ 
cially the diplococcus type, may assume an affinity for 
the appendix, stomach and gall-bladder. 

The clinical and bacteriological research of Poynton 
and Paine, the use of blood agar media by Schottmiiller 
to differentiate members of the streptococcus group 
which are pathogenic for man, and the confirmatory 
work of Rosenow have proven conclusively the charac¬ 
ter of the infectious microorganism which causes rheu¬ 
matic fever with arthritis, myositis, endocarditis, myo¬ 
carditis, pericarditis and pleuritis. 

Rheumatic fever occurs most frequently in the tem¬ 
perate zone, among people who live under conditions 
which are unhealthful and which especially induce focal 
infection. It is most prevalent in the young and in 
the more exposed male of all ages. The excess of 
lymphoid tissue in the pharynx and nose of the young 
explains the frequency of the incidence of the focal 
infection and the subsequent rheumatism. The fre¬ 
quent association of the onset of rheumatic fever with 
lowering of the body temperature by exposure to cold 
and a wetting is explained by the increased specific 
virulency of the bacterial cause acquired by a low tern- 



perature and the coincident lessened resistance of the 
patient due to the exposure. The frequent absence of 
evidence of acute focal infection at the onset of the 
systemic disease is not an evidence that no focus exists. 
The latent chronic streptococcus infection of tonsillitis, 
pyorrhea alveolaris, sinusitis, etc., may suddenly acquire 
increased virulence and specific pathogenic affinity with 
varying degrees of focal tissue reaction. This transmu¬ 
tation of type and pathogenicity certainly occurs in the 
focus of infection. The removal of the tonsils and other 
sites of focal infection has been followed by complete 
recovery of prolonged, subacute and chronic types 
of arthritis and has unquestionably prevented recurrent 
attacks of rheumatic fever to which the susceptibility 
is increased by one or more attacks. The occurrence of 
rheumatic fever after the removal of an apparent focus 
may be due to secondary systemic latent foci in lymph 
nodes proximal to joints, in the neck or elsewhere. The 
streptococci of these secondary foci may take on new 
virulence and specific pathogenicity, from the same 
causes which induced like changes in the pathogenic 
bacteria of the primary focus. 




We have noted the fact that certain strains of the 
streptococcus rheumaticus have a greater affinity for 
the endocardium than others. Endocarditis of the rheu¬ 
matic type may be the only recognizable clinical entity, 
especially in children, and may be so mild that it escapes 



notice. Later a valvular scar defect may be manifest. 
In rheumatic fever endocarditis occurs most frequently 
in children. After twenty years it occurs less frequently 

Fig. 8.—Surendothelial, Nodular, Valvular and Mural Endocarditis 
of Dog Following Injection of “Streptococcus Rheumaticus.” 

during the first attack. The incidence of endocarditis 
increases with the number of attacks, and always in 
larger percentage in children. 

As stated the virulence of the streptococcus rheu- 



maticus is low, compared with other pathogenic strains 
of streptococci. Although this relatively low virulence 
may vary in degree and may become high, the morbid 
changes in joints and muscles consist at most of hyper¬ 
emia and edematous swelling of the infected tis¬ 
sues. The changes in the endocardium are also char¬ 
acteristic of the usually mild virulence of the infectious 
bacteria as evinced by the mild tissue reaction in the 
form of small warty nodes of the endocardium and 
valve segments. Rarely is the endocarditis so severe 
as to be called ulcerative or malignant. When that con¬ 
dition occurs a change in type or in specific patho¬ 
genicity of the invading streptococci has probably oc¬ 
curred. Although rheumatic valvulitis is usually mild 
and is of itself rarely dangerous, the secondary sclerotic 
changes and retraction of the segments is an irremedi¬ 
able and harmful sequel. 


Myocarditis is undoubtedly a common incident in 
rheumatic fever only recognized clinically when marked 
cardiac incompetency occurs with or without dilatation. 
Mild myocarditis alone due to infection with strepto¬ 
cocci which have a pathogenic affinity for muscular tis¬ 
sue undoubtedly occurs from chronic infectious foci. 
The mild reaction excited by the streptococci of low 
virulency in the walls of the heart is naturally in the 
form of proliferative interstitial tissue changes. 




Pericarditis may occur alone, in association with en¬ 
docarditis, and may be involved in pancarditis in the 
course of rheumatic fever. It may occur as a simple 
fibrinous or serofibrinous type. Occasionally purulent 
pericarditis may occur with rheumatic fever in chil¬ 
dren. Pus in the pericardium or in a joint would indi¬ 
cate a coincident infection with pyogenic bacteria or a 
change in pathogenicity of the infectious agent, 
for the streptococcus rheumaticus does not cause 
suppuration. In rheumatic fibrinous and serofibrinous 
pericarditis, the prognosis is good for recovery, but 
adhesions of the pericardial layers is a common sequel 
which later may cause nutritional disturbance of the 
heart muscle. 


Acute chorea is an infectious disease. Its casual re¬ 
lation with rheumatic fever and the frequency of endo¬ 
carditis of the simple rheumatic type in chorea indicate 
the infectious character and a common bacterial cause. 
The incidence of the disease is much the same as rheu¬ 
matism. The first attack occurs most frequently in 
children between the ages of five and fifteen years. 
Seasonal incidence is the same as rheumatism. An at¬ 
tack of chorea may precede, occur with or follow an at¬ 
tack of rheumatic fever. Recurrent attacks usually 
occur. Pericarditis may occur. Recovery is the rule. 
The nervous phenomena, ataxic movements, muscular 
weakness, mental disturbances, mutism, etc., may occur 
by hematogenous infection, with a type of the strepto- 



coccus rheumaticus which has a specific elective affinity 
for the brain. Multiple cerebral bacterial embolism due 
to a type of streptococcus of low virulence would cause 
little anatomical disturbance, but could be provocative 
of all the motor and sensory phenomena of the disease. 
Indeed, gross embolism of the smaller cerebral vessels 
has been found and has been the source of the etiologic 
embolic theory. Simple verrucose endocarditis resem¬ 
bling simple rheumatic endocarditis is the most common 
morbid anatomical change in chorea. The cerebral 
embolism theory is related to the associated endocar¬ 
ditis, with alleged detachment of small emboli composed 
of fibrin, blood cells, etc. During life one may not study 
the tissues of the brain as in other hematogenous in¬ 
fections of muscles, joints, lymph glands, etc. The 
discovery of bacterial emboli in other infected tissues 
of rheumatic fever, and the recognition of very slight re¬ 
sulting tissue reaction, is presumptive evidence that bac¬ 
terial cerebral embolism may be the cause of chorea. 
Rothstein and others have isolated strains of strepto¬ 
cocci post mortem from the meninges of choreic individ¬ 
uals. Animal experimentation with specific strains 
of the streptococcus isolated in rheumatic fever asso¬ 
ciated with chorea has been followed by joint infection 
and characteristic symptoms of chorea in the inoculated 


Gonococcemia may result from a local infection 
of the prostate, seminal vesicles, joints and tendon 
sheaths, from infected thrombi of the veins contigu- 



ous to local gonococcus infection and also from in¬ 
fected thrombi of the venous sinuses of the uterus in 
the puerperium. Gonococcemia is a very serious con¬ 
dition, usually fatal when the cause of malignant endo¬ 
carditis and childbed fever. Like other bacteria the 
gonococcus varies in degrees of virulence, and if mild 
the patient may recover from a gonococcemia even 
though the condition is associated with endocarditis, 
puerperal fever or suppurative arthritis. Thayer (57) 
has reported the recovery of two cases of gonococcus 
endocarditis. I have seen two patients recover who had 
suppurating multiple arthritis with gonococcemia. All 
of the suppurating joints were opened and drained, 
which doubtless aided recovery. The removal of the 
focal cause in all systemic gonorrheal infection may 
aid in overcoming the general disease. 

Gonococcus Arthritis 

Arthritis is the most frequent systemic expression 
of gonococcus focal infection. When monarticular the 
knee joint is most frequently involved. Males suffer 
in the proportion of twelve to one or two of females. 
It usually occurs during an acute gonorrhea, but may 
occur after the subsidence of an acute attack or from 
a long existing focal infection of the genito-urinary 
organs. For some reason the latent bacteria may take 
on new virulence and cause the late systemic manifesta¬ 
tion. In women the focal lesion may be difficult to 

Anatomically it occurs as a synovitis, and peri¬ 
arthritis, with bursitis and tenovaginitis. The synovial 



joint effusion is usually serofibrinous and occasionally 
purulent. Purulent bursitis and tenovaginitis are more 
frequent. Periarthritis of the wrist with suppuration 
extending along the sheaths of tendons of the hands 
may occur. Periostitis of the os calcis with resulting 
exostosis and marked tenderness of the heel is a re¬ 
markable condition due to the gonococcus. 

The gonococcus is present in the infected tissues and 
in the exudate of the joints, bursae and tendon sheaths 
from which with proper technic it may be recovered in 
pure culture. In chronic conditions the infection may 
be mixed with streptococci and staphylococci. 

It is a most damaging and seriously disabling disease. 

When the exudate is purulent, early operative relief 
may save the joint and tendon sheaths and preserve 
function. In non-purulent conditions the tendency is 
to a long obstinate course with resulting damage to the 
blood vessels of the infected tissues. This results in 
local malnutrition with the attendant metabolic changes, 
in the joint and tendons with resulting deformity and 
loss of function. 

Gonococcus arthritis is often mistaken for rheuma¬ 
tism. Unlike rheumatism it more frequently attacks 
tendon sheaths and the exudate is sometimes purulent. 
It may involve the intervertebral, temporomaxillary, 
sternoclavicular and sacro-iliac joints while rheumatism 
rarely does so. Both may be polyarticular. Gonorrheal 
arthritis is often very painful in undue proportion to 
the apparent local infection. As a rule the fever is not 
high. The ordinary antirheumatic drugs do not alter 
the clinical course. In many instances the removal of 



the infectious focus is followed by quick relief of the 
systemic disease. 


Malignant or ulcerative endocarditis, so called because 
of the tendency to local tissue destruction and the high 
mortality which it causes, may be acute or chronic. It 
is always a secondary disease. It may be a local com¬ 
plication of a systemic disease like pneumonia, typhoid 
fever, epidemic cerebrospinal meningitis and rarely of 
rheumatic fever, or it may arise from a focal infection 
anywhere in the body due to the gonococcus, strepto¬ 
coccus, staphylococcus and less frequently to other in¬ 
fectious bacteria. There is always an associated bac- 
teriemia. The bacteria which are most frequently found 
in the infected heart tissues, vegetations and contained 
thrombi, in the blood stream by cultures, are strepto¬ 
cocci, pneumococci, gonococci and staphylococci. 
Streptococci are the most frequent cause and reach the 
blood stream and heart from septic wounds, the septic 
puerperal uterus, and other streptococcus foci about 
the head and elsewhere. While the streptococcus py¬ 
ogenes is the strain which causes most of the acute types 
arising from acute infectious foci, the streptococcus vi- 
ridans may also cause the acute type, but usually is the 
cause of chronic malignant endocarditis. 

Bacteriemia associated with the general diseases 
named or due to a focal infection may not involve the 
heart. The normal endocardium is apparently resistant 
while old sclerotic processes of the valves and congenital 
deformities of the heart and proximal vessels predis- 



pose to malignant endocarditis. Hence malignant endo¬ 
carditis most often occurs in individuals suffering from 
chronic valvular disease and chronic cardiomyopathy. 

Fig. 9. — Vegetative and Ulcerative Endocarditis of Aortic Valves 
and Aorta of Dog Following Injection of Streptococcus Viridans 
from Chronic Vegetative Endocarditis of Man. 

The morbid anatomy is essentially the same in all bac¬ 
terial types of the acute form. Usually vegetations are 
present, often massive, especially when due to the pneu- 



mococcus, and streptococcus viridans. Occasionally the 
vegetations are not large while necrotic destructive 
lesions are dominant in very virulent infections and es¬ 
pecially when staphylococci are the cause. From the cir- 

Fig. 10. —Section Through Vegetations on Mitral Valve Shown in 
Fig. 9. Note the dark areas consisting of clumps of streptococci. 

culating blood thrombus formation occurs in the vege¬ 
tations. Necrosis of endocardium, superficial and deep, 
with perforation of valves and other destructive lesions, 
may occur. The infectious bacteria are present in great 
number in the vegetations, thrombi and involved tis¬ 




When malignant endocarditis occurs as a local com¬ 
plication of a general disease like pneumonia, rheu¬ 
matic fever, cerebrospinal fever, or some other acute 
disease, it may not be recognized because the severe 
symptoms of the systemic disease may overshadow and 
mask the manifestations of the local condition. As a 
rule the other symptoms of the general disease are in¬ 
tensified with evidence of failing heart, leading to a 
rapid fatal issue. Frequently the severe endocarditis 
is first recognized at autopsy. 

