ASPECTS OF INFECTION AND IMMUNITY IN RELAPSING FEVER

105 Pages·03.762 MB·English

by  STEIN, GEORGE JAY

INFORMATION TO USERS
This material was produced from a microfilm copy of the original document. While
the most advanced technological means to photograph and reproduce this document
have been used, the quality is heavily dependent upon the quality of the original
submitted.
The following explanation of techniques is provided to help you understand
markings or patterns which may appear on this reproduction.
1. The sign or "target" for pages apparently lacking from the document
photographed is "Missing Page(s)". If it was possible to obtain the missing
' page(s) or section, they are spliced into the film along with adjacent pages.
This may have necessitated cutting thru an image and duplicating adjacent
pages to insure you complete continuity.
2. When an image on the film is obliterated with a large round black mark, it
is an indication that the photographer suspected that the copy may have
moved during exposure and thus cause a blurred image. You will find a
good image of the page in the adjacent frame.
3. When a map, drawing or chart, etc., was part of the material being
photographed the photographer followed a definite method in
"sectioning" the material. It is customary to begin photoing at the upper
left hand corner of a large sheet and to continue photoing from left to
right in equal sections with a small overlap. If necessary, sectioning is
continued again — beginning below the first row and continuing on until
complete.
4. The majority of users indicate that the textual content is of greatest value,
however, a somewhat higher quality reproduction could be made from
"photographs" if essential to the understanding of the dissertation. Silver
prints of "photographs" may be ordered at additional charge by writing
the Order Department, giving the catalog number, title, author and
specific pages you wish reproduced.
5. PLEASE NOTE: Some pages may have indistinct print. Filmed as
received.
Xerox University Microfilms
300 North Zeeb Road
Ann Arbor, Michigan 48106
'ft. 3 X 4 4 5
LD3907 J
,G7 Stein, George Jay, 1909-
1942 Aspects of infection and immunity
.S7 in relapsing fever... cNew York.
1942.
2p.l.,73,6, d 3 typewritten leaves,
tables,diagr. 29cm.
Thesis (Ph.D.) - Mew York university.
Graduate school, 1942.
Bibliography: 6p. at end.
A84688
Shelf List
Xerox University Microfilms, Ann Arbor, Michigan 48106
THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED.
1,1 T'RARY OF1
NEW :-G!.;v L‘H TVERSTTY
UNIVERSITY HEIGHTS
ASPECTS OP INFECTION AND IMMUNITY IN RELAPSING FEVER
George Jr.*' Slitfte*in
April, 1942
"A dissertation in the Department of Bacteriology
submitted to the Faculty of the Graduate School of
Arts and Science in partial fulfillment of the re*
quirements for the Degree of Doctor of Philosophy.”
TABLE OF CONTENTS
Page
I. INTRODUCTION 1
II. PRESENT KNOWLEDGE OF RELAPSING FEVER
A. General Features of the Disease 4
B. Bacteriology 5
C. Immunology 7
D. Epidemiology and Geographical
Distribution 11
E. Diagnosis, Prognosis, Prophylaxis,
and Therapy 14.
III. HISTORY AND BRIEF SURVEY OF THE
LITERATURE 16
IV. EXPERIMENTAL FINDINGS
INFECTION
A. Cultivation Attempts 21
B. Strains 26
C. Preservation of Spirochetes 28
D. Routes of Infection 29
E. Distribution of Spirochetes in
Infected Mice 31
F. Sedimentation Test 33
C. Minimum Infective Dose of Spirochetes 35
TABLE OF CONTENTS
Page
IMMUNITY
A.. Separation of Spirochetes from
Infected Blood 36
B. Preparation of Antisera 40
C. The Use of Immunological Methods as
a Means of Classifying Relapsing
Fever Spirochetes 41
D. Immunological Studies with Spiro­
chetes Separated from Infected Blood
by the Use of Saponin 53
E. The Use of Spirochetes Separated from
Infected Blood by Means of Saponin as
an Antigen for the Differential Diag­
nosis of Relapsing Fever 57
V. DISCUSSION 65
VI. SUMMARY AND CONCLUSIONS 73
BIBLIOGRAPHY
ASPECTS OF I1N:1F^ECTION AHD IMMUNITY IN RELAPSING F■jEptVl.EaR
I. IHTRQDUCTIOH
Spirochetes axe only slightly less ubiquitous than ordinaxy
baoteria. They thrive in virtually axy natural environment which is
capable of sustaining aicrobial life. They may exist either in a free-
living state, as commensals, or as strict pathogens. Studies on one of
the latter group of microorganisms from the standpoint of infection and
immunity form the subject of this dissertation.
During the formative period, of bacteriology, careful and
sustained investigations of the sp<Tr>f»h«<>+•«> were largely neglected be­
cause of their position in the ill-defined zone between bacteria and
protozoa. Over the last forty years* sporadic reports of the discovery
of pathogenic spirochetes have appeared in the literature. Certain of
these organisms have been found in lesions of Vincent's angina, bronch­
ial spirochetosis, ulcerations, and. other fuso-spirochetal conditions.
Others have been demonstrated to possess a definite causal relationship
in syphilis, yaws, spirochetal jaundice, and the relapsing fevers of
mas and animals.
Knowledge of the relapsing fever spirochetes is still very in­
complete, although the literature is replete with a bewildering nomencla­
