State Medical Society at Grand Rapids, May 27,
1904, and approved for publication by the Com-
niittee on Publication of the Council.
Mamorek (London Lancet, April 26,
1904, page 855) has recently ^further
elaborated.
Briefly expressed it is as follows : Tu-
berculin is only a "reactive," which causes
the tubercle bacilli to secrete another and
hitherto unknown toxin. This toxin, he
believes, causes the fever, which produces
the reaction.
Whatever opinion we may have of the
effect upon a tubercular subject of the
continued use of tuberculin, we must, in
the face of the evidence which we have,
disabuse our mind of the idea that tuber-
culin, when used as a diagnostic measure,
is detrimental to the human organism.
Pottenger (Therapeutic Gazette, 1903)
has recently collected statistics on tuber-
culin from different sources, including
over 3,500 cases, where tuberculin was
used as a diagnostic agent, without ill ef-
fects. There is no evidence to show that
any disease, excepting tuberculosis can re-
act to tuberculin, notwithstanding asser-
tions which have been made to the con-
trary. Therefore we can say, with cer-
tainty, that a "reaction to .tuberculin"
Digitized by VjOOQIC
5i6
VALUE OF TUBERCULIN TEST— NEFP. Jour. M. S. M.S.
means tuberculosis. Unfortunately the
degree of reaction is not indicative of the
degree of infection, as pitients with a
localized tubercular lesion have shown a
marked general reaction ; while cases with
a widespread tubercular process, amenable
to the test may react only mildly.
To appreciate the delicacy of this diag-
nostic measure it would be necessary to
have autopsical findings immediately suc-
ceeding the test. Although this is not
practicable as regards man, it is f ossible
to obtain some facts from cattle which
have been slaughtered after reaction to
tuberculin. It has been the fortune of the
writer to assist in such postmortems —
postmortems which have been made a few
hours after the animal's reaction to tuber-
culin. Although the number (30) has
perhaps been too small for definite con-
clusions, th^ cases have been studied thor-
oughly as regards reaction and postmor-
tem findings. All attempts to establish
the exact relation of the degree of infec-
tion to the reaction obtained were unavail-
ing. Several cases, showing tuberculosis,
involving only one gland, gave intense re-
action; while others with extensive, dis-
seminated tuberculosis reacted only mod-
erately. These conditions were also found
reversed. It seems to me that veterinar-
ians should investigate this question more
extensively, as it is only in this way that
we can obtain any information regarding
this important point.
The tuberculin test in cattle is consid-
ered conclusive, and justly so, if we stop
to consider that in 90 per cent, of the ani-
mals reacting we find tuberculosis. The
value of the test is enhanced when we con-
sider that in the 10 per cent, of failures
are included errors made by the investiga-
tors, such as failure to consider the con-
dition of the animal before the injection
Pulse Rcspi
ITO
70
too
65
I50
60
MO
55
130
SO
GO
45
UO
40
100
55
90
dO
80
25
70
ao
00
ts
50
iU
40
5 .
do
Chart sbowiag exaggerated reaction in an old case of tuberculosis, 12 hours after en initial injection of la ms.,
with a period of latency and the exaggerated reaction 6 hours afteiwaids/' ^ /^^/-\r^\/r>
Digitized by VjOOQ IC
December. 1904. VALUE OF TUBERCULIN TEST— NEFF.
5'7
Temp. Pulse Resp.
107
loe
106
104
lOd
102
101
100
00
06
07
00
Temp.
Resp.
S
I ! 1 jo ' * 1 '
! • <n ,1 J . _ .. .._i. _ ... , 1 ±
*: '
' 'V i * 1 1
^ r ;-t-t-i4 -f- i|j.j- t -p )-. -+
• S^ t /N.
^^f 1/ ^-
i.-4-j-^- ^ - ^- -i-4- ii. ^-^-H~ y - ^-f 4 - 4- -f - - ^- - 1- -
1 1^/ At ' ^
i i 1 1 . Ji . i ' t i ^V-i
â– â– t ^ + I 1 * ^ f < 4 -f j ^
..^ i / 1 ' 1 , Vo-
' â– >^ / M >
1 /\ ^-^ / Vi / , , ^ , S.