There are, however, special and characteristic symp¬ 
toms which may lead to the recognition of the condition 
of the heart and especially if a bacteriemia is found by 
blood culture. Detached small particles of the vegeta¬ 
tions and of thrombi carried in the blood stream may 
cause embolism in the various tissues and organs. Em¬ 
bolism may give rise to delirium, coma, paralysis, peri¬ 
splenitis, with enlargement and tenderness of the spleen, 
varying degrees of hematuria, gangrene of distal tissues 
and petechiae, and at any point local abscesses may de¬ 
velop from the infected emboli. Mycotic aneurism may 
result. Embolism of lung followed by abscess may 
occur if the right heart is involved. Usually the local 
cardiac disease is manifested by endocardial murmurs, 
but may be absent. The septic type is marked by chills 
and an intermittent or remittent type of fever and severe 
sweats. A typhoid type is characterized by a more con¬ 
tinued type of fever, delirium, coma and rapid course. 
In rare instances the clinical picture is that of cerebro¬ 
spinal meningitis. The diagnosis may be difficult, but 
is greatly aided by blood culture. 



Malignant endocarditis usually terminates fatally, but 
recovery has been noted by Herrick (21) and others 
In coroner’s autopsy cases E. R. LeCount has recog¬ 
nized six or more instances of healed scars of ulcerative 


The types of acute infectious nephritis which usually 
rises from a focal infection is embolic because the mode 

Fig. 11.—A Glomerulus Containing a Hyaline Thrombus. From a 
rabbit dying 7 days after inoculation. X 275 (after LeCount and 
Jackson, Jour. Inf. Dis.). 

of infection is hematogenous. It is, therefore, primarily 
a glomerulonephritis. If the dose of infectious bacteria 



reaching the kidney is large enough, the nephritis may 
be diffuse. Usually the condition is expressed clinically 
by bloody urine of varying degree, microscopic blood 
is present with albuminuria and casts of various 

Fig. 12.— Masses of Fibrin in a Glomerulus. From rabbit dying 7 days 
after injection. X 200 (after LeCount and Jackson, Jour. Inf. Dis.). 

types. The urine is lessened in quantity in twenty- 
four hours, soon a secondary anemia develops and 
often within a short period a soft edema. Varying de¬ 
grees of this type of nephritis occur from focal infec¬ 
tion. The most usual site of the focal infection which 
causes the nephritis is the throat. In the milder types 



of this form of nephritis apparent complete resolution 
occurs after the removal of the focus of infection. Bill¬ 
ings (9) has reported clinical observations on the rela¬ 
tion of focal infection to glomerulonephritis and the 

Fig. 13.—A Glomerulus in Which Are Masses of Cocci Filling a Group 
of Capillaries. From a rabbit dying 9 days after inoculation. X 325 
(after LeCount and Jackson, Jour. Inf. Dis.). 

apparent resolution of the infection of the kidneys by 
eradication of the focus. LeCount and Jackson (35) 
have shown the renal changes in rabbits inoculated with 
streptococci. Of these animals six were inoculated with 
strains of streptococci isolated from patients with epi¬ 
demic septic angina. The kidney lesions were primarily 



of the vascular structures, glomeruli, intertubular ves¬ 
sels and arcuate and interlobar veins. They noted a 
pronounced perivascular exudate consisting chiefly of 
lymphocytes and plasma cells. The tendency to repair 
in the acute glomerular lesion, noted by LeCount and 
Jackson, is very important when compared with the 
tendency to recovery of clinical glomerulonephritis of 
man, when the chief etiologic factor is removed. 


Acute appendicitis due to focal infection located in 
the throat and nose and sometimes in the jaws has been 
noted by a great number of clinical observers, notably 
among the French. Kretz (25) has shown the frequent 
infection of the cervical lymph nodes with streptococci. 
When the cause of the lymphogenous infection is acute 
Kretz believes that the bacteria filtrate rapidly through 
the lymph nodes, with resulting severe bacteriemia. In 
less severe types of focal infection of the head and in 
adults especially, the virulence and degree of bac¬ 
teriemia is usually less. In these conditions, local or 
general systemic infection may follow in the form of 
acute multiple arthritis (rheumatism), endocarditis, 
pericarditis, osteomyelitis, nephritis, appendicitis, 
cholecystitis and even streptococcus malignant endo¬ 
carditis. He also believes that acute appendicitis and 
cholecystitis are hematogenous in origin and never pri¬ 
marily caused by infection within the lumen of the ap¬ 
pendix and gall-bladder. Cannon (26) argues that 
appendicitis and cholecystitis are hematogenous infec¬ 
tions, and may be of focal origin. He believes that 



typhoid cholecystitis occurs through the blood stream. 

After animal experimentation and a study of the 
tissues and bacteria of appendicitis, Ghon and Namba 

Fig 14.—Marked Hemorrhage of the Appendix 24 Hours After Injec¬ 
tion of Streptococci from Tonsils in a Case of Human Appendicitis. 

(27) conclude that if appendicitis occurs hematogenous- 
ly it must be due to a specific strain of streptococci. 

Adrian (28) has observed appendicitis as a focal in¬ 
fection of general disease. He apparently considers 
the bacteriemia of a focal infection a general disease. 



Hence he cites clinical observation of angina, with ap¬ 
pendicitis. He very fully reviews the literature quoting 
the opinion of many German, French and a few Amer- 

Fig. 15.—Hemorrhage and Localized Infection of Mucous Membrane 
of Duodenum and Tip of Appendix 48 Hours After Injection of 
Streptococcus from Human Appendicitis After Three Animal 

ican clinicians upon the relation of angina to appendi¬ 
citis and rheumatism. The histologic lymphoid struc¬ 
ture of the tonsils and appendix is compared and the 
similarity of tissue is given as a reason for the etiological 


relation of the angina to appendicitis. The term 
“anginal appendicitis” has been coined to express this 

The confirmatory investigations of Rosenow (8) have 
shown the occurrence of acute appendicitis from strains 

Fig. 16.—Human Appendicitis 12 Hours After Onset in Young Man. 
Note the necrosis and infiltration of lymph follicles. 

of streptococci, colon bacilli and other organisms which 
have attained elective affinity for the tissues of the 
appendix. This elective tissue affinity has been acquired 
by these microorganisms in the tissues of the appendix 
during an attack, for when they are isolated from the 



infected tissues of the appendix and nascent cultures 
are injected intravenously into animals, acute appendi¬ 
citis occurs in the great majority of the inoculated 
animals. The same affinity for tissues of the appendix 
can be induced to appear in strains through variations 
in culture methods and serial animal inoculation. 

Fig. 17. —Diplococci in Peritoneal Coat of Appendix Shown in Fig. 16. 

The invading organisms reaching the tissues of the 
appendix hematogenously cause small hemorrhages in 
the walls of the organ and if this invasion is great 
enough the reaction of the tissues to the invading 
organisms causes a positive chemotaxis with invasion 
of leukocytes and plasma cells and consequent tumefac¬ 
tion of the tissues and obstruction of the canal of the 
appendix. With obstruction there occurs a condition 
which invites the rapid increase in the numerous sapro¬ 
phytic anaerobes and other bacteria usually present in 



the bowel and appendix with resulting increase of mor¬ 
bid tissue change, varying in degree from edema to 
necrosis and gangrene. Until these investigations of 
Rosenow, the presence of colon bacteria and of various 

Fig. 18.—Hemorrhage Necrosis and Leukocytic Infiltration 20 Hours 
After Injection of Streptococcus from Appendix in Human Ap¬ 
pendicitis After One Animal Passage. 

other saprophytic organisms in the tissues of the normal 
as well as the infected appendix, has led to the belief 
that acute appendicitis has been excited by an infection 
within the bowel by the various saprophytic organisms 
usually found there. This secondary invasion of anae- 



Fig. 19. —Streptococci in Lymph Follicle Shown in Fig. 18 of Appen¬ 
dix 20 Hours After Injection of Streptococci. 

robes and other bacteria often found in the tis¬ 
sues closely related to the intestinal tract have been de¬ 
scribed as the primary causes of appendicitis by Heyde 
(29), Aschoff (30) and others. The argument from 

Fig. 20 . —Streptococci and Fusiform Bacilli in Human Gangrenous 
Appendicitis Following Vincent’s Angina. 

Fig. 21.—Hemorrhage, Necrosis and Leukocytic Infiltration of Appen¬ 
dix 24 Hours After Injection of Mixed Culture of Fusiform Ba¬ 
cilli and Streptococci from FIuman Appendix Shown in Fig. 20 . 

Fig. 22 . — Streptococci and Fusiform Bacilli of Appendix of Rabbit 
Shown in Fig. 21 24 Hours After Intravenous Injection. 




this point of view is that these facultative bacteria in¬ 
vade the tissues from the lumen of the bowel, when the 
resistance of the body tissues is low, and especially when 
the lumen of the appendix is partly or wholly closed 
by fecal concretions, kinks of the organ or from other 
causes. The more reasonable relation of these bacteria 

Fig. 23. —Photomicrograph of 24 Hour Culture ix Ascites-Dextrose- 
Broth of a Streptococcus Isolated from a Gall-bladder ix Human 
Cholecystitis. The morphology, size and grouping are quite typical 
of strains from cholecystitis. Gram stain. 

to the disease is that of a mixed infection, secondary to 
the primary hematogenous invasion usually by strepto¬ 

How much the lessened resistance of the tissues 
of the appendix due to the presence of fecal stones and 
other foreign bodies or to kinking of the organ may 
have to do in attracting the streptococci in the blood 
stream to the appendix, needs further investigation. 





Cholecystitis is unquestionably due at times to hema¬ 
togenous infection with strains of streptococci and pos- 

Fig. 24. —Hemorrhagic Cholecystitis in Dog 48 Hours After Intrave¬ 
nous Injection of Streptococcus Shown in Fig. 23, from the 
Thickened and Infiltrated Wall of Human Gall-bladder Soon 
After Isolation. 

sibly to other microorganisms. A patient in the Pres¬ 
byterian Hospital who suffered from an attack of acute 
cholecystitis was operated and it was noted that in the 



fundus of the gall-bladder there was a small softened 
area which was excised. The gall-bladder also contained 
some small soft concretions of bile. From the softened 

Fig. 25 . —Marked Edema or Gall-bladder in Dog 24 Hours After In¬ 
travenous Injection of a Streptococcus from Duodenal Ulcer After 
One Animal Passage. 

tissues of the gall-bladder Rosenow isolated a strain 
of streptococci which injected into animals produced 
cholecystitis. This patient suffered from tonsillitis and 
a short period before the onset of the attack of cholecys- 



titis had suffered from an acute tonsillitis. Strains of 
the streptococci isolated from the tonsil had a like af¬ 
finity for the gall-bladder in intravenously inoculated 

Rosenow has shown also that strains of the strepto¬ 
cocci attain an affinity for the gall-bladder similar to 

Fig. 26. —Streptococci in Lymph Space of Edematous Wall of Gall¬ 
bladder Shown in Fig. 25. Gram-Weigert stain. 

that attained for other tissues, and that this affinity may 
be lost and regained by varying methods of culture and 
by serial animal passage. 

There can be no question that cholecystitis may occur 
through hematogenous infection by typhoid bacilli and 
probably by other pathogenic microorganisms, but the 
more frequent presence of streptococci than the other 
pathogenic bacteria in the center of gall-stones removed 
from patients, as shown by Rosenow, is suggestive of 



the more frequent occurrence of streptococcus cholecys¬ 


Acute peptic, gastric and duodenal ulcer may be pro¬ 
duced experimentally in animals by the intravenous 

Fig. 27. —Photomicrograph of 24 Hour Ascites-Dextrose-Broth Culture 
of Streptococcus from Human Ulcer at the Time the Strain 
Proved to Have the Affinity for the Stomach When Intrave¬ 
nously Injected Into Animals. Grain stain. 

injection of strains of streptococci which have an elec¬ 
tive affinity for the stomach wall and Rosenow has 
isolated this strain from the base of the ulcer and tissue 
of the stomach wall of man. The strain, so isolated, 
proved to have an elective affinity for the stomach wall 
in animals intravenously inoculated. The mode of pro- 

Fig. 28. —Marked Ulceration of Stomach in Guinea Pig 24 Hours After 
Intravenous Injection of Streptococcus from Suppurating Frontal 
Sinus of Man with Stomach Ulcer. 

Fig. 29. —Photomicrograph 24 Hour Ascites-Dextrose-Broth Culture 
of a Streptococcus from Blind Abscess of Jaw in Man Suffering 
with Chronic Ulcer of Stomach. This strain proved to have an 
affinity for the stomach when intravenously injected into animals. 
Gram stain. 


Fig. 30. — Ulcer of Stomach of Dog 5 Days After Intravenous Injection 
of Streptococcus from Human Ulcer. 

Fig. 31. — Capillary Filled with Diplococci in the Apex of the Ulcer 
Shown in Fig. 30. 


