as nearly as can be ascertained, 169 deaths, giving a rate of
mortality of 14.4 per cent. Taking all the cases admitted to the
hospital under our observation, many of which entered at a late period
of the disease and not a few when moribund, the mortality was not less
than 13 per cent. {423} The mortality among the negroes who were
attacked with the disease was considerably greater than among the
whites. Finally, if the mortality of the bilious typhus form be
considered separately--although from the frequency of jaundice in this
epidemic and the numerous gradations of severity presented it is
difficult to form a sharply defined group of this character--it was
certainly not less than 50 per cent.
The date of death varies with the epidemic, the form of the disease,
and the previous condition of vitality of those attacked. Ordinarily,
by far the larger proportion of deaths occur during the first relapse
or the second interval, but in bilious typhoid cases, presenting grave
complications, especially pneumonia or severe hemorrhages at an early
date, or in cases occurring in intemperate subjects, or in those
previously in impaired health, the mortality is much heavier in the
initial paroxysm or the first interval than at later periods.
Youth exerts the same favorable influences upon the result of
relapsing fever as it does in the case of typhus and typhoid.
Murchison states that of 717 male patients under twenty-five years of
age admitted into the London Fever Hospital, not one died, and in most
epidemics similar, though not equally marked, results have been noted.
In some epidemics the mortality among young children has been
considerable. As a rule, the percentage of deaths increases with each
decade after thirty years.
Sex does not exert any definite or constant influence upon the
mortality. The number of males affected is far greater; they are
liable to be exposed to the contagion in its most concentrated form; a
larger proportion of them are probably the subjects of intemperance
than in the case of females; and thus most statistics agree in making
the mortality somewhat greater in the male sex; but, all things being
equal, there is no good reason for holding that sex itself has any
value in determining the result.
As in other zymotic diseases, the mortality from relapsing fever is
highest during the early period of an epidemic, and the type of the
disease grows milder as the epidemic declines. Cases of the bilious
typhoid form have become notably less frequent during the later stages
of some epidemics than at an earlier period.
Marked difference has been observed also as to the action of remedies
at different stages of epidemics, the early cases exhibiting an
extraordinary resistance to remedies, and especially to anodynes,
which passes away later. When typhus and relapsing fevers have
prevailed together, and a clear discrimination between the two sets of
cases has not been made, it has appeared that the mortality increased
as the epidemic advanced, but this apparent exception has been due to
the fact that at first the cases of relapsing fever were in the
majority, while later those of typhus, the much more fatal disease,
preponderated.
Epidemics of relapsing fever prevail at all seasons, but more commonly
they are at their height during the colder months of the year. The
total mortality will of course correspond, but the actual percentage
is not constantly greater during any one season, although it is
probable that the greater liability to chest complications during the
colder months will render the disease more fatal then.
The gravity of relapsing fever has varied so greatly in different
epidemics that it is very difficult to determine what influence upon
the mortality {424} has been exerted by mere difference of race. A
further source of difficulty is found in estimating the differences in
the physical conditions of the poorer classes in the various
communities affected. The mortality has been exceptionally high in the
Russian and Indian epidemics and in some of the German ones, while in
the British epidemics it has uniformly been light. It is interesting
to note that in the Philadelphia epidemic, where the great majority of
patients were Irish or negroes, the mortality was high, over 14 per
cent. The previous condition of the Irish patients must certainly have
contrasted favorably with that of the individuals attacked in the
Dublin and Belfast epidemics, so that the difference in result seems
attributable only to a greater virulence of the disease. As an ample
opportunity was here afforded to judge of the relative severity of
relapsing fever in the negro and white races when the cases occurred
at the same season, at the same stage of the epidemic, and in
individuals living under nearly similar conditions, it may be stated
that the conclusion of all who studied the question closely was that
the disease was much more severe among negroes, and in particular that
they displayed a greater tendency to serious complications and to the
bilious typhoid form.