1 1 i V\ / r "^ ^ M 1 ^
"" j"^' â– "^v_7""" -^Y^-^" r 1'"' ^"^'' ' ""
1 ! ' i ^ 4
j ' t ' j M ^ ^
' • ! U i ,
1 f ■♦ , j f f . ^ ^ ^ 1 j .,
! â– 1 i i ' 1
• 1 t : 1 1
â– â– 'â– â– j i â– â– ": : â– â– â–
j \ \ P M
S^ 'ft'-l • * -• • J H = -1 yi? -■' •■= ^ • ' -■' - i)? i ' • » - 3 ''•■'
N^^>^S*1^^*j-tHV»K|<»khHS«H«*^-i'-^H'iH-H^^^^^»i- 1 1
's: ^^ 4 ^
170
70
100
65
150
60
140
66
IdO
60
120
45
110
40
100
35
00
30
60
25
70
20
60
15
60
to
40
5
30
Chart showing ej^ag/^erated reaction in an old case of tuberculosis, 12 hours after an initial injection of 12 mg.
with a period of latency and the exaggerated reaction 6 hours afterwards.
Temp.
JPay^
Pulse
Resp.
170
70
100
65
150
60
140
55
130
50
120
45
no
40
100
35
00
30
00
25
70
20
00
15
50
10
40
5
30
Chart showing exaggerated reaction in an old case of tuberculosis, 12 hours after an initial injection of 12 mg..
with a period of latency and the exaggerated reaction 6 hours afterwards. ^ ^ 1
Digitized by VjOOQIC
5t8
VALUE OF TUBERCULIN TEST— NEFF. Jour. M.S.M.S.
..i:ii±^
rrrrt-dxb:
;^ [..j.j.!4-.! ki-i-i-n H-
-il J.Li i 4.4..L..;.H..4-i i-.L
i:ri:ritlTiHH-t4!-M-l
50
Chart showing a possible reaction obscured by preliminary temperatures, in a well defined case of tuberculosis.
Temp. Pulse Resp.
i ! • I !
Pulse Resp.
170
70
MO
M
150
CO
MO
55
130
50
CO
45
110
4C
100
55
00
30
80
25
70
20
00
16
50
10
40
5
Chart showing a possible reaction obscured by preliminary temperatures, in a well defined case of tuberculosa.
Digitized by VjOOQIC
December, 1094. VALUE OF TUBERCUUN TEST— NEFF.
_p»y
Chart showing a possible reaction obscured by preliminary temperatures, in a well defined case of tuberculosis.
Temp.
107
100
106
104
103
102
101
100
»9
90
97
96'
Temp..
IHilse
Resp.
]..!.. Mj4.:.
jLtiri "111. J ";":'
.4..4-i.a.„
H-4"- f-t~-f -T • t'i"^ "
yjjj...L.uJ.±.\ .
4.4-..J-
.4..,
M
^J,J...4..4-j
-1 — !"~r— r— r
H-.U-.|.-.i.4-
Pulse Resp.
170
70
100
06'
160
GOV
MO
66
130
60!
120
45"*
HO
40.
100
36^
00
30*
80
26V
TO
20 ••
00
16
50
10*
40
6
30
Chart showing characteristic reaction 12 hours afttr second injection.
Digitized by
Google
520
VALUE OF TUBERCULIN TEST— NEFF. Jour. M. S. M.S.
is made, and mistakes made in placing the
proper value on the individual tempera-
tures. Correspondence and interviews
with those using the tubercuHn test in cat-
tle have confirmed these views.
The value of the tuberculin test in man
is thought to be considerable. A conser-
vative estimate of its failure when used
in the diagnosis of human tuberculosis is
5 per cent. This percentage, however,
would probably be materially reduced if
the errors in conducting the test were
eliminated. It should again be borne in
mind that the test, although a simple one,
is notwithstanding a scientific one, and
like all diagnostic tests is likely to suffer
in the hands of a careless manipulator.-
The following are the facts which we
have regarding the use of tuberculin as a
diagnostic agent: (1) It is an invalua-
ble aid to diagnosis in the early stage of
tuberculosis. (2) A reaction to tubercu-
lin is positive proof that the case is one of
tuberculosis. (3) There is no positive,
clinical proof that any disease, excepting
tuberculosis can react to tuberculin. (4)
A reaction to tuberculin is not significant
of the degree of infection.