Fig. 32.—Section of Wall of Stomach of Rabbit Showing AVedgE' 
Shaped Area of Infiltration, Hemorrhage and Beginning Ulcera¬ 
tion 48 Hours After Intravenous Injection of Streptococci from 
Tonsil of Patient with Herpes Zoster After One Animal Passage. 




duction of the ulcer as noted animals is a strepto¬ 
coccus embolic infection of the submucosa of the stom¬ 
ach with resulting small hemorrhages into the surround¬ 
ing tissues. In consequence of the hemorrhage and the 

Fig. 33 . —Streptococci at Apex of Wedge-Shaped Area Shown in Fig. 32 . 

presence of the infectious microorganisms in the sur¬ 
rounding tissues, anemic necrosis so weakens the over- 
lying mucous membrane that it becomes digested by the 
gastric juice. If the necrosis involves a vessel of suffi¬ 
cient size, visible stomach hemorrhage may occur. If 
the infection and injury is not great, healing takes place. 
If the infection is more virulent, chronic ulcer results. 




Acute pancreatitis of serious degree always requires 
surgical interference. When it is of mild degree sur- 

Fig. 34.—Hemorrhagic Pancreatitis in Dog 24 Hours After Injection 
of Streptococcus from Steno’s Duct in a Case of Epidemic Parotitis. 

gical interference is not usually required, but if it be¬ 
comes a chronic condition degenerative changes may 

Fig. 35.—Section of Pancreas in Dog Showing an Irregular Staining 
of Parenchymatous Cells and Thrombosis of Blood Vessels Two 
Weeks After Intravenous Injection of Streptococci from Rheu¬ 




lead to involvement of the islands of Langerhans with 
disturbed function and diabetes mellitus may result. 

There is a relation more or less close between the 
strains of streptococci which have an elective tissue af- 

Fig. 36.—Photomicrograph Showing Diplococci in Area of Round Cell 
Infiltration Near a Partially Thrombosed Blood Vessel of Fig. 35. 

finity for the appendix, gall-bladder, stomach wall and 
pancreas and this has been beautifully and graphically 
shown in the table, which was presented in Lecture II. 


Erythema nodosum has been recognized as a condi¬ 
tion which may occur with acute or subacute rheuma¬ 
tism or as a part of the syndrome described by Osier 
(17). The syndrome consists usually of polymorphic 
skin lesions, hyperemia, edema, hemorrhage, quite fre¬ 
quently associated with arthritis. At times there may 

Fig. 37. —Subcutaneous Tissues from Erythema Nodosum in Man. Sec¬ 
tions showing a leukocytic and round cell infiltration along tissue 
strands between the layers of fat. 


Fig. 38.—Subcutaneous Tissue from Erythema Nodosum in Man. Sec¬ 
tion showing red blood corpuscles, blood pigment, nuclei of disinte¬ 
grated leukocytes and diplococci and diphtheroid bacilli. 

Fig. 39.—Smear from Single Colony in Ascites-Dextrose-Agar 72 Hours 
After Inoculation with the Emulsion of the Subcutaneous Node 
Showing Diphtheroid Bacilli in Fig. 38. 




be visceral crises, especially gastrointestinal, endocar¬ 
ditis, pericarditis, hematuria, nephritis, nodose erythema 
and peliosis rheumatica. The present knowledge of 
the infectious nature of rheumatism, of endocarditis, 
pericarditis and nephritis, point to a probable focal in¬ 
fection as the cause of the syndrome, which has been 

Fig. 40.—Smear from Blood of Guinea Pig Injected with Culture 
Shown in Fig. 39 After One Animal Passage. Note the typical 
diplococei in chains. 

discussed by clinicians in the past, as infectious, toxic 
or metabolic. 

The discovery of bacteria belonging apparently 
to the members of the streptococcus-pneumococcus 
group in fresh tissues isolated from the nodes removed 
surgically from patients and the production of erythema 
nodosum in the skin of animals intravenously injected 
with the cultures so obtained, has been demonstrated 
many times by Ilosenow. 

The removal of the apparent focus of infection in 

Fig. 41.—Photograph Showing Circumscribed Hemorrhages of the Skin 
and Symmetrical Hemorrhages of the Fascia of the Inner Aspect 
of the Legs of a Rabbit 48 Hours After an Intravenous Injection 
of Culture of Diphtheroid Bacteria Shown in Fig. 39, Obtained 
from an Erythematous Node in Man. 


Fig. 42. —Section of Skin of Rabbit Showing Hemorrhage and Leu¬ 
kocytic and Round Cell Infiltration of Subcutaneous Tissue 72 
Hours After Intravenous Injection of the Diphtheroid Bacilli, 
Shown in Fig. 39. Note the complete absence of involvement of the 
cutis and only slight infiltration of the corium. 


Fig. 43. —A Diplococcus in the Area of Infiltration Shown in Fig. 42. 

Fig. 44. —Section of the Artery from the Area of Subcutaneous Hem¬ 
orrhage Shown in Fig. 42. Note the mural aggregation of leukocytes. 


Fig. 45/—Diplobacilli in the Wall of Artery Shown in Fig. 44. 

Fig. 46. —Photomicrograph of 24 Hour Culture in Ascites-Dextrose- 
Broth of a Streptococcus Isolated from the Spinal Fluid of a Rab¬ 
bit Which Showed Herpes After tile Intravenous Injection of 
Streptococcus Culture from the Tonsil of a Man Who Suffered 
with Herpes Zoster. The morphology is quite characteristic of the 
strains from herpes zoster. 


Fig. 47. —Herpes as Seen on Under Surface of the Skin Over the Lower 
Right Thoracic Region of a Rabbit 24 Hours After an Intrave¬ 
nous Injection of Streptococcus Shown in Fig. 46. 




patients at the Presbyterian Hospital, suffering 
from erythema nodosum, has been followed with relief 
over periods of sufficient length of time to clinically 
prove the etiologic relations of the focus of infection 
to the systemic condition. 


It has long been known that herpetic eruptions may 
be induced in animals and that like lesions occur in man 

Fig. 48.—Diplococci in the Hemorrhagic Spinal Ganglion Correspond¬ 
ing with tpie Area of Herpes Shown in Fig. 47. Gram-Weigert stain. 

from injury or infection of the ganglia on the sensory 
root of the cranial and of the spinal nerves. That herpes 
zoster may be the result of specific infection of the 
ganglia of the posterior roots of the spinal nerves and 
the etiologic infectious microorganisms may be isolated 
from the infected tonsils and other foci has been dem¬ 
onstrated with patients in our clinic. With these strains 

Fig. 49.—Herpes of the Skin of the Inner and Upper Aspect of Right 
Thigh of a Rabbit 48 Hours After Intravenous Injection of Strep¬ 
tococcus from the Tonsil of a Patient Suffering with Herpes 


Fig. 50.—Thrombosis of a Vein (a) and Paravascular Infiltration (b) 
of tile Posterior Spinal Root Adjacent to the Ganglion Within 
the Dura Corresponding to the Area of Herpes Shown in Fig. 49. 


A ^ 
pfc ^ ^ ip iv nr E? 

. ^ 


3. M. J. 

3. ^ ; '0/CAL fc$ 

Fig. 51.—Diplococci in Leukocytes Within a Thrombosed Vein Shown 
in Fig. 50. Gram-Weigert stain. 

Fig. 59 . —Diplococci in Hemorrhagic and Infiltrated Area Shown in 
Fig. 53. Gram-Weigert stain. 


Fig. 53.—Marked Hemorrhage (a) and Leukocytic Infiltration (b) 
Surrounding the Lumbar Nerve Just Outside tfie Spinal Canal 
Corresponding to the Area of Herpes Shown in Fig. 49. 


ig. 54. —Herpes or Tongue, Mucous Membrane About Teeth and Lips 
of Rabbit 24 Hours After Intravenous Injection of Streptococcus 
from the Tonsil in Recurring Herpes. 


ig. 55. — Herpes of Skin of Left Side of Face of a Rabbit 12 Hours 
After an Intravenous Injection of Streptococcus from the Tonsil 
in Herpes Zoster. 


Fig. 56. —Hemorrhage (a) and Round Cell Infiltration (b) of the 
Gasserian Ganglion of Dog with Marked Herpes of the Lip 48 
Hours After an Intravenous Injection of Streptococcus from the 
Tonsil in a Patient with Lobar Pneumonia and Marked Herpes of 
the Lip and Cheek. 




of the isolated bacteria, herpes zoster has been produced 
in intravenously injected animals and the streptococci 
have been recovered from the posterior root ganglia of 
the inoculated animals. 


A recent interesting clinical observation and its re¬ 
lated laboratory experiments as made by Rosenow is 
worthy of record. A young man suffered for three 
years from the mild but typical symptoms of spinal in¬ 
sular sclerosis. When he was admitted to the hospital, 
he suffered from ataxia of gait and station, greatly in- 
increased knee kicks, slight nystagmus, but no intention 
tremor, and his spinal fluid was negative both as 
to abnormal cells and the serum tests. He had 
periods of improvement and of worse conditions 
associated with marked vertigo and falls without 
unconsciousness. He had suffered from chronic ton¬ 
sillitis for years. With a consideration of the possi¬ 
bility of a relation of focal infection to the condition and 
as no other site of infection could be located, the tonsils 
were enucleated. The streptococci isolated from the ton¬ 
sillar tissue, chiefly a strain of the green forming type, 
was intravenously injected into two dogs. In both 
animals focal hemorrhages were produced in the spinal 
cord and the development of ataxic gait and partial loss 
of power in all four extremities. From the focal soft¬ 
ened areas of the spinal cord a like strain of strepto¬ 
cocci was recovered. 

The infectious etiology of focal hemorrhage and soft¬ 
ening of the cerebrospinal axis has been recognized for 



a long time. The possibility that the condition may 
arise from a focus of infection is suggested by the ob¬ 
servation and experiment just mentioned. 


Acute osteomyelitis is often ascribed to injury usually 
involving the extremities. There can be no question 
that the infectious organisms, usually tubercle bacilli, 
streptococci and staphylococci, gain entrance into the 
blood stream from foci in the head or lymph nodes and 
that under certain conditions of increased virulence and 
of lessened resistance upon the part of local tissues due 
to injury of the bones, single or multiple osteomyelitis 
may occur. Kretz (25) records clinical observation in 
support of the focal origin of osteomyelitis. 


Thyroiditis is probably a much more frequent event 
than has been heretofore noted. I have already called 
attention to the frequency with which thyroiditis occurs 
in rheumatism. Vincent (31) has shown the incidence 
of 50 to 80 per cent, of swelling and tenderness of the 
thyroid gland in the course of acute rheumatic fever. 
There can be no question, too, that infection of the 
gland occurs in other general infections. It also occurs 
from focal infection about the mouth, throat, and nose. 
We have observed many instances of thyroid enlarge¬ 
ment, usually of chronic type, associated with evidences 
of thyroid intoxication in many young women patients 
with focal infection in the form of alveolar abscess, ton¬ 
sillitis and sinusitis. 

Fig. 57.—Section of Iris and Ciliary Body of Rabbit Showing Marked 
Leukocytic Infiltration (a) 4 Days After Intravenous Injection 
of Streptococci from Rheumatic Fever. 





Iritis is not an unusual event in rheumatism, syphilis 
and some other general infectious diseases. When 
acute or subacute iritis occurs alone the cause has been 
ascribed to infection, toxins, anaphylaxis and to faulty 

Fig. 58. —Photomicrograph of Streptococci in Area of Infiltration 
Shown in Fig. 57. Gram-Weigert stain. 

metabolism. That infection plays a much more constant 
part in the causation of iritis is apparent from the expe¬ 
rimental work of Rosenow (8), Irons and Brown and 
others. Strains of streptococci in foci of infection 
of the teeth, tonsils and sinuses have an unquestionable 
relation to iridocyclitis alone as well as when the 
eye infection is associated with rheumatic fever, chorea, 
syphilis and other acute general diseases. 

Fig. 59.—Localized Hemorrhages (a) in tlie Sclera Near the Limbus 


48 Hours After Intravenous Injection of Streptococci from Pus 
Pocket of Tonsil. 

Fig. 60. —Diplococcus Adjacent to Area of Hemorrhage Shown in Fig. 





Under the classification of chronic infections arthritis 
our present knowledge justifies the consideration of 
chronic arthritis which may be due to various forms of 
pathogenic bacteria. Investigation has shown that a 
strain of the streptococcus, gonococcus, tubercle 
bacillus, bacillus typhosus and spirocheta pallida are 
the most common infectious causes of chronic arthritis. 
When other bacteria are found in the infected tissues 
of chronic arthritis and myositis, they may have etiologic 
relations to the condition, but are probably present in 
the tissues as a mixed infection or purely as parasites. 

We shall confine the subject to streptococcus, gono¬ 
coccus and tuberculous joint infections because of the 
usual focal origin. The deformities which occur in 
chronic arthritis due to the streptococcus and to the 
gonococcus do not differ essentially because the morbid 
anatomical changes which are produced in the chronic 
type of infection due to the streptococcus and to the 
gonococcus are essentially the same. 