Although the degree and virulence of the infection undoubtedly
constitute the most important elements in determining the mortality,
the previous health and habits of those attacked with relapsing fever
exert an influence upon the result. This is especially true of
habitual intemperance, which, by disposing to disease of the liver and
kidneys, greatly increases the liability to a fatal result. It has
been seen (page 409), however, that even when acute catarrhal
nephritis existed at the time of the attack severe relapsing fever
might terminate favorably. Another observation which we made
frequently, and which coincides with what is well known in regard to
typhoid and typhus, is that improper exertion and exposure during the
stage of incubation and immediately after the invasion produced a
highly unfavorable effect on the subsequent course of the disease, and
seemed in particular to dispose to dangerous or fatal collapse at the
critical periods.
Apart from these general considerations, there are many special points
to be considered in regard to the prognosis of relapsing fever:
If after the crisis of the invasion there is not rapid and decided
improvement, complications should be suspected.
A sharp rebound of temperature quickly following crisis may be
followed by speedy death.
Mere elevation of temperature during the invasion and the relapse,
even though to an extreme height, is not attended with the danger
which even a somewhat lower degree would indicate in other zymotic
diseases.
Increased elevation toward the expected time of crisis should arouse
anxiety, as sudden and dangerous cerebral symptoms may occur.
Prolonged duration of the pyrexia, or the substitution of irregular
gradual defervescence (lysis) for the characteristic crisis often
associated with typhoid symptoms as are these conditions, is
significant of complications and of danger.
Wild delirium during the pyrexia, or transient active delirium about
the time of crisis, is not necessarily unfavorable, but continuous low
delirium, with disposition to stupor, is associated with a typhoid
tendency and is frequently followed by death. Excessive muscular {425}
tremor or convulsions are highly unfavorable, but not necessarily
fatal, symptoms.
Cardiac murmurs are not of serious import. The pulse is not usually as
rapid in proportion to the temperature as in typhus or typhoid, and an
excessively rapid pulse toward the expected time of crisis, especially
if associated with feebleness of the heart's action, points to the
danger of sudden collapse at or soon after that time. Previous cardiac
disease, especially fatty degeneration in habitually intemperate
persons, increases this danger. Continued frequency of pulse after the
crisis indicates some complication or the danger of some accident.
Cough of a bronchial origin is not a specially unfavorable symptom,
but if associated with the physical signs of pneumonia and with marked
disturbance of respiration it indicates extreme danger.
Epistaxis, even when copious, often occurs in favorable cases, but
hemorrhage from the stomach or the kidneys is usually, though not
invariably, followed by death.
An eruption, measly or of pink spots, with or without minute petechiæ,
is rare, and usually occurs in severe cases, but is not of specially
unfavorable significance unless associated with the typhoid state or
with patches of purpura.
Hiccough is a much less unfavorable symptom in relapsing fever than in
typhoid or typhus, and vomiting, even frequent and persistent, may
occur in cases of ordinary severity.
Enlargement of the liver and spleen indicates special risk only when
persistent for some time after the relapse, in connection with
persistent irregular fever. Jaundice has no necessarily unfavorable
signification, is frequent in ordinary cases in some epidemics, but
when it is associated with the other features of the bilious typhoid
form the danger is extreme, at least 33 per cent. of such cases
proving fatal.
Slight transient albuminuria may exist without special danger, but if
associated with evidences of catarrhal nephritis, or if extreme
diminution of urine, with or without albuminuria, exists, cerebral
symptoms are apt to ensue, with a high degree of danger.
All serious complications--parotitis, erysipelas, dysentery, abortion,
pneumonia, and, above all, peritonitis--greatly increase the risk.
It is not possible to determine in what cases the relapse will fail to
occur. Motschutkoffsky's statement, that when a slight post-critical
rise occurs a relapse will follow, must be applicable only to a
limited number of cases.