ture and reports of studies, the latter burdened with highly controversial
conqparisons of the various "species1' in this grotq? of organisms.
This confused state may be attributed to the fact that the spiro­
chetes may be found in the blood of vertebrates in most parts of the world
and are implicated in the production of modified forms of relapsing fever.
The type of fever, the character of the symptoms, the mode of transmission,
and the serological qualities present nueerons variations, with the
result that the causative agent from a'particular locality has often
bean given a specific designation. Thus the nuaber of naued species
is ever increasing. Investigators in almost every country throughout
the world have established different species naans, each inferring
specificity* Hence classification is either descriptive of a spiro­
chete indigenous to a particular geographical area or tends to denote
such singular characteristics as were described by the original ob­
servers.
It eay wall be that all these nuearous relapsing fever
"species" are merely local varieties of one widely distributed species,
which has become adapted to different naans of transmission in various
localities.
With this in mind, it would be of interest to determine whether
or not differentiation of relapsing fever spirochetes into many distinct
species is justifiable. Information pertinent to this problem might be
obtained with the aid of sero-iemunological procedures.
Relapsing fever and other infectious diseases are generally
characterised by periods of fever which on occasions may be intermittent
in nature. Attempts to recover the etiological agent concerned are fre­
quently unsuccessful, Moreover, symptoms typical of the disease may be
v
lacking, as may be effective serodiagnostic measures. In such cases
there is a real problem of ready and accurate diagnosis; it is then
difficult to establish which of many infections is responsible for the
pyretic condition. Of the nmeerous infectious diseases other than relaps­
ing fever which present this difficulty, tuberculosis, tularemia, rat-bite
fever, brucellosis, the spotted fevers, typhus fever, Well's disease, the
enteric diseases, syphilis, pneumonia, rheusatic fever, malaria,
and trypanosomiasis nay be mentioned. For this reason the devel­
opment of a reliable method tp distinguish rolapsing fever from
other Infections would be valuable. Attempts to accomplish this
will be described.
II. PRESENT KNOUPOB OF RELAPSING FEVER
JL. general Features of the Disease
The spirochetes of relapsing fever are exclusively para**
sitic and are present primarily in the blood of their hosts. They
are transmitted through the agency of blood-sucking arthropods,
especially ticks and lice. In these ectoparasites the spirochetes
may persist ixdefinitely. The microorganisms generally produce a
relapsing type of fever which affects man throughout the world.
The disease may be described as an acute infectious process,
the causative agent being characteristically present in the circulating
blood during the height of the infection. To some extent it is olinically
distinguishable from the majority of other febrile infections because of
the occurrence of paroxysms which alternate with intervals of apparent
recovery. However, subsequent pyretic intervals do not always occur,
or if they do, an adequate record of their appearance may be lacking.
Clinical distinction then is haphazard•
In relapsing fever the internal organs commonly exhibit
evidences of toxemia} they may be more or less deeply stained with
bile. Degenerative changes of the arteries may give rise to focal
softening of the brain and infarcts of the kidney and spleen. Char­
acteristically, the liver and spleen especially are enlarged, and
spirochetal emboli of the cerebral vessels may be observed. On oc­
casion a macular rash, not uhlike rose spots, may occur and persist
for several days.
The average incubation period of about 2 to 9 days is
followed in the human by the usual prodromal symptoms. During the
primary attack chills and fever of 104° F. or more are common. The
liver is generally enlarged and tender, and the spleen may be readily
palpated. The initial seizure lasts approximately 5 days, when
defervescence occurs and the temperature rapidly returns to normal
with apparently complete restoration of health. However, this picture
merely represents the end of the first paroxysm and rushers in the
beginning of an afebrile interval.
After about 1 week of seeming normalcy, the primary relapse
sets in. Here the symptoms tend to duplicate those present in the
initial attack, but they are generally less severe and of shorter
duration. A second afebrile period, usually lasting longer th«n the
first, succeeds the primary relapse. As the disease proceeds on its
course, second, third, and even more relapses may take place, each
progressively less prolonged and each interrupted by increasingly
extended apyretic intervals. A case showing as many as eleven relapses
has been recorded.
B. Bacteriology
The spirochete of relapsing fever may be described as a
spiral, loosely wound, flexible, actively motile microorganism,
measuring about 14/u.long and O.^u.thick; it is composed typically