In both instances the mode of infection is hemato¬ 
genous and from a focal infection. In both the obstruc¬ 
tion due to endothelial proliferation or embolism in the 

small arteries due to the hematogenous mode of infec- 





tion is practically the same. In both types of chronic 
infection the virulence of the invading organisms is 
not high. Consequently the tissue reactions excited by 
the organisms is much less than in the more virulent 
type of streptococcus and gonococcus. Consequently 
instead of the production of a positive chemotaxis with 
purulent exudates at the point of infection as with local 
infections due to the streptococcus pyogenes and viru¬ 
lent types of gonococcus, there is in these chronic con¬ 
ditions a tendency to fibrinoplastic exudate and an 
attempt to wall off an area of infection. The variation 
in the virulency of the organisms which produce the 
chronic types may result in serofibrinous exudates in 
joints and tendon sheaths and to small hemorrhages in 
subserous tissues and in muscles. The low virulency 
of the organism, the embolic mode of infection of the 
tissues, the resulting tissue reaction, all tend to lessen 
the blood supply of the infected tissues through the 
partial obliteration and destruction of small blood ves¬ 
sels. In consequence there is a lessened blood supply 
and oxygenation of the tissues which results in marked 
malnutrition. Malnutrition leads to secondary meta¬ 
bolic changes resulting in either hyperplastic or atrophic 
changes in all joint structures, tendons and muscles. 
These changes have been well described by Nichols and 
Richardson (41) as both proliferative or hypertrophic 
and degenerative or atrophic arthritis. Because of 
these morbid changes, deformities result from muscular 
contraction and from the changes which occur in the 
bones, cartilage and other structures entering into the 



Present knowledge is in accord with Nichols and Rich¬ 
ardson in the statement they make that morbid changes 
both proliferative and degenerative of joint tissue can¬ 
not be differentiated etiologically. 

If one considers that the infection of joint tissue is 
hematogenous and that a sufficient dose of infectious 
organisms in the blood stream may reach the peri-artic¬ 
ular tissue or deeper tissue of the joint—that is, the end 
arteries in the subcapsular tissues—or through the 
nutrient arteries and involve the medulla of the 
epiphysis, one can harmonize the morbid anatomical 
changes which have been so clearly described by Nichols 
and Richardson. 

The reaction set up in the tissues of the external joint 
structures in the subcapsular region and in the medulla 
of the bone will depend in all probability upon the 
virulence of the infectious microorganisms and upon 
the resistance of the general body structures and of the 
joint tissues. They may be either proliferative with 
virulent bacteria, especially in young or normal indi¬ 
viduals, and necessarily the reaction will be less, or more 
degenerative in kind in the joint tissues of individuals, 
which are poor because of age, trauma and other con¬ 
ditions which lessen the vitality of tissue. 

Continued doses of infection from the focus would 
necessarily add to the changes described in the joint 
tissue. The repeated hematogenous infection destroys 
more blood vessels, again and again traumatizes the 
infected tissue and continuously lessens the oxygen sup- 


We now know that in chronic arthritis infectious 



organisms, whether streptococci or gonococci, have a 
relatively low virulence. Of course the degree of viru¬ 
lence varies and consequently the proliferative and de¬ 
generative changes especially vary in different indi¬ 

With continued infection of the tissues malnutrition 
necessarily increases, for the reasons named, and this 
necessarily leads to retrograde metabolism. 

Whether the retrograde metabolism is due solely to 
the malnutritions or whether it is also due in part to 
irritants in the tissues of bacterial or biochemic origin, 
does not in any way alter the principles outlined. There¬ 
fore, the proper understanding of chronic infectious 
arthritis involves an understanding of the following 

(1) The infection of the joints, muscles and other 
involved tissues with pathogenic organisms which usu¬ 
ally are members of the streptococcus group and the 
gonococcus which are of relatively low virulence; (2) a 
hematogenous infection with embolism with resulting 
injury of blood vessels and small hemorrhages into the 
infected tissues; (3) lessened blood supply and oxy¬ 
genation and consequent relative starvation of the in¬ 
fected tissues and dependent upon the malnutrition, 
favorable conditions for the continued life and multipli¬ 
cation of the infectious organisms, and finally (4) retro¬ 
grade metabolism due to the malnutrition. 

In the chronic infections due to the streptococcus, 
chronic arthritis may occur alone or associated with 
chronic myositis and chronic myositis may also occur 
alone involving single or groups of muscles. In chronic 



gonococcus arthritis the muscles are rarely, if ever, in¬ 
volved. Tenovaginitis is, however, more apt to occur 
than in chronic streptococcus infection. 

Various anatomical types of chronic infectious arthri¬ 
tis may occur, which doubtless depends upon the de¬ 
gree of bacteriemia, the degree of virulence of the in¬ 
fectious organisms, the resistance of the tissues and the 
fact that the mode of infection is hematogenous. Con¬ 
sequently we may have a peri-arthritis, a synovitis, an 
osteo-arthritis or a panarthritis. Any or all of these 
types may exist in the same individual. The primary in¬ 
fection may be severe enough to simulate acute rheu¬ 
matic fever or mild rheumatic fever. Usually the dis¬ 
ease begins insidiously, but there may be in many pa¬ 
tients periods of increase in temperature usually of a 
febrile type. There is always a great deal of soreness 
of the infected tissues which is aggravated by anything 
which disturbs the general or local circulation, as chilling 
the body, fatigue and general nervous irritability. Be¬ 
cause of the varying degrees of activity of the focus 
there may be reinfection from time to time of the tis¬ 
sues, joints, muscles, etc., with consequent aggravation 
of the symptoms. Usually there is but little pain ex¬ 
cepting with exercise of the involved organs. Chronic 
gonorrheal arthritis is more apt to involve the interver¬ 
tebral joints and ligaments, the sacroiliac, sternoclavic¬ 
ular and temporomaxillary joints than the strepto¬ 
coccus, but inasmuch as the streptococcus may also infect 
the four named joints, involvement of them does not 
necessarily indicate a gonococcus infection. Chronic 
infectious myositis which may occur as a part of the 



chronic streptococcus arthritis or alone, is associated 
with shortening of the muscle bundles due to the embolic 
infection with subsequent hemorrhage and connective 
tissue proliferation. At the time of infection there is 
usually tenderness and pain when an attempt is made 
to contract the muscles. When at rest there is usually 
no discomfort. There is apparently an elective affinity 
of the infectious organism for certain muscles, notably 
the masseters, the biceps humeri, the hamstrings, the 
anterior tibial and erector spinae groups. Other muscles 
are sometimes involved and in some instances practi¬ 
cally all skeletal muscles are included in the infection. 

In all of these chronic types of arthritis and myositis 
there may be general debility with anemia, emaciation 
and nervous irritability due to the long continued infec¬ 
tion. Often these general conditions are aggravated by 
methods of treatment, in starvation diets and purges 
which weaken the patient and by the overuse of drugs. 
In recent years the irrational use of vaccines and of toxic 
extracts of bacteria has added to the miserable condi¬ 
tion of the patients. 

These general weakening influences add to the con¬ 
ditions which promote retrograde metabolism in the in¬ 
fected tissues, so that in the patients who present the 
worst type of the condition there is a tendency to such 
a degree of retrograde metabolism that the connective 
tissue group comprising aponeurosis, tendons and carti¬ 
lage is changed into bone. 

Chronic tuberculous arthritis is always associated with 
focal or with general tuberculosis. It practically always 
occurs as an osteomyelitis usually involving the epiphy- 



sis. The evolution of the tuberculous process in the 
epiphysis leads to infection of the joint with its char¬ 
acteristic morbid anatomy. Tuberculous tenovaginitis 
is usually a secondary infection from the periarticular 
tissues, but may occur alone. 

Spondylitis due to the typhoid bacillus probably 
causes the same anatomical type as the gonococcus and 

Infectious neuritis or perineuritis due to a focus of 
infection may occur alone or as a part of chronic ar¬ 
thritis and myositis or with myositis without arthritis. 
Usually the condition is a perineuritis. The nerves most 
often involved are branches of the brachial plexus and 
the sciatic trunks. Focal infection about the teeth, ton¬ 
sils and sinuses is a frequent cause of neuritis. The 
gonococcus may be the cause of neuritis or perineuritis. 


Chronic infectious nephritis due to focal infection is 
very common. Probably it has first existed as a sub¬ 
acute infectious nephritis and not infrequently occurs as 
a hematogenous infection of the kidney from some focus 
resulting in anatomical changes of various degrees. 
Chronic infectious nephritis, like the subacute and acute 
types, is usually due to strains of the streptococcus 
which have a specific elective affinity for the kidney. 
This specific affinity may be attained in the focus of 
infection. If the bacteriemia due to focal infection is 
severe, undoubtedly nephritis either acute or chronic 
may result from bacteria which have only general path¬ 
ologic virulence. LeCount and Jackson (35) state that 



the most important result of their work was the experi¬ 
mental production of alterations, essentially subacute 
and quite like the acute interstitial nephritis in human 
kidneys, caused by the acute infectious diseases, com- 

Fig. 61.—A Typical Subacute Focal Lesion in the Cortex. X c 200 (after 
LeCount and Jackson, Jour. Inf. Dis.). 


plicated by or due to streptococcus infection. Of the 
rabbits inoculated, eight, or 25 per cent, of the thirty- 
three which died or were killed within the first two 
weeks, showed chronic changes in the kidneys, while fif¬ 
teen, or 62. 5 per cent., of twenty-four rabbits which lived 



from fifteen to one hundred and eighty-six days, showed 
chronic kidney changes. They conclude, therefore, that 
chronic lesions of the kidney of a part of the inoculated 

Fig. 62.—An Interlobular Vein Surrounded by Lymphocytes and 
Plasma Cells. From the kidney of rabbit dying 42 days after inocu¬ 
lation. X 35 (after LeCount and Jackson, Jour. Inf. Dis.). 

rabbits resulted from the subacute nephritis caused by 
the streptococci intravenously injected. 

Ophuls (55) concludes that chronic nephritis is 
usually of infectious origin. Ivlotz (54) states that a 
form of acute interstitial nephritis induced in animals by 



the inoculation with strains of streptococci subsequently 
gives rise to a renal sclerosis of the type known as chronic 
interstitial nephritis. He believes that a similar process 
is common in man. 

In an article on the relation of focal infection to ne¬ 
phritis, we gave the clinical history of a young woman 
who suffered with hemorrhagic nephritis apparently due 
to badly infected tonsils. After enucleation of the ton¬ 
sils there was great improvement of the renal condition 
and a restoration to apparent health. Occasionally, 
slight albuminuria with the presence of hyalogranular 
casts occurred. After one year evidences of chronic in¬ 
terstitial nephritis became constant and three years fol¬ 
lowing the removal of the tonsils and the greatly im¬ 
proved condition, the patient died of renal intoxication 
associated with a high degree of hypertension. 

Every clinician of experience has observed patients 
over long periods of time who have presented primarily 
evidences of acute or subacute nephritis of infectious 
origin and who have finally succumbed to chronic 
nephritis. That a focal infection may be the 
source of the kidney lesions and may lead to a 
chronic irreparable renal disease must be emphasized. 
Early removal of the etiologic focus may prevent fur¬ 
ther anatomical insult of the kidneys and preserve renal 
function and life. 


Chronic cholecystitis with or without gall-stones is 
the result of acute infection as a rule. As we have seen, 
this may be due to hematogenous streptococcus infec- 


tion. The streptococci, which lodge in the small area 
of the fundus of the gall-bladder at the terminus of a 
blood vessel, may cause hemorrhage and exciting tissue 

Fig. 63. —Cholecystitis and Cholelithiasis iist Dog Ten Days After In¬ 
travenous Injection of Streptococcus from Center of Gall-Stone 
from Human Gall-Bladder. Note the black stones imbedded in the 
edematous mucous membrane. 

reaction which weakens the gall-bladder wall and may 
rupture into the cyst. If the infectious organism is of 
high virulency, acute purulent cholecystitis may occur 



or with a less virulent type the infection will be much 
less in degree. If unoperated at the time of the acute 
or subacute attack, gall-stones may form in the chroni¬ 
cally infected gall-bladder. As long as the focal site 
exists reinfection may lead to subsequent acute or sub¬ 
acute attacks of cholecystitis. 

As shown by Rosenow (8) the strain of strepto¬ 
coccus, which seems to acquire an affinity for the tissue 
of the gall-bladder, has a coincident affinity for muscles 
particularly of the myocardium, and in confirmation 
clinicians have noted evidences of myocardial weakness 
in patients who suffer from chronic cholecystitis. 


Chronic peptic ulcers of the stomach and duodenum 
are doubtless the sequence of acute ulceration and we 
have already noted the mode of infection in acute ulcer 

Fig. 64.—Streptococci and Leukocytic Infiltration in Peritoneal Coat 
in Perforating Ulcer of the Stomach of Man. 

Fig. 65.—Streptococci in Peritoneal Coat of Ulcer of Stomach in 
Rabbit 5 Days After Intravenous Injection of Streptococci from 
Perforating Ulcer of Stomach in Man Shown in Fig. 64. 

Fig. 66.—Streptococci and Leukocytic Infiltration in Chronic Ulcer 
of Man with Acute Exacerbation Shortly Before Operation. 