In all cases at least one relapse must be expected; the patient in the
interval must be regarded as still sick, and after the close of the
relapse he must still be treated with rigid care until convalescence
is permanently established. It must be remembered in hospital practice
that many patients enter toward or after the crisis of the first
paroxysm, so that caution is needed in estimating the effect of
remedies and the period of the disease.
The undue prominence of certain conditions during the course of the
disease is apt to be followed by corresponding sequelæ, and
emaciation, anæmia, dyspepsia, diarrhoea, dysentery, enlargement of
the spleen and rheumatoid pains may then be anticipated. The liability
to ophthalmia and affections of the middle ear is not to be forgotten.
{426} CAUSES OF DEATH.--In fatal cases death occurs from exhaustion
dependent on the protracted and severe sufferings of the patient; from
cerebral symptoms; from hyperpyrexia; from the virulence of the
toxæmia; from uræmic poisoning; from sudden collapse; or from some
complication, such as hemorrhagic meningitis, hemorrhages, pneumonia,
dysentery, rupture of the spleen, peritonitis, or abortion.
TREATMENT.--The indications for treatment presented by regular cases
of relapsing fever seem to be--to moderate the pyrexia; to relieve
distressing symptoms, especially pain, insomnia, and gastric
irritability; to sustain the strength of the system; to prevent or
modify the relapses; and to avoid complications and sequelæ.
It is needless to observe that until the nature of the specific cause
of relapsing fever is fully determined, whether the spirillum occupy
that relation or not, it is impossible to direct our efforts
rationally toward its neutralization or elimination. The various
remedies which have been employed for these special purposes have no
clinical support to recommend them. And while experiment has shown
that the activity of the spirillum is readily destroyed by the direct
action of various weak solutions, as of quinine, carbolic acid,
iodine, and mineral acids, no special curative effect follows the
internal administration of these remedies, even in the largest doses
consistent with safety. In fact, there can scarcely be any disease in
which treatment is less satisfactory or its results more difficult to
estimate. The marked difference between various epidemics, and the
wide variation presented by the development of individual symptoms in
different cases of the same epidemic, fully account for this.
Quinine, as might be expected, has been largely used, in the hope that
it might control the pyrexia or prevent the relapse. Murchison[39]
quotes a considerable amount of evidence from various sources to show
that it does not possess either of these powers. It was administered
to a considerable number of our cases, either in small and frequently
repeated doses during the pyrexia or the intermission, or else in
large doses repeated several times in immediate anticipation of the
expected time of the relapse. Thus in some cases three grains of
sulphate of quinia were given every two or three hours until tinnitus
was produced, and then this was maintained during the remainder of the
pyrexia and of the intermission. The amount given daily was from
thirty to forty-two grains. It seemed to rather increase the
discomfort in the head, and in some cases it aggravated the
irritability of the stomach. The pyrexia was certainly not controlled
by it. Given in the same manner during the intermission, it was
usually well borne, but was not effectual in preventing the relapse.
It is true that in some cases the subsequent relapse seemed to be
somewhat modified.
[Footnote 39: _Op. cit._, p. 408.]
Thus in one case 30 grains were given on the 6th of April; 39 grains
on the 7th; 39 grains on the 8th; 42 grains on the 9th; and 60 grains
on the 10th; the critical fall had occurred during the night of the
7th, and the relapse began on the evening of the 9th, but the rise in
temperature was less abrupt than usual, and the relapse lasted less
than five days. It was quite severe, however, so that it is doubtful
whether the apparent modification was anything more than is frequently
observed in cases where no quinine has been administered.
In another case the fall in temperature at the end of the first
paroxysm {427} was from 105.5° to 97° on March 26th: 35 to 40 grains
of sulphate of quinine were given daily on April 4th, 5th, 6th, 7th,
and 8th; the temperature began to rise on the 3d, but the severe
pyrexia and the usual symptoms of the relapse were limited to a period
of less than thirty-six hours. This is a less common irregularity, and
yet does not afford sufficient evidence of the efficiency of quinine.