The debatable points are as follows:
(1) The time necessary for preliminary
temperature — namely, the temperatures
taken before the injection. (2) The dos-
age when used for diagnostic purposes.
(3) The reaction. (4) The possibility
of a reaction in a case apparently cured.
It is to these questions which I have at-
tempted to answer that your attention is
asked.
(1) Tuberculosis is an infectious dis-
ease, and like all infectious diseases, has
a temperature involvement. Fever is only
absent when the disease is in its early in-
cipiency; or when the vitality of the pa-
tient is such as to prevent a reaction of
the organism.
When taking temperatures preparatory
to the tuberculin test it is of extreme im-
portance that we also consider the daily
fluctuations of temperature which are
commonly found in adults. It is essential
that we bear in mind the influence of in-
ter-current disease and conditions on the
bodily temperature. I would emphasize
these requisites, as a failure to consider
these conditions might lead to serious
error. In order to detect these variations
in temperature the teriiperature of every
individual to be subjected to the test
should be taken bi-hourly for a period of
at least 24 hours. The necessity of hav-
ing accurate preliminary temperatures
will be better appreciated when we con-
sider the import of the reaction.
(2) When tuberculin was first used for
diagnostic purposes, extremely small
doses were employed and the employment
of as much as two mgs. for a dose was
strenuously opposed by its most sanguine
promoters. We now know more of tu-
berculin and recognize that the effects at-
tributed to the larger dose were not
founded on authentic, clinical experience.
The continued use of tuberculin has
convinced us that small doses often pro-
duce no reaction; but tend to establish a
tolerance against larger doses. An ini-
tial dose of six mgs. is recommended,
which can be followed by a second dose
of twelve mgs. if necessary, 24 hours
after the primary injection. The dosage
advised is the one which I have employed
during the past few years witli satisfac-
tory results.
(3) The general reaction to tuberculin,
as is well known, consists of a fever, with
ordinary febrile symptoms,^ appearing at
Digitized by VjOOQIC
Decembbr, 1904. VAI,UE OF TUBERCULIN TEST— NEFF.
521
Pulse
Reap.
170
70
KM)
05
160
00
140
65
130
60
120
45
^
110
40
100
35
00
30
fiO
25
70
20
00
15
50
10
40
6
.^0
Temp.
107
100
105
104
103 [-X.|_l - 4 - -i - i- L.| - l - 4 -
> . I . .....
102
101
100
99
98
97
90
Temp.
Pulse
Resp.
Chart showing characteristic reaction is hours after second injection
1 ! I ! ! ! I I J
±ffl3TH3STCTtl:E:t:E
U_4..1..J-..i_i_.:.J..l
j_4_4_4-.....i_i..i.]...;-^.' '
â– .i:m:;a;j
•i.-j. .L.4...J....
H^
H-fnfl-f-nrm- I â– jT-J- ;-t-i-i-j: jg -] -:-r-|- j - r
: : i ! < i i ! i . â–
4.4-i.4-U-T4- * ' ' i
it;
-4-f-T-i-hti-+-' 4.
jxnx:
! I i !
â– rrtT'
Pulse Resp.
170 70
100
150
140
150
120
110
100
90
00
70
i.- 00
50
'lO
30
05
60
55
50
45
-40
35
30
26
20
15
10
3
Chart showing characteristic reaction 12 hours after second injection.
Digitized by
Google
522
VALUE OF TUBERCULIN TEST— NEFF. Jour. M. S. M. S.
Resp.
^
•v^>-5|t
5.
- â– â– A- -4.
i=
XS
H
-^HH^l
i^^
^^
K,
l*HV-?lt
-i-^^
^ > 4 ' ^
u
.•N-* - ^^
'it
^«*5|C
Pnlae Resp.
170
70
160
0&
150
00
140
55
130
50
120
45
no
40
100
55
00
50
80
25
70
20
GO
15
50
10
40
5
30
Chart showing exaggerated reaction 12 hours after second injection of tuberculin.
Temp.
107
100
105
104
103
102
101
100
90
90
07
90
Temp.
Resp.
.T>«y —
.....{
"I" i-H
-4-1-
4...L
-4 _.j.„4..-.,.. 4.