Fig. 67. Chronic Ulcer of Duodenum of Dog 13 Weeks After Single 
Intravenous Injection of Streptococcus from Ulcer of the Duo¬ 
denum of Man. 

Fig. 68. — Chronic Ulcer of Duodenum of Dog 13 Weeks After a Single 
Intravenous Injection of Streptococcus from Human Ulcer. Note 
the displacement of muscular layer (a) by connective tissue and the 
thickened peritoneal coat (b). 




and the immediate morbid tissue changes which occur. 
In the hematogenous embolic infection of the stom¬ 
ach with a strain of the streptococcus which has an 
elective affinity for the stomach wall, a local sub¬ 
mucous hemorrhage occurs. In consequence of the 
hemorrhage and infection, anemic necrosis results with 
consequent lessened resistance and the necrosed tissues 
of this small area are digested by the gastric juice. The 
continued infection of the tissues around the acute ulcer 
prevents the healing of the mucous membrane of the 
stomach in all probability, for it is well known that 
uninfected wounds of the stomach readily heal. The 
continued action of the gastric juice upon the ulcer base 
results in the characteristic anatomical picture of chronic 
peptic ulcer. 


In 1903 Schottmiiller (10) reported the isolation of 
a green-forming streptococcus in blood agar plates from 
the blood of patients suffering from endocarditis. This 
report was made in connection with the investigation 
which Schottmiiller was at that time making of the 
growth characteristics of streptococci upon blood agar. 
He called this green-producing microorganism strepto¬ 
coccus viridans. Its low virluency led also to the name, 
streptococcus mitior. 

The character of the endocarditis in which the strepto¬ 
coccus viridans seemed to be the infectious agent has 
proved to be one of a paradoxical nature in the sense 
that the clinical course, in the early stages, is frequently 
very mild and the patient is able often to be up and 



about, even attending to ordinary affairs of life, but it is 
progressive and in a few weeks or months, sometimes as 
late as a year and a half, the patient usually succumbs 
to the disease. 

It is, therefore, a malignant type of endocarditis al¬ 
though usually chronic in its clinical course. As I have 
before stated the streptococcus viridans endocarditis 
may sometimes be very acute and associated with a septic 
type of temperature with a very high maximum and 
low minimum temperature, and may run its entire clin¬ 
ical course within two or three weeks. During the last 
few years since routine blood cultures have been made, 
the frequent incidence of this disease has become noted. 
Osier (17), Horder (18), Libman (20), Lenhartz (22) 
and others have reported a series of patients suffering 
from what they have termed chronic infectious endo¬ 
carditis, infective endocarditis, subacute infective endo¬ 
carditis, subacute bacterial endocarditis and the report 
which Rosenow and Billings made was under the title 
of “chronic pneumococcus endocarditis.” 

The characteristics of this type of malignant endo¬ 
carditis are usually a mild clinical course in which the 
patient may complain of lessened strength and endur¬ 
ance; usually a poor appetite; more or less dyspnoea 
of exertion; slight to severe chills and fever in periods 
often mistaken for malaria; cough, in some cases with 
more or less expectoration, often with a septic type of 
fever mistaken for tuberculosis, and in severe grades 
sometimes treated for mild typhoid fever. The major¬ 
ity of these patients have suffered at some time from 
rheumatism and endocarditis or from endocarditis alone 



and upon examination it is usual to find the evidences 
of old valvular disease with varying conditions as to the 
heart muscle. Those patients who have not previously 
suffered from endocarditis may present no heart mur¬ 
murs or other evidence of heart involvement. While 
in bed the temperature is usually a mildly febrile one 
of septic type and there may he rigors amounting at 
times to severe chills. Sooner or later with involvement 
of the left heart there are evidences of embolism in 
petechia of the skin and elsewhere. Frequently there are 
infarcts of the spleen manifested by enlargement and 
tenderness of that organ. Infarcts of the kidney mani¬ 
fested by hematuria usually microscopic (See Baehr 
(23) and Lohlein (24) ), embolism of brain with varying 
degrees of sensory or motor disturbance and in some 
patients embolism of sufficient size of the arteries of 
the extremities to obliterate the pulse below the site of 
the embolus and to cause gangrene of the extremities. 
Mycotic aneurism may occur usually situated in the 
smaller arteries. Death supervenes with severe embol¬ 
ism of the brain or from exhaustion with mixed infec¬ 
tion. The duration may be from two to three weeks in 
the really acute types of the disease and may last for 
eighteen or more months. 

The streptococcus viridans may be isolated from the 
blood and is characterized by the fact that in culture 
media it soon loses its affinity for the heart and may be 
converted, as shown in the immunological studies of 
Rosenow (8), into any of the other types of the mem¬ 
bers of the streptococcus-pneumococcus group. 

The lesion of the heart in streptococcus viridans en- 



docarditis is characterized by the growth of massive 
vegetations upon the valves and upon the mural endo¬ 
cardium. (See Figs. 9 and 10.) It is not usually 
attended with ulcerations, but there is an enormous 
deposit of thrombus in the vegetations which serves as 
a rich culture medium for the invading organism and 
also because of the size and friability of the vegetations 
and the thrombus formation is a ready source for the dis¬ 
semination of emboli of all sizes through the systemic 

It is a non-pus-forming organism and consequently 
suppuration does not follow in the tissues involved in 
the embolism. In rare instances the mycotic aneurism 
may break into the surrounding tissues and in two pa¬ 
tients under my observation abscesses formed and a 
pneumococcus was obtained in pure culture therefrom, 
while in the blood stream was found the streptococcus 
viridans in pure culture. 

The streptococcus viridans endocarditis is usually 
fatal. Streptococcus viridans bacteriemia unassociated 
with endocarditis, although there may be an endocardial 
murmur present, is not necessarily fatal. The reports 
of recoveries of streptococcus viridans endocarditis may 
be of those patients who have streptococcus viridans bac¬ 
teriemia without a real endocarditis. Libman has re¬ 
ported recoveries, and in a series reported by Horder 
the mortality was not absolute. In my own experience 
only three patients out of more than one hundred who 
have had a streptococcus viridans bacteriemia have recov¬ 
ered from that condition. In one of these there was no 
recognizable heart murmur and the condition was asso- 



ciated with streptococcus viridans infarct of the right 
lung with suppuration, evacuation of abscess and recov¬ 
ery. In another, a boy of sixteen, with a systolic mitral 
murmur and moderate septic fever, the bacteria finally 
disappeared from the blood and recovery ensued with 
moderate mitral insufficiency fully compensated. In a 
third patient, a Jewess, with mitral stenosis and mod¬ 
erate septic fever of long duration mistaken before en¬ 
tering the Presbyterian Hospital for tuberculosis of 
the lung, the bacteriemia disappeared and five years later 
the patient was entirely well except for the mitral sten¬ 
osis, fully compensated. 

Even with evidences of endocarditis in the last two 
patients described, it was not proved that there was an 
endocarditis of recent origin. 

The character of the changes in the myocardium and 
valves is so serious in this disease, very much like that of 
the acute malignant endocarditis due to the pneumo¬ 
coccus, that one can appreciate the fatal nature of the 

That healing may occur though rarely cannot be 
doubted when one examines the heart in an accidental 
death with coroner’s inquest where the enormous vegeta¬ 
tions can still be recognized but so infiltrated with cal¬ 
cium salts that a practical cure has resulted. This condi¬ 
tion has been noted as I have stated previously in the ob¬ 
servation of LeCount. 

The focus of infection which undoubtedly causes the 
streptococcus viridans bacteriemia and chronic malig¬ 
nant endocarditis is often alveolar abscess. Of this we 
have had numerous clinical examples. Coincident cul- 



tures from the alveolar abscess and from the blood 
have yielded strains of streptococcus viridans. When 
these nascent cultures were intravenously injected into 
animals, typical endocardial lesions resulted. Doubt¬ 
less a focus containing this streptococcus may be lo¬ 
cated in the tonsil or nasal sinus or elsewhere which 
may be the source of the cardiac infection. 




Prevention of focal infection is an important prin¬ 
ciple in the consideration of the treatment of the etio- 
logic factor and the related systemic infections. 

We may not hope so to modify the actions of indi¬ 
viduals or of society that communicable diseases will dis¬ 
appear or that susceptibility to infection will be over¬ 
come in the evolution of a mentally and physically bet¬ 
ter developed race, for we cannot wholly prevent or 
abolish the marriage or procreation of the unfit; vice; 
alcoholic and drug addictions; poverty, unhealthful 
domiciliary and occupational environment; the use of 
contaminated food and drink; community uncleanliness, 
and other causes of mental and physical debility which 
directly diminish the natural body defenses. 

The control of these debility-producing factors is a 
function of national, state and municipal public health 
bodies. Politics, greed for wealth and ignorance are 
influences which prevent the administration of well-es¬ 
tablished laws which, if properly enforced, would do 
much to abolish unhealthful conditions and disease. 

As far as possible, as individuals and collectively, phy¬ 
sicians should exert an influence to promote cleanliness 

of mind and body and thus lessen the incidence of focal 




and systemic infection. The encouragement of per¬ 
sonal cleanliness and especially the care of the skin and 
its appendages, and of the mouth and throat should be 
a duty of the family physician. The necessity of cleans¬ 
ing the mouth, teeth and throat of all particles of food 
after eating should be taught as a prevention of local 
infection, decay of teeth and of general disease. When 
other measures fail the removal of the persistent over¬ 
growth of lymphoid tissue, a good culture medium for 
bacteria, of the nasopharynx and throat should be ad¬ 
vised. Chronically enlarged pharyngeal tonsils, which 
obstruct the upper respiratory tract and prevent proper 
ventilation and drainage, invite local infection of the 
mucous tracts of the head and should be totally re¬ 

The foregoing statements are applicable chiefly in 
childhood, for children are especially susceptible to in¬ 
fection of the tissues of the mouth, throat, nose, acces¬ 
sory sinuses, middle ear and mastoid cells. We know 
that freedom from streptococcus infection of the mucous 
membrane and lymphoid tissues of the head would very 
much lessen the incidence of rheumatism, chorea and 
endocarditis in children and also in adults. We may not 
as confidently expect to prevent acute appendicitis, pep¬ 
tic ulcer, cholecystitis and nephritis by these measures; 
still, the evidence of the etiologic relations of these dan¬ 
gerous local infections to focal nose, mouth and throat 
infection is so strong that the correction of these confined 
infections is rationally indicated. I do not wish to seem 
to be an advocate of unnecessary operations, for many 
operations of all kinds are irrationally performed, in- 



eluding the removal of overgrowth of the tonsils and 
other lymphoid and mucous tissues of the nose and 
throat. These conditions of the nose and throat may 
disappear with a proper hygienic management. I believe 
that tonsillectomy is often needlessly performed for the 
relief of a systemic infection, when the real focal cause 
is situated elsewhere. Doubtless the normal faucial ton¬ 
sillar tissue has a beneficent function and uninfected, 
should not be molested. But too often the tonsillar 
tissue in children and also in some adults is a culture 
medium of pathogenic bacteria and as such is a constant 
source of danger as a portal of entry of infectious bac¬ 
teria through the lymph and blood streams to the tissues 
of the body. Infected tonsils cannot be successfully 

any known method of treatment and entire 
removal is the only safe procedure. If necessary a prop¬ 
erly directed surgical treatment of the easily recog¬ 
nized morbid anatomical condition of the nasopharynx 
and nares will establish normal ventilation and drainage 
and lessen the incidence of middle ear, mastoid and 
accessory sinus disease with the resulting possible sys¬ 
temic involvement from these sites of focal infection. 
Until recently the importance of pyorrhea dentalis and 
alveolar abscess as an etiologic factor in systemic infec¬ 
tion has not been recognized. Clinical and laboratory 
observation and research have definitely settled the 
question. As has been stated in the first lecture, the 
members of the streptococcus group, but occasionally 
other bacteria, are the pathogenic agents of pyorrhea 
which cause systemic infection. The endameba buccalis 
may have an etiologic relation to the pyorrhea of the 

sterilized by 



teeth and alveoli, may intensify the destructive local dis¬ 
ease and may be the agents of communicating the dis¬ 
ease to others by direct personal contact or through fo- 
mites. The existence of focal infection of the jaws in the 
form of chronic alveolar abscess, without the manifesta¬ 
tion of much discomfort, is remarkable. The condition 
is often not discoverable by inspection and escapes the 
attention of the physician and the dentist. It is only 
when destructive lesions of the gum, tooth and alveolus 
make the condition visible that a diagnosis is usually 
made. Properly made Rontgen ray films of the jaws 
will enable one to recognize the real morbid and ana¬ 
tomical condition. The definite recognition of the con¬ 
dition and the character of the mechanical dentistry 
which should be practiced demands the use of Rontgen 
ray films of the jaws. The use of emetin in the destruc¬ 
tion of the endameba may rid the mouth temporarily of 
an etiologic factor of pyorrhea, but the drug does not 
remove the infectious bacteria in the focus, nor does it 
restore the periosteum of the root of the tooth without 
which the tooth ceases to be living bone and as a foreign 
body invites added and continued bacterial infection. 