In other cases, however, as already stated, no appreciable effect
followed its administration in this manner.
To illustrate the other method of giving quinia, a case may be quoted
in which 20-grain doses every three or four hours were given from
April 25th to April 29th, so that in four days 575 grains were taken.
The initial paroxysm was of average severity, and terminated at the
end of the seventh day, April 20th. The quinine did not postpone the
relapse, which occurred on April 28th, but was of much less than the
usual duration.
In no other case in which these large doses were given was there even
as much reason as in the above instance to attribute to quinine any
positive influence upon the course of the disease.
In order to demonstrate that the failure of quinine was not dependent
upon a want of absorption, Muirhead injected large amounts
subcutaneously with no better results.
In conclusion, it may be said that the evidence shows positively that
quinine possesses no specific influence whatever upon relapsing fever;
that in only occasional cases, if at all, will even enormous doses
given during the intermission postpone or modify the subsequent
relapse; and that it is not effective in reducing the temperature. In
view, therefore, of the usual gastric irritability and tendency to
vertigo and headache, which seem to be increased by large doses of
quinine, and, further, in view of the small mortality, and of the fact
that when death occurs it usually comes from causes over which large
doses of quinine could exert no influence, it seems clear that this
drug should be prescribed only in tonic doses and only in cases where
it is well tolerated by the stomach.
Arsenic was used in a considerable number of our cases with the view
of determining if it possessed any power of relieving the severe pains
or of influencing the relapse. It was administered in the form of
Fowler's solution (Liq. potassii arsenitis), and was given exclusively
by the mouth. If given during the intermission, it was well borne in
doses of five to ten drops every four or even every three hours, given
freely diluted with water and immediately after food. In several cases
it quickly induced puffiness about the eyes, but no effect whatever
was produced on the pains or on the succeeding relapse. In more than
one such case there was an unusually profuse crop of sudamina during
the relapse, many of the vesicles breaking and being followed by
brownish stains. When given during the pyrexia it aggravated the
nausea and vomiting, so that it had to be suspended. In one
unfortunate case, indeed, although promptly suspended, the arsenical
solution seemed to have assisted in the establishment of vomiting and
purging, which proved uncontrollable and contributed greatly to the
fatal result. Hypodermic injections of arsenic have been used
considerably with no better results. There seems, therefore, to be no
reason whatever for any further use of this drug in relapsing fever.
{428} The high pyrexia and the severe rheumatoid pains have naturally
suggested the use of salicylic acid and the salicylate of soda. We
were not sufficiently aware of their antipyretic properties in 1869-70
to have recourse to them, but in more recent epidemics Unterburger[40]
and Riess[41] have found that large doses of the latter substance (one
hundred grains or more daily) will reduce the temperature either in
the initial paroxysm or in the relapse, but that the disease is not
cut short nor are the lesions of the blood or solids prevented.
[Footnote 40: _Jahrb. f. Kinderheilk._, v. x., 1876.]
[Footnote 41: _Deutsch. Med. Wochnsch._, Dec., 1879.]
It must be borne in mind here, as in connection with the action of
quinine, that apparent modifications of the relapse are to be viewed
with great distrust, since such great irregularities therein naturally
present themselves. Care must further be taken lest such attempts to
reduce the temperature aggravate the irritation of the stomach, and by
lessening the power of taking food induce more serious exhaustion than
would have resulted from the unchecked pyrexia. The evidence in our
possession is not sufficient to justify a positive decision as to the
therapeutic value of the salicylates in relapsing fever, but,
apparently, they are applicable to only a portion of the cases, and in
these are of but limited utility.
The same failure which has followed the use of quinine, of arsenic,
and of salicin and the salicylates has attended the effort to prevent
the relapse by berberine, benzoate of soda, tincture of eucalyptus,
and other reputed antiperiodics.