..„ ; .4....J .4... ...4.. ....♦
' I i
• - I - I — \ -4
-♦ -< â–
U...\..
t±t
-i-i-
XXI
Pulse Resp.
i i !
nxu
Ktffiri-t-H
170
70
MO
65
ITjO
60
140
55
130
StO
UO
45
no
40
100
35
00
30
80
25
70
20
60
15
50
10
40
5
30
Chart showing exaggerated reaction 13 hours after second injection of tuberculin,
Digitized by
Google
Dkoember, 1904 VALUE OF TUBERCULIN TEST— NEFF.
523
Temp.
107
..i-^._ 1 [_^.J 1 K..,.]...!
- 1- -r -1 i i J 1 1 . 1 1
L » ^ 1 i - 1 ^
..J.J.: _.r.4-izl 1 r t"
foe
j . J J 1 1
j ! 1
[ t r "^ ' i
105 ...^..,
j~^ 4 i i ^ "1
i 1
« ..i. . A J . 1.. i
104 . |Z
] ~i .•o( liy 1 . ^ 1
f + 1 ♦ r - |-f -• ^
_ XjiLj-l- .- ji|j^ -n/i- ..;... _.i...u-4..-.|-.- -
103 . -H
r:l::fl;:^±:l::;^::
14-1 3^ 1 \I I la
10?
L .iTi L t I ^ i?
i i 1- I *'^iJ- i \ 1 ' 1
; 1 C / ^ ) ^ ^
101 . _^
f.„^_l„ ^^_. -j-4 - .-|
~4 j • jS 1 / i - . ^- - j
\ * ^ y-*"\- ^ /J
" ; 1 / \ f
100 -+-H
U4 .{- f -4â„¢, ^ JJ.
"T t- — - +— t- - n > jf-»- j-V- - 4— t— ...4.-.
90 ...j H
;::i±.i+tW
-. ._ _i T :. J; t .:3 _. ±iA.„.|_.r .j1 .: , ,LLl
96 _H H
rr. H~^ -]-i-^..|.
- ip- - j-JA^jll'^-.'J - yi^
07 ..^
96 -4—
TMnn
p,:-'^-ia'-9±^qji^q^.::ri:Fp^^^^^^^^^^^
U^;B:li:iA
:ktj...::li:;.H
J^ - t - !-[ - -| - -+ - 4 - -
j . 1 1 "^
Pulse ...4
! f f ^ ' ' 1 t
> zji . X :. :.. ip' : z\ ..nq: :. . " :: r: :: :r r
Resp. . —-.
^. ;=;=f. â– -^p
«-r ii^
^lt^t.«^:i^Jj:[.jJ:^i -
"Hd^^
^r* ^iV'^i^^'^'»^5i>'^r^>5ii Hy-^y^i^^r^-Ji^ 5i^^i^-»^ 5i^^r^^vj
£3£ V
>^
ZC ^ â– D
[â–ºulae
Resp.
170
70
160
66
150
60
MO
55
150
50
120
45
110
40
100
35
DO
30
60
25
70
20
60
15
50
10
40
5
30
Temp.
.107
.100
.106
104
103
102
101
100
00
96
97
90
Temp.
Piilse
Resp.
Chart showing exaggerated reaction 12 hours after second injection of tuberculin.
!':"!:â– '!:; i ' I i i i ;-! i i;- i i i i !' i !â– i I!!; 1 ! i j i !
_:.„^...; ,i. i...^...i_.,.i,. ...i....i_..i.:...4. I.. ,...:. .;...,:.„4. ., -f . L |.. ;..4- f-4 - '- 4 -j -i.-.I - 4 - -: -4"-t-+-'-M-
_LJ..J..,.;...4-.J .-.;... i-J. - i^.Ui.. L.X.I.. I. I :...|.. IJ...LJ.X.J..JJ J: - .UJ - Uia-j.-J-.X-xJ-..Li4
! : ; : : I i I : i ! i i ! : : ! ! i i i i i i •■: I ' ! i i I i i i i ! : !
..i...i.4..-ui..j-i.4 - ..iJ-.-i - .i-p<-. -.ui-.!-j.j. - i..r.Ljg:.L. X. j..,L.L
Pulse Resp.
^.i-l-xi......