In a consideration of amebic dysentery, Phillips (51) 
states that emetin will kill the parasite in the active 
stage, while the drug has but little or no effect on the 
cysts. He suggests the hypodermic use of emetin in ten- 
day periods, with gradually increasing intervals, until 
repeated examinations finally fail to find endamebas in 
the stool. Inasmuch as emetin destroys endameba 
buccalis, the same method of management may more 
certainly rid the mouth of the parasite. 



Dentists everywhere are interested in the better man¬ 
agement and correction of alveolar infection. We must 
look to them for a treatment which will destroy the 
focal infection of the jaws and safeguard the individual 
from systemic infection. Deplorable as the loss of teeth 
may be, that misfortune is justified if it is necessary to 
obliterate the infectious focus which is a continued 
menace to the general health. 

Malnutrition and general debility due to chronic dis¬ 
ease, old age, and other causes may lead to focal infec¬ 
tion of the jaws. Such foci of infection tend to add in¬ 
fection to already infected systemic tissues. These in¬ 
fectious foci, which in a way are secondary to the sys¬ 
temic disease causing the general debility, are just as 
dangerous as primary foci and should be removed. 

Persistent lymph node infections which do not dis¬ 
appear with hygienic measures instituted to improve the 
defenses of the body should be surgically removed as a 
matter of protection against the further dissemination 
of tuberculosis or of some other disease from the specifi¬ 
cally infected nodes. 

The conditions which may promote infection of the 
gastro-intestinal tract are usually not brought to the 
attention of the physician until too late to use measures 
of prevention. Myriads of infectious bacteria are swal¬ 
lowed in infected food, especially milk, and in the 
muco pus of the nose, throat and bronchi. The gastric 
juice and other digestive fluids probably destroy most 
of these bacteria in robust individuals. The surviving 
microorganisms may reach the tissues of the bowel 
and the adjacent lymph nodes, under favor- 



able conditions may continue to have or may 
attain pathogenic virulence, and cause local or 
systemic disease. Habitual constipation, with or 
without congenital or acquired anatomical de- 
formities of the intestinal tract, may lower the natural 
resistance of the tissues to invasion by the bacteria of 
the intestine. Again the morbid anatomical conditions 
which favor intestinal stasis may promote increased 
general virulence or elective tissue affinity of the in¬ 
vading bacteria. Rosenow (8) has demonstrated an 
acquired virulence and also an elective tissue affinity 
for the appendix of a strain of colon bacilli isolated in 
cultures from the exudate and tissues in patients with 
appendicitis. When injected intravenously appendi¬ 
citis developed in the inoculated animals. After a time 
the general virulence and specific tissue affinity was lost 
in subcultures of this strain. Beaussenat quoted by 
Adrian (28) was unable to produce appendicitis by 
the intravenous injection of ordinary strains of colon 
bacilli without first injuring the mucous membrane of 
the organ. 

Infection of the digestive tract may he prevented 
or at any rate its incidence may he diminished very 
much by obliterating the sources of the mucopus in the 
throat and nose, which at the same time removes the 
foci of infection of the head, and also by avoiding in¬ 
fected food. 

Stasis of the bowels, whether due to habitual consti¬ 
pation or to congenital or acquired anatomical condi¬ 
tions, should have a proper medical management or, if 
necessary, surgical treatment. I very much doubt if 



the removal of the entire colon is justifiable for ntestinal 
stasis alone; certainly not to the degree practiced by 
some surgeons. Chronic appendicitis with lessened tis¬ 
sue resistance invites acute attacks, disturbs the gastric 
digestion and may be a focus of systemic infection. The 
same is true of chronic cholecystitis and especially as 
the experiments of Rosenow (8) seem to show that the 
streptococcus strains, which acquire an elective affinity 
for the gall-bladder, have also an affinity for muscular 
tissue, especially the myocardium. This confirms the 
clinical observation of the occurrence of cardiac muscle 
disease with cholecystitis. Therefore, surgery is indi¬ 
cated in appendicitis and cholecystitis to relieve the in¬ 
dividual of a local menace to life, of reflex dyspepsia 
and quite as important to remove etiologic factors of 
systemic disease. 

The morbid conditions of the rectum, which makes 
it a dangerous source of lymphogenous and hematoge¬ 
nous infection especially of colon bacilli and strepto¬ 
cocci, should receive rational surgical treatment. 

The focal acute and chronic infectious diseases of the 
pelvic organs of woman, particularly of the uterus in 
the puerperium and of the parametrium and fallopian 
tubes, are so important that they should be rationally 
managed and surgically treated when necessary to safe¬ 
guard health and life. 

The alleged etiological relation of chronic streptococ¬ 
cus infection to cystic degeneration of the ovary needs 
confirmatory bacteriologic research. This is especially 
needed if the supposed infectious cause of diseases of the 
ovary is accepted as an additional excuse for the too 



frequent sacrifice of the ovary for the numerous real 
and fancied ills of women. 

The infectious foci of the male pelvic organs requires 
a management and surgical treatment which will re¬ 
move a constant source of systemic diseases and in 
gonorrheal infection in addition, a source of the most 
frequent cause of pelvic disease of women, many of 
whom are morally innocent wives. As demonstrated 
by Sugimura (4) and Franke (5), lymphogenous in¬ 
fection in addition to other sources of hematogenous 
infection of the ureter, kidney pelvis and kidney, from 
the bladder, indicates additional reasons for effective 
treatment medical or surgical to overcome acute and 
chronic cystitis. So, too, may rational medical or surgi¬ 
cal treatment of pyogenic and tuberculous kidney and 
kidney pelvis infections prevent corresponding infection 
of the ureter, bladder, other pelvic organs, and from all 
of these sources a general systemic infection. 

Infected wounds, often insignificant, of the skin and 
mucous membranes and furuncles and purulent infec¬ 
tion about the finger and toe nails should receive the 
management which is indicated by the rare, yet often 
serious, systemic infections which they may cause. 



In the treatment of disease it is an axiom to remove 
the cause if possible. This law of good medical practice 
is applicable in diseases due to focal infection. In some 
acute diseases it is impossible to remove the focal dis¬ 
ease, either because it is inaccessible or the serious con- 



dition of the patient contraindicates it. In bacteriemia 
due to puerperal sepsis, or to an infectious thrombo¬ 
phlebitis of the deep veins, surgery cannot be utilized 
without danger of death from shock or from an over¬ 
whelming degree of bacteriemia by a physical disturb¬ 
ance of the infected thrombus or other tissue sources of 
the infection. 

In acute rheumatic fever associated with en¬ 
docarditis, pericarditis or a pancarditis, the serious 
condition of the patient usually contraindicates tonsil¬ 
lectomy for the removal of the most general etiologic 
focus. Experience teaches that removal of the tonsils 
during an attack of acute rheumatic fever usually does 
not modify the clinical course. It is the better practice 
to remove the focal cause, wherever it may be, in the late 

In mild rheumatic fever and in chronic infectious 
forms of arthritis the focal cause should be removed 
early. Even in these mild and chronic types of infec¬ 
tious arthritis and myositis one occasionally witnesses 
serious results. A girl of eighteen who had suffered for 
a year from a disabling chronic polyarthritis and myo¬ 
sitis, due apparently to multiple chronic alveolar ab¬ 
scesses, had many teeth extracted and the alveolar ab¬ 
scesses curetted. Streptococcus bacteriemia developed 
with acute hemorrhagic myositis, pleuritis, pericarditis, 
myocarditis with submucous and subcutaneous hemor¬ 
rhages and death. The streptococci isolated from the al¬ 
veolar pus, the blood and after death from the muscles, 
when injected intravenously into animals caused rheu¬ 
matic arthritis, myositis, endocarditis and pericarditis. 



A girl of ten, now a patient in the Presbyterian Hos¬ 
pital, suffered from a mild arthritis and myositis. The 
family physician had the enlarged and apparently in¬ 
fected tonsils removed. Immediately, there developed 
an acute general myositis, which gradually changed to a 
non-febrile type with much deformity due to the shorten¬ 
ing of the muscles. Experience of this kind affords proof 
of the focal origin of certain systemic conditions and 
that the operative technic of removal of foci of infec¬ 
tions should be of a kind which will not overwhelmingly 
inoculate the patient. In acute rheumatic infections the 
removal of the original focus, usually tonsillitis, may 
not prevent future attacks, for the streptococcus rheu- 
maticus may occur in other focal sites, notably in 
alveolar abscess and maxillary sinusitis. The prompt 
removal of every recognizable local infection of the head, 
in people who suffer from repeated attacks of acute 
rheumatism, may prevent the disease. This result ex¬ 
perience of recent years has conclusively proved. What 
has been said of the treatment of the acute rheumatic in¬ 
fections is also true of chorea. But experience has 
shown that arsenic does modify the cause of chorea. 
It is interesting to note, in this connection, that arsenic 
has also a striking influence on the clinical course of 
rheumatic pericarditis and pleuritis. I have used caco- 
dylate of soda as a relatively non-toxic form of arsenic 
in the treatment of chorea and of serofibrinous rheu¬ 
matic pericarditis and pleuritis. From five to fifteen 
grains in divided doses, each twenty-four hours, injected 
deep in the muscles, has a remarkable effect within two 
or three days. The uniformly constant result suggests 



a chemotherapeutic result similar to that of salvarsan 
for spirochetes. 

Salicylic acid seems to have a specific bactericidal 
effect upon the streptococcus rheumaticus if it is given 
in sufficient quantity in the first days. Large sterilizing 
doses given early seem necessary. Perhaps the strepto¬ 
coccus becomes immune to ineffectual doses of the drug, 
and this may explain the lack of specific effect in the 
prolonged clinical course. It is of interest to record 
the apparent good effect of large doses of salicylic acid 
during the first hours of acute appendicitis, which as 
we have noted may be caused 
the streptococcus rheumaticus. 

Acute gonorrheal arthritis must first be recognized 
by the pathognomonic signs sometimes present, purulent 
exudate in joints and tendon sheaths, the gonococcus 
in exudates and blood and the recognition of a focus 
in the genito-urinary tract. The specific von Pirquet 
skin and the complement fixation tests are not always 
to be relied upon in diagnosis unless suitably controlled, 
according to Irons (36), Irons and Nicoll (37). The 
almost uniform benefit of the early removal of the focal 
cause is notable in systemic gonococcus infection. Even 
with gonococcemia, if no involvement of the endocar¬ 
dium occurs and if there is no gonococcus thrombo¬ 
phlebitis, the removal of the focus is often followed by 
recovery. Purulent exudates must be surgically treated. 

Malignant endocarditis of all types is usually fatal 
because the invading bacteria find lodgment and suit¬ 
able conditions for growth and multiplication in large 
vegetations filled with thrombi or in the necrotic tissue 

by a modified strain of 



of the valves and heart walls of the ulcerative form. This 
insures continued infection and increasing diminished 
resistance of the patient. Multiple embolism and the 
result upon all the involved organs hastens the fatal 
end. Drug treatment is unavailing. 

Infectious acute nephritis due to the specific elec¬ 
tive tissue affinity of certain bacteria, especially mem¬ 
bers of the streptococcus group, demands an early re¬ 
moval of the focal cause. By this means death may be 
prevented and if the anatomical injury of the kidney is 
not too great the function may be preserved to a degree 
consistent with health for many years. A woman 
years under treatment for chronic arthritis 
at the Presbyterian Hospital acquired coryza and 
an acute frontal sinusitis. Hemorrhagic nephritis 
immediately occurred, associated with some edema of 
the face, legs and dependent portions of the body. 
Drainage of the infected sinus was followed by rapid 
general improvement and a gradual disappearance of 
the albuminuria and the abnormal formed elements of 
the urine. One month later the urine and functional 
tests for phthalein, nitrogen and chlorid output were nor¬ 
mal. A strain of streptococci, which was hemolytic, 
isolated from the exudate of the sinus, when injected 
intravenously into rabbits caused hemorrhagic ne¬ 

Many like examples of improvement or recovery from 
acute hemorrhagic nephritis could be reported from 
our observation and the experience of others recorded 
in medical literature. So, too, one may cite examples 
of nephritis which have progressed to a hopeless stage 



due to repeated anatomical insults of the kidney by 
infectious microorganisms from the neglected focus. 

Even types of chronic nephritis evidenced by albumi¬ 
nuria, cylindruria and more or less hyper arterial ten¬ 
sion show manifest improvement by the removal of 
chronic focal infection of the dental alveoli, tonsils, 
sinuses, gall-bladder, appendix and pelvic organs. A 
rational after-treatment consisting of a properly selected 
diet and attention to personal hygiene is of course an 
important factor in the improved condition of these 

Appendicitis, acute and chronic, requires surgical in¬ 
tervention to conserve life and to obliterate a focal in¬ 
fection which may seriously infect other tissues through 
the lymph channel or blood stream. The incidence of 
appendicitis may be reduced by the prevention of focal 
infection about the head and by the early removal of 
existing foci. 