Digitalis, veratrum viride, and aconite were used by us quite freely
as antipyretics. The first two of these were often suspended on
account of the irritability of the stomach, and no valuable results
followed their use when well tolerated. Aconite in small doses,
frequently repeated, as one drop every two hours, seemed to aid in
allaying nausea and to exert some slight influence upon the fever. In
cases where there was a distinct tendency to heart-failure, digitalis
was given freely with advantage.
Cold baths were not used to reduce the temperature in any of the cases
under our observation. They have been employed in other epidemics,
but, as far as we know, with no other effect than to cause merely
temporary lowering of temperature, without any decided relief to the
other symptoms and without any apparent influence upon the course of
the disease. Frequent spongings with cool water and the application of
ice to the head gave only slight and temporary relief.
Simple febrifuge remedies, such as effervescing draught or spirit of
nitrous ether with solution of acetate of ammonium, were well received
by the stomach, and appeared to promote perspiration and the more free
secretion of urine.
Finding all our efforts to control the pyrexia so unsuccessful,
recourse was had in a large proportion of our cases to the
hyposulphite of soda, given, dissolved in two ounces of water, in
doses of twenty grains every two or three hours. In two cases it
seemed to increase nausea, and at times it caused some purging, but
otherwise it was well borne by the stomach, and, indeed, frequently
appeared to aid in controlling vomiting. The records show that this
drug was given in only two or three of the fatal cases, so that
although the patients who took it regularly presented every grade of
severity of the disease, they did well uniformly. It is certain,
however, that the hyposulphite of soda exerted no specific effect
{429} upon the disease; it did not reduce temperature, it did not
prevent or modify the relapses nor relieve the severe pains; it may
have promoted more free and healthy secretions, and, by tending to
prevent vomiting, may have aided in maintaining nutrition; but, on the
whole, it may fairly be doubted whether this remedy merits any more
extended trial.
One chief reason of the failure of antipyretics in relapsing fever is
to be found in the existence of widespread irritative lesions of the
glandular and mucous tissues, which combine with the specific
blood-changes in causing and maintaining the high temperature. It is
not surprising, therefore, that the remedies which afford the greatest
relief in this disease are opiates and sedatives to the
gastro-intestinal mucous membrane. Opium, or morphia, must indeed be
regarded as the basis of the rational treatment of relapsing fever. It
is called for by the insomnia, the severe headache and the pains in
various parts of the body, the nausea and vomiting, and the pyrexia.
It does not appear to have been as prominent a feature in the
treatment of other epidemics as we found it necessary to make it in
Philadelphia. Parry[42] used it very freely, chiefly in the form of
opium, by the mouth, and found a singular tolerance exhibited by his
patients, several of whom took as large a dose as three grains every
two hours during the afternoon and night without producing any sleep
or even any contraction of the pupils. This resistance to the action
of opium was observed chiefly in the early part of the epidemic, and
we may add that it was exhibited chiefly when opium was given by the
mouth. When morphia was used hypodermically we found that one-fourth
of a grain, given at intervals of six to twelve hours, afforded very
great relief to the pains, aided and relieved vomiting, and often
induced quiet, refreshing sleep. Its use was not contraindicated by
jaundice, by cough or pulmonary congestion, or by moderate contraction
of the pupils. It was frequently given so as to maintain decided
drowsiness throughout the pyrexia. When the pains persisted during the
intermission the morphia was continued in smaller doses or at longer
intervals. It occasionally happened that when patients were thus kept
continuously under opium influence no relapse occurred; but here, as
in regard to the action of quinine, it may safely be asserted either
that what was regarded as the initial paroxysm was in reality the
relapse, or else that the absence of a relapse was a mere
irregularity, and in no way to be attributed to the action of the
opium. On the other hand, in cases presenting a tendency to the
typhoid state, with a disposition to stupor, or where the urine was
scanty and albuminous, no opiate was administered.
[Footnote 42: _Loc. cit._]
We have already stated that in our cases quinine in acid solution was
frequently ordered, and it answered very well to add to each dose of
this a suitable amount of morphia.