TtiX-
f—T-f
i_L.i..1
tu:i:r:i:i:i±i-4
ilxixIxiT'T
...4~j- j- L.-i-.-i-4~i - t~l-
J. J 5.
|...i..
j..4^L| - |...f-jXj-...i.^â– .-j - â– [-â– 4â– ..i-4-.i-.â– f.|a - i^^
^ , |..:a.u5-|<:t:!:fjxu44j:4":rffl^^^
,|..a_.
170
70
100
65
150
00
140
55
130
50
120
'15
110
40
100
35
OC
30
CO
25
70
20
CO
l^>
50
10
40
5
30
Chart showing maximum and characteristic reaction 14 hcurs after second injection of^is^mg.
Digitized by
524
VALUE OF TUBERCULIN TEST-NEFF. Jour. M. S. M. S. f
a variable time after the injection. The
uncertainty of some of the general symp-
toms of the reaction, such as increased
pulse rate and the subjective sensations
of the patient, make it imperative that we
place our dependence on the induced
fever. In the classical reaction we have
a rise in temperature of four degrees or
more. As a matter of fact, such an ex-
aggerated reaction is seen in compara-
tively few cases, and we have been com-
pelled to establish a minimum rise, which
to us would signify a characteristic feb-
rile reaction. We have from our experi-
ence fixed the minimum rise of tempera-
ture at two degrees over the highest pre-
liminary temperature. Fever less marked
may be suggestive, but not conclusive.
(4) To the question whether a healed
tubercular lesion can react to tuberculin,
we can only give a reserved opinion. Just
what are the anatomical conditions in a
so-called "recovered" case we can only
conjecture. All opinions must necessar-
ily be modified. Personally, I am rather
skeptical of recovery in many of these
cases. Although perhaps inconsistent, I
would speak for more conservatism when
the percentage of cures is estimated. The
continued absence of bacilli from sputum,
absence of cough, fever, emaciation, and
the negative results of physical examina-
tions have been shown to l^e the objective
signs of recovery.
We have proven in a series of cases,
where marked improvement and apparent
cure have resulted from dietetic-hygienic
treatment, that these cases continue to re-
act to tuberculin. A further study of
these patients has convinced us that the
recoveries were apparent and not real.
Our experience as shown by the tubercu-
lin test has proven to us that these cases
are not cured ; but that the disease should
be considered as temporarily arrested or
in a latent condition.
A REVIEW OF TECHNIQUE.
The patient to be subjected to the test
should have temperatures taken bi-hourly
for a period of at least 24 hours preceding
an injection. These temperature takings
should be supplemented by other temper-
atures which have been taken before the
bi-hourly temperatures had been begua
If the chart of the preliminary tempera-
tures is a favorable one (maximum pre-
liminary temperature not exceeding 99,5
degrees), the preliminary injection of six
mgs. may he given. After 24 hours, if
there is no reaction — namely, a rise of
temperature of two degrees over the high-
est preliminary temperature — a second in-
jection of 12 mgs. may be g^ven. If no
reaction is then secured, there should be
an interval of at least two weeks before
the test is repeated. It seems unneces-
sary to say that other means of diagnosis
should not be neglected. Sputum exam-
inations, weight observations, and physi-
cal examinations should be systematically
and conscientiously made.
The simplicity of the test has led to its
quite general adoption; but as mentioned
before, its limitations have not always
been recognized, and this, with the failure
of the physician to use proper technique,
has to some extent placed the test in dis-
repute. It is entirely consistent with
what we know of the. tuberculin test for
the physician in general practice to use
tuberculin for diagnostic purposes ; but he
must bear in mind that, though the test is
a simple one, it is a delicate one, and its
essentials must be considered and all pos-
sible errors eliminated. If these precau-
tions are used by the physician, the em-
Digitized by VjOOQIC
Dbcbmber, 1904. VALUE OF TUBERCULIN TEST— NEFF.
525
107
^
\ ! !
•
» „.i-..^ -I.-
1
"t'i"'
.1- -
....
-~t~
1
-
~i~-
]
1-
• T
106
M
14..
L-
-
-
— i
r
â–
T^
i
.._
! 1 1
106
|^_.i__l.„
^
â–º
1
1
â– -1-
....