Acute and chronic cholecystitis demand early surgi¬ 
cal treatment to relieve pain and dyspepsia and quite 
as much to remove a dangerous focus of systemic in¬ 
fection, especially of the myocardium. Babcock (40) 
and others have noted the improvement of clinical chron¬ 
ic myocarditis by the drainage of a coexisting chronic 
cholecystitis. The prevention of focal infection of den¬ 
tal alveoli, tonsils and sinuses and the early removal of 
existing infection at these sites may diminish the inci¬ 
dence of cholecystitis and of gall-stones. 

In the treatment of gastric and duodenal ulcer the 
experiments of Rosenow demand the primary removal 
of the etiologic foci of infection as a means of preven- 



tion of the recurrence of the ulcer through reinfection. 
A coincident rational medical management if consistent¬ 
ly carried out, as advised by Sippy (56), may be success¬ 
ful in healing the ulcer. Surgical treatment is indicated 
when the unhealed ulcer or the scar produces deformi¬ 
ties which persistently interfere with gastric and 
intestinal function and also when accidents, like 
perforation and medically unmanageable hemorrhage, 

Recurring erythema nodosum alone or as a part of 
the syndrome described by Osier (17) may be entirely 
controlled by the removal of the etiologic infectious 
focus. A young woman of twenty-four years had re¬ 
curring attacks of erythematous nodes of the arms and 
lower extremities, associated with mild arthritis. She 
suffered from a chronic maxillary sinusitis. Drainage 
of the sinus gave coincident freedom from the nodes and 
arthritis. After three months a recurrence of the sys¬ 
temic disease proved to be due to a corresponding re¬ 
currence of the sinus infection. Complete obliteration 
of the sinus infection has been followed by the continued 
absence of the attacks of arthritis and erythematous 
nodes for three years. 

A young married woman of twenty-six had recurrent 
attacks of erythematous nodes and muscular soreness 
for a year. She had also frequent mild tonsillitis and 
pharyngitis. Enucleation of the tonsils was followed 
by the absence of erythematous nodes for nearly a year, 
then a recurrence. Re-examination revealed the pres¬ 
ence of an infected lower pole of one tonsil. The re¬ 
moval of the remaining portion of infected tonsil has 


resulted in the permanent cessation of the systemic dis- 

The relation of focal infection to acute pancreatitis 
often associated with cholecystitis has been noted. Early 
surgical intervention to relieve the acute process is im¬ 
peratively demanded. Chronic pancreatitis is of espe¬ 
cial interest because of the relation the internal secre¬ 
tion of the gland bears to carbohydrate metabolism. The 
probable infectious origin of chronic pancreatitis as well 
as the acute process from streptococcus foci, affords an 
interesting problem for clinical investigation in the man¬ 
agement of diabetes mellitus. We have removed exist¬ 
ing focal infection about the head of diabetic patients, 
have inoculated animals with the isolated streptococcus 
strains, and have kept the patients under clinical ob¬ 
servation. The results have not been uniform enough 
to warrant a conclusive statement at this time. 

Chronic pancreatitis which is etiologically related to 
chronic cholecystitis and calculous cholecystitis as de¬ 
termined by Opie (32) may disappear clinically by the 
surgical removal of the etiologic factors. 

Osteomyelitis may not be benefited by the removal 
of the pyogenic bacteria containing focus of the tonsils, 
jaws, sinuses and other tissues. Rationally the etiologic 
focus should be removed coincidentally with the surgi¬ 
cal treatment of the bone infection. 

Infectious thyroiditis which occurs during a general 
infection, like rheumatic fever, may subside during con¬ 
valescence from the general infection. When infectious 
goiter is due to a focal infection of the tonsils and alveo¬ 
lar abscess, removal of the focus is usually followed by 



diminution in the size of the gland and by a disappear¬ 
ance of the symptoms of thyroid intoxication. This has 
been demonstrated in many individuals, chiefly young 
women patients. The majority of these women were 
overworked and often poorly nourished, with resulting 
lowered immunity to the focal infection. Many of the 
patients are under continued observation and without 
exception there has been no instance of relapse of the 
goiter or of hyperthyroidism. 

Hematogenous focal infection of the nervous appa¬ 
ratus, involving the gasserian and posterior spinal root 
ganglia and spinal cord, affords confirmation of the 
infectious nature of herpes, of insular sclerosis and 
myelitis of the spinal cord. Removal of the primary 
etiologic foci of infection about the upper air tract and 
mouth may modify favorably the course of the spinal 
cord infection. 

The treatment of chronic types of infectious arthritis 
and myositis is usually neglected or so irrationally con¬ 
ducted that failure to benefit the sufferer is the usual 
result. This unfortunate condition is due chiefly to a 
want of knowledge by most physicians of the principal 
factors which cause the morbid tissue changes. An 
attempt was made to explain these principles in Lecture 

In the treatment the primary necessity is to obtain 
a knowledge of the patient’s general condition and to 
locate existing foci of infection which may have been 
the chief primary cause, or still continue to be sources 
of systemic infection. The result of rational manage¬ 
ment will depend, partly in any event, upon the degree 



and character of the morbid tissue changes in the joints 
and muscles, upon the command one may have in the 
management and upon the age of the patient. Destruc¬ 
tive lesions of bones and cartilege, bony ankylosis, ex¬ 
tensive sclerotic changes and atrophy of muscles can¬ 
not be repaired. Indeed because of the destruction of 
blood vessels and the resulting want of nutrition, con¬ 
tinued retrograde metabolism favors the change of the 
connective tissue group, tendons, aponeurosis, ligament 
and cartilage into bone. This is true of all types 
of chronic infectious non-purulent arthritis of what¬ 
ever bacterial type. Therefore, if the treatment is to 
result in the arrest of the disease with advanced mor¬ 
bid anatomical changes or in the recovery of those 
with non-destructive morbid tissue changes, insti¬ 
tutional care is required to insure the necessary 
command of the patient over a sufficiently long pe¬ 
riod of time to remove all focal sources of infection, to 
build up general nutrition and to restore as nearly as 
possible the blood circulation in the infected tissues. This 
method of management is necessary to stop the sources 
of systemic infection, to build up the body defenses 
against the existing systemic infection and to improve 
the general and local nutrition as the chief means of 
arresting retrograde metabolism and at the same time to 
promote resolution of the morbid infectious processes. 
Rationally the younger the patient the readier will be 
the response to the management. 

In the preliminary general examination one may need 
the aid of qualified specialists in the examination of the 
nasopharynx, ears, accessory sinuses, pelvic organs and 



blood, and Rontgen films of jaws and plates of joints 
to locate etiologic infectious foci and to determine the 
degree of the joint changes. Microscopic examination 
and cultures of blood, accessible exudates of joints and 
of foci in the head, pelvis and elsewhere and of the urine 
and feces may give valuable information of the char¬ 
acter of the bacterial infection. Intravenous injection 
of the nascent cultures of the bacteria into animals may 
produce lesions corresponding with the morbid changes 
of the patients’ tissues. With the consent of the patient 
always, a harmless and, under local anesthesia, painless 
removal of pieces of infected muscle, joint capsule, 
fibrous nodes and lymph nodes proximal to the infected 
tissues enables one to study the morbid histology and 
with a proper technic to isolate the causative infectious 
microorganisms from the tissues. But important as the 
study of the exudates, tissues and bacteria may be, the 
real and important principle is to know all that one 
may of the physical condition of the patient. Follow¬ 
ing this diagnosis the management includes: 

1. The removal of all primary and, if necessary, all 
secondary foci of infection. To make sure that all 
sources of focal infection have been obliterated, repeated 
examination should be made. Buried tonsillar tissue 
may be left at the primary tonsillectomy. An infected 
sinus may not have been adequately treated. Alveolar 
abscess may finally require the extraction of the tooth. 
An apparently cured gonococcus infection of the pros¬ 
tate and seminal vesicles may recur. Constant vigilance 
is necessary to insure the abolition of continued systemic 



2. To build up the natural defenses of the body. To 
accomplish this involves close attention to important 

principles including mental and physical rest, nourish¬ 
ing food, restorative tonics when indicated, cheerful en¬ 
vironment, good air and sunshine and with some patients 
the use of suitable bacterial antigens as vaccines to stim¬ 
ulate the formation of specific antibodies in the tissues 
of the patient. Mental and physical rest must be ra¬ 
tionally supervised to meet the idiosyncrasies of the indi¬ 
vidual. Isolation and continuous bed confinement may 
be exchanged for open ward and partial chair treat¬ 
ment to meet the viewpoint of the patient and thus pro¬ 
mote the most efficient rest of mind and body. This 
absolute rest must be maintained until in febrile cases 
all fever shall have disappeared and also until the severe 
soreness of the joints and muscles aggravated by motion 
shall have diminished, for until then the exercise of in¬ 
fected tissues lowers the natural resistance to infection 
and thereby increases the infection of the joints and 
muscles. Often the temporary application of restrain¬ 
ing bandages, splints and casts may favor the diminu¬ 
tion of the local infection. The usually poor general 
nutrition of patients with chronic infectious arthritis 
calls for a generous mixed diet including an abundance 
of fats, oils, green vegetables and fruits. The emaciated 
tissues demand a full allowance of protein-containing 
food, both animal and vegetable. A plentiful amount 
of water, milk, buttermilk, cream and fruit juices must 
be taken. 

When necessary, hematinic and other tonics, laxa¬ 
tives, and simple analgesic palliatives, such as the sali- 



cylic acid compounds, may be judiciously given. There 
are no specific drugs to be used and narcotics should 
be avoided in these chronic diseases. 

The mental depression of this class of patients re¬ 
tards improvement, hence the need of a constant, cheer¬ 
ful environment and an optimistic attitude of all who 
come in contact with them. 

With the sources of systemic infection obliterated, and 
the existing systemic infection diminished or entirely 
controlled by the management described, other measures 
must be added to the treatment which may stop further 
retrograde metabolism, and in favorable conditions 
may result in the restoration of normal anatomical and 
functional conditions of the tissues of the joints and 

These measures are so important that the failure 
to apply them adequately means failure in the whole 
management. The object of their use is to attempt to 
restore nutrition to the starved tissues of joints and 
muscles which have been deprived more or less of blood 
and oxygen by the embolic mode of repeated infection 
from the primary focus, for as long as the infected tis¬ 
sues are starved, conditions exist which are favorable 
to continued infection and furthermore, local malnutri¬ 
tion leads to retrograde tissue metabolism. 

In addition to the measures already advised to in¬ 
crease the general nutrition, the local malnutrition may 
be wholly or partly overcome by an improvement of 
the genera] and local blood circulation. The measures 
consist of hydrotherapy, active and passive exercise, 
local application of superheated dry air and the Bier 



blood congestion method by the application of the rub¬ 
ber bandage. 

Hydrotherapy in the form of alternating hot and 
cold shower or spray baths, applied daily for a few 
minutes, flushes the blood to all the parts of the body 
without fatigue to the patient. If the force with which 
the water strikes the body is relatively high, the im¬ 
provement of the circulation is greater. The tonic 
effect upon the circulatory organs of the application of 
cold water to the skin is well known. A cold plunge 
bath is disagreeable to these enervated patients. The 
alternating hot-cold spray repeated several times in a 
few minutes, is borne without complaint, and the result 
is quite as good as the use of the cold bath alone. In 
the absence of facilities for applying shower or spray 
baths, salt glows and alcohol rubs may be utilized as 
poor substitutes of the cold bath. 

Passive exercise of joints and muscles may be given 
by nurses or more efficiently by individuals trained to 
give massage. Mechanical aids in the form of the Zan¬ 
der apparatus if rationally used give good results. 

Active calisthenic exercises may be so taught that un¬ 
der proper supervision each patient will have the bene¬ 
fit of periods of exercise modified to meet individual 

Other active exercise, like walking, riding, driving, 
swimming and gymnastic work, may be taken up at the 
proper time. An individual qualified by education and 
experience should have the supervision of the treatment 
by baths, and mechanotherapy. Every general hospital 
should have a mechanotherapeutic department with a 



qualified director for the treatment at the right stage 
of the management of the large number of patients, in 
all communities, who suffer from chronic infectious ar¬ 
thritis and of other chronic diseases. If rationally and 
efficiently managed many would be restored to health, 
while in others with more advanced morbid anatomical 
changes the further progress of disease would be more 
or less checked and an improvement of function would 
be gained. 


Serum Therapy 

The prophylactic and therapeutic use of antitoxic 
sera in diphtheria and tetanus is established upon a sci¬ 
entific basis. The specific neutralization of the poison 
excreted by the exotoxic bacillus of diphtheria and bacil¬ 
lus of tetanus, when the respective antitoxic serum is 
properly administered, may be accurately ascertained by 
clinical and laboratory methods. 