.
i-X^
â„¢| -
I
-
-
^
L
r 'â– ""
104
-.J4-
>
.4-
— L...
1
1-
...
-
—
-
—
â– i+1
j
-t^^-
-
\ j"^
-•
I
...
-._
i-.i J
_
lOd
i3f
-
-
—
„„
....
.._
—
—
....
....
â– f c
-
ii^
i$
102
.J *
-r
~
-
-
„..
-
-4
101
....
—
1
A
l^
<
1
i-J7"^^
100
iS
y
â– n
y
i>
.. ....^
4>
*%
s,
-
V
»*
^
\
-
00
—
—
!W.
J
._
- *.
^
...
~
v^
^
/^
Sii
yr
- i
^
-
06
r^
^
^^
y
„
-
__
~
T
t
...
-
-
07
-
i
00
-
-~
i r ! \
....
.1.
I
Temp.
^
:
1
•-f-
E
—
«
J
/
»
i
.
-
~
—
"i"
Puis*
-
j
-
Reap.
i
1
i
i
T
â–
"
5
^
_
<i * •
is.
...
1
«
••
s-
-S?^
t
:
=
'
s
•
"
:
«
S{M
.ii
H^
^
S*
^^
^
f^
>^^
l^v
^^
^1^
V
^
h
^\
-*
v3|\c^
i.|^
-^^
^
\'>-
1
SS2.
s
,^*
K
u
,
Pulse Resp.
170
70
100
05
ISO
GO
140
55
130
50
120
45
110
40
100
35
00
30
80
25
70
20
00
15
50
10
'10
5
30
Chart showing maximum and characteristic reaction 14 hours after second injection of 12 mg.
.4_.L.i_.i...| . .14...!.:.].. j. .4_.[4 - i. . i. 'l-H-H t
♦-_..:. -4...., _l_.i... 4. ..:..... ^_
i..U..-i-..lJ...Li-..=.X-!-.
....ix!::J:l:t:!:t:H:
tmi
PI*
^
n
:^"^
~>S
MM
i~r"i RrT^i I n-.'^ ! T r
]^= !
Pulse
Resp.
170
70
ICO
O.S
150
00
140
55.
130
50
120
45
JIO
40
100
35
f>0
30
fi<)
25
70
20
rio
15
50
10
40
5
30
Chart showing maximum and characteristic reaction 14 hours after second injection of 12 tpg,
Digitized by
526
VALUE OF TUBERCULIN TEST— NEFF. Jour. M. S. M.S.
ployment by him of the tuberculin test is
practicable and to be commended.
The following conclusions are founded
on 130 men who have been injected with
tulDerculin : Eighty of these patients were
injected for suspected tuberbulosis, and
the remaining 50 were used as control
cases. (It is interesting to note that not
one of these control cases gave a reac-
tion.) Of the 80 patients injected, who
were suspected of having tuberculosis, a
reaction was secured in 26, or 32.5 per
cent. In 20 of these cases physical and
bacteriological examinations were possible
at that time, or a short time subsequently,
and were confirmatory of the disease.
Fourteen of these cases are still under
treatment, 9 have died, and 2 have been
discharged. One of the discharged pa-
tients later succumbed to tuberculosis, and
the other is still living, and unmistakably
tubercular.
Of the 54 cases not reacting where tu-
berculosis was suspected, 3 were cases of
well advanced pulmonary tuberculosis, as
was proven on postmortem. We have
every reason to suppose that in these cases
the reaction was prevented by the pro-
nounced degree of tubercular invasion.
This theory is supported by the fact that
before the injection was made the fever
was practically absent, although physical
examination gave evidence of wide-
spread tubercular disease.
The remaining 51 cases of the series
not reacting have been under observation
for periods extending from six months to
seven years, and repeated examinations
have failed to show any symptoms which
would indicate tubercular trouble. It
should be stated that each of these cases
has received individual study, and has
been subjected to many tuberculin tests
at stated intervals.
SUMMARY.
(1) A reaction to tuberculin is posi-
tive proof of tuberculosis.
(2) The failure to react may be of
negative value if the tuberculin test is
used when the disease is far advanced.
(3) When the errors of the diagnosti-
cians using the tuberculin are eliminated,
the percentage of failures must be exceed-
ingly small.
(4) Owing to the variability of all the