The use of specific antisera in the treatment of dis¬ 
eases caused by endotoxic bacteria has been far from 
successful. The principle upon which the value of an¬ 
tisera is based, is that when injected subcutaneously, 
there will be aroused in the body of the patient specific 
defensive forces, in the form of antibodies, leukocytic 
phagocytosis and bactericidal substances which may fa¬ 
vorably modify the course of the disease. In epidemic 
cerebrospinal meningitis the specific antimeningococcal 
serum of Flexner, when injected directly into the spinal 
subarachnoid space, apparently has specific bactericidal 
properties. The injected serum probably arouses tis- 



sue reactions, which mobilizes the defenses of the body, 
increasing cellular phagocytosis, digestion of the invad¬ 
ing meningococci and even acting directly as a bac¬ 
tericide. Other therapeutic antisera obtained by im¬ 
munizing animals with strains of the streptococcus, 
pneumococcus, bacillus of dysentery and other endo- 
toxic bacteria have not given uniform results. The fail¬ 
ure of these sera generally now is recognized to be due 
to several factors, including the existence of variant 
strains of bacteria which may not be differentiated mor¬ 
phologically. Moreover, there may be a marked dif¬ 
ference in the various strains in pathogenicity and viru¬ 
lence and in the tissue reactions of the infected individ¬ 
ual. Each strain may arouse specific effects and the 
results thereof will be influenced only by the therapeutic 
serum obtained from an animal immunized with a like 
strain. This principle has been successfully utilized by 
Cole and his co-workers in pneumonia. They have clas¬ 
sified the pneumococcus into four types, of which types 
I, II and III represent single specific strains and type 
IV a group of strains unlike the first three types. The 
antiserum must be prepared by immunizing an animal 
with the type of pneumococcus which is to be attacked. 
The same principle has been proved to exist in reference 
to the pathogenic strains of streptococci and of the 
strains of the bacillus of dysentery. The principle of 
the necessary possession of “type” specificity of the bac¬ 
teria used in the production of antisera to obtain any¬ 
thing like satisfactory therapeutic results has been ap¬ 
parently established. While it may not prove to be a 
principle to be applied to the preparation of antisera 



of all endotoxic, pathogenic bacteria, perhaps to a few 
only, yet there is in its adoj^tion the hope that a broader 
field of specific antiserum treatment may be developed. 

In our study of focal and systemic infections we used 
the antiserum of the horse immunized with strains of 
streptococcus viridans in the treatment of streptococcus 
viridans endocarditis and in chronic arthritis without 
notable good effect. Apparently unavoidable anaphy¬ 
lactic shock and other objectionable effects compelled 
us to abandon its use. Therefore, the production of and 
the use of antisera in the treatment of diseases due to 
focal infection present problems which present knowl¬ 
edge may not solve. 

Vaccine Therapy 

We know that a degree of immunity to some infec¬ 
tious diseases may be produced in man and animals by 
inoculation with non-lethal doses of living or dead path¬ 
ogenic bacteria. In a few diseases, a mild form of in¬ 
fection or intoxication is produced by the inoculation 
with resulting immunity of variable duration. Attenu¬ 
ation of the virulence of living virus used for inocula¬ 
tion has been successfully practiced to produce a mild 
disease which affords protection to the protean malady. 
Vaccinia in man produced by inoculation with cowpox 
protects against variola. Inoculation with living or 
dead typhoid bacteria and paratyphoid bacilli with 
proper technic will afford immunity of variable time 
duration to typhoid and paratyphoid fevers. These ex¬ 
amples of the use of vaccines in prophylaxis have a very 
limited application in practice. Probably the field of 



application may become broader when we finally recog¬ 
nize the specific etiologic microdrganisms of all infec¬ 
tious diseases which usually give a lasting immunity by 
one attack. Then, as in typhoid fever, prophylactic 
vaccination may become of the greatest use in preven¬ 
tive medicine. 

Vaccination with attenuated virus during a long in¬ 
oculation stage of infection, as successfully practiced 
by Pasteur in man bitten by animals suffering with ra¬ 
bies, will probably not be applicable in other infections 
which have comparatively shorter incubation stages. 
The present use of therapeutic vaccines is based upon 
less stable scientific principles. In 1902 Wright evolved 
the use of autogenous vaccines in chronic infectious dis¬ 
eases. He believed that the natural defenses of the 
body, exhausted by long infection, would be increased 
and mobilized by inoculation with microorganisms of 
the same type and kind which caused the chronic disease. 
He judged the improvement in the defensive forces of 
the patient’s body after autogenous vaccination by esti¬ 
mating the opsonins in the patient’s blood. He argued 
that with an increase of specific antibodies in the blood 
of the patient, the fibrinoplastic exudative barrier sur¬ 
rounding local infectious processes, which afforded pro¬ 
tection to the localized bacteria, would be broken down 
by the mobilization of immune substances. The bac¬ 
teria so exposed would then be readily overcome. Thus 
furunculosis of the skin, due usually to a staphylococcus, 
was more readily overcome by autogenous staphylococ¬ 
cus vaccine. 

It would seem rational, too, that a general chronic 



infectious process would be more readily overcome by 
the use of an autogenous vaccine which would increase 
the natural defenses of the body which have become ex¬ 
hausted by the long battle with the invading bacteria. 
Unfortunately the question involves many unknown fac¬ 
tors. A certain type of pathogenic bacterium, used as 
an antigen, may excite the formation of antibodies in 
the nature of opsonins, agglutinins, precipitins, leukocy¬ 
tosis, phagocytosis and other offensive or defensive proc¬ 
esses, but we may not depend upon a similar result with 
other pathogenic bacteria etiologically related to other 
infectious diseases. We cannot, from present knowl¬ 
edge, definitely expect the same tissue reactions and re¬ 
sulting formation of immune substances in man and 
laboratory animals infected with the same type of in¬ 
fectious bacteria. Indeed the resulting tissue reactions 
and formation of defensive and offensive substances to 
a strain of pathogenic microdrganisms may differ in de¬ 
gree and kind in human beings, dependent on age, race, 
occupation and other factors. Variations of type of 
strains of pathogenic bacteria with corresponding dif¬ 
ferences in the tissue reactions of infected individuals, 
is an important factor in immunological experimenta¬ 
tion. We know that the pneumococcus and strains of 
streptococci not only differ in type, but also differ in 
virulence, and that each type probably arouses defensive 
and offensive forces in the infected individual, differing 
more or less for each type; and possibly the tissue re¬ 
actions are still further modified by the degree of viru¬ 
lence of the invading bacteria. Pathogenic bacteria may 
possess a mono- or polytropism; that is, an elective affin- 



ity for a certain kind of tissue or for several kinds of 
tissues. Therefore, if specific vaccine is necessary to 
arouse specific immune substances to combat offensively 
or defensively the invading infectious bacteria, it implies 
the use of an autogenous antigen. In this sense an au¬ 
togenous vaccine means the use of dead bacteria, proved 
to be of the same specific type in virulence and tropism 
as that which causes the infection of the individual who 
receives the vaccine. In chronic infectious diseases, it is 
often difficult to isolate definitely the microorganisms 
which are the real etiologic factors in a given case. 
Without an accurate bacterial diagnosis one is unable 
to discuss the other vexatious problems which must be 
considered in the elaboration and use of the autogenous 

In our work we have isolated the suspected bacteria 
from the blood, lymph nodes, fibrous nodes, joint exu¬ 
dates, joint tissues, muscles, skin and other infected tis¬ 
sues of patients. To ascertain the tissue tropism we 
have injected animals intravenously and from the in¬ 
fected tissues of the experimental animals, have again 
isolated the bacteria. Vaccines have been prepared from 
cultures made from the microorganisms isolated from 
patients and also from the cultures derived from pa¬ 
tients after animal passage with especial regard to tissue 
tropism. We have also sensitized some of these vac¬ 
cines with antiserum. 

We have used these autogenous vaccines in the treat¬ 
ment of many types of chronic infectious disease. More 
than five hundred patients suffering with infectious ar¬ 
thritis have received the vaccines subcutaneously in doses 



varying from 10,000,000 to 2,000,000,000 and more, 
given every five to seven days, and in rare instances 
daily. The focal, local and general reaction of patients 
was carefully noted. For two years the opsonic index 
and the phagocytic index of each patient were estimated 
painstakingly before and after each vaccination. 

The difficulty of estimating the opsonins and the final 
conclusion that the opsonic index obtained by the most 
careful technic is unreliable led us to abandon that 
method of estimating the results of autogenous vacci¬ 

In place thereof we managed some patients with and 
some without vaccination, but all of them upon the same 
hygienic treatment. The final result was quite as satis¬ 
factory without as with vaccine, in patients suffering 
with chronic infectious arthritis and acute rheuma¬ 

Patients suffering with chronic streptococcus viridans 
endocarditis were not benefited by autogenous vaccines. 
Indeed I believe some of them were made distinctly 
worse when moderately large doses of vaccines were 

The problems which confront the clinician in the use 
of therapeutic vaccines, must be solved by the immunolo¬ 
gist. The views of Theobald Smith (39), Richard M. 
Pearce (38) and others in regard to therapeutic vac¬ 
cines should be read by every clinician. 

Based upon the work of Wright, but disregardful 
of the principles developed by him, therapeutic vacci¬ 
nation has progressed in this country into an irrational 
fad which is intensified and made degrading to the med- 



ical profession and harmful to the patients by commer¬ 
cial greed. 

We are forgetful of the principles of medical practice 
of our fathers. They recognized the influence of old 
age, exposure to extreme cold, poverty and poor nutri¬ 
tion, physical and mental exhaustion, faulty personal 
hygiene and other debility-producing factors in the cau¬ 
sation and also in the prolongation of infectious and 
other diseases. They also recognized the necessity of 
the removal as far as possible of all these contributory 
etiologic factors in the management of the patient. 
The modern vaccinationist pins his faith on the adver¬ 
tised specific virtues of stock vaccines, which he may em¬ 
ploy in polyvalent form to insure a sure-shot effect. 
He believes vaccines will arouse specific defenses in the 
tissues of the patient in spite of all contributory etio¬ 
logic factors of disease. Therefore, the rational diet, 
proper baths, passive and active exercise, correction of 
personal uncleanliness and alcohol misuse are neglected. 
The practitioner usually is ignorant of all laws of im¬ 
munology. It is this want of knowledge which makes 
him believe the ridiculous statements made by the manu¬ 
facturers of vaccines. 

Modern experimental investigation of the physiologic 
action of drugs has done much to restrict the abuse of 
drug therapy of the past. So, too, must the practitioner 
be made acquainted with what we know and do not know 
of immunology. We must restrict the therapeutic use 
of bacterial antigens to those conditions which the 
known laws of immunity and scientific clinical experi¬ 
ence have proved to be safe and of value. 



The Therapeutic Use of Non-specific Protein Anti¬ 
gens Injected Intravenously 

In recent time the intravenous injection of non-spe¬ 
cific proteins (bacterial and others) has been used in 
the treatment of both acute and chronic infectious dis¬ 
ease. The phenomena aroused by a proper intra¬ 
venous dosage consist of a chill followed by high fever, 
great general discomfort, usually a relatively slow pulse 
rate, leukocytosis sometimes of a high degree, not in¬ 
frequently preceded by an immediate leukopenia. Gay 
and Chickering (49) have used the protein, non-toxic 
remnant of the typhoid bacillus by intravenous injec¬ 
tion in the treatment of typhoid fever. The characteris¬ 
tic phenomena noted above resulted. When used after 
the first week of typhoid fever, the reaction was fol¬ 
lowed by a critical fall of the temperature and conva- 
lesence was established in 41.5 per cent. A gradual fall 
of temperature occurred with abbreviation of the course 
in 24.5 per cent, and no permanent benefit occurred in 
34 per cent, of the patients treated. We have used the 
non-toxic protein remnant of pneumococci obtained by 
autolysis of the bacteria, first suggested by E. C. Rose- 
now, in pneumonia. When injected intravenously, the 
typical phenomena occurred with apparent beneficial 
effect, which was most marked if used early in the 
course of the disease. 

In acute rheumatism and also in chronic infectious ar¬ 
thritis, astonishing beneficial effects have been noted 
in a few instances from the intravenous injection of ty¬ 
phoid, of colon and of other non-specific protein anti- 



gens. Jobling and Peterson (48) injected animals in¬ 
travenously with dead bacteria and found that non-spe¬ 
cific ferments were mobilized. They believe that these 
ferments are bactericidal and that at the same time toxic 
substances are rendered non-toxic. The suggestion has 
been made that the severe reaction caused by the intra¬ 
venous injection of a foreign protein, is followed by a 
condition of refraction (anti-anaphylaxis) and the or¬ 
ganism fails to react to the invading bacteria. Jobling 
believes that it will be possible in the near future to use 
intravenously the non-toxic portion of protein to ex¬ 
cite the mobilization of the helpful ferments without the 
painful, disagreeable and even dangerous clinical phe¬ 
nomena which attend the intravenous use of unmodified 
protein antigen. The mode of action of the non-specific 
albumose antigens, injected intravenously, is not well 
understood. Their use in acute and chronic infectious 
diseases affords a fruitful field of combined research by 
the immunologist and clinician. 


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